Six-month formulation of prostate cancer drug approved in U.S.
Abbott's lipid disorder treatment approved in new formulation
FDA approves Bristol-Myers Squibb antipsychotic to treat bipolar mania
Purdue Pharma L.P.'s Palladone Capsules approved for pain management
Lilly's drug approved for diabetic peripheral neuropathic pain
Pfizer wins FDA approval for drug to treat acute bipolar mania
FDA approves TNF blocker to improve physical function in RA patients
Merck wins approval for initial treatment of severe hypertension
Topical cream approved for treatment of superficial basal cell carcinoma
FDA approves hyperparathyroidism medication for children and teens
FDA approves Bayer's antibiotic to fight multidrug-resistant S pneumoniae
Combination of Proscar and doxazosin approved for treatment of benign prostatic hyperplasia symptoms
FDA approves Biovail's Cardizem LA for the treatment of angina
New dosage of medication for diarrhea-predominant IBS available
Intermittent dosing of SSRI approved for the treatment of pMDD
New formulation of Imitrex available for treatment of migrane
Expanded indications of provigil for those with excessive sleepiness associated with OSAHS and SWSD
GlaxoSmithKline's Lamictal approved for adults with partial seizures
New formulation of Roche's protease inhibitor Invirase approved
FDA approves more environmentally friendly inhaler from Boehringer Ingelheim
Merck wins approval for fungal infection treatment in febrile neutropenic patients
Remicade approved for first-line treatment of rheumatoid arthritis in the U.S.
Biologic approved to induce major clinical response in RA patients
Novartis drug approved to treat chronic idiopathic constipation
Boehringer Ingelheim's NSAID approved for rheumatoid arthritis
FDA approves Pfizer’s Lipitor to lower risk of heart attacks
Combined with paclitaxel, Gemzar wins U.S. approval for treatment of metastatic breast cancer
Taxotere, combined with prednisone, approved for prostate cancer
FDA approves Vitrase for increased dispersion of other drugs
New formulation of Protonix IV stomach acid suppressant wins FDA approval
Merck's arthritis and pain medicine approved for treatment of migraine
pfizer wins FDA approval for 3-day treatment for acute bacterial sinusitis
FDA approves schizophrenia drug for treatment of bipolar disorder
Eloxatin wins FDA approval for first-line treatment of colon cancer
December 28, 2004
ST. LOUIS (MD Consult) - Barr Pharmaceuticals Inc announced on December 21, 2004, that its subsidiary, Duramed Pharmaceuticals, Inc, has received U.S. Food and Drug Administration (FDA) approval for Enjuvia (synthetic conjugated estrogens, B) 0.3-mg and 0.45-mg tablets. The company's 0.625- and 1.25-mg doses of the drug received FDA approval in May 2004.
Enjuvia is the lowest-dose plant-derived, synthetic conjugated estrogen product approved for the treatment of vasomotor symptoms. The tablets contain a blend of 10 synthetic estrogenic substances, including the component delta 8,9-dehydroestrone sulfate. The patent on Enjuvia expires in 2020.
Barr hopes to launch a 0.9-mg tablet of Enjuvia as well; this dose is awaiting FDA approval.
Estrogen use that is unopposed by progestin is associated with an increased risk of endometrial cancer in postmenopausal women with intact uteri. Estrogens should not be used in women with undiagnosed abnormal genital bleeding, known or suspected breast cancer, estrogen-dependent neoplasia, active deep vein thrombosis, thromboembolic disorders, active or recent arterial thromboembolic disease, or pregnancy. Estrogens should not be used for the prevention of cardiovascular disease. The Women's Health Initiative study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis associated with estrogen. Due to these risks, estrogen with or without progestins should be prescribed at the lowest effective dose for the shortest duration, while maintaining consistency with treatment goals and risks for each individual woman; periodic clinical reevaluation of such therapy is also advised.
December 20, 2004
ST. LOUIS (MD Consult) - On December 17, 2004, the U.S. Food and Drug Administration approved a new 500-mg tablet formulation of the HIV protease inhibitor, Invirase (saquinavir mesylate). The dosage and administration for Invirase in adults (older than the age of 16 years) is 1,000 mg twice a day (taken as either two 500-mg tablets or five 200-mg capsules) in combination with ritonavir 100 mg twice a day, to be taken after a meal. The new tablet formulation reduces the pill burden compared with the capsule formulation.
Below is the Dosage and Administration section as it appears in the package insert.
| Dosage and Administration Invirase capsules and Fortovase (saquinavir) soft gelatin capsules are not bioequivalent and cannot be used interchangeably. Invirase may be used only if it is combined with ritonavir because it significantly inhibits saquinavir's metabolism to provide plasma saquinavir levels at least equal to those achieved with Fortovase at the recommended dose of 1,200 mg tid. When using saquinavir as the sole protease inhibitor in an antiretroviral regimen, Fortovase is the recommended formulation (see Clinical Pharmacology: Drug Interactions). Adults (Over the Age of 16 Years)
|
In combination with ritonavir and other antiretroviral agents, Invirase is inicated for the treatment of HIV infection. The efficacy of Invirase with ritonavir or Fortovase (with or without ritonavir coadministration) has not been compared against the efficacy of antiretroviral regimens currently considered standard of care.
Invirase is contraindicated in patients with clinically significant hypersensitivity to saquinavir or to any of the components contained in the capsule. When administered with ritonavir, Invirase is contraindicated in patients with severe hepatic impairment.
Invirase/ritonavir should not be administered concurrently with terfenadine, cisapride, astemizole, pimozide, triazolam, midazolam, or ergot derivatives. Inhibition of CYP3A4 by saquinavir could result in elevated plasma concentrations of these drugs, potentially causing serious life-threatening reactions such as cardiac arrhythmias or prolonged sedation.
Invirase is a product of Roche Laboratories, Inc, of Nutley, New Jersey. Complete product information is available at rocheusa.com/products/invirase/pi.pdf.
December 16, 2004
ST. LOUIS (MD Consult) - Canadian pharmaceutical company QLT Inc announced on December 15, 2004, it has received approval from the U.S. Food and Drug Administration (FDA) for a 6-month formulation of Eligard 45 mg (leuprolide acetate for injectable suspension). The medication is indicated for the palliative treatment of advanced prostate cancer.
Eligard is a luteinizing hormone-releasing hormone (LHRH) agonist. It works by lowering the levels of testosterone in the body, which may result in a reduction of symptoms related to prostate cancer. According to QLT, about 220,000 new cases of prostate cancer are diagnosed each year.
The 6-month Eligard product is the first of its kind to be approved for prostate cancer by the FDA. Eligard is already approved for 1-month (7.5 mg), 3-month (22.5 mg), and 4-month (30 mg) dosages.
Sustained levels of leuprolide decrease testosterone levels to suppress tumor growth in patients with hormone-responsive prostate cancer. Liquid Eligard products are injected subcutaneously with a small-gauge needle, forming a solid implant in the body that slowly releases leuprolide as the implant is bioabsorbed.
Eligard 45 mg, like other hormonal treatments for prostate cancer, causes a transient increase in serum concentrations of testosterone during the first week of treatment. Patients may experience worsening of symptoms or onset of new signs and symptoms during the first few weeks of treatment. Response to Eligard 45 mg should be monitored by measuring serum concentrations of testosterone and prostate-specific antigen periodically.
Eligard is a registered trademark of Sanofi-Aventis and was developed by Vancouver, BC–based QLT's subsidiary QLT USA, Inc. For more information, visit qltinc.com.
November 30, 2004
ST. LOUIS (MD Consult) - Boehringer Ingelheim Pharmaceuticals, Inc, announced on November 18, 2004, that the U.S. Food and Drug Administration had approved Atrovent HFA (ipratropium bromide HFA) Inhalation Aerosol as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Atrovent HFA is a new drug formulation that was developed to provide COPD patients a therapeutic benefit comparable to Atrovent Inhalation Aerosol, a leading treatment for COPD that contained chlorofluorocarbons (CFCs). New Atrovent HFA is formulated with a non-CFC propellant called hydrofluoroalkane (HFA) that was developed in response to the Montreal Protocol on Substances that Deplete the Ozone Layer. The Montreal Protocol, a global agreement to protect the ozone layer, requires the removal of ozone-depleting substances including CFC propellants. The agreement recognizes the special needs of persons throughout the world who have respiratory ailments and require inhalation therapy, as well as the essential role of the pressurized metered-dose inhaler, and therefore grants these products an exemption until they can be replaced by non-CFC alternatives. Boehringer Ingelheim supports the Montreal Protocol and will replace the company's CFC inhalers as the replacement products become available.
In 2005, Boehringer Ingelheim will distribute educational materials about new Atrovent HFA to patients through doctors and pharmacies, while it begins phasing out the Atrovent (CFC) metered-dose inhalers.
A 12-week, double-blind, placebo- and active-controlled trial established the comparable safety and efficacy of Atrovent HFA to Atrovent (CFC). The data were confirmed in a 1-year randomized, open-label, parallel-group multicenter trial comparing Atrovent HFA to Atrovent (CFC). Both products were shown to be safe and effective with no statistically significant differences between them. Both products significantly improved lung function in patients with COPD. The most common drug-related adverse events in clinical trials with Atrovent HFA were dry mouth (1.6%) and taste perversion (bitter taste) (0.9%).
Atrovent HFA is contraindicated in patients with a history of hypersensitivity to ipratropium bromide or other Atrovent HFA components and should also not be taken by patients hypersensitive to atropine or its derivatives.
Atrovent HFA is not indicated for the initial treatment of acute episodes of bronchospasm for which rapid response is required. Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.
COPD, the fourth leading cause of death in the United States, is a respiratory disease primarily caused by smoking that is more commonly known as chronic bronchitis or emphysema. There are an estimated 24 million Americans who currently have COPD; however, only 10 million have been diagnosed with the illness and approximately 6 million are receiving therapy. Most people with COPD are at least 40 years old when they begin to notice symptoms, which may include shortness of breath after exertion, chronic cough, excess mucus production, and wheezing.
Boehringer Ingelheim Pharmaceuticals, Inc, based in Ridgefield, Conn, is a member of the Boehringer Ingelheim group of companies, which are headquartered in Ingelheim, Germany.
November 30, 2004
ST. LOUIS (MD Consult) - AstraZeneca announced on November 29, 2004, that a new indication for its prescription proton pump inhibitor Nexium (esomeprazole magnesium) had been approved by the U.S. Food and Drug Administration (FDA). Nexium is now indicated for reducing the risk of gastric ulcers developing among at-risk patients on continuous therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). The FDA also issued an approvable letter for the indication of the healing of gastric ulcers associated with NSAID therapy.
"NSAIDs play a crucial role in providing relief to many pain sufferers. However, potentially serious gastrointestinal side effects are often a deterrent to continue long-term treatment," says James Scheiman, MD, gastroenterologist at University of Michigan Health System. "Health care professionals now can offer their patients on NSAID therapy, who may be at risk for developing gastric ulcers, a therapeutic option that may lessen possibility of such stomach injury occurring."
A total of 1,429 patients (aged 19-89 years) were evaluated in 2 separate multicenter, double-blind, placebo-controlled clinical studies. Patients included in both studies had a chronic condition requiring daily NSAID treatment (including cyclo-oxygenase 2–selective NSAIDs). They were randomly assigned to receive treatment with Nexium (40 or 20 mg once daily) or placebo for up to 6 months. Nexium 20 mg and 40 mg demonstrated comparable benefits in providing risk reduction, with the proportion of NSAID patients remaining free of gastric ulcers ranging from 95.4% to 96.7% in one study and 94.7% to 95.3% in the other.
It is estimated that over 100 million prescriptions are written for NSAIDs each year in the United States. Every day, approximately 30 million people worldwide take NSAIDs. NSAIDs, which include such popular pain medications as aspirin, ibuprofen, and naproxen, are a common cause of stomach ulcers and have been associated with adverse effects ranging from stomach upset to potentially life-threatening stomach bleeding. In fact, NSAID use leads to more than 103,000 hospitalizations and 16,500 deaths each year in the United States.
Beyond its newest indication in the United States for the reduction in the occurrence of gastric ulcers associated with continuous NSAIDs therapy in patients at risk for developing gastric ulcers, Nexium is also approved for healing erosive esophagitis. Studies show that up to 94% of patients were healed with Nexium. Most erosions heal in 4 to 8 weeks. Individual results may vary, and only a doctor using endoscopy can determine whether erosions to the esophagus have occurred. The drug is also indicated for treating heartburn and other symptoms associated with acid reflux disease.
November 15, 2004
ST. LOUIS (MD Consult) - Sanofi-Synthelabo announced on November 5, 2004, that the U.S. Food and Drug Administration (FDA) had approved Eloxatin (oxaliplatin for injection), in combination with conventional chemotherapy (infusional 5-fluorouracil/leucovorin [5-FU/LV]), for the adjuvant (postsurgical) treatment of patients with stage III colon cancer who have undergone complete resection of the primary tumor.
The American Cancer Society (ACS) estimates that, by the end of 2004, 106,370 new cases of colon cancer will have been diagnosed in the United States. According to the ACS, colorectal cancer is the second leading cause of malignancy-related death in the United States, accounting for 10% to 15% of all cancer deaths. Over a lifetime, about 1 in 18 people develops colorectal cancer, and, each year, more than 56,000 people die from it in the United States. Most patients undergo surgery to remove the primary tumor, but many of these patients will still be at risk for recurrence. This latest approval of Eloxatin helps to decrease the risk of cancer recurrence and spread.
The FDA based its decision on results from the MOSAIC study, a large, international, randomized phase III trial involving 2,246 patients in 146 centers. At a median follow-up of 4 years, there was a statistically significant improvement in the primary end point, disease-free survival (DFS), for the Eloxatin combination compared with infusional 5-FU/LV, both in the overall study population (4-year DFS: 76% vs 69%; P = .0008) and in the subgroup with stage III disease (4-year DFS: 70% vs 61%; P = .002). Survival data were not mature at the time of the analysis. No statistical difference in overall survival was shown between the treatment arms in the overall study population or in stage III patients. No statistical difference was observed either in DFS or survival in stage II patients.
These results demonstrated that the addition of Eloxatin to conventional adjuvant chemotherapy for colon cancer (5-FU/LV) reduced the risk of recurrence of cancer by 24% in the overall patient population who had undergone surgery to remove a primary tumor.
In the United States, Eloxatin received approval on January 9, 2004, for the first-line treatment of advanced carcinoma of the colon or rectum in combination with infusional 5-FU/LV. This combination had had previously (August 2002) received approval for second-line treatment of this patient population.
Eloxatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.
Anaphylactic-like reactions to Eloxatin have been reported, and may occur within minutes of Eloxatin administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms.
Adjuvant Colon Cancer Setting
In the context of adjuvant treatment of colon cancer, the incidence of grade 3 or 4 events was 70% and 31% on the Eloxatin combination arm and infusional 5-FU/LV arm, respectively. Granulocytopenia, paresthesia, diarrhea, vomiting, and nausea were the most common grade 3 or 4 adverse events. Paresthesia was seen in 92% of patients taking the Eloxatin combination; 21% had residual paresthesia at 18-month follow-up. Three percent and 0.5% had grade 2 or 3 paresthesias, respectively, at 18-month follow-up. Grade 3 or 4 hypersensitivity was noted in 3% and may require discontinuation of therapy. Hepatotoxicity, evidenced by increase in transaminases (57% vs 34%) and alkaline phosphates (42% vs 20%), was observed more commonly in the Eloxatin arm. The incidence of increased bilirubin was similar on both arms. Hepatic vascular disorders should be considered and investigated if abnormal liver function tests or portal hypertension are present and cannot be explained by liver metastases or other known etiologies.
Advanced Colorectal Cancer Setting
Fatigue, neuropathy, nausea, vomiting, diarrhea, stomatitis, neutropenia, and thrombocytopenia were the more common adverse events in the setting of advanced colorectal cancer. Neither febrile neutropenia nor requirement for platelet transfusion was increased as compared with treatment with irinotecan plus bolus 5-FU/LV. Eloxatin has been associated with pulmonary fibrosis (<1% of study patients), which may be fatal. There have been reports from clinical trials and postmarketing surveillance of prolonged prothrombin time and international normalized ratio occasionally associated with hemorrhage in patients who received Eloxatin plus 5-FU/LV while taking anticoagulants. Patients requiring oral anticoagulants may require closer monitoring. Hypersensitivity has been observed (<2% grade 3/4) in clinical studies and trials. It was usually managed with standard epinephrine, corticosteroid, and antihistamine therapy and may require discontinuation of Eloxatin therapy.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications, is available at fda.gov/cder/foi/label/2004/021492s004lbl.pdf.
November 9, 2004
ST. LOUIS (MD Consult) - On November 5, 2004, Illinois-based health care company Abbott announced it had received U.S. Food and Drug Administration approval to market a new formulation of TriCor (fenofibrate) tablets for the treatment of lipid disorders such as mixed dyslipidemia. The new formulation of TriCor can be taken with or without food.
Until now, TriCor had to be taken with food to enable optimal absorption of TriCor in the body. Taking the previous version of TriCor with food (compared with taking it on an empty stomach) could result in a difference of approximately 35% in the body's absorption of the medicine. New TriCor 145- and 48-mg tablets offer the same effectiveness at a lower dose than the previous 160- and 54-mg tablets, but the medication can now be taken with or without food. TriCor remains a once-daily treatment
Nanoparticle technology was applied in the development of the new formulation of TriCor to allow the drug to dissolve faster and more completely in the gastrointestinal tract, which makes the drug more easily absorbed by the body.
TriCor, in addition to appropriate diet, is used to treat adults with high cholesterol or mixed dyslipidemia, with or without elevated triglycerides, after results of lifestyle changes are unsuccessful. TriCor reduces elevated low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and apolipoprotein B and increases high-density lipoprotein (HDL) cholesterol.
A recent report published in Circulation, which proposes changes to the National Cholesterol Education Program Adult Treatment Panel III Guidelines, stated that one class of drugs that modestly raises HDL cholesterol is the fibrate class. The report also suggests that treatment with fibrates, a class of drugs that includes fenofibrate, may have a complementary role in the treatment of patients with high triglyceride and low-HDL cholesterol levels.
Cholesterol is a natural, waxy, fat-like substance found in the body. There are 2 sources of cholesterol in the body: some cholesterol is made in the liver, and the rest comes primarily from animal products that are eaten, such as meats, poultry, eggs, and cheese.
Elevated LDL cholesterol can lead to heart attacks and other cardiovascular-related problems. Unlike high-LDL cholesterol, a high-HDL cholesterol level is considered good because it can often help reduce the risks for heart disease. Triglycerides are another type of fat in the bloodstream. It is not clear whether high triglyceride levels alone increase the risk of heart disease. However, an excessive amount of triglycerides can be a medical concern. The independent effect of raising HDL cholesterol or lowering triglycerides on the risk of cardiovascular morbidity and mortality has not been determined with TriCor.
TriCor should not be taken by people with serious liver, kidney, or gallbladder disease or by those who may be allergic or sensitive to the drug.
The combined use of TriCor and statin drugs is not advised because it can produce potentially serious adverse effects that could lead to acute renal failure. Therefore, it is important for health care professionals to determine whether the benefits of the combined use of these drugs are likely to outweigh the increased risks of the drug combination.
TriCor tablets may cause changes in laboratory reports, especially in liver chemistry results. Regular periodic liver tests should be performed while patients are taking TriCor. Patients should contact their doctors if they feel pain in the stomach area while taking TriCor; this can be a sign of gallstones or inflammation of the pancreas. TriCor can cause muscle pain or serious muscle disease, allergic-type reactions, and possible changes in blood chemistry. If patients experience unexpected muscle pain, tenderness, or weakness while taking TriCor, a health care provider should be contacted immediately.
Patients should notify a doctor if they are taking any other drugs while taking TriCor, including any other cholesterol-lowering medications. TriCor may have an effect on drugs that help prevent blood clotting, such as the blood thinner warfarin sodium, and doctors should monitor blood-clotting tests more frequently during administration of this medication.
Patients should tell their doctors about any adverse effects they experience, including breathing problems, back pain, and headaches.
For more information about TriCor tablets, including full prescribing information, visit TriCortablets.com.
November 4, 2004
ST. LOUIS (MD Consult) - On October 26, 2004, Johnson & Johnson announced the U.S. Food and Drug Administration (FDA) had approved Concerta (methylphenidate hydrochloride) Extended-release Tablets CII for use in adolescents with attention deficit–hyperactivity disorder (ADHD), expanding the product's labeling to include a 72-mg dosing regimen.
The administration of Concerta 72 mg may be warranted when symptoms of ADHD are not responding to lower doses of the medication. Previous clinical research demonstrates that a few weeks after taking an initial dose of Concerta, 8 of 10 patients were given higher doses of the medication to achieve effective symptom management. In a clinical study of adolescents aged 13 to 18 years, Concerta 72 mg significantly reduced ADHD symptoms.
Concerta tablets are currently available in 18-, 27-, 36-, and 54-mg strengths. There is no 72-mg tablet. Although physicians will determine how the medication should best be taken by adolescents for whom it is prescribed, it is believed Concerta 72 mg will most often be taken as a once-a-day morning dose of two 36-mg Concerta tablets.
Symptoms of ADHD generally first occur before the age of 7 years. The classic ADHD symptoms include inattention, distractibility, impulsivity, and hyperactivity. Some experts focus on deficits in "executive functions" in the brain to understand and describe ADHD behaviors. Such impaired executive functions in ADHD children can cause problems such as an inability to hold information in short-term memory, impaired organization and planning skills, and an inability to keep emotions from becoming overpowering.
Concerta CII is a once-daily extended-release formulation of methylphenidate approved to treat ADHD. The efficacy of Concerta has been demonstrated in studies conducted in children and adolescents. Only a doctor can determine whether medication is the right treatment for individuals with ADHD.
Concerta uses an extended-release delivery system to deliver a controlled rate of medication throughout the day. One advantage of this system is the minimization of the ups and downs within blood levels experienced with stimulant medications taken several times a day.
Concerta should not be taken by patients with significant anxiety, tension, or agitation; allergies to methylphenidate or other ingredients in Concerta; glaucoma, Tourette's syndrome, tics, or family history of Tourette's syndrome; or current/recent use of monoamine oxidase inhibitors. Abuse of methylphenidate can lead to dependence. Concerta should not be taken by children younger than 6 years of age.
In clinical studies with children using Concerta, the most common adverse effects were headache, stomach pain, sleeplessness, and decreased appetite. In clinical studies with adolescents using Concerta, the most common adverse effects were headache, accidental injury, and sleeplessness.
For more information about Concerta, including full U.S. prescribing information, visit concerta.net.
November 4, 2004
ST. LOUIS (MD Consult) - Ortho-McNeil Pharmaceutical, Inc, announced on October 28, 2004, that the U.S. Food and Drug Administration had approved a new, once-a-day formulation of Levaquin (levofloxacin) Oral Solution, 25 mg/mL. The new liquid formulation provides a convenient option for adult patients who have trouble swallowing tablets. According to published data, as many as 1 in 17 people may experience trouble swallowing; this includes 25% of all hospitalized patients and up to 40% of patients in nursing homes.
Levaquin Oral Solution is indicated to treat infections currently approved for the tablet and intravenous formulations and is effective against Staphylococcus aureus, Streptococcus pneumoniae (including all multiple drug–resistant strains), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae. The new oral solution has the same efficacy as the tablet formulation and continues to provide the flexible dosing required for renally impaired patients. Levaquin oral solution should be taken 1 hour before or 2 hours after eating.
Levaquin has demonstrated safety and a low incidence of gastrointestinal and central nervous system adverse events, including nausea (1.2%), diarrhea (1.0%), insomnia (0.4%), and dizziness (0.3%).
The safety and efficacy of levofloxacin in pediatric patients, adolescents (younger than 18 years), pregnant women, and nursing mothers have not been established. Levofloxacin is contraindicated in persons with a history of hypersensitivity to levofloxacin, quinolone antimicrobial agents, or any other components of this product. Serious and occasionally fatal hypersensitivity or anaphylactic reactions have been reported in patients receiving therapy with quinolones, including levofloxacin. These reactions often occur after the first dose is taken. The drug should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity.
As with other quinolones, levofloxacin should be used with caution in patients with known or suspected central nervous system disorders or peripheral neuropathy or in patients who have a predisposition to seizures.
Antacids containing magnesium, aluminum, or sucralfate; metal cations such as iron; and multivitamin preparations with zinc or didanosine (Videx; Bristol-Myers Squibb) chewable/buffered tablets or the pediatric powder for oral solution should be taken at least 2 hours before or 2 hours after levofloxacin administration. For the full U.S. prescribing information, including warnings, precautions, and additional adverse reactions associated with Levaquin, visit levaquin.com.
Levaquin Oral Solution is marketed in the United States by Ortho-McNeil Pharmaceutical, Inc, which is a Johnson & Johnson company based in Raritan, NJ.
November 2, 2004
ST. LOUIS (MD Consult) - On October 25, 2004, Connetics Corporation, a pharmaceutical company specializing in dermatology products, announced that the U.S. Food and Drug Administration had approved Evoclin (clindamycin) Foam 1% for the treatment of acne vulgaris. Evoclin (formerly referred to as "Actiza") will be available in the fourth quarter of 2004 in 50-g and 100-g unit sizes.
According to an Evoclin study investigator, the once-a-day medication leaves minimal residue, dissolves rapidly on contact with skin, and is easy to apply. Evoclin is indicated for topical application in the treatment of acne vulgaris. Treatment with this drug is contraindicated in persons with a history of hypersensitivity to preparations containing clindamycin or lincomycin, a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis.
Approximately 17 million people in the United States have acne, resulting in approximately 5.5 million office visits per year.
