FDA approves extended-release formulation of bipolar disorder treatment
FDA approves new indications for Abbott's arthritis treatment
Pfizer's Lipitor approved to reduce risk of heart attack and stroke
FDA approves new formulation of drug to lower intraocular pressure
Hepatitis A vaccine approved for children 12 months and older
Anticoagulant approved for use in percutaneous coronary intervention
Adjuvant chemotherapy agent approved for Dukes' C colon cancer
Sanofi vaccine approved to deter tetanus, diphtheria, whooping cough
Extended-release medication approved to treat ADHD, says Novartis
FDA approves oral disintegrating tablet to treat moderate to moderately severe pain
FDA grants full approval for Velcade as second-line multiple myeloma treatment
FDA approves angiotensin-receptor blocker to treat heart failure
FDA okays generic transdermal patches for chronic pain treatment
Oral solution of schizophrenia and bipolar disorder treatment approved
Pfizer's antifungal approved to treat bloodstream infections
FDA approves Avelox for complicated intra-abdominal infections
FDA approves new chemotherapy combination for treatment of pancreatic cancer
Pfizer's Aromasin approved as adjuvant therapy for early breast cancer
New formulation and indication for Emtriva approved by US FDA
Orally disintegrating prescription antihistamine approved in US
Treatment for Cryptosporidium-induced diarrhea approved for adults and teens
FDA approves capsule formulation of secondary hyperparathyroidism drug
Indications for Atacand include use without other ACE inhibitors
FDA approves fixed-dose combination hypertension medicine to prevent stroke
Pegasys and Copegus now approved to treat Hepatitis C and HIV coinfection
Serono's growth hormone deficiency treatment approved for adults
December 22, 2005
ST. LOUIS (MD Consult) - On December 22, 2005, Roche announced that the US Food and Drug Administration (FDA) has approved a supplemental new drug application extending the prophylaxis indication for Tamiflu (oseltamivir phosphate) to include children aged 1 to 12 years. An antiviral medication prescribed for the prevention and treatment of influenza, Tamiflu was previously approved for prophylaxis in adolescents (age 13 years and older) and adults. Tamiflu is also the only antiviral medication indicated for the treatment of influenza type A or type B infection in patients aged 1 year and older and is available in both capsule and liquid suspension formulations.
When administered within 48 hours of exposure, clinical data show that prophylaxis with Tamiflu reduced the incidence of flu from 17% (18/106) in the group not receiving Tamiflu to 3% (3/95) in the group receiving prophylaxis. The dosing for the new indication is 30 to 60 mg once daily (dependent on body weight) for a duration of 10 days. Therapy should begin within 2 days of exposure, following close contact with an infected person.
The supplemental new drug application was filed based on results from a subset of pediatric patients in a clinical study where Tamiflu was used for the management of influenza in households. The study, which included more than 1,000 patients (including adults and children), showed that postexposure prophylaxis is effective in preventing secondary spread of influenza infection and illness in households and that the protective efficacy of Tamiflu was the same in children aged 1 to 12 years as in the whole population.
Influenza is particularly dangerous for vulnerable populations including young children and infants. Children younger than 2 years old are as likely as those over the age of 65 years to be hospitalized because of influenza. It is estimated that children are 3 times more likely to get sick with influenza—on average, 1 in 10 adults is affected by influenza annually, compared with 1 in 3 children. Therefore, prevention of influenza in children can have a significant impact on the spread of influenza in the household and the whole community.
According to Roche, Tamiflu delivers:
In addition, Tamiflu is shown to provide up to 89% overall protective efficacy against clinical influenza in adults and adolescents who had been in close contact with influenza-infected patients.
In children, treatment with Tamiflu delivers:
The World Health Organization (WHO) advises that stockpiling antiviral agents in advance is presently the only way to ensure that sufficient supplies are available in the event of a pandemic. Roche, headquartered in Basel, Switzerland, has been working closely with WHO and national governments to ensure that governments are aware of the importance of stockpiling antiviral medications in the event of a pandemic situation. Roche has received and fulfilled pandemic orders for Tamiflu from approximately 50 countries worldwide. To meet this demand, Roche states that it has already significantly expanded its Tamiflu production capacity several times and will continue to do so.
Additional information about the Roche Group is available on the company's Web site.
November 30, 2005
ST. LOUIS (MD Consult) - On December 7, 2005, Abbott Laboratories announced that the US Food and Drug Administration (FDA) has approved a new indication for Depakote ER (divalproex sodium extended-release tablets) for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. Compared with Depakote (divalproex sodium delayed-release tablets), Depakote ER taken once a day helps provide more consistent levels of medication in the body.
Approximately 2.3 million American adults have bipolar disorder, also known as manic-depressive illness. Bipolar disorder is a brain disorder that causes unusual shifts in a person's mood, energy, and ability to function. The symptoms of bipolar disorder can be severe. Symptoms of acute mania may include, among others, abnormally elevated mood, irritability, marked increase in energy, grandiose thinking, and thought disorders. Mixed mania is a state of mind characterized by symptoms of both mania and depression. Patients may feel agitated, angry, irritable, and depressed all at once. Like other serious illnesses, bipolar disorder can have a negative impact on a patient's spouse, family members, friends, and coworkers. Depakote ER now provides a useful treatment option for the acute manic and mixed episodes of bipolar disorder.