Connetics Corporation is based in Palo Alto, California. For more information about the company and its products, visit connetics.com.
November 2, 2004
ST. LOUIS (MD Consult) - In a press release dated October 29, 2004, Swiss pharmaceutical company Novartis announced its medication Femara (letrozole) had won approval by the U.S. Food and Drug Administration (FDA) for the extended adjuvant treatment of postmenopausal women with early breast cancer who have received adjuvant (postsurgery) tamoxifen therapy for 5 years.
The term extended adjuvant describes the period after adjuvant (postsurgery) treatment with tamoxifen. Even years after breast cancer diagnosis and primary treatment, the ongoing risk of breast cancer recurrence remains significant for all patients. Globally, approximately one third of women with estrogen receptor–positive early breast cancer experience a recurrence, and over half of those recurrences occur more than 5 years after surgery. Although tamoxifen is beneficial for 5 years after surgery, if used beyond that period, the risks associated with it outweigh the benefits. Extended adjuvant treatment with Femara is the first therapy to effectively reduce the ongoing risk of breast cancer recurrence.
The approval for the extended adjuvant indication was based on results from the landmark, international, independent MA-17 study, which included more than 5,100 postmenopausal women and was coordinated by the National Cancer Institute of Canada Clinical Trials Group at Queens University in Kingston, Ontario, Canada, and supported by Novartis. Initial results were published in The New England Journal of Medicine in October 2003.
The study showed that Femara reduced the risk of cancer coming back by 38% and significantly increased a woman's chance of staying cancer-free. This is particularly important because when breast cancer recurs, it has very often metastasized beyond the breast, which can have serious consequences. Femara also greatly reduced the chance of breast cancer returning to another part of the body by 39%.
Femara is a once-a-day oral aromatase inhibitor that is also indicated for first-line treatment of postmenopausal women with hormone receptor–positive or hormone receptor–unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression after antiestrogen therapy, and as neo-adjuvant (preoperative) therapy. Not all indications are available in every country.
The most common adverse events experienced with Femara are hot flashes, arthralgia/arthritis, and myalgia. Other commonly reported adverse reactions include nausea, fatigue, anorexia, appetite increase, peripheral edema, headache, dizziness, vomiting, dyspepsia, constipation, diarrhea, alopecia, increased sweating, rash, myalgia, bone pain, arthritis/arthralgia, and weight increase.
Femara is contraindicated in women who are pregnant or breast-feeding as well as in women with premenopausal endocrine hormone receptor status. Femara is contraindicated in patients with known hypersensitivity to letrozole or any of its excipients.
Additional information regarding Femara or Novartis Oncology can be found by visiting femara.com or novartisoncology.com.
October 27, 2004
ST. LOUIS (MD Consult) - Eisai Global Clinical Development announced on October 21, 2004, that the U.S. Food and Drug Administration (FDA) had approved Aricept (donepezil hydrochloride) orally disintegrating tablets (ODT), the first such medication approved by the FDA to treat the symptoms of mild to moderate Alzheimer's disease.
The new dosage form was designed to make administration easier for patients. Studies have shown that patients with Alzheimer's disease may develop difficulty with swallowing.
Aricept ODT will be available in the United States in 5- and 10-mg tablets in blister packaging and will provide the same dosage strength as Aricept tablets. It will be available in the second quarter of 2005 and will be copromoted by Eisai Inc and Pfizer Inc.
Although there is no cure for Alzheimer's disease, medical treatments are available to manage symptoms of the disease. Once-a-day prescription Aricept is indicated for mild to moderate Alzheimer's disease.
Aricept is generally well tolerated, but people at risk for stomach ulcers should inform their doctors before beginning treatment because serious stomach problems, such as bleeding, could be exacerbated by this medication.
According to Eisai, some persons taking Aricept may vomit, have nausea or diarrhea, or experience troubled sleep. Some may experience fainting, fatigue, muscle cramps, or loss of appetite. In studies, these adverse effects were usually mild and went away over time.
For full prescribing information, visit aricept.com.
October 13, 2004
ST. LOUIS (MD Consult) - Merck & Co, Inc, announced on October 12, 2004, that the U.S. Food and Drug Administration had approved the once-daily antifungal medicine Cancidas (caspofungin acetate) as empirical therapy for presumed fungal infections in febrile neutropenic patients.
Approval was based on results from the largest prospective antifungal empirical therapy trial published to date involving treatment of neutropenic patients with persistent fever. This study, recently published in The New England Journal of Medicine, showed that Cancidas was as effective as AmBisome (amphotericin B) for empiric therapy of presumed fungal infections in these patients.
"Invasive fungal infections are particularly life-threatening in neutropenic patients undergoing chemotherapy for malignancies such as acute myelogenous leukemia and non-Hodgkin's lymphoma and those who undergo hematopoietic stem cell transplantation," said Issam Raad, professor of medicine, and chairman of infectious diseases, infection control, and employee health at the University of Texas M.D. Anderson Cancer Center, Houston. "When clinical signs, such as persistent fever despite the presence of broad spectrum antibiotics, suggest the possible presence of a fungal infection in this population, it is important to intervene with an effective treatment."
Cancidas is the first in a class of antifungal drugs called echinocandins that inhibit fungal cell wall synthesis of β (1,3)-D-glucan, an integral component of the fungal cell wall. Cancidas is contraindicated in patients with hypersensitivity to any component of the product. Concomitant use of Cancidas with cyclosporine is not recommended unless the potential benefit outweighs the potential risk to the patient.
The multicenter, double-blind trial showed that Cancidas (n = 556) was as effective as AmBisome (n = 539), a frequently used antifungal agent, in treating presumed fungal infections in neutropenic patients with persistent fever.
The study enrolled patients who had received chemotherapy or undergone hematopoietic stem-cell transplantation (HSCT, such as bone marrow transplantation) and presented with neutropenia (<500 cells/mm3 for 96 hours) and fever (>38.0°C [100.4°F]) that did not respond to antibacterial therapy. An overall favorable response required meeting each of the following 5 criteria: (1) survival for 7 days after completion of study therapy; (2) no breakthrough fungal infections during treatment or within 7 days after the end of therapy; (3) no discontinuation of study drug because of drug-related toxicity or lack of efficacy; (4) resolution of fever during the period of neutropenia; and (5) successful treatment of any baseline fungal infection (identified on days 1 and 2).
Overall favorable response rates showed Cancidas to be as effective as AmBisome with 33.9% and 33.7% of patients, respectively, meeting all 5 criteria in each group. Favorable response rates for Cancidas and AmBisome on each of the following strictly defined components of the primary end point were:
The safety profile of Cancidas was superior to AmBisome with regard to several prespecified safety measures. Among patients with normal to moderately impaired renal function, the occurrence of nephrotoxicity was significantly lower for patients treated with Cancidas versus AmBisome (2.6% vs 11.5%). The percentage of patients with either a drug-related clinical or drug-related laboratory adverse experience was significantly lower among patients receiving Cancidas versus AmBisome (54.4% vs 69.3%). The percentage of patients who discontinued therapy due to a drug-related clinical or laboratory adverse experience was significantly lower among patients receiving Cancidas versus AmBisome (5.0% vs 8.0%). The proportion of patients who experienced an infusion-related adverse event was significantly lower in patients treated with Cancidas versus AmBisome (35.1% vs 51.6%).
In this study, the most common drug-related clinical adverse experiences in patients treated with Cancidas were fever (17%), chills (13.8%), rash (6.2%), headache (4.3%), hypokalemia (3.7%), and vomiting and nausea (3.5%).
Laboratory abnormalities in liver function test results have been seen in healthy volunteers and in patients treated with Cancidas. In some patients with serious underlying conditions who were receiving multiple concomitant medications along with Cancidas, clinical hepatic abnormalities have also occurred. Isolated cases of significant hepatic dysfunction, hepatitis, or worsening hepatic failure have been reported in patients; a causal relationship to Cancidas has not been established. Patients who develop abnormal liver function tests during Cancidas therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing Cancidas therapy.
For patients receiving Cancidas and tacrolimus, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended. Patients taking rifampin should receive 70 mg of Cancidas daily. When Cancidas is coadministered with inducers of drug clearance, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a daily dose of 70 mg of Cancidas should be considered.
Cancidas should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether caspofungin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Cancidas is administered to a nursing woman.
Possible histamine-mediated symptoms have been reported, including isolated reports of rash, facial swelling, pruritus, sensation of warmth, and bronchospasm.
The Caspofungin versus Liposomal Amphotericin B for Empirical Antifungal Therapy in Persistently Febrile Neutropenic Patients study was a prospective, double-blind study conducted from January 2000 through August 2002 at 116 sites in the United States and 25 other countries. An independent Data and Safety Monitoring Board monitored all blinded safety data and, at a predefined point (after 512 patients completed the study), reviewed the unblinded efficacy and safety data to assess whether the study should continue. No changes to the study conduct were made based on this review. An Adjudication Committee reviewed blinded data from all cases of suspected fungal infection to determine, according to international criteria, whether an invasive fungal infection was present.
Patients enrolled were men and women older than age 16 years who had received chemotherapy for malignancy or undergone HSCT, had documented neutropenia (absolute neutrophil count, <500/µL) for at least 96 hours that was not expected to dissipate within 48 hours, had fever higher than 38.0°C at randomization, and had received more than 96 hours of parenteral systemic antibacterial therapy before enrollment. Patients received either intravenous caspofungin (70 mg once on day 1 and 50 mg once daily thereafter) plus placebo to liposomal amphotericin B or liposomal amphotericin B (3.0 mg/kg once daily) plus placebo to caspofungin.
Cancidas is an intravenous antifungal medicine that was first approved in 2001 for the treatment of invasive aspergillosis in patients who do not respond to or cannot tolerate other antifungal treatments. Cancidas is indicated for the first-line treatment of candidemia and other Candida infections—intra-abdominal abscesses, peritonitis, and pleural space infections—and is also approved for the treatment of esophageal candidiasis.
For more information, visit merck.com.
October 4, 2004
ST. LOUIS (MD Consult) - On October 1, 2004, Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co, Ltd, announced that the U.S. Food and Drug Administration (FDA) had approved Abilify (aripiprazole) for the treatment of acute bipolar mania, including manic and mixed episodes associated with bipolar disorder.
The FDA approval is based on positive results from 2 placebo-controlled, 3-week trials of 516 hospitalized patients with bipolar I disorder who were experiencing an acute manic or mixed episode. In these studies, Abilify demonstrated significant improvement in the symptoms of acute manic or mixed episodes. The most common adverse effects reported in clinical trials (=5% incidence and occurring at least twice as frequently in the Abilify-treated group compared with the placebo group) were akathisia, constipation, and accidental injury. The rate of discontinuation due to adverse effect was low (aripiprazole-treated, 11%; placebo-treated, 9%). In these clinical trials with Abilify, there was no significant difference from placebo with respect to weight gain, blood sugar levels, or lipids. The proportion of patients meeting a weight gain criterion of =7% of body weight was 3% for Abilify compared with 2% for placebo.
In short-term, placebo-controlled trials of bipolar mania, somnolence was reported in 14% of patients taking Abilify compared with 7% of patients receiving placebo.
According to Bristol-Myers Squibb, bipolar I disorder affects more than 2 million Americans, and onset generally occurs before the age of 30 years. Bipolar I disorder can include manic, depressive, or mixed phases or episodes. During the manic phase of the illness, patients experience elation of mood and impairment of judgment, and they are likely to deny that they are ill and need help. During the depressive phase, patients may feel so hopeless that they are incapable of seeking or accepting help, and they may believe that they cannot be helped. Mixed episodes involve the simultaneous occurrence of depressive and manic symptoms. People with bipolar I disorder may also experience some psychotic symptoms, including hallucinations and paranoia. The duration of mood episodes range from hours or days to many months. Bipolar I disorder can be difficult to recognize, and even after a diagnosis is made it is often extremely challenging to convince a person with bipolar I disorder to seek and maintain treatment.
A rare but potentially fatal complex of symptoms referred to as neuroleptic malignant syndrome has been reported with antipsychotic medicines, including Abilify. Another condition associated with these medicines is tardive dyskinesia.
Hyperglycemia, in some cases extreme and associated with coma or death, has been reported in patients treated with atypical antipsychotics, including Abilify. It is important that patients tell their health care providers if they are diabetic, have risk factors for diabetes (eg, obesity, family history of diabetes), or are experiencing unexpected increases in thirst, urination, or hunger. Before starting treatment with atypical antipsychotics, patients should have their glucose levels tested; they should also be monitored during treatment.
Orthostatic hypotension has also been reported with these medicines. Abilify should be used cautiously if a patient has a history of seizures.
Patients should not drive or operate heavy machinery until they know how Abilify affects them.
Patients should talk to their health care providers if they are pregnant or intend to become pregnant. Patients should also discuss with their health care providers all prescription and non-prescription medicines they are taking or plan to take.
Other common adverse effects associated with Abilify are headache, agitation, anxiety, insomnia, nausea, upset stomach, sleepiness, akathisia, lightheadedness, vomiting, constipation, and tremors.
Abilify was approved by the FDA in 2002 for the treatment of schizophrenia. The efficacy and tolerability of Abilify in schizophrenia was established by short-term and longer-term controlled trials.
For more details including full prescribing information, visit ABILIFY.com.
October 1, 2004
ST. LOUIS (MD Consult) - On September 30, 2004, Centocor, Inc, announced that the U.S. Food and Drug Administration (FDA) had approved an expanded label for Remicade (infliximab) in combination with methotrexate (Remicade regimen), as a first-line regimen to treat patients with moderate to severe rheumatoid arthritis (RA). The expanded label eliminates the requirement that patients must fail to respond to methotrexate, the current standard of treatment for RA, before starting on the Remicade regimen. This regimen has been shown to reduce signs and symptoms, inhibit further joint destruction, and improve physical function.
Early intervention is critical to change the course of joint destruction in this debilitating disease. In the Active Controlled Study of Patients Receiving Infliximab for Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) study, more than 80% of patients had evidence of erosive joint damage despite the fact that the median disease duration was only 7 months. This study demonstrated that the Remicade regimen was superior to methotrexate alone in changing the course of the disease when given early. The majority of patients treated with the Remicade regimen experienced no progression of structural damage, whereas the majority of patients treated with methotrexate alone progressed significantly despite titration to high doses of methotrexate.
"The ASPIRE trial demonstrated that with early, intensive intervention patients can achieve substantial symptomatic improvement," said David E. Yocum, MD, director, Arizona Arthritis Center, the University of Arizona College of Medicine, and ASPIRE investigator. "Moreover, in a subset of patients without joint damage at baseline, Remicade plus methotrexate provided greater benefit than methotrexate alone in maintaining an erosion-free state."
The FDA approval is based on the results of ASPIRE, the largest controlled trial ever conducted exclusively in RA patients with early disease, (< 3 years' duration), which found Remicade plus methotrexate to be superior to methotrexate alone in patients with moderately to severely active disease. ASPIRE was a 54-week, randomized, double blind, active control study involving 1,004 patients with early disease enrolled in 125 centers in North America and Europe. At randomization, all patients received methotrexate and either placebo, 3 mg/kg of Remicade, or 6 mg/kg of Remicade at weeks 0, 2, and 6 and then every 8 weeks thereafter. The ASPIRE trial demonstrated superiority of the Remicade regimen over methotrexate alone on all 3 primary end points, including reduction of signs and symptoms, inhibition of the progression of structural damage, and improvement in physical function.
The most commonly reported adverse events were upper respiratory infection, nausea, and headache. Serious infections included pneumonia, tuberculosis (TB), and sepsis.
As Centocor states, RA is a chronic, progressive disease, and research suggests that a critical therapeutic window may exist within the first 2 years of disease onset when the rate of radiographic progression of the disease can be "reset." Radiographic changes occur within 2 years of disease onset in 50% to 70% of pateints with RA. The American College of Rheumatology (ACR) suggests control of disease progression should start early to limit joint damage in RA. RA is associated with substantial disability and economic losses, and one study showed that one third of patients in the United Kingdom who were employed became work-disabled within 2 years of disease onset. Rheumatologic disorders also account for 25% of Social Security disability payments.
Many people with heart failure should not take Remicade; before treatment, patients should discuss any heart condition with their doctors. Patients developing new or worsening symptoms of heart failure (such as shortness of breath or swelling of ankles or feet), should alert their doctors.
There are reports of serious infections, including TB and sepsis. Some of these infections have been fatal. Patients who have had recent or past exposure to people with TB should tell their doctors, who will then evaluate for TB and perform a skin test. If a patient has latent (inactive) TB, the doctor should begin TB treatment before beginning the administration of Remicade. Remicade can lower the ability to fight infections, so patients who are prone to or have a history of infections, or who develop any signs of an infection such as fever, fatigue, cough, or influenza while taking Remicade should inform their doctors immediately. It should also be mentioned if a patient lives in a region where histoplasmosis or coccidioimycosis is common. Blood disorders have been reported, and some have been fatal. Patients developing possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking Remicade should alert their physicians. Nervous system disorders have also been reported, therefore any disease that affects the nervous system should be pointed out to a patient's doctor, as should any numbness, weakness, tingling, or visual disturbances experienced during treatment with Remicade.
Serious infusion reactions have been reported with Remicade, including hives, difficulty breathing, and low blood pressure. Reactions have occurred during or after infusions. In clinical studies, some people experienced the following common adverse effects: respiratory infections (that may include sinus infections and sore throat), coughing, and stomach pain or mild reactions to infusion such as rash or itchy skin.
Remicade is a monoclonal antibody that specifically targets and irreversibly binds to tumor necrosis factor a (TNF-α) on the cell membrane and in the blood. Overproduction of TNF-α is believed to play a role in RA, ankylosing spondylitis (AS), Crohn's disease (CD), and psoriatic arthritis (PSA), in addition to a wide range of immune-mediated inflammatory disorders (IMID) in which Remicade is currently being studied.
Remicade is unique among available anti-TNF biologic therapies. Unlike self-administered therapies that require patients to inject themselves frequently, Remicade can be administered directly by caregivers in the clinic or office setting. In RA and CD patients, Remicade is a 2-hour infusion administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2, and 6. As a result, Remicade patients may require as few as 6 treatments each year.
More details regarding Remicade, including full prescribing information, are available at remicade.com.
September 9, 2004
ST. LOUIS (MD Consult) - On September 28, 2004, Illinois-based Abbott Laboratories announced the U.S. Food and Drug Administration (FDA) had approved a 250 mg/5 mL dosing option of the antibiotic Omnicef (cefdinir) Oral Suspension (OS) for use in pediatric patients aged 6 months to 12 years old. The more concentrated formulation allows parents to administer fewer teaspoons per dose of the antibiotic to their children. When using the 250 mg/5 mL formula, parents administer half of the volume used in the standard formula (125 mg/5 mL).
Omnicef OS is proven to effectively treat mild to moderate bacterial infections such as ear infections, sinus infections, strep throat, and skin infections.
The FDA based its approval on the supplemental New Drug Application filed by Abbott on March 26, 2004. Omnicef OS was originally approved in 1997 at 125 mg/5 mL to treat bacterial infections in children. Omnicef is included in many treatment guidelines, such as those published by the American Academy of Pediatrics.
The new formulation was approved based on a bioequivalence study of the Omnicef OS new 250 mg/5 mL dosage compared with the original 125 mg/5 mL. To be considered bioequivalent, the two dosage formulations must perform in the same ways when given under similar conditions in clinical studies.
Omnicef Oral Suspension is indicated for pediatric patients (ages 6 months to 12 years) for the treatment of mild to moderate infections, including acute bacterial otitis media due to Haemophilus influenzae (including beta-lactamase–producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), and Moraxella catarrhalis (including beta-lactamase–producing strains); and pharyngitis/tonsillitis due to Streptococcus pyogenes. Omnicef is also effective in the eradication of S. pyogenes from the oropharynx.
Omnicef has not, however, been studied for the prevention of rheumatic fever after S. pyogenes–induced pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Omnicef OS is also indicated for the treatment of uncomplicated skin and skin structure infections due to Staphylococcus aureus (including beta-lactamase–producing strains) and S. pyogenes.
To reduce the development of drug-resistant bacteria and to maintain the effectiveness of Omnicef and other antibacterial drugs, Omnicef should be used only to treat or prevent infections that are strongly suspected to be caused by susceptible bacteria.
Omnicef is contraindicated in patients with known allergy to the cephalosporin class of antibiotics. Patients with previous hypersensitivity to penicillins should be closely monitored when taking Omnicef. If allergic reaction to Omnicef occurs, the drug should be discontinued.
In clinical studies, Omnicef was well tolerated. In pediatric trials, the most common adverse events were diarrhea (8%), rash (3%) and vomiting (1%).
For complete details including full prescribing information, please visit omnicef.com or omnicefforkids.com.
September 29, 2004
ST. LOUIS (MD Consult) - On September 28, 2004, Amgen Inc and Wyeth Pharmaceuticals announced that Enbrel (etanercept) became the first biologic agent to receive an indication by the U.S. Food and Drug Administration (FDA) to induce a major clinical response in patients with rheumatoid arthritis (RA). In addition, the FDA approved updated radiographic data in the Enbrel label, which demonstrated that more than half of Enbrel patients observed in an open-label long-term study experienced no progression of joint damage for up to 5 years.
Major clinical response is defined as achieving an American College of Rheumatology 70 response (ACR 70) for 6 consecutive months. ACR response scores are categorized as ACR 20, ACR 50, and ACR 70; ACR 70 is the highest level of sign and symptom control in this evaluation system. ACR response scores measure improvement in RA disease activity, including joint swelling and tenderness, pain, level of disability, and overall patient and physician assessment.
In addition to the major clinical response indication, the Enbrel label was updated to include data that showed that at 5 years' follow-up patients with early, active RA continued to demonstrate inhibition of joint damage and more than half (55%) had no progression of joint damage.
More than 2 million Americans have RA, which is a chronic and progressive disease that causes stiffness, swelling, and limitation in the motion and function of multiple joints. If RA is left untreated, patients can become disabled from progressive joint damage caused by the disease, limiting their ability to function.
Enbrel is the only fully human tumor necrosis factor (TNF) receptor approved to reduce signs and symptoms, induce major clinical response, to inhibit the progression of structural damage, and to improve the physical function in patients with moderately to severely active RA. Enbrel is also indicated to reduce the signs and symptoms and to inhibit the progression of structural damage of active arthritis in patients with psoriatic arthritis. Enbrel is the only biologic therapy approved in the United States for first-line treatment of RA patients and can be used alone or in combination with methotrexate.
Enbrel is approved to reduce the signs and symptoms of moderately to severely active polyarticular-course juvenile RA (JRA) in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs. It is also the only biologic agent approved in the United States to treat the signs and symptoms in patients with active ankylosing spondylitis (AS). Enbrel is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
Enbrel acts by binding TNF, one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immune function and the cascade of reactions involved in the inflammatory process of RA, JRA, psoriasis, psoriatic arthritis, and AS. The binding of Enbrel to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity.
Since the product was first introduced, some serious infections have been reported in patients using Enbrel. Many occurred in people prone to infection, such as those with advanced or poorly controlled diabetes, and some serious infections were fatal. There were rare cases of tuberculosis.
Patients with an infection or those who are allergic to Enbrel or its components should not take Enbrel. Those prone to infection should alert their doctors, as should those who have ever been treated for heart failure. If serious infection occurs, use of the drug should be discontinued.
Serious nervous system disorders such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes are contraindications to Enbrel use. Patients who have ever had any of these disorders or who develop them after beginning treatment with Enbrel should alert their doctors.
Rare reports of serious blood disorders (some fatal) have occurred with this medication. Patients experiencing symptoms such as persistent fever, bruising, bleeding, or paleness should contact their physicians. In medical studies of all TNF blockers, a higher rate of lymphoma was seen compared with the general population; however, the risk of lymphoma may be up to several-fold higher in RA and psoriasis patients. The role of TNF blockers in the development of lymphoma is unknown. The incidence of other cancers has not increased with exposure to Enbrel and is similar to the expected rate.
Enbrel can also cause injection site reactions. In a medical study of patients with JRA, infections, headaches, abdominal pain, vomiting, and nausea occurred more frequently than in adults. The kinds of infections reported were generally mild and similar to those usually seen in children. Other serious adverse reactions were reported rarely and included serious infections (2%) and depression/personality disorder (1%).
Additional information about Enbrel, including full prescribing information, can be found at enbrel.com or by calling 888-4ENBREL (888-436-2735).
September 29, 2004
ST. LOUIS (MD Consult) - On September 24, 2004, Purdue Pharma L.P. announced that the U.S. Food and Drug Administration (FDA) had approved Palladone (hydromorphone HCl extended-release) Capsules (CII) for the management of persistent, moderate to severe pain in patients requiring continuous, around-the-clock analgesia with a high potency opioid for an extended period of time (weeks to months or longer). The painful conditions may arise from either cancer or non-cancer conditions.
The efficacy of Palladone Capsules was established in a 4-week, double-blind, randomized trial. The multicenter placebo-controlled trial used a parallel-group model to evaluate patients aged 18 years and older with pain that was present for at least 1 month. The majority of these patients had moderate to severe pain due to musculoskeletal disorders while maintained on one or more opioid analgesics, often in addition to non-opioid analgesics.
Two hundred twenty-one patients with persistent moderate to severe pain were randomly assigned to receive once-daily 12-mg Palladone Capsules or placebo after they had demonstrated they needed approximately 12 mg of immediate-release hydromorphone (in addition to non-opioid medication) around the clock for control of their pain. Patients taking Palladone Capsules maintained adequate analgesia for a significantly longer time compared with patients in the placebo group.
Palladone Capsules should be administered once every 24 hours.
Palladone Capsules should only be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a minimum total daily dose of opioid medication equivalent to 12 mg of oral hydromorphone. Palladone Capsules should not be used as the first opioid product prescribed for a patient, nor in patients who require opioid analgesia for a short period of time. Patients considered opioid tolerant are those taking any of the following for a week or longer: at least 60 mg oral morphine/day, at least 30 mg oral oxycodone/day, at least 8 mg oral hydromorphone/day, or an equianalgesic dose of another opioid. Use in non–opioid-tolerant patients may lead to fatal respiratory depression.
Palladone Capsules are contraindicated for use on an as-needed (i.e., p.r.n.) basis and in situations of significant respiratory depression, especially in unmonitored settings where there is a lack of resuscitative equipment. They also are contraindicated in patients who have acute or severe bronchial asthma, in patients who have or are suspected of having paralytic ileus, and in patients with known hypersensitivity to any of its components or to the active ingredient, hydromorphone.
The most common adverse events reported in clinical trials with Palladone Capsules include constipation, nausea, infection, headache, and somnolence. Serious adverse reactions that may be associated with Palladone Capsules therapy in clinical use are similar to those of other opioid analgesics, including respiratory depression, apnea, respiratory arrest, and to a lesser degree, circulatory depression, hypotension, shock, or cardiac arrest. Acute overdosage with hydromorphone can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, bradycardia, hypotension, and death. Patients who receive an overdose will require an extended period of monitoring and treatment that may go beyond 18 hours.
Palladone Capsules are to be swallowed whole and are not to be broken, chewed, opened, dissolved, or crushed. Taking broken, chewed, dissolved, or crushed Palladone Capsules or their contents can lead to the rapid release and absorption of a potentially fatal dose of hydromorphone.
Overestimating the Palladone dose when converting the patient from another opioid medication can result in fatal overdose with the first dose. With the long half-life of Palladone (18 hours), patients who receive the wrong dose will require an extended period of monitoring and treatment that may go beyond 18 hours. Even in the face of improvement, continued medical monitoring is required because of the possibility of extended effects.
When prescribing any opioid medication, patients should be assessed for their clinical risks for opioid abuse or addiction and should be closely monitored for signs of misuse, abuse, and addiction throughout the course of therapy.
Palladone Capsules contain the potent Schedule II opioid agonist hydromorphone. Schedule II opioid agonists (which include hydromorphone, fentanyl, methadone, morphine, oxycodone, and oxymorphone) have the highest risk of fatal overdoses due to respiratory depression, as well as the highest potential for abuse. These risks should be considered when administering, prescribing, or dispensing Palladone in situations where the health care professional is concerned about increased risk of misuse, abuse, or diversion.
Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients should be assessed for their clinical risks for opioid abuse or addiction before they are prescribed opioids. All patients receiving opioids should be routinely monitored for signs of misuse, abuse, and addiction. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require intensive monitoring for signs of misuse, abuse, or addiction.
Purdue Pharma has designed a comprehensive Risk Management Program (RMP) that is intended to facilitate proper patient selection, reduce abuse, minimize diversion, and avoid pediatric exposure and other improper uses of Palladone Capsules. The RMP includes extensive medical education, detailed prescribing information, surveillance of medication use and drug diversion, and appropriate interventions when merited.
For the first 18 months following the launch of Palladone, the company will market the product to a limited number of medical practitioners experienced in prescribing opioid analgesics. During this 18-month period, the company will monitor and collect data on medication use and drug diversion and will report these data to the FDA.
Palladone will be available in 12-mg, 16-mg, 24-mg, and 32-mg dosage strengths. Palladone Capsules are expected to be available in retail pharmacies in the first half of 2005.
Full prescribing information for Palladone Capsules is available at purduepharma.com/PI/Prescription/Palladone.pdf.
September 9, 2004
ST. LOUIS (MD Consult) - Merck & Co Inc announced on September 8, 2004, that its arthritis and pain medicine Vioxx (rofecoxib) had received approval from the U.S. Food and Drug Administration (FDA) for a new indication. The medication is now approved for the treatment of the signs and symptoms of the most common forms of juvenile rheumatoid arthritis (JRA), pauciarticular or polyarticular, in children 2 years and older and who weigh at least 22 pounds. Vioxx is the only cyclooxygenase 2 (COX-2)-specific inhibitor approved for the treatment of JRA.
The approval of Vioxx for the relief of the signs and symptoms of JRA follows the approval of this drug in March 2004 for the acute treatment of migraine in adults. In addition, the medication is also approved for the relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis in adults, management of acute pain in adults, treatment of primary dysmenorrhea, and acute treatment of migraine attacks with or without aura in adults. The drug's safety and effectiveness have not been established for cluster headache, which is present in an older, predominantly male population.
JRA is the most common form of arthritis in children, affecting an estimated 30,000 to 50,000 children in the United States. It can occur in children of any age, but girls are more likely to be affected than boys. In March 2004, Merck was granted orphan drug designation for Vioxx for the treatment of JRA, a designation given to medicines that have been researched for the treatment of medical conditions that affect 200,000 people or fewer in the United States.
JRA is known to cause persistent joint inflammation and stiffness that can affect any joint in the body. There are 3 major types of JRA: pauciarticular, which affects 4 or fewer joints; polyarticular, which affects 5 or more joints; and systemic onset, which affects at least 1 joint but also causes inflammation of internal organs. The drug's new indication for JRA is only for patients with pauciarticular or polyarticular JRA.
The FDA approval of Vioxx for JRA was based on the largest JRA study ever conducted, which included 310 pediatric and adolescent patients aged 2 to 17 years with active pauciarticular or polyarticular JRA. Results from the pivotal 12-week, multinational, double-blind study showed once-daily Vioxx provided measurable improvement in reducing joint symptoms. Improvement was evaluated based on JRA "Definition of Improvement = 30%" (DOI 30) criterion, a core set of standardized criteria used to measure arthritis impact. A 1-year open-label extension to the pivotal study also was conducted to evaluate the long-term safety of Vioxx.
Vioxx was generally well tolerated among pediatric and adolescent patients in the study. The most commonly reported adverse events in patients taking Vioxx over the 12-week period were upper abdominal pain, nasopharyngitis, diarrhea, upper respiratory tract infection, abdominal pain, headache, and rhinitis.
Vioxx is available in once-daily dosing in both tablet and strawberry-flavored liquid (oral suspension) formulations. For adolescents 12 to 17 years of age, the recommended dose of Vioxx is 25 mg once daily. For children and adolescents 2 to 11 years of age, dosing is dependent on weight: for children weighing 22 to 88 pounds, the recommended dose is 0.6 mg/kg to a maximum of 25 mg once daily, and for those over 88 pounds, 25 mg once daily is recommended. To improve dosing accuracy among young children, use of Vioxx 12.5 mg/5 mL oral suspension is recommended.
People with allergic reactions (such as asthma) to aspirin or other arthritis medicines should not take Vioxx. In rare cases, serious stomach problems such as bleeding can occur without warning. Patients should inform their physicians if they have or have had liver or kidney disease, angina, a heart attack, or a blocked artery in the heart. Vioxx cannot take the place of aspirin for the prevention of heart attack or stroke, and it should not be used by women in late pregnancy.
Commonly reported adverse effects in clinical trials with Vioxx in adults have included upper-respiratory infections, diarrhea, nausea, and high blood pressure.
The recommended starting dose of Vioxx for the treatment of osteoarthritis is 12.5 mg once daily, although some patients may receive additional benefit by increasing the dose to 25 mg once daily. For rheumatoid arthritis, the recommended dose is 25 mg once daily. The maximum recommended daily dose for osteoarthritis and rheumatoid arthritis is a once-daily dose of 25 mg.
Vioxx 50 mg given once daily is the recommended dose for acute pain and primary dysmenorrhea. Use of Vioxx for more than 5 days in the management of pain has not been studied. Chronic use of this dosage is not recommended.
For the treatment of migraine attacks, the recommended starting dose is 25 mg once daily. Some patients may receive additional benefit with 50 mg, which is the maximum recommended daily dose. The safety of treating more than 5 migraine attacks in any given month has not been established. Chronic daily use of Vioxx for the acute treatment of migraine is not recommended.
For full prescribing information and patient package insert, visit vioxx.com.
September 8, 2004
ST. LOUIS (MD Consult) - On September 7, 2004, Eli Lilly and Co. announced that the U.S. Food and Drug Administration (FDA) had approved the antidepressant Cymbalta (duloxetine hydrochloride), judging it safe and effective for the management of diabetic peripheral neuropathic pain. This symptom of nerve damage affects up to 5 million Americans, according to the Indianapolis-based drug maker.
Cymbalta, a balanced and potent serotonin and norepinephrine reuptake inhibitor, is the first FDA-approved treatment for pain elicited by this disorder. The approval came after a 6-month priority review. More than 18 million Americans have diabetes and are at risk for developing persistent pain as a result of nerve damage believed to be caused by high blood sugar levels.
Cymbalta's safety and efficacy in the treatment of pain caused by diabetic peripheral neuropathy at doses of 60 and 120 mg/day was proved in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose studies in nondepressed adults who had the disorder for at least 6 months. However, doses of 120 mg/day, although safe and effective, were not as well tolerated as 60 mg/day. On average, patients in the studies were 60 years old, suffered from diabetes for 11 years and from related diabetic neuropathy for 4 years, and at the beginning of the studies, rated their pain as moderate to moderately severe.
In both studies, Cymbalta significantly reduced 24-hour average pain compared with placebo. Improvements were noted as early as the first week of treatment and continued for the duration of the studies. In addition, the medication showed rapid onset of action and sustained effect in reducing pain caused by diabetic neuropathy at both 60 and 120 mg/day and was effective in relieving pain at night. Nighttime pain is especially troublesome to many patients with diabetic neuropathy because it can interfere with sleep.
Although Cymbalta does not change the underlying nerve damage caused by diabetic peripheral neuropathy, it does help relieve the stabbing, burning, and shooting pain often associated with the disorder. Scientists believe it does this by increasing levels of serotonin and norepinephrine, 2 neurotransmitters believed to be important in regulating a person's emotions as well as sensitivity to pain. Increasing these levels in a balanced way is thought to improve the body's natural ability to regulate pain. Relatedly, on August 3, 2004, the FDA approved Cymbalta for the treatment of major depression in adults.
Cymbalta is available in 20-, 30-, and 60-mg capsules and can be taken once a day. The recommended daily dose is 60 mg. The effects of the drug have not been studied in children, and therefore Lilly discourages its use in those younger than 18 years of age.
According to the National Institute of Diabetes & Digestive & Kidney Diseases, approximately half of those with diabetes have some form of neuropathy, but not all will develop symptoms. While nerve problems can occur at any time, the highest rates are among those who have had diabetes for at least 25 years. People who have had problems controlling their blood sugar levels, have high blood pressure, are overweight, have high levels of blood fat, or are over the age of 40 years may also have a greater risk of developing diabetic peripheral neuropathy.
Symptoms can include numbness, tingling, or pain and weakness in the toes, feet, legs, hands, arms, and fingers. These symptoms are often worse at night.
People who are allergic to duloxetine hydrochloride or the other ingredients in Cymbalta should not take it. If a patient has recently taken a monoamine oxidase inhibitor, is taking thioridazine, or has uncontrolled narrow-angle glaucoma, he or she should not take Cymbalta. Patients should talk with their doctors before taking this medication if they have serious liver or kidney problems, have glaucoma, or consume large quantities of alcohol, as should women who are pregnant or breast-feeding.
In clinical studies of Cymbalta for pain caused by diabetic neuropathy, the most common adverse effects were nausea, sleepiness, dizziness, constipation, dry mouth, increased sweating, decreased appetite, and fatigue. Most people were not bothered enough by the adverse effects to stop taking Cymbalta. Physicians administering this drug should periodically check their patients' blood pressure. Patients should not stop taking Cymbalta without discussing the cessation with their doctors.
For full prescribing information, visit Cymbalta.com.
September 3, 2004
ST. LOUIS (MD Consult) - Schering-Plough Corporation announced on September 1, 2004, that the U.S. Food and Drug Administration (FDA) had approved the use of Clarinex (desloratadine) Syrup for the relief of symptoms associated with seasonal allergic rhinitis in children 2 years and older as well as perennial allergic rhinitis and chronic idiopathic urticaria in children as young as 6 months. The new Clarinex Syrup is expected to be available in the United States during the first half of 2005.
The FDA approval of this prescription non-sedating antihistamine syrup results from 3 double-blind, placebo-controlled safety studies involving 246 pediatric subjects 6 months to 11 years of age with a documented history of allergic rhinitis or chronic idiopathic urticaria, or subjects who were candidates for antihistamine therapy. The results of these studies demonstrated the safety of Clarinex Syrup in pediatric subjects 6 months to 11 years of age.
In clinical trials, the overall incidence of adverse events in children between the ages of 6 and 11 years was similar for the group taking desloratadine syrup and the placebo groups. In pediatric patients 6 months to 5 years of age, the most frequently seen adverse events were upper respiratory tract infection, diarrhea, fever, urinary tract infection, varicella, irritability, and coughing.
Full prescribing information is available at www.spfiles.com/piclarinex.pdf.
August 24, 2004
ST. LOUIS (MD Consult) - In an announcement made August 23, 2004, Pfizer Inc announced that the U.S. Food and Drug Administration (FDA) had approved the use of its atypical antipsychotic medication Geodon (ziprasidone hydrochloride) for the treatment of acute bipolar mania including manic and mixed episodes.
Prompt and effective control of acute mania is an important goal because patients affected by this disorder are at an increased risk for impulsive and dangerous behaviors, often requiring psychiatric hospitalization. Geodon was shown to rapidly improve acute manic symptoms and to sustain these improvements over a 3-week study period. Consistent with Geodon's overall clinical profile, no significant adverse effects on weight gain or lipids were seen.
In 2 randomized double-blind trials involving 416 hospitalized patients with acute bipolar mania, Geodon-treated patients showed greater improvement compared with placebo from day 2 through the end of the trial (day 21). Patients treated with Geodon were initially given a dose of 80 mg/d with an increase permitted to 160 mg on day 2 in the first study and day 3 in the second study.
Efficacy was measured using standardized psychiatric assessment scales. The most common adverse effects in the studies were somnolence, dizziness, and extrapyramidal symptoms.
According to a survey conducted by Harris Interactive of 554 bipolar patients in the United States older than 30 years, 7 of 10 have gained weight—on average, 50 pounds, with 1 in 10 gaining an alarming 100 pounds or more—while taking bipolar medications. This medication-induced weight gain caused almost half of patients surveyed to stop taking or change their medication.
More than one third of patients (39%) surveyed who had gained weight while taking bipolar medications reported developing high cholesterol, and 3 of 10 developed high triglyceride levels. Some even reported having other serious conditions including diabetes (13%) and abnormal lipid levels (18%).
As Pfizer reports, despite the serious consequences that bipolar patients may experience when not properly treated, the majority (67%) say that they are unwilling to take a medication that controls symptoms but could cause them to gain 10 pounds or more. Patient compliance in taking prescribed medication is key to reducing physician office visits and expenses of hospitalization as well as providing best outcomes of the treatment.
Weight gain may be one reason that the patients surveyed have tried, on average, 6 medications to satisfactorily treat their bipolar disorder. In fact, 1 in 6 bipolar patients has taken 11 or more medications seeking relief from their troubling condition that affects their ability to function in daily life.
It is important to note that patients should not discontinue their medication without first consulting their physician. With appropriate diagnosis and treatment, most patients can improve substantially and even resume normal functioning.
Bipolar disorder, also referred to as manic-depressive illness, is a common and persistent psychiatric condition. Patients suffer from profound mood swings ranging from severe depression to unnatural "highs." During manic periods, which can last for a week or more, patients may appear to be overly energetic, irritable, extremely talkative, or excessively happy.
Geodon was approved in the United States in February of 2001 for the treatment of schizophrenia and in 2004 for acute bipolar mania. The drug is contraindicated in patients with a known history of QT prolongation, recent acute myocardial infarction, or uncompensated heart failure, and it should not be used with other QT-prolonging drugs. Geodon has a greater capacity to prolong the QTc interval than several antipsychotic agents. With some drugs, QT prolongation has been associated with torsades de pointes, a potentially fatal arrhythmia.
Hyperglycemia-related adverse events, sometimes serious, have been reported in patients treated with atypical antipsychotic drugs. There have been few reports of hyperglycemia or diabetes in patients treated with Geodon, and it is not known whether Geodon is associated with these events. Patients treated with an atypical antipsychotic medication should be monitored for symptoms of hyperglycemia.
Full Geodon prescribing information is available at pfizer.com/download/uspi_geodon.pdf.
(Click here to download and install Adobe Reader if it is not already available on your computer.)
August 24, 2004
ST. LOUIS (MD Consult) - On August 23, 2004, Novartis Pharma AG announced that the U.S. Food and Drug Administration had approved a supplemental indication for its promotility agent Zelnorm (tegaserod maleate) for the treatment of chronic idiopathic constipation in male and female patients younger than 65 years of age.
The effectiveness of Zelnorm in patients 65 years or older with chronic idiopathic constipation has not been established.
The new indication is supported by safety and efficacy data from the 2 largest and longest randomized, double-blind, placebo-controlled, multinational phase III clinical trials ever conducted in chronic constipation. The two 3-month trials included more than 2,600 patients. In addition, one of the studies included a 13-month extension safety study of 840 patients. Zelnorm was found to significantly increase the frequency of complete spontaneous bowel movements as well as to provide relief of the multiple symptoms of chronic constiptation that patients complain about most, including straining, hard stool, incomplete evacuation, infrequent defecation, bloating, and abdominal discomfort.
Zelnorm has been available since July 2002 to treat abdominal discomfort or pain, bloating, and constipation associated with irritable bowel syndrome (IBS) in women. IBS with constipation and chronic idiopathic constipation are both lower gastrointestinal (GI) dysmotility disorders.
Constipation, including that due to other diseases or drugs, is one of the leading GI complaints in the United States, affecting nearly 18% of the population, or 37 million people. More than 4.5 million Americans report they are constipated most of the time. Chronic constipation, as a whole, accounts for more than 5.7 million constipation-related outpatient visits each year, with 990,994 to emergency rooms and 586,868 to hospital outpatient facilities. More than 282,000 in-patient hospitalizations carry constipation as the primary diagnosis. Diagnosed cases of chronic constipation are evenly distributed across age groups and in both genders, although it is slightly more frequent in women.
Zelnorm is indicated for the short-term treatment of women with IBS whose primary bowel symptom is constipation. The safety and effectiveness of Zelnorm in men with IBS with constipation have not been established.
In chronic constipation studies, the incidence of adverse events with Zelnorm was similar to that of placebo. The only adverse event reported more often with Zelnorm (6 mg twice a day) than placebo was diarrhea (6.6% vs 3%). Diarrhea rarely led to discontinuation of the study (0.9%). Typically, diarrhea was transient, lasting 2 days, and generally resolved without rescue medication or interruption of treatment. Data from the trial that incorporated a 13-month extension study showed Zelnorm to be generally safe and well tolerated in the long term.
In clinical trials involving IBS with constipation, tolerability to Zelnorm was similar to placebo. The only adverse event reported notably more often with Zelnorm than with placebo was diarrhea (9% vs 4%). The majority of patients reporting diarrhea had a single episode and, in most cases, diarrhea occurred in the first week of treatment. Typically, it resolved with continued therapy. Serious consequences of diarrhea, including hypovolemia, hypotension, and syncope, have been reported in the clinical studies (0.04%) and during marketed use of Zelnorm. In some cases, these complications have required hospitalization for rehydration.
Novartis AG is headquartered in Basel, Switzerland. For more information, visit novartis.com.
August 20, 2004
ST. LOUIS (MD Consult) - Eli Lilly and Company announced on August 19, 2004, that the anti-cancer drug Alimta (pemetrexed) had received its second U.S. approval in 2004. The U.S. Food and Drug Administration (FDA) granted accelerated approval for Alimta for the treatment of locally advanced or metastatic non–small cell lung cancer in previously treated patients. In February 2004, Alimta was approved, in combination with cisplatin, for the treatment of malignant pleural mesothelioma, a cancer often associated with asbestos exposure.
Over the past decade, lung cancer rates have continued to rise, and now the disease is the leading cause of cancer death in men and women. According to the American Cancer Society, approximately 174,000 individuals in the United States are diagnosed with lung cancer each year.
Due to the aggressive nature of lung cancer, the disease recurs in the majority of patients and only 40,000 to 50,000 are well enough to tolerate treatment in the second-line setting. Patients treated with the current standard of care in the second-line setting, Taxotere (docetaxel), usually experience severe toxic adverse effects such as diarrhea, hair loss, neutropenia, and neutropenia with fever.
Alimta is an antifolate that simultaneously blocks 3 separate enzyme targets vital to the survival of cancer cells. Alimta's administration includes vitamin supplementation with folic acid and vitamin B12. A team of researchers led by Lilly discovered that this vitamin regimen significantly reduces the drug's adverse effects without negatively affecting its ability to kill cancer cells. The administration cycle for Alimta is a 10-minute infusion, once every 3 weeks.
The FDA-accelerated approval is based on Alimta's efficacy and safety profile as evidenced in one of the largest phase III studies to date in the second-line setting. The study compared Alimta directly to Taxotere. In July, the study was the basis for a unanimous recommendation for accelerated approval by the FDA's Oncologic Drug Advisory Committee.
Alimta's approval was based on the drug's ability to reduce tumor size (response rate) in patients with advanced non–small cell lung cancer.
The FDA also cited Alimta's significantly improved safety profile compared with Taxotere as a supporting basis for approval. Patients taking Alimta also experienced less grade 3 or 4 neutropenia, less neutropenia with fever, less diarrhea, fewer hospitalizations due to adverse events, and less hair loss. As with all chemotherapy agents, patients taking Alimta and Taxotere experienced low blood cell counts. Patients treated with Alimta experienced higher rates of grade 3 or 4 alanine transaminase. Some of the most common grade 3 or 4 toxicities associated with Alimta (regardless of causality) include anemia (8% vs 7% for Taxotere), fatigue (16% vs 17%), anorexia (5% vs 8%), and infection without neutropenia (6% vs 4%).
In accordance with the FDA's accelerated approval, Lilly will continue to gather data for Alimta in non–small cell cancer.
For full prescribing information about Alimta, visit lillyoncology.com.
August 20, 2004
ST. LOUIS (MD Consult) - French pharmaceutical company Aventis announced on August 19, 2004, that the U.S. Food and Drug Administration (FDA) has approved Taxotere (docetaxel) Injection Concentrate in combination with doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) for the adjuvant (post-surgery) treatment of patients with operable, node-positive breast cancer. The supplemental New Drug Application received a Priority Review designation by the FDA, which is assigned to those applications that have the potential for providing a significant therapeutic advance. The additional indication is also under review by the European regulatory authorities.
Taxotere, a drug in the taxoid class of chemotherapeutic agents, inhibits cancer cell division by essentially "freezing" the cell's internal skeleton, which is comprised of microtubules. Microtubules assemble and disassemble during a cell cycle. Taxotere promotes their assembly and blocks their disassembly, thereby preventing many cancer cells from dividing and resulting in death in some cancer cells.
The FDA based its decision on results from a second interim analysis from the pivotal Breast Cancer International Research Group (BCIRG) 001/TAX 316 study, which demonstrated that women with node-positive, early-stage breast cancer who received a Taxotere-based chemotherapy regimen (TAC) after surgery experienced a significant 25.7% reduction in their risk of relapse compared with women treated with another adjuvant combination regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). Notably, with nearly 5 years of follow-up (55 months), the significant reduction in the risk of relapse of this Taxotere-based regimen was observed regardless of a woman's hormone receptor status.
Additionally, at the time of this interim analysis, based on a total of 219 deaths, overall survival was longer for TAC than FAC (hazard ratio, 0.69; 2-sided 95% confidence interval, 0.53, 0.90). There will be further analysis when survival data mature.
The primary end point of the BCIRG 001/TAX 316 multicenter study was to compare the disease-free survival after treatment with Taxotere in combination with doxorubicin and cyclophosphamide to a standard regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide. The nearly 5-year follow-up results of the study were presented at the San Antonio Breast Cancer Symposium on December 5, 2003.
The study enrolled 1,491 premenopausal and postmenopausal women with node-positive, early-stage breast cancer from 112 sites in 20 countries between June 1997 and June 1999. Women were randomly assigned to receive either TAC or FAC in the adjuvant setting.
Follow-up data (55 months) of women in the study did not identify unexpected safety concerns and confirmed the results already presented at the time of the first interim analysis (33 months). Specifically, the TAC regimen was associated with a higher rate of febrile neutropenia compared with FAC (24.7% vs 2.5%). However, incidence of severe infection were similar (3.9% vs 2.2%), and there were no treatment-related deaths due to infection in the study. Patients in the study were not treated with primary prophylactic granulocyte colony-stimulating factor (G-CSF), but G-CSF was required for subsequent cycles after the first episode of febrile neutropenia or infection.
Other severe adverse events occurring in 5% or more of patients treated with TAC included neutropenia, nausea, stomatitis, and asthenia, and with FAC included neutropenia, nausea, vomiting, and asthenia.
More than 90% of patients in both treatment groups received all 6 cycles of treatment.
Breast cancer is the most common cancer among women other than skin cancer. It is the second-leading cause of cancer death in women after lung cancer and is the leading cause of cancer death among women aged 40 to 59 years. More than 1,000,000 new cases of breast cancer are reported worldwide annually, and more than 400,000 women die each year from the disease. The risk of a woman developing breast cancer during her lifetime is approximately 11% (about 1 in 9 of all women worldwide). In the United States alone, breast cancer this year is expected to account for 32% (215,990) of all new cancer cases among women, and approximately 40,110 women will die from the disease.
It is estimated that more than 300,000 women per year worldwide will be diagnosed with node-positive, early-stage breast cancer. Most patients with early-stage breast cancer (cancer localized to the breast with or without invasion of the lymph nodes under the arm) undergo surgery to remove the tumor. After surgery, most patients receive additional treatments, which may include chemotherapy to reduce the probability of tumor recurrence. Earlier diagnosis of breast cancer results in earlier treatment and may offer a better chance for cure.
For more information on Taxotere, visit aventis.com or taxotere.com.
August 13, 2004
ST. LOUIS (MD Consult) - On August 12, 2004, the U.S. Food and Drug Administration (FDA) approved Topamax (topiramate) Tablets and Topamax Sprinkle Capsules for the prophylaxis of migraine headaches in adults. Clinical trials found that about half of all patients receiving the recommended daily dose of Topamax experienced a significant reduction in monthly migraine attacks, compared with placebo.
Migraines are a chronic, debilitating condition characterized by sharp throbbing pain on one side of the head, nausea or vomiting, visual disturbances, and/or sensitivity to noise and light. Approximately 14 million Americans suffer from frequent or severe migraines. Many prescription migraine medicines currently available are taken to treat migraines at the start of an attack. Patients with frequent or severe migraines may be candidates for treatment that may reduce the frequency of their migraine attacks.
According to the National Headache Foundation (NHF), a leading advocacy organization, people with migraines are often forced to cope with their attacks. Whereas some retreat to a quiet, dark room and wait out an attack, many attempt to endure them, struggling through even the simplest tasks such as completing household chores.
People with migraines should talk to their doctors about the treatment options that are right for them. Factors to discuss include the frequency and severity of the migraines, medications they are currently using, how often they are using their migraine medications, and how well their current migraine medications are working.
Topamax has been approved for migraine prophylaxis in 22 countries. The usefulness of Topamax in the acute treatment of migraine headaches has not been studied. Like most medicines, Topamax may cause adverse effects. The most common adverse effect is tingling in the extremities. Others include fatigue, loss of appetite, nausea, taste alteration, diarrhea, cognitive side effects, and weight loss. Serious, as well as minor, adverse effects have been reported with Topamax.
Ortho-McNeil Pharmaceutical, Inc, markets Topamax in the United States. Johnson & Johnson Pharmaceutical Research & Development, LLC, discovered Topamax and conducted the research for the new indication. For more information, or for full U.S. prescribing information, visit ortho-mcneil.com or topamax.com or call 1-800-682-6532.
August 13, 2004
ST. LOUIS (MD Consult) - Shire Pharmaceuticals Group, PLC, announced on August 12, 2004, that its treatment for attention deficit hyperactivity disorder (ADHD), Adderall XR (mixed salts of a single-entity amphetamine) has been approved by the U.S. Food and Drug Administration (FDA) as a once-daily treatment for adults.
Shire will begin promoting the adult indication in the United States immediately.
In addition, the FDA has confirmed to Shire that new 40-mg, 50-mg, and 60-mg dose strengths of Adderall XR will require additional clinical data for approval.
Adderall XR is a once-daily extended release, single-entity amphetamine product available in 5-mg, 10-mg, 15-mg, 20-mg, 25-mg, and 30-mg doses. The capsule contains 2 types of drug-containing beads designed to give a double-pulsed delivery of amphetamines, which prolongs the release of amphetamine from Adderall XR compared with the conventional Adderall (immediate-release) tablet formulation. The FDA approved Adderall XR in November 2001 for the treatment of ADHD in children.
Shire Chief Executive, Matthew Emmens, noted that physicians have been prescribing Adderall XR for adults in an off-label capacity for some time, stating that adults represent 15% to 20% of those currently receiving prescriptions of the drug.
According to Shire, studies have shown that up to 65% of children with ADHD continue to exhibit symptoms into adulthood, and an estimated 4.4% of the U.S. adult population is affected by ADHD. If left untreated, this disorder can lead to other psychological difficulties, such as depression and occupational and social disability. Appropriate diagnosis and treatment of ADHD in adults helps improve self-esteem, work performance and skills, educational attainment, and social competencies. Over 8 million adults in the U.S. may exhibit the symptoms of ADHD, and only an estimated 600,000 are being treated.
Shire Pharmaceuticals is a global company headquartered in London. For more information, visit shire.com.
August 12, 2004
ST. LOUIS (MD Consult) - Abbott Laboratories announced on August 10, 2004, that the U.S. Food and Drug Administration (FDA) had approved an expanded indication for its rheumatoid arthritis (RA) treatment, Humira (adalimumab), to include improvement in physical function for adult patients with moderately to severely active RA.
Improvement in physical function is an important goal of therapy for patients with RA, who often experience disability and loss of function that can greatly reduce quality of life. "It is not uncommon for RA patients to live with such debilitating pain and loss of function that they cannot perform simple activities such as bathing or even cutting up food," said Arthur Kavanaugh, MD, rheumatologist and professor of medicine at University of California, San Diego. Many people with RA are unable to groom or dress themselves, and some cannot walk due to the crippling effects of their disease.
The FDA based its approval on a supplemental Biologics Licensing Application (sBLA) filed by Abbott on September 30, 2003. In 2002, Humira was approved to reduce signs and symptoms and to inhibit the progression of structural damage in adult patients with moderately to severely active RA who have had an inadequate response to 1 or more disease-modifying antirheumatic drugs (DMARDs).
The physical function approval was based on a 52-week open-label continuation study of 457 RA patients with inadequate response to methotrexate who were previously enrolled in a double-blind, placebo-controlled, 52-week lead-in study. The continuation study was designed to assess the maintenance of improved physical function in patients treated with Humira.
Improvement in physical function was measured using the Health Assessment Questionnaire Disability Index (HAQ). HAQ is a measure of physical function that assesses a patient's ability to perform normal daily activities such as getting dressed, walking, and climbing stairs.
In this study, meaningful improvements in HAQ were achieved as soon as 2 weeks after the first Humira dose, and improvements in physical function were maintained with Humira through 2 years of treatment. Sustained improvement in HAQ scores beyond 2 years has also been seen in other trials with Humira: in one long-term open-label study presented previously in 2004, HAQ response was maintained for up to 5 years.
Improvement in physical function was also demonstrated using the Short Form 36-item Health Survey (SF-36), a broad questionnaire that examines the physical and mental impact of RA on patients. SF-36 assesses several quality-of-life factors, including vitality, mental health, bodily pain, general health perceptions, and limitations in physical, social, and emotional functioning. Data showed that clinically meaningful improvements in SF-36 measures for patients taking Humira were sustained for 2 years.
Cases of tuberculosis have been observed in patients receiving Humira. Serious infections and sepsis, including fatalities, have been reported with the use of tumor necrosis factor (TNF)-blocking agents, including Humira. Many of these infections occurred in patients also taking other immunosuppressive agents that, in addition to their underlying disease, could predispose them to infections. The combination of Humira and anakinra is not recommended.
TNF-blocking agents, including Humira, have been associated in rare cases with demyelinating disease and severe allergic reactions. Rare reports of serious blood disorders and lymphoma have been reported with TNF-blocking agents. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of TNF-blocking therapy in the development of malignancies is not known.
The most frequent adverse events seen in the placebo-controlled clinical trials of RA (Humira vs placebo) were injection site reactions (20% vs 14%), upper respiratory infection (17% vs 13%), injection site pain (12% vs 12%), headache (12% vs 8%), rash (12% vs 6%), and sinusitis (11% vs 9%). Discontinuations due to adverse events were 7% for Humira and 4% for placebo. As with any treatment program, the benefits and risks of Humira should be carefully considered before therapy is initiated.
More than 5 million people worldwide suffer from RA, a chronic autoimmune disease that causes pain, swelling, and stiffness in the joints of the hands, feet, and wrists and often leads to the destruction of joints. Unlike osteoarthritis, the most common form of arthritis, RA is an autoimmune disease in which joints are inflamed, resulting in the eventual destruction of the joints interior and the surrounding bone.
More information on RA and current treatment options can be found at RA.com.
Humira is the only fully human monoclonal antibody approved by the FDA for reducing the signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adults with moderately to severely active RA who have had insufficient response to 1 or more DMARDs. Humira can be used alone or in combination with methotrexate or other DMARDs. The efficacy and safety of Humira have been studied in 23 clinical trials and in more than 2,300 patients, making it the most studied TNF antagonist for RA at the time of regulatory submission. Humira was approved by the FDA on December 31, 2002.
Humira is available in every-other-week dosing by subcutaneous injection via a specially designed prefilled syringe.
Humira is the first fully human monoclonal antibody approved in Europe for RA and the first TNF-a antagonist approved with an indication for use with methotrexate or as monotherapy. In April 2004, the European Medicines Evaluation Agency granted a positive opinion for a Humira label extension for reducing the rate of progression of joint damage as measured by x-ray and improving physical function in adults with RA. To date, Humira has been approved in 51 countries.
Clinical trials are currently underway evaluating the potential of Humira in other autoimmune diseases, including juvenile RA, psoriasis, psoriatic arthritis, Crohn's disease, and ankylosing spondylitis.
Abbott Laboratories is headquartered in Abbott Park, Illinois. More information about Abbott Immunology and Humira, including full prescribing information, is available at abbottimmunology.com and HUMIRA.com.
August 10, 2004
ST. LOUIS (MD Consult) - Boehringer Ingelheim Pharmaceuticals, Inc, announced on August 9, 2004, that the U.S. Food and Drug Administration (FDA) had approved the use of Mobic (meloxicam) tablets for the management and treatment of rheumatoid arthritis (RA). Mobic is a nonsteroidal anti-inflammatory drug (NSAID) and has been available to patients in the United States since June 2000 for the relief of the signs and symptoms of osteoarthritis. RA is a systemic disease that affects the entire body and is one of the most common forms of arthritis.
An estimated 2.1 million Americans have RA, according to the Arthritis Foundation.
The FDA approval follows a review of data from a placebo-controlled 12-week study of 1,184 patients with RA. Patients receiving Mobic tablets at the recommended starting doses of 7.5 and 15 mg were more likely to complete the study than those receiving placebo. No incremental benefit was observed with the 22.5-mg dose compared with the 15-mg dose. Mobic is approved in the United States for the treatment of osteoarthritis and RA at the same starting doses. The starting and maintenance dose is 7.5 mg once daily. Some patients may receive additional benefit by increasing the dose to 15 mg once daily. Higher doses of Mobic (22.5 mg and greater) have been associated with an increased risk of serious gastrointestinal events; therefore, the daily dose of Mobic should not exceed 15 mg.
Mobic is contraindicated in patients who have experienced asthma, itching, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients. As with all NSAIDs, serious gastrointestinal toxicity such as inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine can occur at any time, without symptoms. As with other NSAIDs, Mobic is not indicated for the prevention of thromboembolic events and is not a substitute for aspirin or other drugs indicated for cardiovascular prophylaxis.
Mobic was developed by Ridgefield, Conn–based Boehringer Ingelheim and is co-marketed with Abbott Laboratories. For more information, including full prescribing information, visit MOBICtablet.com.
August 9, 2004
ST. LOUIS (MD Consult) - On August 6, 2004, Merck & Co, Inc, announced that the U.S. Food and Drug Administration had granted a new indication for Hyzaar (losartan potassium–hydrochlorothiazide tablets) for initial use in appropriate patients with severe hypertension. This fixed-dose combination is not indicated for initial therapy of hypertension, except when the hypertension is severe enough that the value of achieving prompt blood pressure control exceeds the risk of initiating combination therapy in these patients.
In the 1999-2000 National Health and Nutrition Examination Survey (NHANES), of the estimated 60 million people in the United States with high blood pressure, approximately 2 million had a blood pressure reading equal to or greater than 180 mm Hg systolic or equal to or greater than 110 mm Hg diastolic.
Widely used guidelines for the treatment of hypertension recommend the initial use of 2 drugs in certain patients with hypertension. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the latest guidelines issued by the International Society on Hypertension in Blacks (ISHIB) inform physicians to consider the option of initiating therapy with 2 drugs, 1 of which should usually be a thiazide-type diuretic, either as separate prescriptions or in fixed-dose combination when the physician has determined that the patient's blood pressure is highly elevated. Importantly, when evaluating therapy, physicians should bear in mind that the basis of the new indication for Hyzaar was a study of patients whose diastolic blood pressure reading was 110 mm Hg or higher.
The safety and efficacy of Hyzaar as initial therapy for severe hypertension (defined as mean sitting diastolic blood pressure = 110 mm Hg confirmed on 2 separate occasions off all antihypertensive therapy) was studied in a 6-week, double-blind, randomized, multicenter study of 585 patients, including 264 (45%) women, 124 (21%) black patients, and 21 (4%) patients 65 years of age or older. The mean age was 53 years. The mean blood pressure at baseline for the total population was 171/113 mm Hg.
The primary end point of the study was a comparison at 4 weeks of patients who achieved goal diastolic blood pressure (trough sitting diastolic blood pressure <90 mm Hg) on Hyzaar 50-12.5 mg versus patients taking Cozaar (losartan potassium tablets) 50 mg titrated to 100 mg as needed to reach goal diastolic blood pressure. The results of the study at week 4 showed the average reduction in diastolic blood pressure was 13.6 mm Hg for patients taking Hyzaar versus 10.5 mm Hg for those taking Cozaar, a difference of 3.1 mm Hg lower for those treated with Hyzaar. In addition, the average reduction in systolic blood pressure was 18.0 mm Hg for those taking Hyzaar versus 12.4 mm Hg for those on Cozaar, a difference of 5.6 mm Hg for those treated with Hyzaar.
As a result, a greater proportion of the patients taking Hyzaar reached the target diastolic blood pressure (17.6% for Hyzaar, 9.4% for Cozaar; P = .006). Similar trends were seen when the patients were grouped according to sex, race, or age (younger than 65 years and 65 or older).
The secondary end point was a comparison at 6 weeks of patients who achieved goal diastolic blood pressure on Hyzaar 50-12.5 mg titrated as needed to Hyzaar 100-25 mg versus patients taking Cozaar 50 mg titrated to 100 mg and then to 150 mg. The results of the study at week 6 showed the average reduction in diastolic blood pressure was 17.8 mm Hg for patients taking Hyzaar versus 11.9 mm Hg for those taking Cozaar. Furthermore, the average reduction in systolic blood pressure was 25.1 mm Hg for those taking Hyzaar versus 14.1 mm Hg for those taking Cozaar. At 6 weeks, more patients in the group treated with Hyzaar reached target diastolic blood pressure than those treated with Cozaar (29.8% vs 12.5%).
"In the clinical study supporting this new indication, we saw that more patients with severe hypertension reached their diastolic blood pressure lowering goal of less than 90 mm Hg at 4 weeks with Hyzaar as opposed to being titrated to higher doses of Cozaar," said Dr. George L. Bakris, MD, FACP, FCP, director of the Hypertension/Clinical Research Center, Rush University Medical Center in Chicago.
In clinical trials, treatment with Hyzaar was generally well tolerated. In the clinical study supporting this new indication, the overall adverse effect profile for patients with severe hypertension treated with Hyzaar as initial therapy was similar to the adverse effect profile in patients with severe hypertension initially treated with Cozaar. During the study period there were no reported cases of syncope in either treatment group. There were 2 (0.6%) cases and no cases of hypotension reported in the groups treated with Hyzaar and Cozaar, respectively. There were 3 (0.8%) cases and 2 (1.2%) cases of increased serum creatinine (>0.5 mg/dL) in the groups treated with Hyzaar and Cozaar, respectively.
In other clinical trials, the overall incidence of adverse events with losartan potassium–hydrochlorothiazide was comparable to placebo. The most common adverse events occurring with various doses of losartan potassium–hydrochlorothiazide (n = 858) at a rate of 1% or more above placebo (n = 173) were upper respiratory infection (6% vs 5%), dizziness (6% vs 3%), back pain (2% vs 1%), palpitations (1% vs 0%), and rash (1% vs 0%).
When used in pregnancy during the second or third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, administration of Cozaar and Hyzaar should be discontinued as soon as possible.
Cozaar and Hyzaar are contraindicated in patients who are hypersensitive to any component of these products. Because of the hydrochlorothiazide component, Hyzaar is also contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. Hyzaar is not recommended for patients with severe renal impairment (creatinine clearance = 30 mL/min) or as a means of titration for patients with hepatic impairment. Hyzaar is not recommended for use as initial therapy in patients with intravascular volume depletion (eg, those treated with diuretics). All patients receiving thiazides should be observed for clinical signs of fluid or electrolyte imbalance, including hypokalemia. As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics, potassium supplements, or salt substitutes containing potassium can lead to increases in serum potassium.
The starting dose of Hyzaar for initial treatment of severe hypertension is 1 tablet of Hyzaar 50-12.5 mg once daily. For patients who do not respond adequately to Hyzaar 50-12.5 mg after 2 to 4 weeks of therapy, the dosage can be increased to 1 tablet of Hyzaar 100-25 mg once daily. The maximum dose is 1 tablet of Hyzaar 100-25 mg once daily. Hyzaar is not recommended as initial therapy in patients with hepatic impairment because the appropriate 25-mg starting dose of losartan cannot be given.
The usual starting dose of Cozaar in patients with hypertension is Cozaar 50 mg once daily. The maximum daily dose is 100 mg. If the antihypertensive effect measured at trough using once-a-day dosing is inadequate, a twice-a-day regimen at the same total daily dose or an increase in dose may give a more satisfactory response. The 150-mg dose of Cozaar has not been shown to give a greater effect than 50 or 100 mg. In patients who are volume-depleted, symptomatic hypotension may occur after initiation of therapy with Cozaar. This condition should be corrected before administration of Cozaar, or a dosage of Cozaar 25 mg should be used. In patients with a history of hepatic impairment, a starting dose of Cozaar 25 mg should be used.
Patients whose blood pressure is not controlled by monotherapy with either Cozaar or hydrochlorothiazide alone can be switched to Hyzaar 50-12.5 mg once daily. If blood pressure remains uncontrolled, physicians can titrate to Hyzaar 100-25 mg once daily.
August 5, 2004
ST. LOUIS (MD Consult) - On August 4, 2004, Pfizer Inc. announced that the U.S. Food and Drug Administration had approved its cholesterol-lowering therapy Lipitor (atorvastatin calcium) for the prevention of cardiovascular disease by reducing heart attack risk in persons with normal to mildly elevated cholesterol levels who have other cardiovascular risk factors.
The FDA’s decision was based on the findings of the landmark Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), which found that the lowest dose of Lipitor (10 mg) reduced the relative risk of heart attack by 36% compared with placebo. Because these significant benefits were seen so early, the trial was stopped nearly 2 years ahead of schedule.
Another Lipitor study also ended 2 years ahead of schedule and also demonstrated Lipitor's early cardiovascular benefits to patients. The Collaborative Atorvastatin Diabetes Study (CARDS) showed that patients with diabetes who took Lipitor had 48% fewer strokes than those who received placebo. In addition, Lipitor-treated patients had significantly fewer fatal and non-fatal heart attacks and required fewer surgical procedures.
With starting doses of 10 mg, 20 mg, or 40 mg, 98% of patients taking Lipitor reach their target LDL goal level. Updated guidelines recently issued by the National Cholesterol Education Program (NCEP) confirm the added benefit of prescribing cholesterol-lowering medication like Lipitor, along with diet modification and exercise, to patients at risk for cardiovascular disease. The NCEP panel cited the ASCOT trial as one of the landmark studies instrumental in concluding the revision of the guidelines.
Since the introduction of Lipitor 7 years ago, its safety and effectiveness have been supported through the Atorvastatin Landmark Program, an extensive clinical program with more than 400 ongoing and completed trials involving more than 80,000 patients.
Lipitor is a prescription drug used with diet to lower cholesterol and to reduce the risk of heart attacks. Lipitor should not be prescribed for persons with liver disease or possible liver problems nor for women who are nursing, pregnant, or may become pregnant.
Patients taking Lipitor should inform their physician about any unusual muscle pain or weakness, which could be a sign of serious muscle side effects. Patients should also inform their physician about any medications they are currently taking to avoid possible serious drug interactions. Prescribing physicians should perform simple blood tests to monitor liver function before and during drug treatment.
The most commonly reported adverse effects are gas, constipation, stomach pain, and indigestion; these are usually mild and temporary.
For full prescribing information, please visit lipitor.com or call 1-888-LIPITOR.
July 30, 2004
ST. LOUIS (MD Consult) - On July 26, 2004, MedImmune, Inc, announced that the U.S. Food and Drug Administration (FDA) had approved a new liquid formulation of Synagis (palivizumab). In 1998, the original formulation of Synagis was approved by the FDA to prevent serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients at high risk of RSV disease. Synagis is the first monoclonal antibody approved for prevention of an infectious disease and the first such drug to be proved safe for use in children.
The new liquid Synagis offers health care providers, parents, and high-risk infants improved convenience. The original formulation is a freeze-dried preparation that is reconstituted with sterile water, a process that takes approximately 20 minutes, from which the final product must be used within the next 6 hours. The new liquid formulation of Synagis is already supplied as a sterile solution ready for injection, thus eliminating the additional preparatory steps and reducing the time a high-risk infant will spend in a physician's waiting room among other sick children.
In October 2004, Maryland-based MedImmune plans to end production of the current U.S. formulation and to begin manufacturing liquid Synagis, which should be available for use in the United States for the 2005-2006 RSV season.
RSV is the most common respiratory infection experienced in infancy or childhood, resulting in over 125,000 hospitalizations in the United States annually in children younger than 1 year of age. Approximately half of all infants are infected with RSV during the first year of life, and nearly all children have been infected at least once by the time they reach their second birthday. Children born prematurely as well as those with chronic lung disease or congenital heart disease are at highest risk of severe disease and hospitalization due to RSV.
Synagis is marketed for the prevention of serious lower respiratory tract disease caused by RSV in pediatric patients at high risk of RSV disease, which is prominent in the northern hemisphere between October and May. Synagis is a humanized monoclonal antibody given through a simple intramuscular injection once a month during the RSV season. Synagis was initially licensed by the FDA in 1998, and in 2003 its label was expanded to include safety and efficacy data supporting its use in young children with hemodynamically significant congenital heart disease to prevent hospitalization caused by RSV.
For full prescribing information for Synagis, visit www.medimmune.com.
July 29, 2004
ST. LOUIS (MD Consult) - On July 26, 2004, New Jersey–based Reliant Pharmaceuticals, Inc, announced the introduction and the availability of Axid (nizatidine) Oral Solution, a liquid formulation of the company's Axid capsules. Approved by the U.S. Food and Drug Administration (FDA) in May 2004, Axid Oral Solution is indicated for use in pediatric patients age 12 and older for the treatment of endoscopically diagnosed esophagitis, including erosive and ulcerative esophagitis, and associated heartburn due to gastroesophageal reflux disease (GERD) for up to 12 weeks. In adults, Axid Oral Solution is also approved for the treatment of active duodenal ulcers.
Axid Oral Solution is an alcohol-free treatment option for children age 12 and older and for adults who prefer a liquid formulation. Axid Oral solution offers twice-daily dosing and features a bubble-gum flavor.
Axid Oral Solution has demonstrated equivalence to Axid capsules in a 150-mg dose. Both products contain the active ingredient nizatidine for the treatment of GERD and related conditions. Axid Oral Solution will be available in a 480-mL bottle. Acid reflux disease is a digestive disorder caused when the acid content of the stomach regularly backs up into the esophagus. Heartburn is the most common symptom of GERD, but regurgitation, difficulty swallowing, chronic cough, hoarseness, and a feeling of a lump in the throat may be associated symptoms. Nizatidine belongs to the class of drugs referred to as H2-receptor antagonists, which prevent histamine from stimulating stomach acid production.
Reliant plans to introduce the product to the medical community by the end of the August 2004.
July 21, 2004
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration announced on July 20, 2004, that it had approved botulinum toxin type A (Botox) to treat severe underarm sweating known as "primary axillary hyperhidrosis" that cannot be managed by topical agents such as prescription antiperspirants. Botox has already been approved for several other purposes.
Botulinum toxin type A is a protein produced by the bacterium Clostridium botulinum. When used to treat primary axillary hyperhidrosis, small doses of an injectable form of the sterile purified botulinum toxin stop release of the chemical messenger acetylcholine, temporarily blocking the nerves in the underarm that stimulate sweating.
Botox was first approved in December 1989 to treat 2 eye muscle disorders (blepharospasm and strabismus). Since then it has been approved to treat cervical dystonia, a neurologic movement disorder causing severe neck and shoulder muscle contractions. Most recently, in 2002, it was approved as Botox Cosmetic to temporarily improve the appearance of moderate to severe frown lines between the eyebrows.
In 2 placebo-controlled, multicenter, randomized, double-blind clinical trials involving more than 600 adults, those who received Botox had significantly reduced underarm sweating compared with the placebo group. In one study, 4 weeks after being injected, the percentage of people showing a 50% reduction in sweating was 91% in the group receiving Botox compared with 36% in the placebo group. In another study, the average duration of response after the first treatment was 170 days.
The most common adverse events after treatment (occurring in 3% to 10% of patients) included injection site pain and hemorrhage, sweating in other parts of the body, flu-like symptoms, headache, fever, itching, and anxiety.
Before being treated for primary axillary hyperhidrosis, patients should be evaluated for other potential causes of the problem, such as hyperthyroidism, to avoid symptomatic treatment of hyperhidrosis with Botox without addressing a potentially serious underlying disease that requires other forms of treatment.
The safety and effectiveness of Botox for hyperhidrosis in body areas other than the axillae (armpits) has not been established.
Because Botox is a prescription drug, it must be used carefully and under medical supervision for all of the product's approved indications.
Botox is manufactured by Allergan, Inc, which is based in Irvine, Calif.
July 16, 2004
ST. LOUIS (MD Consult) - On July 15, 2004, Ortho-McNeil Pharmaceutical announced that the U.S. Food and Drug Administration (FDA) had approved the fluoroquinolone antibiotic Levaquin (levofloxacin) tablets/injection and Levaquin (levofloxacin in 5% dextrose) injection to treat multidrug-resistant strains of Streptococcus pneumoniae in community-acquired pneumonia (CAP).
Approximately 4 million people in the United States develop CAP each year. S pneumoniae is one of the primary bacteria that causes CAP. Multidrug-resistant S pneumoniae are forms of bacteria resistant to 2 or more therapeutic classes of antibiotics including penicillin, second-generation cephalosporins, macrolides, tetracyclines, and sulfonamides. The presence of multidrug-resistant S pneumoniae has increased significantly over time and today represent up to 23% of all strains.
Data from Tracking Resistance in the United States Today (TRUST) demonstrated that 98% of multidrug-resistant S pneumoniae isolates are susceptible to Levaquin. TRUST, the largest and most comprehensive respiratory pathogen surveillance study in the United States, has been conducted annually since 1997. In vitro activity does not necessarily correlate with clinical results.
Levaquin is indicated to treat mild to severe CAP due to Staphylococcus aureus, S pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae. Levaquin can be used to treat CAP in a 5-day, 750-mg once-daily dosing regimen called the Leva-pak. Levaquin is also approved to treat CAP at a dose of 500 mg daily for 7 to 14 days.
Levaquin is dosed once daily and indicated for a wide variety of infections in addition to CAP including acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, nosocomial pneumonia, mild to moderate cases of complicated and uncomplicated urinary tract infections, acute pyelonephritis, and chronic bacterial prostatitis. The same dose of treatment is used in both inpatient and outpatient settings.
The safety and efficacy of levofloxacin in pediatric patients, adolescents (younger than 18 years), pregnant women, and nursing mothers have not been established. Levofloxacin is contraindicated in persons with a history of hypersensitivity to levofloxacin, quinolone antimicrobial agents, or any other components of this product. Serious and occasionally fatal hypersensitivity or anaphylactic reactions have been reported in patients receiving therapy with quinolones, including levofloxacin. These reactions often occur after the first dose. Administration of the drug should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity.
Antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc, or didanosine (Videx) chewable/buffered tablets or the pediatric powder for oral solution should be taken at least 2 hours before or 2 hours after levofloxacin administration. For more information on warnings, precautions, and additional adverse reactions that may occur, regardless of drug relationship, full U.S. prescribing information is available at levaquin.com.
Ortho-McNeil Pharmaceutical, Inc, a Johnson & Johnson company, is headquartered in Raritan, NJ.
July 15, 2004
ST. LOUIS (MD Consult) - On July 15, 2004, the U.S. Food and Drug Administration (FDA) announced the approval of a new indication for Aldara (imiquimod) topical cream. This product is currently approved for the treatment of actinic keratosis and external genital warts. The newly approved indication is for the treatment of superficial basal cell carcinoma (sBCC).
This type of skin cancer is diagnosed by a health care provider after biopsy and is different from other types of skin cancer, including other types of basal cell carcinoma.
SBCC is usually treated by surgical removal. Aldara should be used for treatment of sBCC only when surgery is medically less appropriate because the chances of effectively treating sBCC are generally greater with surgery. Patients treated with Aldara for sBCC should have regular follow-up visits after treatment to make sure the skin cancer is completely treated.
The safety and effectiveness of Aldara were established in 2 double-blind controlled studies with approximately 364 patients. In these studies, 75% of patients (139/185) who had their sBCC treated with Aldara had no evidence clinically or on repeat biopsy of their sBCC 12 weeks after finishing treatment. In a separate long-term study involving 182 patients, 79% of patients had no evidence of their sBCC 2 years after finishing treatment.
Skin cancer can occur anywhere on the body, but it is most common on skin that has been exposed to sunlight. The most common type of skin cancer is basal cell carcinoma, affecting at least 800,000 Americans each year. The superficial type of basal cell carcinoma usually occurs on the arms, legs, or on parts of the body such as the chest or back. With this new approval, the FDA is sanctioning use of Aldara for treatment of sBCC on the body, neck, arms, or legs, but not for treatment of sBCC on the face.
Most patients using Aldara Cream for the treatment of sBCC experienced skin reactions at the treatment site, which include redness, swelling, a sore or blister, peeling, itching, and burning.
Aldara Cream is manufactured by 3M Pharmaceuticals of St. Paul, Minn.
July 14, 2004
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has approved Prevacid (lansoprazole) for the short-term treatment of symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis in children aged 12 to 17 years, according to a June 30, 2004, announcement made by TAP Pharmaceutical Products Inc. This approval expands Prevacid's sanctioned use in children to 1 to 17 years. Currently, Prevacid is the only proton pump inhibitor (PPI) approved for use by children as young as 1 year old.
In an open-label, U.S. multicenter study, 87 adolescent patients (12-17 years of age) with symptomatic GERD were assigned to receive Prevacid 15 or 30 mg once daily. At the beginning of the study, most patients (89%) had mild to moderate overall GERD symptoms. Sixty-four patients had nonerosive GERD and were treated with Prevacid 15 mg daily for 8 weeks, whereas 23 patients had erosive esophagitis and were treated with Prevacid 30 mg daily for 8 to 12 weeks. Erosive esophagitis is a condition in which the lining of the esophagus has been damaged.
At the end of the study period, Prevacid was found to be safe and effective in treating patients with symptomatic GERD, including erosive esophagitis. Of 22 patients with erosive esophagitis evaluated, 95.5% (21 patients) were healed after 8 weeks of Prevacid treatment, which is similar to healing rates found in adults (92% to 95%).
Prevacid offers a variety of administration options that can be used by children and teens. Prevacid for oral suspension is the only PPI available in this type of formulation, as well as the only PPI to offer an orally disintegrating tablet, Prevacid SoluTab. Prevacid SoluTab is a formulation that disintegrates quickly in the mouth, usually in less than 60 seconds, and can be taken with or without water. Prevacid SoluTab should not be chewed. Patients should simply place the tablet on the tongue and allow it to disintegrate until the particles can be swallowed.
Symptomatic response to therapy does not preclude the presence of gastric malignancy. Prevacid is contraindicated in patients with known hypersensitivity to any component of the formulation. The most frequently reported adverse events in patients aged 12 to 17 years include headache (7%), abdominal pain (5%), nausea (3%), and dizziness (3%). In patients between the ages of 1 to 11 years, the most frequently reported adverse events were constipation (5%) and headache (3%). There were no adverse events reported in U.S. clinical studies that were not previously observed in adults.
Use of Prevacid in patients aged 1 to 17 years is supported by evidence from adequate and well-controlled studies of Prevacid in adults with additional clinical, pharmacokinetic, pharmacodynamic, and safety studies performed in pediatric patients. Safety and effectiveness have not been established in patients younger than 1 year old.
For more information about Prevacid, visit prevacid.com.
Prevacid is indicated for the short-term (up to 8 weeks) treatment of heartburn and other symptoms of GERD, as well as for the following:
In adults, the most frequently reported adverse events were diarrhea (3.8%), abdominal pain (2.1%), and nausea (1.3%).
TAP Pharmaceutical Products Inc, located in Lake Forest, Ill, is a joint venture between Abbott Laboratories of Abbott Park, Ill, and Takeda Chemical Industries, Ltd, in Osaka, Japan.
July 7, 2004
ST. LOUIS (MD Consult) - On July 6, 2004, TAP Pharmaceutical Products Inc. announced the U.S. Food and Drug Administration (FDA) has approved Prevacid (lansoprazole) SoluTab Delayed-Release Orally Disintegrating Tablets to be given using an oral syringe or nasogastric (NG) tube. Prevacid SoluTab is the first orally disintegrating formulation of a proton pump inhibitor (PPI).
Prevacid SoluTab is a tablet that has been microengineered to disintegrate quickly in the mouth, usually in less than 60 seconds. The tablet can be taken with or without water and is strawberry flavored. For children or other patients who have difficulty swallowing tablets, Prevacid SoluTab can now be given in 2 other ways. For administration via either an oral syringe or NG tube, the tablet can be dissolved in water (4 mL for 15-mg tablet, 10 mL for 30-mg tablet) and should be administered within 15 minutes. After administration, the syringe should be flushed according to package directions.
When taking Prevacid SoluTab by mouth, patients should simply place the tablet on the tongue and allow it to disintegrate with or without water until the particles can be swallowed. Prevacid SoluTab should not be chewed. Prevacid SoluTab is bioequivalent to Prevacid capsules, does not require dose conversion, and can be used to treat the same conditions.
Symptomatic response to therapy does not preclude the presence of gastric malignancy. Prevacid is contraindicated in patients with known hypersensitivity to any component of the formulation. The most frequently reported adverse events include diarrhea (3.8%), abdominal pain (2.1%), and nausea (1.3%). For further information about Prevacid, please see the complete prescribing information at prevacid.com.
Oral Prevacid formulations have the most approved indications and the most administration options of any PPI.
Prevacid is the only PPI approved for use in children as young as 1 year old and is approved for use by children aged 1 to 17 years. Safety and efficacy in children younger than 1 year have not been established. In patients between the ages of 1 to 11 years, the most frequently reported adverse events were constipation (5%) and headache (3%). The most frequently reported adverse events in patients aged 12 to 17 years include headache (7%), abdominal pain (5%), nausea (3%), and dizziness (3%).
Prevacid is indicated for the short-term (up to 8 weeks) treatment of heartburn and other symptoms of gastroesophageal reflux disease, as well as for the following:
TAP Pharmaceutical Products Inc, located in Lake Forest, Ill, is a joint venture between Abbott Laboratories, headquartered in Abbott Park, Ill, and Takeda Chemical Industries, Ltd, of Osaka, Japan.
June 7, 2004
ST. LOUIS (MD Consult) - On June 4, 2004, Paris-based pharmaceutical company Sanofi-Synthelabo announced that its synthetic, selective factor Xa inhibitor Arixtra (fondaparinux sodium) was approved by the U.S. Food and Drug Administration (FDA) for two new indications. The drug is now indicated for the treatment of acute deep venous thrombosis (DVT) when administered in conjunction with warfarin sodium and the treatment of acute pulmonary embolism (PE) when administered in conjunction with warfarin sodium when initial therapy is administered in the hospital.
Arixtra is already approved in the United States for the prophylaxis of DVT, which can lead to PE in patients undergoing hip fracture surgery, including extended prophylaxis, hip replacement surgery, and knee replacement surgery.
The file for the new indications for Arixtra was submitted to the FDA on July 31, 2003. The clinical dossier was based on the findings of the MATISSE PE and MATISSE DVT studies, which demonstrated that a new strength of Arixtra, 7.5 mg given as a once daily subcutaneous injection, when administered in conjunction with warfarin sodium, can effectively and safely treat the acute phases of both DVT and PE. (The 7.5-mg dose was adjusted to 5 mg in patients with a body weight <50 kg and 10 mg in patients with a body weight >100 kg.) Arixtra is the first antithrombotic agent to be registered in the United States specifically for the treatment of acute PE since the introduction of unfractionated heparin.
The MATISSE PE study is the largest worldwide trial ever performed in the treatment of PE. This open-label trial involved 2,213 patients with symptomatic PE enrolled in 214 centers in 20 countries worldwide, including 67 centers in the United States. The study showed that a fixed, once-daily, subcutaneous, 7.5-mg dose of Arixtra, without need for coagulation monitoring, appears to be at least as effective and as safe as continuous intravenous and dose-adjusted unfractionated heparin. Moreover, 15% of patients in the study (26.4% in the United States) received Arixtra on an outpatient basis after receiving the first dose in the hospital, compared with none of those taking unfractionated heparin.
The MATISSE DVT trial involved 2,205 patients in 23 countries in a total of 154 centers around the world with symptomatic DVT and without symptomatic PE. The study showed that 7.5 mg of Arixtra, given once daily in a fixed subcutaneous dose, appears to be at least as effective and safe as dose-adjusted low molecular weight heparin (LMWH) administered subcutaneously twice a day.
DVT and PE represent two manifestations of the same disease known as venous thromboembolism (VTE), a condition in which blood clots in the lower limbs (DVT) may travel to the lungs where they can cause a PE. VTE is the third most common cardiovascular disease after heart attack and stroke. VTE affects about 2 million Americans annually, at least 60,000 of whom will die of PE. VTE represents an annual cost of at least $2.9 billion in the United States alone.
As with other antithrombotic agents, the most common adverse effect during Arixtra administration is bleeding. Arixtra is contraindicated in patients with severely impaired kidney function. Arixtra prophylactic therapy is contraindicated in patients who weigh less than 50 kg (110 pounds) and are undergoing hip fracture, hip replacement, or knee replacement surgery because they may have an increased risk for major bleeding. Patients older than 75 years of age also may be more likely to experience major bleeding complications. As with other antithrombotics, the labeling for Arixtra includes a boxed warning regarding possible spinal/epidural hematomas when spinal anesthesia or spinal puncture is used.
Arixtra was launched in the United States on February 8, 2002, and in Europe on March 27, 2002.
Full prescribing information for Arixtra is available at arixtra.com.
June 4, 2004
ST. LOUIS (MD Consult) - Health care company Abbott Laboratories announced on May 27, 2004, that the U.S. Food and Drug Administration (FDA) had approved its medication Zemplar (paricalcitol injection) for use in 5- to 19-year-old hemodialysis patients with secondary hyperparathyroidism (SHPT). Zemplar was initially introduced in 1998 and is indicated for the prevention and treatment of SHPT associated with chronic renal failure in adults.
Patients with kidney failure are unable to produce the active form of vitamin D. As a result, many patients on dialysis have vitamin D deficiency and develop SHPT, a disorder that causes bone disease and can affect many organs and tissues, including the bones, red blood cells, heart, nerves, and muscles.
"Because of the unique characteristics of the growing skeleton, children are particularly vulnerable to the complications of kidney failure and secondary hyperparathyroidism that can lead to bone deformities and growth retardation," said Isidro B. Salusky, MD, a pediatric nephrologist and professor of pediatrics at the David Geffen School of Medicine at the University of California at Los Angeles. Salusky was the lead investigator for the clinical research and data collection used to support Abbott's application to the FDA seeking expanded use of Zemplar.
According to Abbott, approximately 1,400 American children between the ages of 5 and 19 years currently undergo hemodialysis.
Kidneys help keep bones healthy by metabolizing vitamin D, converting it into the active D compound that helps regulate parathyroid hormone secretion and bone metabolism, as well as calcium and phosphorus levels. In the absence of active vitamin D, many patients with kidney failure develop SHPT, in which the parathyroid glands produce excess amounts of parathyroid hormone. Without proper management, SHPT can lead to weak and brittle bones, anemia, and cardiac and neurologic problems. Because bones and other organs are still developing in children, and because they are typically patients for longer periods of time, complications related to SHPT can be more difficult to treat than in adults. Left untreated, SHPT can be a factor in growth retardation and can lead to severe disability.
Joel Melnick, MD, global medical director of Abbott Laboratories and a pediatric nephrologist, stated, "One of the reasons that controlling secondary hyperparathyroidism in children is especially challenging is that their diets frequently may be high in phosphorus, the control of which is critical in dialysis patients. A third-generation D compound like Zemplar that did not cause hyperphosphatemia and hypercalcemia in clinical studies is an incredibly important asset for younger patients and can help them lead more normal lives."
The safety and effectiveness of Zemplar were examined in a 12-week randomized, double-blind, placebo-controlled study of 29 pediatric patients, aged 5 to 19 years, who had chronic renal failure and were undergoing hemodialysis. Nearly all had received some form of vitamin D therapy before the study.
Sixty percent of patients in the Zemplar group had two consecutive 30% decreases in parathyroid hormone levels compared with only 21% of patients in the placebo group. Fewer Zemplar patients than placebo patients (23% vs 31%) experienced elevated serum calcium levels. The overall percentage of serum calcium measurements (defined as 10.3 mg/dL or greater) was 7% in the Zemplar group and 7% in the placebo group. No subjects in either the Zemplar group or placebo group developed hypercalcemia (defined as at least one calcium value >11.2 mg/dL) during the study. Another side effect measurement used in the study was the product of serum calcium and phosphorus levels (Ca × P), measured in terms of mg2/dL2. In this study, 40% of patients taking Zemplar (compared with 14% of the patients taking placebo) had at least one Ca × P greater than 72. The overall percentage of patients with Ca × P greater than 72, however, was 8% in the Zemplar group and 7% in the placebo group.
According to the National Institute of Diabetes and Digestive and Kidney Disease at the National Institutes of Health, of every 100,000 children 19 years and younger, 1 or 2 will develop kidney failure each year. African American teenagers are 3 times more likely than white teens to develop kidney failure, and boys are twice as likely as girls to develop kidney failure due to birth defects or other hereditary conditions. Because poorly functioning kidneys can leave the body's vitamin and mineral resources out of balance, the National Kidney Foundation notes that children with kidney disease are at risk for stunted growth and poor bone density.
As observed in phase II and III clinical trials, adverse effects with greater than 5% frequency with Zemplar versus placebo, regardless of causality, were nausea (13% vs 8%), vomiting (8% vs 4%), and edema (7% vs 0%). Zemplar is contraindicated in patients with vitamin D toxicity, hypercalcemia, or hypersensitivity to product ingredients. Administration may place patients at risk for hypercalcemia, elevated Ca × P product, and metastatic calcification.
For full prescribing information on Zemplar, visit abbottrenalcare.com.
June 1, 2004
ST. LOUIS (MD Consult) - On May 19, 2004, the U.S. Food and Drug Administration (FDA) granted approval of Gemzar (gemcitabine hydrochloride), in combination with Taxol (paclitaxel), providing an additional option in first-line therapy for women with metastatic breast cancer.
The approval of the Gemzar/Taxol combination was granted after analysis of phase III data that demonstrated favorable treatment outcomes. Patients diagnosed with metastatic breast cancer and treated with a combination of Gemzar and Taxol experienced a significant delay in time to disease progression of their disease and an improvement in response rate compared with Taxol alone. The time to disease progression data (5.2 vs 2.9 months, respectively; P < .0001) were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in 2003. Survival results will be formally presented at the 2004 ASCO meeting, June 5-8, 2004.
"The Gemzar/Taxol combination is one of the few combinations to surpass the single-agent efficacy of Taxol," said Paolo Paoletti, MD, vice president of oncology clinical research at Eli Lilly and Company. "In a disease that is marked by high recurrence rates, this added benefit is welcome news to patients and physicians."
The official label on the approval states that Gemzar, in combination with paclitaxel, is approved in the United States for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.
In addition to the United States, Gemzar has been approved for this indication in 32 other countries.
According to the World Health Organization, more than 1 million cases of breast cancer will be diagnosed in 2004. Breast cancer is the most common malignancy occurring in women. In the United States, breast cancer is one of the leading causes of cancer deaths, with 40,580 estimated deaths in 2004. About 40% of patients with breast cancer develop metastatic breast cancer after receiving treatment during the primary breast cancer phase, and the average survival time for patients after diagnosis of metastatic disease is 18 to 30 months.
This FDA approval is the second indication in 2004 for Gemzar and its third indication in the United States. Gemzar was granted U.S. approval for the treatment of locally advanced or metastatic pancreas cancer in 1996 and, in combination with cisplatin, for the treatment of locally advanced or metastatic non–small cell lung cancer in 1998. The drug is a nucleoside analog that interferes with the process of DNA production, thereby preventing cancer cells from replicating and thus slowing or stopping tumor growth.
Gemzar is manufactured by Lilly, which is headquartered in Indianapolis, Indiana. Additional information is available at www.lilly.com.
June 1, 2004
ST. LOUIS (MD Consult) - The United States Food and Drug Administration (FDA) on May 19, 2004, approved a supplemental new drug application for Avelox (moxifloxacin hydrochloride) tablets and intravenous (IV) formulation for the treatment of community-acquired pneumonia (CAP) caused by multidrug-resistant Streptococcus pneumoniae (MDRSP). Avelox is the first antibiotic available in both tablet and IV forms approved to treat CAP caused by these strains, which are resistant to the antibiotics most commonly used to treat pneumonia.
According to Bayer HealthCare, manufacturer of Avelox, 2 to 3 million cases of CAP are reported annually in the United States, resulting in 10 million physician visits, 500,000 hospitalizations, and 45,000 deaths each year. Currently, CAP is the sixth leading cause of death in the United States. Although the majority of CAP cases are caused by S pneumoniae, the number of cases of this bacteria becoming resistant to antibiotics is rising. Common antibiotics used to treat CAP such as azithromycin and penicillin have S pneumoniae resistance rates of 29% and 25%, respectively, and resistance is continuing to rise, says Bayer.
Avelox demonstrated clinical and bacteriologic success against strains resistant to 2 to 5 commonly used antibiotics, including macrolides such as clarithromycin and azithromycin, penicillin, second-generation cepholosporins such as cefuroxime, trimethoprim-sulfamethoxazole, and tetracyclines with eradication rates of 93% to 100%.
"The rise of resistance among S pneumoniae is complicating the treatment of pneumonia worldwide," said Paul MacCarthy, MD, vice president of Medical Science at Bayer Pharmaceuticals. "Antibiotic failure due to resistance can result in prolonged suffering for patients, time lost from work, increased healthcare costs, and serious illnesses that can lead to increased mortality. With approval to treat MDRSP in tablet and IV forms, Avelox will be an important treatment option for CAP, especially during this time of emerging resistance to conventional therapies."
Avelox is approved to treat CAP caused by S pneumoniae (including multidrug-resistant strains), Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydia pneumoniae; acute bacterial exacerbations of chronic bronchitis caused by S pneumoniae, H influenzae, Haemophilus parainfluenzae, K pneumoniae, S aureus, or M catarrhalis; acute bacterial sinusitis caused by S pneumoniae, H influenzae, or M catarrhalis; and uncomplicated skin and skin structure infections caused by S aureus or Streptococcus pyogenes.
Avelox is a prescription medication that is generally well tolerated. The most common adverse effects, which are usually mild, include nausea, diarrhea, and dizziness. Patients taking Avelox should be careful about driving or operating machinery until they are sure the medication is not causing dizziness.
Patients who have had an allergic reaction to Avelox or any of the other group of antibiotics known as "quinolones," such as ciprofloxacin or levofloxacin, should not take Avelox. In addition, the drug is contraindicated in those who have been diagnosed with an abnormal heartbeat such as an arrhythmia or are using certain medications used to treat an abnormal heartbeat. These medications include quinidine, procainamide, amiodarone, and sotalol.
Patients who are pregnant or planning to become pregnant while taking Avelox should discuss this with their health care providers. Avelox is not recommended for use during pregnancy or nursing because the effects on the unborn child and nursing infant are unknown.
Avelox is not recommended for persons younger than 18 years of age.
Many antacids and multivitamins may interfere with the absorption of Avelox and may prevent it from working properly. Patients should take Avelox either 4 hours before or 8 hours after taking these products. In addition, patients should inform their health care providers of any medical conditions they have and all prescription and non-prescription medications or supplements they are taking.
Avelox prescribing information and indicated organisms are available at www.AveloxUSA.com or by calling Bayer Clinical Communications at 800-288-8371.
May 24, 2004
ST. LOUIS (MD Consult) - On May 19, 2004, the U.S. Food and Drug Administration (FDA) approved Taxotere (docetaxel) injection in combination with prednisone for use in patients with advanced metastatic prostate cancer. This is the first drug approved for hormone refractory prostate cancer that has shown a survival benefit.
"We consider this approval an important advance in the treatment of prostate cancer because it can help some patients live longer. Patients need as many effective treatment options as possible and Taxotere, in combination with prednisone, offers hope to certain patients who have not responded to other treatments," said Dr. Lester M. Crawford, Acting FDA Commissioner.
Prostate cancer is the second leading cause of cancer death in men. Taxotere works by inhibiting tubulin, a protein essential to cell division, thus preventing cancer cells from dividing and growing in number.
The safety and effectivness of Taxotere was established in a randomized, multicenter global clinical trial with over 1,000 patients comparing chemotherapy with taxotere and prednisone to mitoxantrone and prednisone in men with metastatic, hormone-refractory prostate cancer. Taxotere in combination with prednisone, given every 3 weeks, showed a survival advantage of approximately 2.5 months over the control group in the trial.
The most common adverse events reported were nausea, alopecia, and bone marrow suppression. In addition, fluid retention and peripheral neuropathy, known effects of Taxotere, were also observed.
The American Cancer Society estimates there will be about 230,900 new cases of prostate cancer in the United States in 2004. About 29,900 men will die of this disease this year alone.
Taxotere is distributed by Aventis Pharmaceuticals Inc. of Bridgewater, NJ.
May 12, 2004
ST. LOUIS (MD Consult) - On May 11, 2004, Barr Pharmaceuticals, Inc, announced that it had received U.S. Food and Drug Administration (FDA) approval for Enjuvia (synthetic conjugated estrogens, B) 0.625- and 1.25-mg tablets. Enjuvia is the only plant-derived, synthetic conjugated estrogen product that includes the component delta 8,9-dehydroestrone sulfate, an additional active estrogenic component.
In December 2003, Barr announced that it had signed an asset purchase agreement with Endeavor Pharmaceuticals to acquire the NDA and intellectual property related to Enjuvia synthetic conjugated estrogens product, and two early-stage development female health care products.
In March 2002, Endeavor filed its application for approval of Enjuvia 0.3-, 0.45-, 0.625-, and 1.25-mg tablets for the treatment of moderate to severe vasomotor symptoms associated with the menopause. In April 2003, the FDA issued an approvable letter for the 0.625-mg and the 1.25-mg tablets and a nonapprovable letter for the 0.3-mg and the 0.45-mg tablets. Barr's application for Enjuvia 0.3-mg and 0.45-mg tablets is currently pending at the FDA.
Estrogen use that is unopposed by progestin is associated with an increased risk of endometrial cancer in postmenopausal women with intact uteri. Estrogens should not be used in women with undiagnosed abnormal genital bleeding, known or suspected breast cancer, estrogen-dependent neoplasia, active deep vein thrombosis, thromboembolic disorders, active or recent arterial thromboembolic disease, or pregnancy. Estrogens should not be used for the prevention of cardiovascular disease. The Women's Health Initiative study reported increased risks of myocardial infraction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis. Due to these risks, estrogen with or without progestins should be prescribed at the lowest effective dose for the shortest duration, consistent with treatment goals and risks for the individual woman; periodic clinical reevaluation of such therapy is also advised.
Barr Pharmaceuticals, a holding company that operates through its principal subsidiaries, Barr Laboratories, Inc. and Duramed Pharmaceuticals, Inc., is based in Pomona, New York. Its patent on Enjuvia expires in 2020.
For complete indications, warnings, and contraindications of Enjuvia, contact Barr Laboratories' Product Information Department at 1-800-Barr Lab.
May 7, 2004
ST. LOUIS (MD Consult) - On May 6, 2004, the U.S. Food and Drug Administration (FDA) announced its approval of Ista Pharmaceuticals' medication Vitrase (hyaluronidase for injection). Vitrase is an injectable drug approved as an adjunct to other injected drugs to increase their absorption and dispersion. Hyaluronidase has been used most commonly in combination with local anesthetics in the setting of ophthalmic surgery. Hyaluronidase increases tissue permeability and promotes the spread or dispersion of other drugs, for example, speeding the onset of action for an anesthetic. Vitrase is also approved for use as an adjunct to rehydrating agents and for use with certain imaging agents. Vitrase is a sheep-sourced form of hyaluronidase.
Hyaluronidase has not been available in the United States for the past 3 years due to the previous manufacturer's business decision to no longer market the product. The efficacy of hyaluronidase was evaluated and confirmed under the Drug Efficacy Study Implementation process (DESI) in 1970. DESI was a retrospective evaluation of the effectiveness of the drug products that the FDA had permitted on the market as safe through the new drug review process between 1938 and 1962.
This approval was based on product-specific manufacturing information together with published literature on hyaluronidase and other available public information. The manufacturer, Irvine, Calif–based Ista Pharmaceuticals, Inc, also conducted a clinical safety study. Clinical studies have shown hyaluronidase to be effective, and most adverse reactions that may occur with the use of hyaluronidase are allergic reactions. These have been noted to occur infrequently. In large published studies, the frequency of events including anaphylactic-like reactions has been less than 0.1%.
The Vitrase labeling warns against using the drug in situations where it could cause harmful effects. The warnings state that Vitrase should not be used to reduce the swelling of bites, stings, and infected or inflamed areas because of the possibility of spreading a localized infection.
May 4, 2004
ST. LOUIS (MD Consult) - On April 30, 2004, Amgen Inc. and Wyeth Pharmaceuticals, a division of Wyeth, announced that Enbrel (etanercept) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The psoriasis indication marks the fifth disease for which Enbrel has received an FDA approval in just over 5 years.
Psoriasis is a chronic immune disorder in which certain immune cells become overactive and release proteins called cytokines. Tumor necrosis factor (TNF) is one of those cytokines that helps regulate the body's immune response to infection and inflammation. In patients with psoriasis, TNF causes inflammation, which can lead to the formation of painful, often disfiguring psoriasis plaques. As an anti-TNF therapy, Enbrel binds to the overproduced TNF and renders it biologically inactive, which can result in a significant reduction in inflammation.
The approval was based on data from two phase 3 studies totaling more than 1,200 adults with plaque psoriasis who were treated with Enbrel for up to 12 months. Enbrel was approved with a step-down dosing regimen of 50 mg administered twice-weekly for 3 months, followed by a maintenance dose of 50 mg weekly thereafter. Enbrel demonstrated rapid and significant clearing in many patients at this recommended dosing regimen. Patients who are treated with Enbrel require no routine laboratory monitoring specific to Enbrel therapy other than standard medical oversight.
In a phase 3 study, 46% of patients receiving 50 mg twice-weekly of Enbrel achieved the primary end point of a 75% or greater improvement in the Psoriasis Area Severity Index (PASI 75) at 3 months. These patients were "stepped down" to half the dose and then continued treatment for an additional 3 months. At 6 months, the percentage of patients achieving a PASI 75 response was maintained after dose reduction.
"Psoriasis can be a chronic, disabling disease requiring continuous treatment. Enbrel was shown to provide rapid and significant relief of psoriasis in many patients," said Alice Gottlieb, MD, PhD, director of the Clinical Research Center at the University of Medicine and Dentistry of the New Jersey–Robert Wood Johnson Medical School. "Additionally, in one clinical trial, patients who stopped treatment did so without experiencing disease flare or rebound. The trial also demonstrated, that upon retreatment with Enbrel the overall response rates were similar to those seen after initial treatment."
Enbrel was generally well tolerated in both phase 3 studies. Adverse events were similar to those reported in previous clinical trials in other indications. The most common adverse events in the Enbrel group when compared with placebo were injection site reactions.
An estimated 4.5 million people in the United States suffer from psoriasis, and 1.5 million have moderate to severe plaque psoriasis. The disease is characterized by chronic inflammation of the skin. This inflammation helps drive the formation of red, itchy skin plaques that are often painful and disfiguring. TNF is found at increased levels in psoriatic plaques and plays a critical role in their formation and continued existence.
Enbrel is the only fully human TNF receptor approved to reduce signs and symptoms, improve physical function, and inhibit the progression of structural damage in patients with moderately to severely active rheumatoid arthritis (RA), and to reduce the signs and symptoms and inhibit the progression of structural damage of active arthritis in patients with psoriatic arthritis. Enbrel is the only biologic therapy approved for first-line treatment of RA and can be used alone or in combination with methotrexate. It is approved to reduce the signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis (JRA) in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). It is also the first biologic agent approved to treat the signs and symptoms in patients with active ankylosing spondylitis (AS). Enbrel is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
Enbrel acts by binding TNF, one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immune function and the cascade of reactions that causes the inflammatory process of RA, JRA, psoriasis, psoriatic arthritis, and AS. The binding of Enbrel to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity.
Since the product was first introduced, some serious infections have been reported in patients using Enbrel. Many occurred in people prone to infection, such as those with advanced or poorly controlled diabetes. Some serious infections were fatal, and there were rare cases of tuberculosis.
Patients who have an infection or are allergic to Enbrel or its components should not take the medication. Patients who are prone to infection or have been treated for heart failure should notify their doctors, and administration of Enbrel should be stopped if a serious infection occurs. Questions about Enbrel should be directed to one's physician, and the physician should be notified if an infection develops.
Serious nervous system disorders such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes have been reported. Patients should tell their doctors if they have ever had any of these disorders or develop them after starting to take Enbrel.
There have been rare reports of serious blood disorders (some fatal) associated with Enbrel. If symptoms such as persistent fever, bruising, bleeding, or paleness appear, the patient's physician should be notified.
In medical studies of all TNF-inhibitors, a higher rate of lymphoma was seen compared with the general population; however, the risk of lymphoma may be up to several-fold higher in patients with RA and psoriasis. The role of TNF inhibitors in the development of lymphoma is unknown. The incidence of other cancers has not increased with extended exposure to Enbrel and is similar to the expected rate.
Enbrel can cause injection site reactions. In addition, a medical study of patients with JRA, infections, headaches, abdominal pain, vomiting, and nausea occurred more frequently than in adults. The kinds of infections reported were generally mild and similar to those usually seen in children.
Other serious adverse reactions were reported rarely, including serious infections (2%) and depression/personality disorder (1%).
Additional information about Enbrel, including full prescribing information, can be found at enbrel.com or by calling 888-436-2735.
April 23, 2004
ST. LOUIS (MD Consult) - On April 22, 2004, GlaxoSmithKline announced that the U.S. Food and Drug Administration (FDA) approved the use of Advair Diskus 100/50 mcg (fluticasone propionate 100 mcg and salmeterol 50 mcg inhalation powder) in children 4 to 11 years of age with asthma who are symptomatic when taking inhaled corticosteroid therapy alone. Advair contains an inhaled corticosteroid (ICS) and a long-acting beta2-agonist (LABA) and is the only long-term preventive product that treats the two main components of asthma: airway inflammation and bronchoconstriction.
According to the National Institutes of Health's treatment guidelines, an ICS in conjunction with an LABA is a preferred treatment for patients who still have symptoms while taking low-dose ICS.
Asthma is a chronic lung disease with two main components: inflammation and bronchoconstriction. Both cause the airways to narrow, making it difficult to breathe. Asthma symptoms include wheezing, shortness of breath, chest tightness, and difficulty breathing.
"Treating inflammation and airway constriction is critical to controlling asthma symptoms," said Dr. Spahn. "An important advantage of Advair is that it combines two highly effective medicines in one device to treat these components."
Advair has been available in the United States since April 2001 to treat asthma in patients 12 years of age and older and is the most commonly prescribed inhaled asthma maintenance therapy in the United States.
Asthma has been increasing in prevalence in the United States since 1980. A recent report issued by the U.S. Centers for Disease Control indicates 9 million children (younger than 18 years) have been diagnosed with asthma, and 3.8 million of those children are between the ages of 5 and 11 years. Of these 3.8 million, 6.3% have had an asthma attack in the last year. Children with asthma miss more than 14 million school days every year, making asthma the number one cause of school absences due to chronic conditions.
The safety profile of Advair was studied in a 12-week trial conducted with 203 children (aged 4-11 years) who had asthma and were symptomatic when taking low doses of an ICS. The primary objective of this study was to evaluate the safety of Advair 100/50 mcg twice daily compared with 100 mcg fluticasone propionate (FP) given twice daily. The results showed that Advair had a similar safety profile to FP.
The study also included secondary efficacy measures of lung function as measured by forced expiratory volume in one second (FEV1) in children aged 6 to 11 years. Patients receiving Advair and patients receiving FP experienced improved FEV1 over the course of the study.
The findings of this study, along with extrapolation of efficacy data from patients 12 years of age and older, support that Advair 100/50 mcg is effective in the maintenance treatment of asthma in patients 4 to 11 years of age who are symptomatic while taking an ICS.
Advair is a long-term maintenance treatment that will not replace fast-acting inhalers for sudden symptoms and should not be taken more than twice a day. Rare but serious asthma episodes and asthma-related fatalities occurred in a study with Serevent, one of the components of Advair. These risks may be greater in African Americans.
While adjusting to a switch from an oral steroid, such as prednisone, to the inhaled steroid in Advair, patients and doctors should take care because patients may be less able to heal after surgery, infection, or serious injury. Patients should tell their doctors if they have a heart condition or high blood pressure. Some people may experience increased blood pressure, heart rate, or changes in heart rhythm. Advair contains an ICS. ICS, as well as poorly controlled asthma, can cause a reduction in growth rate. The long-term effect on final adult height is unknown. Patients should visit their doctors if their asthma does not improve.
For more information, call GlaxoSmithKline at 888-825-5249 or visit gsk.com.
April 22, 2004
ST. LOUIS (MD Consult) - On April 20, 2004, New Jersey–based pharmaceutical company Merck & Co, Inc, announced that the U.S. Food and Drug Administration (FDA) had approved changes to the prescribing information for Proscar (finasteride) based on a landmark National Institutes of Health (NIH) study. Proscar administered in combination with the alpha-blocker doxazosin (Cardura; Pfizer, Inc) is now indicated to reduce the risk of the symptoms of benign prostatic hyperplasia (BPH) progressing over time (a confirmed rise of 4 or more points in American Urological Association [AUA] symptom score).
BPH is a common condition that occurs in more than 50% of men between the ages of 51 and 60 years and up to 90% of men over the age of 90. BPH can block the flow of urine through the urethra and may cause symptoms such as slow urinary stream, straining to urinate, frequent urination, nighttime urination, and an urgency to urinate.
The new indication is based on the Medical Therapy of Prostatic Symptoms (MTOPS) study published in December 2003 in The New England Journal of Medicine. In this 3,047-patient study, Proscar combined with doxazosin significantly reduced the risk of BPH symptoms progressing when compared with placebo and either Proscar or doxazosin alone.
The MTOPS study was a multicenter, double-blind, placebo-controlled study conducted and funded by the National Institute of Diabetes and Digestive and Kidney Diseases, a part of the NIH. In the 4- to 6-year study (average, 5 years), 3,047 men with moderate to severe BPH symptoms were randomly assigned to receive placebo (n = 737), Proscar 5 mg/d (n = 768), doxazosin 4 or 8 mg/d (n = 756), or a combination of the two active treatments (n = 786).
The primary end point of the study was a composite measure of the first occurrence of any of the 5 following outcomes: a confirmed rise of 4 or more points from baseline in the AUA symptom score (0 = no symptoms, 35 = severe symptoms), acute urinary retention, renal insufficiency due to BPH, recurrent urinary tract infections, or incontinence. The most common event in the composite primary end point was an increase in AUA symptom score of 4 points or greater above baseline, referred to as symptom score progression. This accounted for 274 of the 351 events, or 78%, of the primary end point events.
Compared with placebo, treatment with combination therapy, Proscar alone, and doxazosin alone significantly reduced the risk of experiencing 1 of the 5 outcome events. Combination therapy also resulted in a significant reduction in the risk of the composite primary end point compared with treatment with Proscar alone or doxazosin alone.
Combination therapy with Proscar and doxazosin significantly reduced the risk of the primary end point by 67% compared with placebo (from 17.4% with placebo [128 events] to 6.2% with combination therapy [49 events], for an absolute risk reduction of 11.2%). Combination therapy also significantly reduced the risk by 49% compared with Proscar alone (from 11.6% with Proscar [89 events] to 6.2% with combination therapy [49 events], for an absolute risk reduction of 5.4%) and by 46% compared with doxazosin alone (from 11.2% with doxazosin [85 events] to 6.2% with combination therapy [49 events], for an absolute risk reduction of 5.0%).
Combination therapy with Proscar and doxazosin significantly reduced the risk of symptom score progression by 64% compared with placebo (from 13.6% with placebo [100 events] to 5.2% with combination therapy [41 events], for an absolute risk reduction of 8.4%). Combination therapy significantly reduced the risk of symptom score progression compared with the effect of Proscar alone (P < .001) and compared with doxazosin alone (P = .037).
The results of the MTOPS study are consistent with the findings of the 4-year, placebo-controlled study Proscar Long-term Efficacy and Safety Study (PLESS) in that treatment with Proscar reduced the risk of acute urinary retention, a component of the MTOPS primary end point, and reduced the need for BPH-related surgery, another outcome in the MTOPS study.
In MTOPS, Proscar reduced the risk of developing acute urinary retention by 67% compared with placebo (from 2.4% with placebo [18 events] to 0.8% with Proscar [6 events], for an absolute risk reduction of 1.6%). Proscar also reduced the risk of requiring BPH-related surgery by 64% compared with placebo (from 5.4% with placebo [40 events] to 2.0% with Proscar [15 events], for an absolute risk reduction of 3.4%).
The individual adverse experiences that occurred more frequently in the combination group compared with either drug alone were asthenia (16.8% in the combination group vs 7.1% for placebo), postural hypotension (17.8% vs 8.0%), peripheral edema (3.3% vs 0.9%), dizziness (23.2% vs 8.1%), decreased libido (11.6% vs 5.7%), rhinitis (2.4% vs 0.5%), abnormal ejaculation (14.1% vs 2.3%), impotence (22.6% vs 12.2%), and abnormal sexual function (3.1% vs 0.9%). Of these, the incidence of abnormal ejaculation in patients receiving combination therapy was comparable to the sum of the incidences of this adverse experience reported for the two monotherapies (4.5% with doxazosin alone and 7.2% with Proscar alone). Combination therapy with Proscar and doxazosin was associated with no new clinical adverse experiences.
During the MTOPS study, there were 4 cases of breast cancer in men treated with Proscar but no cases in men not treated with Proscar. During the PLESS study that enrolled 3,040 men, there were 2 cases of breast cancer in placebo-treated men, but no cases were reported in men treated with Proscar. The relationship between long-term use of Proscar and male breast cancer is currently unknown.
Proscar is indicated for the treatment of symptomatic BPH in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary retention, and reduce the risk of the need for surgery, including transurethral resection of the prostate and prostatectomy. Proscar administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of BPH (a confirmed > 4-point increase in AUA symptom score).
Proscar is not indicated for use in children or women. Proscar is contraindicated in patients who are hypersensitive to any components of this medication and in women when they are or may potentially be pregnant. Women should not handle crushed or broken Proscar tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Proscar tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed.
Adverse effects caused by Proscar may include impotence (8.1% for Proscar vs 3.7% for placebo) or less desire for sex (6.4% vs 3.4%). Some men taking Proscar may have changes (3.7% vs 0.8%) or problems (0.8% vs 0.1%) with ejaculation. In addition, some men may have breast swelling (0.5% vs 0.1%) or tenderness (0.4% vs 0.1%). Physicians should instruct their patients to promptly report any changes in their breasts such as lumps, pain, or nipple discharge. Some men have reported allergic reactions such as rash, itching, hives, and swelling of the lips and face. Rarely, testicular pain has been reported.
In a 7-year placebo-controlled trial that enrolled 18,882 men, 9,060 had prostate needle biopsy data available for analysis. In the group taking Proscar, 280 (6.4%) men had prostate cancer with Gleason scores of 7 to 10 detected on needled biopsy versus 237 (5.1%) men in the placebo group. Of the total cases of prostate cancer diagnosed in this study, approximately 98% were classified as intracapsular (stage T1 or T2). The clinical significance of these findings is unknown.
April 19, 2004
ST. LOUIS (MD Consult) - On April 12, 2004, pharmaceutical company GlaxoSmithKline announced the availability of a new dosage strength of Zantac (ranitidine hydrochloride effervescent) Efferdose tablets. New Zantac 25 Efferdose tablets (25 mg) is indicated for the treatment of gastroesophageal reflux disease (GERD) in children 1 month and older.
The new 25-mg Zantac Efferdose tablet accommodates dosing regimens for patients weighing 11 to 22 lbs who have GERD. In a recent single-center study of 102 healthy children (age, 4-8 years), 7 out of 10 preferred the taste of Zantac Efferdose over Zantac Syrup. The Zantac Efferdose 25-mg tablet is dissolved in at least 5 mL of water before administering the solution to the infant or child. It can be administered with a dosing cup, medicine dropper, or oral syringe. Zantac Efferdose Tablets are available in single-dose packets, do not require refrigeration, and do not contain alcohol.
Zantac Efferdose contains phenylalanine. The following have been reported as adverse events in clinical trials or in the routine management of patients treated with Zantac: rash, diarrhea, constipation, abdominal discomfort/pain, nausea and vomiting, and headache, sometimes severe. The drug's safety and effectiveness in neonates (younger than 1 month of age) have not been established. Safety and effectiveness in pediatric patients for the treatment of pathologic hypersecretory conditions or the maintenance of healing of erosive esophagitis have not been established. Use of Zantac in pediatric patients with GERD is supported by adequate and well-controlled studies in adults with GERD, as well as additional pharmacokinetic data in pediatric patients and an analysis of the published literature.
For more information, including full prescribing information, visit gsk.com or call GlaxoSmithKline at 919-483-2839.
April 13, 2004
ST. LOUIS (MD Consult) - On April 12, 2004, Wyeth Pharmaceuticals announced the U.S. Food and Drug Administration (FDA) had approved the reformulation of the stomach acid suppressant, Protonix IV (pantoprazole sodium) for injection. The reformulation eliminates the need for an in-line filter, a previously required extra step in an already time-sensitive procedure to administer the medication to patients requiring immediate acid suppression.
Protonix is the first and only proton pump inhibitor (PPI) in the United States to be offered in both oral and intravenous (IV) formulations.
The new formulation will replace the existing Protonix IV formulation, which has been used clinically for 7 years in more than 5 million patients worldwide.
The new formulation has been approved for administration either as a 2-minute or 15-minute infusion. Protonix IV received FDA approval in December 2003 for administration as a 2-minute infusion. This alternative infusion approach may reduce drug preparation time and administrative costs in hospitals because the intravenous admixture bag can be replaced with a less expensive syringe for administration.
The FDA first approved Protonix IV in March 2001 for the short-term (7- to 10-day) treatment of patients with gastroesophageal reflux disease (GERD) with a history of erosive esophagitis, as an alternative to oral therapy in patients who are unable to continue taking Protonix delayed-release tablets. Safety and efficacy of Protonix IV as an initial treatment of patients having GERD with a history of erosive esophagitis have not been demonstrated.
Protonix IV received expedited FDA approval in October 2001 for the treatment of pathologic hypersecretory conditions associated with Zollinger-Ellison syndrome or other neoplastic conditions.
In clinical trials, the most frequently reported adverse events with Protonix IV were injection site reactions (including thrombophlebitis and abscess), headache, diarrhea, nausea, and dyspepsia. Protonix IV is contraindicated in patients with known hypersensitivity to any component of the formulation. Anaphylaxis has been reported. As with any other intravenous products containing edetate disodium, zinc supplementation should be considered in patients treated with Protonix IV who are prone to zinc deficiency. Treatment with Protonix IV should be discontinued as soon as the patient is able to be treated with Protonix delayed-release tablets.
For more information, including full prescribing information, visit wyeth.com.
April 6, 2004
ST. LOUIS (MD Consult) - On April 5, 2004, Ontario-based Biovail Corporation announced that the U.S. Food and Drug Administration (FDA) had approved Cardizem LA (diltiazem hydrochloride) for the treatment of chronic stable angina. Cardizem LA can be given orally once daily, either in the evening or in the morning.
Cardizem LA already had been granted FDA approval for the treatment of high blood pressure. The medication provides 24-hour blood pressure control with a single daily dose. Cardizem LA may blunt a rise in blood pressure in the early morning, which is when risk of an ischemia-associated cardiovascular event is highest.
Angina pectoris (also referred to as simply angina) is a recurring pain or discomfort in the chest that occurs when some part of the heart does not receive enough blood. It is a common symptom of coronary heart disease, which occurs when vessels that carry blood to the heart become narrowed and blocked due to atherosclerosis. Angina is a prevalent disease, currently affecting 6.4 million people in the United States, with 400,000 new cases diagnosed each year. On average, patients with chronic angina currently need to receive 2 drugs to treat the disease, and only 17% of those patients report their pain as satisfactorily controlled.
Angina is often controlled by drugs. The choice of drug is usually dependent on the acuity and severity of the symptoms as well as the presence of other existing conditions. Cardizem LA, a calcium channel blocker, is effective in reducing the frequency and severity of angina attacks either used alone or in combination with other medications. In many patients, a combination of agents is more effective than therapy involving only 1 medication.
The effects of Cardizem LA on angina were evaluated in a randomized, double-blind, parallel-group, dose-response trial of 311 patients with chronic stable angina. Evening doses of 180, 360, and 420 mg were compared with placebo and with 360 mg administered in the morning. All doses of Cardizem LA administered at night increased exercise tolerance compared with placebo after 21 hours. The mean effect, placebo-subtracted, was 20 to 28 seconds for all 3 doses, and no dose-response was demonstrated. Cardizem LA, 360 mg, when given in the morning also improved exercise tolerance when measured 25 hours later.
In the angina study, the adverse event profile of Cardizem LA was consistent with what has been previously described for Cardizem LA and other formulations of diltiazem HCl. Among the Cardizem LA dose groups, adverse events occurred at a rate equivalent to or less than placebo. Adverse events were generally mild to moderate in nature. The most frequent adverse effects experienced by Cardizem LA–treated patients were lower limb edema, dizziness, fatigue, bradycardia, first-degree atrioventricular block, and cough.
Chronic oral administration of diltiazem HCl to patients in doses up to 540 mg/d has resulted in small increases in pR interval and on occasion produces abnormal prolongation. patients taking other drugs that are substrates of CYp450, especially patients with renal or hepatic impairment, may require dosage adjustment when starting or stopping concomitantly administered diltiazem to maintain therapeutic blood levels.
For full prescribing information for Cardizem LA, visit biovail.com or contact Biovail at 905-286-3000 or ir@biovail.com.
April 5, 2004
ST. LOUIS (MD Consult) - On March 29, 2004, Serono Inc. announced the U.S. Food and Drug Administration (FDA) had granted approval to new presentations of Gonal-f (follitropin alfa for injection) including a 450-IU multi-dose vial and a 75-IU mono-dose vial.
The new 450-IU multi-dose vial will be available in addition to the currently marketed multi-dose presentation, and the new 75-IU mono-dose vial will replace the current ampules. Gonal-f is indicated for induction of ovulation and pregnancy as part of hormonal treatment for infertility and development of multiple follicles as part of an assisted reproductive technology program.
Gonal-f is a highly consistent recombinant human follicle-stimulating hormone (r-hFSH) prescribed to supplement or replace naturally occurring FSH, which stimulates the development of follicles in the ovaries. It is the only FSH available in multi-dose and mono-dose vials for maximum dosing flexibility and individualized treatment.
Infertility is defined as the inability to achieve pregnancy after 1 year of regular, unprotected intercourse (6 months if the woman is 35 years or older). It affects about 6.1 million Americans, which represents about 10% of couples in their childbearing years. About 70% of patients who are treated succeed in having children.
Adverse effects may occur with the use of infertility drugs and, therefore, they should only be prescribed by physicians who are thoroughly familiar with infertility problems and their management. Ovarian hyperstimulation syndrome, with or without vascular and pulmonary complications, can occur with the use of infertility drugs. Reports of multiple births have been associated with Gonal-f treatment. Adverse effects in women using Gonal-f for ovulation induction can include headache, ovarian cysts, and nausea.
Serono, Inc., located in Rockland, Mass, is the U.S. affiliate of Serono, a biotechnology company headquartered in Geneva, Switzerland.
For more information, visit seronousa.com.
April 1, 2004
ST. LOUIS (MD Consult) - On April 1, 2004, pharmaceutical company Merck & Co announced it had won approval from the U.S. Food and Drug Administration to market its arthritis and pain medicine Vioxx (rofecoxib) for the acute treatment of migraine with or without aura in adults. Vioxx is the first COX-2–specific inhibitor approved to relieve migraine pain and associated migraine symptoms.
Clinical investigator Stephen Silberstein, MD, professor of Neurology at Jefferson University Hospital School of Medicine and director of the Jefferson Headache Center in philadelphia stated, "Studies have shown that just one Vioxx relieved migraine headache pain for most patients within 2 hours, a standard measurement for evaluating the efficacy of migraine treatments."
Vioxx offers a new treatment option for the estimated 28 million Americans who suffer from the effects of migraines. In addition to the new indication to treat migraine pain, Vioxx is approved for the management of acute pain based on studies that have shown Vioxx provided effective analgesic relief for moderate to severe dental pain, primary dysmenorrhea, and post-orthopedic surgical pain. Vioxx is also approved for the treatment of the chronic conditions of osteoarthritis and rheumatoid arthritis in adults.
The new indication for Vioxx for migraine was based on 2 double-blind, placebo-controlled multicenter studies that enrolled approximately 1,600 patients who were treated for a single migraine attack including headache pain of moderate to severe intensity.
Results from the studies demonstrated that a single dose of Vioxx (25 or 50 mg) provided significant migraine headache pain relief compared to placebo. Both doses of Vioxx also reduced the incidence of migraine symptoms including sensitivity to light (photophobia), sensitivity to sound (phonophobia), and nausea.
The findings from the 2 pivotal single-dose studies among patients taking 25 mg of Vioxx (n = 363), 50 mg of Vioxx (n = 375), or placebo (n = 362) revealed the following:
In studies, Vioxx was effective regardless of sex, race, age, or the presence of aura, menses, or dysmenorrhea. Vioxx was also effective regardless of whether there was a history of prior response to nonsteroidal anti-inflammatory drugs. Use of Vioxx in conjunction with common migraine preventative medications (eg, ß-blockers, calcium channel blockers, tricyclic antidepressants) or oral contraceptives did not affect efficacy.
The most common adverse events occurring in patients taking Vioxx compared with placebo in the single-dose studies were dizziness, nausea, somnolence, and dyspepsia. In a 3-month extension of one migraine study, the most common adverse events among patients taking Vioxx were dizziness, dry mouth, nausea, and vomiting.
For the acute treatment of migraine attacks, the recommended starting dose for Vioxx is 25 mg once daily. Some patients may receive additional benefit with 50 mg. The maximum recommended daily dose is 50 mg. The safety of treating more than 5 migraine attacks in any given month has not been established. Chronic daily use of Vioxx for the acute treatment of migraine is not recommended. The safety and effectiveness of Vioxx have not been established for cluster headache, which is present in an older, predominantly male, population.
people with allergic reactions, such as asthma, in response to ingestion of aspirin or other arthritis medicines should not take Vioxx. In rare cases, serious stomach problems such as bleeding can occur without warning. patients should inform their physicians if they have liver or kidney disease or a history of angina, heart attack, or a blocked artery in the heart. Vioxx cannot take the place of aspirin for the prevention of heart attack or stroke. Vioxx should not be used by women in late pregnancy.
Commonly reported adverse effects in clinical trials with Vioxx have included upper respiratory infections, diarrhea, nausea, and high blood pressure.
According to Merck, migraine is a disease that affeacts approximately 28 million Americans, the majority of whom are women. Unlike a bad headache, a migraine is characterized by attacks of intense, usually one-sided, throbbing head pain that can last anywhere from 4 to 72 hours. The pain associated with migraine is frequently accompanied by other unpleasant symptoms, including nausea, vomiting, and increased sensitivity to light, sound, or both.
For more information, visit merck.com.
March 31, 2004
ST. LOUIS (MD Consult) - In a press release dated March 30, 2004, Indianapolis, Ind–based pharmaceutical company Lilly announced approval of Zyprexa IntraMuscular (olanzapine for injection) by the U.S. Food and Drug Administration (FDA). The drug, previously available in tablet form, is approved to control acute agitation in patients with schizophrenia and bipolar mania.
According to the psychiatrist International project conducted by pKS Research partners in February 2004, hospital-based psychiatrists or emergency room physicians are not satisfied with current intramuscular antipsychotic therapies, primarily due to side effects that are difficult for patients to tolerate and because patients must be switched to a different oral therapy once their conditions are stabilized. In addition, 60% of these physicians said that currently available intramuscular treatments are not adequate in rapidly calming agitated patients.
"Acute agitation is terribly frightening and potentially dangerous for patients and their caregivers," said Barry Jones, MD, professor of psychiatry, McMaster University, Toronto, Canada. "Zyprexa IntraMuscular enables doctors to help patients regain control quickly, often with just a single injection. Further, because Zyprexa IntraMuscular is not overly sedating, it can help the physician and patient to begin communicating and working together to achieve treatment goals and help move the patient's life forward."
Acute agitation is a well-recognized behavioral syndrome with a range of symptoms, including hostility, extreme excitement, poor impulse control, tension, and uncooperativeness. The syndrome can occur with a number of conditions, including schizophrenia and bipolar disorder. patients suffering from agitation in its severe forms are usually in an emergency situation and require immediate treatment to alleviate personal distress and to prevent harm to themselves and others.
FDA labeling for Zyprexa IntraMuscular specifically states that if ongoing Zyprexa therapy is needed, physicians can transition patients with schizophrenia and bipolar mania from Zyprexa IntraMuscular to oral Zyprexa as soon as clinically appropriate.
More than 56% of physicians say it is very important or important that an antipsychotic agent can be used in an injectable formulation for agitation and an oral formulation for long-term disease management.
Zyprexa IntraMuscular's efficacy in controlling acute agitation was evaluated in 3 randomized, double-blind, placebo-controlled studies in patients with schizophrenia (2 studies) and bipolar mania (1 study). In these studies, the control of agitation with Zyprexa IntraMuscular was assessed using several scales, including the positive and Negative Symptom Scale Excited Component (pANSS EC).
Using these scales, Zyprexa IntraMuscular was statistically superior to placebo in all studies. On the primary efficacy measure (the pANSS EC), 10-mg injections of Zyprexa IntraMuscular were significantly superior to placebo at the first time point measured (15 or 30 minutes) after injection.
In the two studies in agitated patients with schizophrenia, Zyprexa IntraMuscular was compared with haloperidol (Haldol) intramuscular and placebo. The injectable formation of haloperidol, a first-generation or "typical" antipsychotic, has been the standard of care for acutely agitated patients for many years.
Results showed that both Zyprexa IntraMuscular and haloperidol intramuscular were superior to placebo. No adverse event occurred significantly more often with Zyprexa IntraMuscular than with haloperidol intramuscular. In fact, in these studies, painful muscle contractions called dystonia occurred in 6.6% of haloperidol intramuscular–treated patients but did not occur with Zyprexa IntraMuscular. Additional adverse effects that occurred significantly more often with haloperidol intramuscular, but not with Zyprexa IntraMuscular, included tremors, muscle spasms, indigestion, and blurred vision.
Zyprexa IntraMuscular was compared with lorazepam (Ativan) intramuscular and placebo in the study involving agitated patients with bipolar mania. Lorazepam, which is an anti-anxiety, sedative, and anticonvulsant medication, has also been used for decades. In this study, Zyprexa IntraMuscular was superior to placebo. No adverse event occurred significantly more often with Zyprexa IntraMuscular than with lorazepam intramuscular. In contrast, nausea and vomiting were reported significantly more often in patients treated with lorazepam intramuscular than in those receiving Zyprexa IntraMuscular.
In the 3 Zyprexa IntraMuscular trials, adverse events included drowsiness, dizziness, and muscle weakness. In addition, Zyprexa IntraMuscular was associated with infrequent decreases in blood pressure and heart rate that were clinically manageable. However, in an open-label clinical pharmacology study in non-agitated patients with schizophrenia in which the safety and tolerability of intramuscular olanzapine were evaluated under a maximal dosing regimen (three 10-mg doses administered 4 hours apart), approximately one third of these patients experienced a significant orthostatic decrease in systolic blood pressure (ie, decrease > 30 mm Hg). The risk for hypotension, bradycardia, and sinus pause may be greater in nonpsychiatric patients compared with psychiatric patients who are possibly more adapted to certain effects of psychotropic drugs.
Oral Zyprexa is indicated in the United States for the short-term and long-term treatment of schizophrenia, for maintenance in the treatment of bipolar disorder, and either alone or in combination with lithium or valproate (Depakote) for the short-term treatment of acute mixed or manic episodes associated with bipolar disorder.
The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was drowsiness. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, restlessness, episodes of low blood pressure, dry mouth, weakness, upset stomach, increased appetite, and tremor. A small number of patients experienced asymptomatic elevations of certain liver enzymes; none of these patients experienced jaundice.
Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotic agents including Zyprexa. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. The available data are insufficient to provide reliable estimates of differences in hyperglycemia-related adverse event risk among the marketed atypical antipsychotics. All patients taking atypical antipsychotic agents should be monitored for symptoms of hyperglycemia. persons with diabetes who begin taking atypical antipsychotic drugs should be monitored regularly for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.
prescribing should be consistent with the need to minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia, seizures, and low blood pressure.
In short-term (6-week) acute bipolar mania trials in combination with lithium or valproate, the most common treatment-emergent adverse event associated with Zyprexa and lithium or valproate was dry mouth. Other common events were weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, and abnormal burning or tingling of the skin.
Full prescribing information is available at zyprexa.com.
March 31, 2004
ST. LOUIS (MD Consult) - In a March 24, 2004, press release, pharamaceutical company Organon announced approval of Follistim-AQ cartridge (follitropin beta injection) by the U.S. Food and Drug Administration (FDA). Follistim-AQ cartridge is the first follicle-stimulating hormone treatment available in a prefilled, premixed solution.
Follistim-AQ cartridge is designed to be used only with the Follistim pen, which facilitates delivery of individualized doses of premixed follitropin beta injection, a widely used prescription fertility medication. Follistim is prescribed for women undergoing assisted reproductive treatments such as in vitro fertilization and for the induction of ovulation to achieve pregnancy. Follistim-AQ cartridge provides women with a discreet, convenient method to self-administer fertility treatment; with this method, the need for patients to mix one or more vials of medication is eliminated.
Results of clinical studies have shown that self-injection with Follistim-AQ cartridge is safe, convenient, and well tolerated by patients. According to a recent study conducted by the Follistim pen COH Study Group, 59 (98.3%) of the 60 women who participated in the study rated the overall experience of self-injecting with the Follistim pen as "very good" to "good."
Infertility affects about 6 million American couples, approximately 10% of the U.S. population of reproductive age. The U.S. Centers for Disease Control and prevention reported there were nearly 110,000 cycles of assisted reproductive technology in the year 2001.
Follistim-AQ cartridge is marketed in the United States by Roseland, New Jersey–based Organon USA, a division of Azko Nobel. In Europe, the product is marketed under the brand name puregon pen.
For more information including complete prescribing information, visit organon.com or follistim.com.
March 23, 2004
ST. LOUIS (MD Consult) - On March 22, 2004, the U.S. Food and Drug Administration announced its approval of new dosing recommendations for Viracept (nelfinavir) in patients 2 years of age or older. This decision was based on clinical and pharmacokinetic data from 5 pediatric studies.
In patients younger than 2 years of age, Viracept was found to be safe at the doses studied, but a reliably effective dose could not be established. Summary data from all pharmacokinetic studies submitted is included in the revised label for completeness. The major revisions made to the product label based on this review are described below:
Viracept is contraindicated in patients with clinically significant hypersensitivity to any of its components. Also contraindicated is the coadministration of Viracept and any of the following drugs: amiodarone and quinidine (antiarrhythmic agents); dihyroergotamine, ergonovine, ergotamine, and methylergonovine (ergot derivatives); pimozide (neuroleptic agent); and midazolam and triazolam (sedative/hynotic agents). patients taking Viracept are encouraged to ask their physicians which other medicines should not be taken.
Nelfinavir is an inhibitor of the CYp3A enzyme. Coadministration of Viracept and drugs primarily metabolized by CYp3A can result in increased plasma concentrations of the other drug that could increase or prolong its therapeutic and adverse effects. Caution should be exercised when inhibitors of CYp3A, including Viracept, are coadministered with drugs that are metabolized by CYp3A and that prolong the QT interval.
Concomitant use of St. John's wort (hypericum perforatum) or St. John's wort–containing products and Viracept is not recommended. Coadministration of St. John's wort with protease inhibitors, including Viracept, is expected to substantially decrease protease inhibitor concentrations and may result in suboptimal levels of Viracept and lead to loss of virologic response and possible resistance to Viracept or to the class of protease inhibitors.
Nelfinavir is principally metabolized by the liver. Therefore, caution should be exercised when administering this drug to patients with hepatic impairment.
There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors. In some patients, additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced. As causal relationship has not been established.
Viracept, from La Jolla, California–based Agouron pharmaceuticals, was originally approved for pediatric use in 1997.
March 16, 2004
ST. LOUIS (MD Consult) - On March 9, 2004, London-based pharmaceutical company GlaxoSmithKline announced it would be marketing its irritable bowel syndrome (IBS) medication Lotronex (alosetron hydrochloride) in a new dose. The drug, approved for use in female patients with severe diarrhea-predominant IBS who meet the conditions stated in the labeling, is now available as 0.5-mg tablets in addition to the currently marketed 1-mg tablets.
Lotronex is to be used by women with severe diarrhea-predominant IBS who have failed to respond to conventional therapy, whose IBS symptoms are chronic, and who have had other gastrointestinal medical conditions that could explain their symptoms ruled out. Diarrhea-predominant IBS is considered severe if, in addition to diarrhea, the patient experiences at least one of the following symptoms: frequent and severe abdominal pain/discomfort, frequent bowel urgency/fecal incontinence, or disability/curtailment of daily activities because of IBS.
Serious gastrointestinal adverse events have been reported with the use of Lotronex. These events, including ischemic colitis and serious complications of constipation, have resulted in hospitalizations, blood transfusions, surgery, and fatalities. Lotronex may be prescribed only by physicians who have enrolled in GlaxoSmithKline's prescribing program for Lotronex.
For safety reasons, the recommended starting dosage of Lotronex is 1 mg orally once a day for 4 weeks. If, after 4 weeks, the 1-mg/day dosage is well tolerated but does not adequately control IBS symptoms, the physician can increase the dosage to 1 mg twice a day, the dose used in controlled clinical trials. Although the efficacy of the 1-mg/day dosage in treating diarrhea-predominant IBS has not been evaluated in clinical trials, for safety reasons consideration should be given to continuing this dosage if it is well tolerated and IBS symptoms are controlled adequately. Lotronex should be discontinued in patients who have not had adequate control of IBS symptoms after 4 weeks of treatment with 1 mg twice a day.
Although the recommended adult dosages have not changed, the new 0.5-mg tablet can provide an option to physicians who need to customize dosing based on individualized patient needs.
IBS is a chronic, recurring condition that affects an estimated 18.5 million Americans, approximately 67% (12.4 million) of whom are women. Although the cause is currently unknown, IBS is characterized by multiple symptoms that include chronic or recurrent abdominal pain and discomfort together with irregular bowel function, such as diarrhea, constipation, or alternating diarrhea and constipation. Approximately 30% of women with IBS have diarrhea-predominant IBS (3.7 million).
The prescribing program for Lotronex and educational materials are available by calling 1-888-825-5249 or by visiting Lotronex.com.
For more information about the Risk Management plan and for full prescribing information, call Ramona DuBose at 919-483-2839.
March 9, 2004
ST. LOUIS (MD Consult) - On March 3, 2004, 3M pharmaceuticals announced the U.S. Food and Drug Administration (FDA) had granted marketing approval for Aldara (imiquimod) Cream, 5%, a topical prescription treatment for clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp in immunocompetent adults. Aldara Cream is the first immune response modifier approved for actinic keratosis.
The FDA's approval of Aldara Cream for actinic keratosis is based on positive results from two double-blind, randomized, placebo-controlled clinical trials involving 436 patients with multiple actinic keratosis lesions. patients were treated with Aldara Cream or placebo twice a week for 16 weeks. Nearly half of the patients treated with Aldara Cream achieved complete clearance of all lesions compared with only 3% in the placebo group. A majority of patients experienced lesion clearance of 75% or more.
The clinical studies also revealed another important feature of Aldara Cream. Among patients treated with Aldara Cream, a number of previously undetectable lesions appeared and cleared during treatment.
"Recent studies suggest that chronic sun exposure may cause immunosuppression in the skin," stated lead investigator Mark G. Lebwohl, MD, FACp, professor and chairman, Department of Dermatology, Mount Sinai Medical Center, New York. "Aldara, an immune response modifier, is an exciting treatment advance for patients with [actinic keratosis]."
The most frequently reported adverse reactions were local skin reactions, including edema, erythema, flaking/scaling/dryness, scabbing or crusting, erosion or ulceration, weeping/exudates, and itching or burning at the application site. Only 2% of patients reported pain at the lesion site. Although 16% of patients had a rest period during treatment, only 2% discontinued treatment due to local skin or application-site reactions.
According to the American Academy of Dermatology, actinic keratosis affects as many as 10 million Americans each year. Actinic keratoses are precancerous skin lesions that appear as rough, red, scaly patches, or crusts on the skin. Actinic keratosis lesions usually measure less than ¼ inch in diameter, and more than 80% of lesions occur on the upper limbs, head, and neck. Individuals with fair skin, light hair, and light-colored eyes are at greatest risk for actinic keratosis. Because actinic keratosis is caused by cumulative sun exposure, it can take years to develop. The condition usually appears first in older people, although cases have been reported in people in their 40s.
Common actinic keratosis treatments include cryotherapy (freezing), excisional surgery, electrodesiccation (burning) and curettage, lasers, topical chemotherapy and photodynamic therapy.
For more information about Aldara Cream or actinic keratosis, including full prescribing information, call 1-877-4-AK-NEWS or visit aldara.com.
March 2, 2004
ST. LOUIS (MD Consult) - On February 24, 2004, GlaxoSmithKline announced the U.S. Food and Drug Administration (FDA) had approved paxil CR (paroxetine HCl) tablets in an intermittent dosing regimen for the treatment of premenstrual dysphoric disorder (pMDD). With the new dosing option, women with pMDD can take paxil CR once daily during the 2-week period before the onset of their menstrual cycles rather than throughout the month. paxil CR, the first and only controlled-release selective serotonin reuptake inhibitor (SSRI) indicated for intermittent treatment of pMDD, is also indicated for the continuous treatment of pMDD, depression, social anxiety disorder, and panic disorder.
pMDD is a severe form of premenstrual syndrome that can significantly impair a woman's ability to carry out daily activities. According to the FDA, pMDD affects more than 5 million women of reproductive age in the United States. It is characterized by intense emotional symptoms including severely depressed mood, irritability, and tension, as well as the debilitating physical symptoms associated with the menstrual cycle.
"In my experience, women like the flexibility of taking their medication during the 2 weeks they would normally experience the worst of their symptoms," said Kimberly A. Yonkers, MD, Associate professor of psychiatry, Yale University of Medicine, and lead investigator of the largest clinical trial database of pMDD patients. "The new dosing option with paxil CR is appealing because patients can achieve relief from the debilitating physical and emotional symptoms of pMDD at a low dose and with a treatment schedule that suits their lifestyle."
The tolerability and efficacy of intermittent dosing with paxil CR tablets for the treatment of pMDD was established in a placebo-controlled study of 366 patients. In this study, the lowest dose of paxil CR (12.5 mg/d), given for the 2 weeks before the onset of menses (luteal phase dosing), was significantly more effective than placebo in reducing the emotional and physical symptoms of pMDD. Similar results were seen at 25 mg/d. Compared with women taking a placebo, patients taking paxil CR reported fewer symptoms that interfered with regular daily activities.
pMDD symptoms commonly emerge in the second half of the menstrual cycle and subside when menstruation begins or shortly thereafter. The symptoms follow this pattern every month or almost every month. Being familiar with pMDD symptoms is a critical element in the appropriate diagnosis and treatment of the condition. According to American psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, at least 5 of the following symptoms are required for a diagnosis of pMDD, including at least 1 of the first 4 symptoms:
paxil CR tablets offer the proven efficacy of paroxetine in a Geomatrix oral drug delivery system. The tablet is a multi-layered formulation that controls dissolution and absorption of the drug in the body. paxil CR offers flexible dosing with 3 dosing strengths: 12.5, 25, and 37.5 mg.
Most common adverse events (incidence of 5% or greater and incidence for paxil CR at least twice that for placebo) in studies for major depressive disorder, panic disorder, pMDD, and social anxiety disorder include infection, trauma, nausea, diarrhea, dry mouth, constipation, decreased appetite, somnolence, dizziness, decreased libido, tremor, yawning, sweating, abnormal vision, asthenia, insomnia, abnormal ejaculation, female genital disorders, and impotence.
patients should not abruptly discontinue taking antidepressant medication, including paxil CR. Concomitant use of paxil CR in patients taking monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated.
For more information on paxil CR, visit paxilcr.com or CRBalance.com, or contact GlaxoSmithKline at 919-483-2839.
February 12, 2004
ST. LOUIS (MD Consult) - On February 10, 2004, Ranbaxy pharmaceuticals Inc. announced the launch of Riomet (metformin HCl oral solution) 500 mg/5 mL, the first liquid form of metformin available in the United States. Riomet was approved by the U.S. Food and Drug Administration (FDA) in September 2003 as monotherapy to serve as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Riomet will offer an alternate dosage form to the tablet dose that has been in the U.S. marketplace for a number of years.
As a liquid form of metformin, Riomet may significantly improve the lives of people with diabetes who are unable to swallow tablets. This condition, dysphagia, is a relatively unknown but widespread problem, affecting 1 in 17 people in some form.
Jeffrey Thomas, vice president of brand marketing and sales at Ranbaxy USA Inc., an affiliate of Jacksonville, Fla–based Ranbaxy pharmaceuticals, said, "Ranbaxy has recognized that non-compliance with treatment is a major problem among people with type 2 diabetes.... By arming physicians with Riomet, Ranbaxy is providing an alternative for the dsyphagic patient and those that are averse to taking a tablet, which may help to improve patient compliance."
Diabetes is a major health concern in the United States, where 6.3% of the population has the disease. The risk increases with age—the incidence of diabetes among Americans age 60 years and older is 18.3%. In addition, older people are also at much higher risk of having difficulty swallowing pills; 45% of seniors have dysphagia.
Type 2 diabetes is the most common form of the disease, affecting between 90% and 95% of all diabetics. In type 2 diabetes, insulin, which carries sugar from the blood into the body's cells, is either not produced by the body in sufficient quantities or is not accepted by the cells. This causes glucose to build up in the blood, which can starve the body's cells for energy and ultimately damage the eyes, kidneys, nerves, and heart. In fact, 2 out of every 3 people with diabetes die of heart disease or stroke.
For more information, contact Ranbaxy at 609-720-5615 or visit ranbaxyusa.com.
February 10, 2004
ST. LOUIS (MD Consult) - On February 4, 2004, GlaxoSmithKline announced the availability of new Imitrex (sumatriptan succinate) tablets, a novel formulation of GlaxoSmithKline's migraine therapy. The new formulation contains the same active ingredient with the same proven efficacy and safety profile of the conventional Imitrex tablets, with the added feature of rapid disintegration of the product in the stomach.
The rapid-release mechanism of the new Imitrex tablets works differently from oral disintegrating tablets, also known as oral melts, which dissolve on the tongue. New Imitrex tablets, which replace the old tablets, are swallowed whole with water like conventional tablets. The new formulation has been designed to dissolve within minutes. In an in vitro study, the new tablet dissolved 5 times faster than conventional tablets, which may allow the drug to be absorbed into the bloodstream quickly.
GlaxoSmithKline notes that the relationship between dissolution and efficacy has not been established, and further studies are needed on this front.
Imitrex was the first migraine medication to deliver proven pain-free results. previous studies with conventional Imitrex tablets showed that 57% of patients treated with 100-mg tablets in the mild pain phase, and 50% with 50-mg, were pain free at 2 hours.
A recent study with the new tablets showed that 66% of patients treated with 100 mg of Imitrex in the mild pain phase, and 51% with 50 mg, were pain free at 2 hours. These results are based on a multicenter, randomized, double-blind, placebo-controlled single-attack study in the intent-to-treat population. patients (n = 432) were instructed to treat during the mild pain phase of their migraine, within 1 hour of the onset of pain, and to avoid the use of other medications. Not all of these patients complied with these instructions. In a prospective analysis of those patients who did follow the instructions (n = 313), 75% of patients who took new Imitrex 100-mg tablets (and 53% of those taking 50-mg tablets) reported being pain free at 2 hours.
Imitrex also treats the associated symptoms of migraine, including nausea, vomiting, and sensitivity to light and sound. The medication was generally well tolerated. In the clinical trial, the most common adverse effects reported with new Imitrex 100-mg and 50-mg tablets, respectively, were nausea and vomiting (5% and <1%, vs 2% with placebo), chest symptoms (3%, 2%; 0 placebo), and malaise and fatigue (3%, 1%; <1% placebo). Individual results may vary. If pain returns, a second dose can be taken after 2 hours.
"This new formulation is designed to help overcome the problems associated with gastric stasis, the slow movement of the stomach which commonly occurs during migraine attacks. This condition may slow the absorption of oral medications," said Dr. Frederick Taylor, headache specialist and neurologist at park Nicollet Health Services and Associate professor of Clinical Neurology at the University of Minnesota School of Medicine. "A recent clinical trial showed that two thirds of patients who were instructed to take new Imitrex 100-mg tablets during the mild pain phase were pain free at 2 hours."
Migraine affects 28 million Americans, 70% of whom are women. Imitrex targets the nerves and blood vessels that are believed to trigger the total migraine—pain, nausea, and sensitivity to light and sound.
"I see many patients who have endured the painful symptoms of severe headaches for years—thinking they were sinus or tension headaches—before finally coming in for a medical evaluation," said Dr. Susan Hutchinson director and founder, Headache Center Women's Medical Group of Irvine. "Once diagnosed, migraineurs should know that they do not have to suffer and that there are effective treatments, like new Imitrex tablets, available to help patients return to their daily activities."
Imitrex tablets are approved for the acute treatment of migraines with or without aura in adults and are available by prescription in pharmacies nationwide. Imitrex should only be used when a clear diagnosis of migraine has been established by a physician.
In the cases of diagnosis of migraine with or without aura, migraine-specific prescription therapies, like Imitrex, are available for the acute treatment of migraine attacks without drowsiness. Imitrex was the first prescription drug in a class of drugs called triptans to receive U.S. Food and Drug Administration approval for the acute treatment of migraine in adults.
Imitrex has been used to treat more than 646 million migraines over the last decade, equal to treating a migraine headache every second. patients should not take Imitrex if they have certain types of heart disease, history of stroke or transient ischemic attacks, peripheral vascular disease, Raynaud syndrome, or blood pressure that is uncontrolled. patients with risk factors for heart disease, such as high blood pressure, high cholesterol, diabetes, or smoking, should be evaluated by a doctor before taking Imitrex. Very rarely, certain people, even some without heart disease, have had serious heart-related problems. patients who are pregnant, nursing, or taking medications should talk to their doctors before taking Imitrex.
Full prescribing information is available at Imitrex.com or by calling GlaxoSmithKline at 919-483-2839.
January 27, 2004
ST. LOUIS (MD Consult) - On January 26, 2004, Cephalon Inc. announced it had received approval from the U.S. Food and Drug Administration to market provigil (modafinil) [C-IV] Tablets to improve wakefulness in patients with excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome (OSAHS) and shift work sleep disorder (SWSD). Originally approved in 1998, provigil was the first wake-promoting agent approved in the United States for improving wakefulness in patients with narcolepsy. For patients with OSAHS, provigil is approved as an adjunct to standard treatment for the underlying airway obstruction.
"The approval of provigil for these conditions provides clinicians with a therapeutic option to treat the debilitating excessive sleepiness that affects the daily lives of patients with obstructive sleep apnea/hypopnea syndrome and shift work sleep disorder," said paul Blake, MB, FRCp, Senior Vice president of Clinical Research and Regulatory Affairs at West Chester, pennsylvania–based Cephalon.
Joseph Lieberman, MD, MpH, professor of Family Medicine, Jefferson Medical College, philadelphia, added, "Currently, many patients suffer needlessly from excessive sleepiness because they simply don't recognize it as a symptom of a medical condition and therefore don't talk to their doctors about it. primary care physicians are in a position to identify excessive sleepiness and initiate appropriate diagnosis and care of their patients, including educating them about the dangers of engaging in certain activities while impaired by excessive sleepiness. Now with the approval of provigil, we have a new treatment option for our patients—when they have been appropriately diagnosed and treatment of their underlying condition does not resolve their excessive sleepiness."
provigil promotes wakefulness in preclinical studies without causing generalized stimulation in the brain. The drug is believed to work selectively through the sleep/wake centers to activate the cortex of the brain. Activation of the cortex is essential for wakefulness. The exact mechanism of action of provigil is not known.
The safety of provigil has been demonstrated in clinical trials enrolling more than 3,500 patients. In studies of OSAHS and SWSD, the overall safety profile of provigil was demonstrated to be consistent with the profile already established in patients with narcolepsy.
provigil has been shown to have no effect on a patient's ability to sleep when sleep is desired. Studies have demonstrated that the sleep of patients taking provigil was of similar quality and quantity to individuals taking placebo. In clinical trials, provigil was well tolerated, with an incidence of adverse events generally comparable to placebo. Most adverse events were mild to moderate. The most frequently reported adverse events were headache, nausea, nervousness, diarrhea, anxiety, dizziness, back pain, stuffy nose, trouble sleeping, and upset stomach.
Excessive sleepiness is the primary symptom—and often the most debilitating feature—associated with OSAHS, SWSD, and narcolepsy. Excessive sleepiness is defined as difficulty in maintaining wakefulness and an increased likelihood of falling asleep in inappropriate situations.
In OSAHS, sleep disruption is most commonly caused by airway obstruction, usually the relaxation and collapse of the soft tissue in the back of the throat during sleep. Symptoms of OSAHS may include restless sleep, obesity, irritability, forgetfulness, morning headaches, loss of energy, trouble concentrating, mood or behavior changes, anxiety or depression, falling asleep during the day (e.g., at work, watching TV), and loud, heavy snoring (often interrupted by silence and then gasps). According to the National Institutes of Health, approximately 12 million Americans suffer from OSAHS, and the disorder is twice as common in men as in women.
Continuous positive airway pressure, a medical device that blows air through the nasal passage, is the primary treatment for OSAHS. Despite adequate regular use of continuous positive airway pressure, many patients continue to experience excessive sleepiness. For these patients, provigil may be an appropriate adjunctive treatment.
SWSD is defined as a persistent or recurrent pattern of sleep disruption leading to excessive sleepiness or insomnia that is due to a mismatch between the sleep-wake schedule required by a person's environment and his or her circadian sleep-wake pattern. Characterized by extreme sleepiness, insomnia, headaches, and difficulty concentrating, SWSD can affect those who frequently rotate shifts or work at night. Six million people in the United States work permanent or rotating night shifts and therefore are at risk for SWSD.
provigil is supplied as oral tablets containing either 100 or 200 mg of modafinil. The recommended dose of provigil is 200 mg once daily. For patients with narcolepsy and OSAHS, provigil should be taken as a single dose in the morning. patients with SWSD should take provigil approximately 1 hour before the start of their work shifts.
For full prescribing information, visit provigil.com or call 1-800-896-5855.
January 27, 2004
ST. LOUIS (MD Consult) - On January 22, 2004, pennsylvania-based Mylan Laboratories Inc. announced that the U.S. Food and Drug Administration had granted final approval for Mylan pharmaceuticals' Abbreviated New Drug Application, which provides for a new strength (25 mg) of metoprolol tartrate.
According to the pharmaceutical company's president and COO Louis J. DeBone, Mylan is the largest U.S. supplier of generic metoprolol tartrate in 50-mg and 100-mg strengths.
The new 25-mg product will be available soon.
For more information, visit mylan.com or contact Mylan Laboratories by mail at 1500 Corporate Drive, Suite 400, Canonsburg, pA 15317 or by telephone at 724-514-1800.
January 21, 2004
ST. LOUIS (MD Consult) - On January 20, 2004, pfizer Inc announced that the U.S. Food and Drug Administration (FDA) had approved its drug Zithromax (azithromycin) as a once-daily, 3-day treatment for acute bacterial sinusitis (ABS). Zithromax is the only antibiotic approved as a 3-day treatment regimen for ABS.
Most antibiotics commonly prescribed for ABS require 7 to 14 days of multi-dose therapy. Zithromax has unique attributes, including high and sustained drug levels in infected tissues, that make a shortened dosing regimen possible.
"Zithromax administered once a day for 3 days represents a breakthrough for physicians in treating acute bacterial sinusitis," said Joseph Feczko, MD, president Worldwide Development. "The dosing regimen offers an efficacious treatment option that may help patients complete the course of treatment."
ABS is an acute infection of the sinuses most often caused by the pathogens Strepococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. Symptoms include nasal discharge, nasal congestion, fever, and facial pain or tenderness. Symptoms of untreated ABS generally last longer than 10 days and perhaps as long as 3 months. Approximately 20 million Americans develop ABS annually, resulting in an estimated 25 million physician visits and associated health care costs of up to $6 billion.
In one randomized, double-blind controlled study, 500 mg of Zithromax administered once daily for 3 days was compared with the antibiotic Augmentin (amoxicillin/clavulanate), 500/125 mg, given 3 times daily for 10 days. Clinical efficacy for the 3-day dosage of Zithromax was comparable to 10 days of Augmentin. Furthermore, 99% of patients taking Zithromax once daily for 3 days completed the course of therapy versus 82% for the comparator.
Fewer patients receiving Zithromax reported treatment-related adverse effects than those receiving Augmentin. The most common treatment-related adverse effects in this study were diarrhea (Zithromax, 17%; Augmentin, 32%) and nausea (7% vs 12%). The discontinuation rate due to adverse events was lower for 3-day Zithromax (2.2%) than for Augmentin (8.9%).
Zithromax should not be taken by patients with hypersensitivity to azithromycin, erythromycin, or any macrolide antibiotic. Antibiotic treatment should only be used for those infections caused by bacteria, and only a health care provider can decide whether antibiotic therapy is appropriate.
Developed and marketed by pfizer, Zithromax was first approved in the United States in 1992 for adults as the first once-daily, 5-day oral antibiotic treatment of community-acquired respiratory infections and skin infections. In 1995, Zithromax was approved as a once-daily, 5-day treatment for use in children with acute otitis media. In December 2001, Zithromax received FDA approval as both a single-dose regimen and 3-day regimen for the treatment of acute otitis media in pediatric patients.
January 21, 2004
ST. LOUIS (MD Consult) - On January 14, 2004, U.S. pharmaceutical company GlaxoSmithKline announced the U.S. Food and Drug Administration (FDA) had granted approval for Lamictal (lamotrigine) tablets for use as monotherapy in the treatment of partial seizures in patients 16 years and older when converting from the older antiepileptic drug, valproate, which includes valproic acid (Depakene) and divalproex sodium (Depakote).
This is the third new indication for Lamictal approved by the FDA in the past 12 months. In January 2003, Lamictal was approved by the FDA as adjunctive therapy for partial seizures in pediatric patients 2 years of age or older. In June 2003, Lamictal received approval for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy.
"This FDA approval for Lamictal supports the overall trend toward monotherapy as a goal of therapy that may help both seizure control and tolerability for many epilepsy patients," said John Messenheimer, MD, director of the epilepsy clinical research group at GlaxoSmithKline.
The expanded indication and dosing recommendations are based on results of an 18-week study during which Lamictal and valproate trough blood concentrations were carefully monitored at regular intervals. Seventy-seven patients with epilepsy were converted to monotherapy with Lamictal from valproate over the course of the study. The study demonstrated that withdrawal to monotherapy with Lamictal from valproate can be achieved while maintaining consistent blood concentrations of lamotrigine. Conversion was achieved using a 4-step dosing algorithm that increased Lamictal to a target maintenance dose while decreasing the amount of valproate administered.
The most common adverse events considered by the investigators to be caused by study medication were dizziness (23%), nausea (16%), headache (14%), tremor (13%), and asthenia (12%). Of the 77 patients enrolled in the study, 21% withdrew due to adverse events.
"This important expanded indication confirms for clinicians that they can safely switch patients to monotherapy with Lamictal from valproate," commented Blanca R. Vazquez, MD, Clinical Assistant professor, Department of Neurology, New York University School of Medicine. "This is good news for patients who are concerned about troubling side effects with valproate or who have not been able to achieve effective seizure control."
Epilepsy, defined by recurrent unprovoked seizures, is a change in sensation, awareness, or behavior brought about by an electrical disturbance in the brain. The kind of seizure a person has depends on which part and how much of the brain is affected by the electrical disturbance that produces seizures. partial seizures are the most common type of epilepsy disorder in adults, affecting approximately 70% of all people with the illness. partial seizures begin with abnormal electrical activity in a particular location in the brain. According to the Epilepsy Foundation, epilepsy affects 2.3 million Americans of all ages.
Lamictal is indicated as adjunctive therapy for partial seizures and for the generalized seizures of Lennox-Gastaut syndrome in adult and pediatric patients (=2 years of age). Lamictal is also indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with a single enzyme-inducing antiepileptic drug (AED) or now with valproate. The safety and effectiveness of Lamictal have not been established as initial monotherapy, for conversion to monotherapy from non–enzyme-inducing AEDs except valproate, or for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. The safety and effectiveness in patients younger than the age of 16, other than those with partial seizures and the generalized seizures of Lennox-Gastaut syndrome, have also not been established.
Lamictal is also approved for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania, mixed episodes) in patients treated for acute mood episodes with standard therapy. The effectiveness of Lamictal in the acute treatment of mood episodes has not been established.
Serious rashes requiring hospitalization and discontinuation of treatment have been reported in association with the use of Lamictal. The incidence of these rashes, which have included Stevens-Johnson syndrome, is approximately 0.8% in pediatric patients younger than the age of 16 years receiving Lamictal as adjunctive therapy for epilepsy and 0.3% in adults receiving adjunctive therapy for epilepsy. In the bipolar clinical trials, the rate of serious rash was 0.08% of adult patients who received Lamictal as initial monotherapy and 0.13% of adult patients who received Lamictal as adjunctive therapy. In a prospectively followed cohort of 1,983 pediatric patients taking adjunctive Lamictal, there was 1 rash-related death. In worldwide post-marketing experience, rare cases of toxic epidermal necrolysis (TEN) and rash-related death have been reported in adult and pediatric patients, but their numbers are too few to permit a precise estimate of the rate.
Because the rate of serious rash is greater in pediatric patients than in adults, GlaxoSmithKline emphasizes that Lamictal is only approved for use in pediatric patients younger than the age of 16 years if they have partial seizures or seizures associated with the Lennox-Gastaut syndrome.
Other than age, there are as yet no factors identified that are known to predict the risk of occurrence or the severity of rash associated with Lamictal. There are suggestions, yet to be proved, that the risk of rash may also be increased by coadministration of Lamictal with valproic acid, exceeding the recommended initial dose of Lamictal, or exceeding the recommended dose escalation for Lamictal. However, cases have been reported in the absence of these factors. Lamictal should ordinarily be discontinued at the first sign of rash unless the rash is clearly not drug related.
For more information on Lamictal, visit the manufacturer's web site at gsk.com.
January 15, 2004
ST. LOUIS (MD Consult) - On January 14, 2004, the U.S. Food and Drug Administration (FDA) approved Zyprexa (olanzapine) for maintenance in the treatment of bipolar disorder. Zyprexa, manufactured by Indianapolis-based Eli Lilly and Company, can now be used to delay relapse into either mania or depression in patients with bipolar disorder.
"Bipolar disorder is a serious condition that can be difficult to treat. For those who achieve stability on existing medications, relapse of symptoms is all too common," said Frederick K. Goodwin, MD, director, Center on Neuroscience, Medical progress and Society, at the George Washington University Medical Center, Washington, DC.
Zyprexa was approved by the FDA in 2000 for the short-term treatment of acute mixed or manic episodes associated with bipolar disorder and is the first medication approved to both treat acute mania and delay relapse of symptoms associated with bipolar disorder since lithium received approval from the FDA in 1974.
The new indication is based on data from a double-blind, placebo-controlled study that showed time to relapse of either mania or depression was significantly longer for patients taking Zyprexa than patients treated with placebo. Zyprexa-treated patients had a significantly lower rate of either a mania (16.4% for Zyprexa vs 41.2% for placebo) or depression relapse (34.7% vs 47.8%).
"We believe that physicians are looking for treatments, like Zyprexa, that demonstrate that they can effectively delay relapse, not only into the manic phase, but also into the depressive phase of bipolar disorder," said Mauricio Tohen, MD, phD, Lilly clinical research fellow at Lilly Research Laboratories and Zyprexa product team leader. "This new indication provides a treatment option to clinicians and patients that is dependable in treating both acute manic episodes and delaying new episodes. Longer stable periods may provide greater opportunities for clinicians to work with their patients on improving work or family life."
In the placebo-controlled study, common and significant adverse events for the Zyprexa patients were weight gain, fatigue, and inner and outer restlessness (akathisia).
Bipolar disorder, also known as manic-depressive illness, is a complex mental illness characterized by debilitating swings in mood. These swings range from manic episodes, marked by abnormal euphoria, elation, and irritability, to episodes of deep depression, marked by extreme sadness and difficulty functioning. These periods of illness are interspersed with periods of normal mood. A lifelong illness, bipolar disorder typically emerges in adolescence or young adulthood, and episodes continue intermittently throughout life.
More than 2.5 million Americans live with a diagnosis of bipolar disorder, but recent research indicates the real number of those with the disorder may be as high as 10 million. The results of untreated bipolar disorder can be catastrophic. According to the National Institute of Mental Health, nearly 1 in every 5 people with the illness ends his or her life by suicide. The World Health Organization estimates that bipolar disorder is the sixth leading cause of disability in the world.
During relapse into mania or depression, people with bipolar disorder may experience disruptions in relationships and jobs, suffer feelings of failure, or become suicidal. Recurring relapse may lead to a worsening of the disease itself and may contribute to more frequent episodes of relapse.
In addition to the newly approved indication, Zyprexa is indicated in the United States for the short-term and long-term treatment of schizophrenia, either alone or in combination with lithium or valproate (Depakote, Abbott) for the short-term treatment of acute mixed or manic episodes associated with bipolar disorder.
The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was drowsiness. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, restlessness, episodes of low blood pressure, dry mouth, weakness, upset stomach, increased appetite, and tremor. A small number of patients experienced asymptomatic elevations of certain liver enzymes; none of these patients experienced jaundice.
Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotic agents including Zyprexa. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. The available data are insufficient to provide reliable estimates of differences in hyperglycemia-related adverse event risk among the marketed atypical antipsychotic agents. All patients taking atypicals should be monitored for symptoms of hyperglycemia. persons with diabetes who are taking atypicals should be monitored regularly for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. patients who develop symptoms of hyperglycemia during treatment should also undergo fasting blood glucose testing.
prescribing should be consistent with the need to minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia, seizures, and low blood pressure.
In short-term (6-week) acute bipolar mania trials in combination with lithium or valproate, the most common treatment-emergent adverse event associated with Zyprexa and lithium or valproate was dry mouth. Other common events were weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia, and abnormal burning or tingling of the skin.
The efficacy of Zyprexa in elderly patients with dementia has not been established in clinical trials, and Zyprexa is not approved for use in this patient population. It is important to note that the label for Zyprexa includes a warning for elderly patients with dementia. The warning states that strokes or mini-strokes (also called transient ischemic attacks or TIAs), including fatalities, were reported in elderly patients with dementia-related psychosis who participated in Zyprexa clinical trials.
For more information, including full prescribing information, visit zyprexa.com.
January 14, 2004
ST. LOUIS (MD Consult) - On January 13, 2004, pharmaceutical company AstraZeneca announced that the U.S. Food and Drug Administration (FDA) had approved its medication Seroquel (quetiapine) as a monotherapy and adjunct therapy for the treatment of mania associated with bipolar disorder (manic-depressive illness). Seroquel was first approved for the treatment of schizophrenia in 1997.
The FDA's latest approval is based on the positive results of a comprehensive bipolar disorder clinical trial program involving more than 1,000 patients in 28 countries, which found Seroquel to be effective across a broad range of symptoms and well-tolerated in treating manic episodes as both a monotherapy and in combination with lithium or divalproex. Seroquel was also found to be fast-acting; improvements in patients' manic symptoms were seen within the first week of treatment.
Bipolar disorder is a serious mental illness that affects approximately 3% to 4% of the adult population and is the sixth leading cause of disability in the world. Adverse effects associated with treatment (e.g., extrapyramidal symptoms [EpS], which cause movement disorders, or serum prolactin elevation, which can cause menstrual irregularities, decreased libido, and impotence) can often cause patients great distress and can lead to issues with treatment compliance. A lack of compliance results in patients subjecting themselves to a high risk of relapse and increased risk of suicide; therefore, a well-tolerated and effective treatment is pivotal to the successful treatment of this condition.
Seroquel has also recently received approval from the Mutual Recognition procedure (MRp) involving 14 European countries to extend its use to treat mania associated with bipolar disorder. Health authority approvals have also been received in the United Kingdom, Italy, Mexico, and New Zealand.
For more information, visit astrazeneca.com.
January 13, 2004
ST. LOUIS (MD Consult) - In a January 12, 2004, press release, French manufacturer Sanofi-Synthélabo announced that its drug Eloxatin (oxaliplatin for injection) in combination with 5-fluorouracil (5-FU) and leucovorin (LV) has been approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of advanced colorectal cancer.
Eloxatin had already been approved in August 2002 for second-line treatment of metastatic carcinoma of the colon or rectum in the United States. This new approval recommends the use of Eloxatin, in combination with infusional 5FU/LV, for the treatment of advanced carcinoma of colon or rectum.
About 1 million new cases of colorectal cancer are diagnosed worldwide every year, with about 150,000 new cases in the United States annually. According to the American Cancer Society, colorectal cancer is the second leading cause of malignancy-related death in the United States, accounting for 10% to 15% of all cancer death. Over a lifetime, about 1 in 18 people develop colorectal cancer, and, each year, about 56,000 people die from it in the United States.
Clinical data show that patients with advanced colorectal cancer treated with Eloxatin given in combination with 5-FU/LV as first-line chemotherapy had a statistically significant improvement of nearly 5 months in median survival time compared with patients treated with a standard treatment of irinotecan in combination with 5-FU/LV.
"The finding that the oxaliplatin-based regimen demonstrated a longer survival time for patients is a major step forward," said Richard M. Goldberg, M.D., professor and Division Chief at University of North Carolina, Chapel Hill School of Medicine. "This is the greatest increase in survival time we have seen in a chemotherapy regimen used in advanced colorectal cancer and positions the oxaliplatin-based regimen as an emerging standard of care for patients with colorectal cancer."
The study upon which the FDA approval was based was a trial sponsored by the National Cancer Institute (NCI), trial N 9741. The study demonstrated that patients treated first with Eloxatin combined with infusional 5-FU and LV, a regimen known as FOLFOX, had an overall median survival time of 19.4 months after the initiation of treatment, compared with 14.6 months in patients treated with a standard combination of irinotecan plus bolus 5-FU/LV, a regimen known as IFL. This represents a median survival advantage of 4.8 months for patients treated with FOLFOX, a 35% improvement.
In addition to the survival advantage, patients taking FOLFOX also had a significantly higher overall tumor response rate when they had measurable disease at baseline (45% vs. 33%), and patients experienced a significantly longer time to disease progression (8.7 months vs. 6.9 months) than those on IFL. The adverse effects experienced by the group taking FOLFOX also were less severe, more manageable, and more often reversible than those reported by the IFL group. The most commonly reported adverse effects in patients treated with FOLFOX included neutropenia and paresthesia. Based on these results, the investigators concluded that FOLFOX should be considered a standard first-line therapy for advanced colorectal cancer.
In March 2003, Eloxatin was incorporated into the National Comprehensive Cancer Network (NCCN) colorectal cancer treatment guidelines.
Eloxatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.
Anaphylactic-like reactions to Eloxatin have been reported and may occur within minutes of Eloxatin administration. Epinephrine, corticosteroids, and antihistamines have been used to alleviate symptoms.
Eloxatin should not be administered to patients with a history of known allergy to Eloxatin or other platinum compounds. Women of childbearing potential should be advised not to become pregnant while receiving treatment with Eloxatin. As with other platinum compounds, hypersensitivity and anaphylactic/anaphylactoid reactions have been reported.
Eloxatin is associated with pulmonary toxicity, which may be fatal, and with two types of primarily peripheral sensory neuropathy: an acute, reversible type of early onset and a persistent type (>14 days). paresthesias occurred in 77% (all grades) of previously untreated patients. Acute and persistent neuropathy occurred in 56% and 48% (all grades) of previously treated patients, respectively. An acute syndrome of pharyngolaryngeal dysesthesia seen in 1% to 2% (grade 3/4) of patients may also occur, characterized by subjective sensations of dysphagia or dyspnea, without any laryngospasm or bronchospasm (no stridor or wheezing).
Both 5-FU and Eloxatin are associated with gastrointestinal and hematologic adverse events. When Eloxatin is administered in combination with 5-FU, the incidence of these events is increased. In patients previously untreated/treated for advanced colorectal cancer, the most frequently reported adverse events (all grades) with Eloxatin in combination with infusional 5-FU/LV were fatigue (70%/68%), diarrhea (56%/67%), nausea (71%/65%), and vomiting (41%/40%). Changes in hematology parameters were also seen (all grades): anemia (27%/81%), leukopenia (85%/76%), neutropenia (81%/73%), and thrombocytopenia (71%/64%).
Eloxatin is currently marketed by Sanofi-Synthélabo in more than 60 countries for first- and/or second-line treatment of metastatic colorectal cancer. An extensive worldwide clinical development program is ongoing to explore the benefit of Eloxatin in other types of cancers.
Full prescribing information including boxed warning is available upon request. For more information, visit en.sanofi-synthelabo.com/index.asp.
News Updates are brought to you by
An Imprint of .
To order a Mosby's Drug Consult product or to check on your order, please call Elsevier Science Customer Service Department at 800-545-2522 or Order Online