The effectiveness of Depakote ER was confirmed in a randomized, double-blind, placebo-controlled parallel group, 3-week, multicenter study. The primary efficacy measurement was the Mania Rating Scale (MRS) total score evaluated on day 21 as the mean change from baseline to final evaluation (day 21). Depakote ER was significantly more effective than placebo in the reduction of the MRS total score (mean change, –11.5 vs –9.0 with placebo). The approval of Depakote ER for the treatment of acute mania associated with bipolar disorder was based in part on studies establishing the effectiveness of Depakote.
In Depakote ER acute mania trials, adverse events with a frequency of greater than 5% and at least twice as frequent as those seen with placebo were dyspepsia (23% vs 11%), vomiting (13% vs 5%), and abdominal pain (10% vs 5%).
Depakote ER is the once-daily formulation of Depakote delayed-release tablets, which was approved for the treatment of mania associated with bipolar disorder in 1995. Depakote ER is also approved as monotherapy and adjunctive therapy in the treatment of adults and children 10 years of age or older with complex partial seizures that occur either in isolation or in association with other types of seizures. Depakote ER is also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures in adults and children 10 years of age or older, and adjunctively in adults and children 10 years of age or older with multiple seizure types that include absence seizures. Additionally, Depakote ER is approved for migraine prevention in adults.
Valproate products should not be administered to patients with hepatic disease or significant hepatic dysfunction. Hepatic failure resulting in fatality has occurred in patients receiving valproic acid and its derivatives, usually during the first 6 months of treatment.
Valproate may produce teratogenic effects in the offspring of women receiving the drug during pregnancy. Benefits of Depakote should be weighed against the risk of injury to the fetus in women of child-bearing potential.
Cases of life-threatening pancreatitis, some rapidly progressing to death, have been reported in both adults and children receiving valproate. Valproate is contraindicated in patients with known urea cycle disorders, a group of uncommon genetic abnormalities, because of reports of sometimes fatal cases of hyperammonemic encephalopathy. Concomitant administration of valproic acid and topiramate has been associated with hyperammonemia with and without encephalopathy.
The frequency of adverse effects, particularly elevated liver enzyme levels and thrombocytopenia, may be dose related. Multiorgan hypersensitivity reactions have been reported after the initiation of valproate therapy. In a clinical trial of valproate administered to elderly patients with dementia, some patients taking valproate experienced somnolence, sometimes requiring discontinuation of the drug.
Common adverse events (>5% incidence) associated with Depakote ER or Depakote in clinical studies of patients with acute mania were somnolence, dyspepsia, nausea, vomiting, diarrhea, dizziness, pain, abdominal pain, accidental injury, asthenia, and pharyngitis.
For more details on Depakote and Depakote ER, including full prescribing information, visit depakote.com or call 1-800-633-9110.
November 30, 2005
ST. LOUIS (MD Consult) - Bayer HealthCare announced on November 30, 2005, that the US Food and Drug Administration (FDA) has approved its quinolone antibiotic Avelox (moxifloxacin) for the treatment of complicated intra-abdominal infection (cIAI). This news comes 6 months after the agency approved Avelox in complicated skin and skin structure infections and represents a further broadening of Avelox's key indications beyond respiratory tract infections.
Avelox is now the only promoted fluoroquinolone monotherapy approved by the FDA for the treatment of cIAI.
Intra-abdominal infections can be caused by conditions such as trauma, intra-abdominal surgery, or other diseases that result in spillage or spread of bacteria from the gastrointestinal tract into the abdomen. There are approximately 3.5 million cases each year in the United States.
Clinical trials demonstrated that sequential intravenous (IV) to oral Avelox therapy given once daily was as effective as IV piperacillin/tazobactam given 4 times daily followed by oral amoxicillin/clavulanic acid twice daily. A second study compared Avelox with IV ceftriaxone plus metronidazole followed by oral amoxicillin/clavulanic acid. Avelox was effective at eradicating the key pathogens in cases of cIAI including Escherichia coli and Bacteroides fragilis.
In the United States, Avelox is approved to treat acute exacerbations of chronic bronchitis, acute bacterial sinusitis, community-acquired pneumonia, complicated and uncomplicated skin and skin structure infections, and cIAI. US marketing is handled by Bayer's partner Schering-Plough Corporation.
For more details, including prescribing information and indicated organisms, visit avelox.com or send an email to global.avelox@bayer.com.
November 22, 2005
ST. LOUIS (MD Consult) - On November 18, 2005, the US Food and Drug Administration (FDA) approved Effexor XR (venlafaxine hydrochloride) for the treatment of panic disorder in adults. According to Wyeth, the drug's manufacturer, this marks the first antidepressant approval for panic disorder since 2002.
Panic disorder affects 2.4 million American adults annually. It is characterized by recurrent, unexpected panic attacks; that is, a discrete period of intense fear or discomfort in the absence of real danger, where 4 of 13 specific symptoms such as accelerated heart rate, shortness of breath, trembling, or fear of dying develop abruptly, reach a peak within 10 minutes, and are followed by at least 1 month of persistent concern about having another panic attack. In one study, less than 20% of persons with panic disorder were diagnosed and treated to remission. Because this disorder is under-recognized and not always treated to remission, patients are likely to experience a chronic and cyclical course of symptoms.
The efficacy of Effexor XR as a treatment for panic disorder was established in 2 double-blind, 12-week, placebo-controlled studies. Adult patients received fixed doses of 75 or 150 mg/d in one study and 75 or 225 mg/d in the other. In these studies, Effexor XR was significantly more effective than placebo at all 3 doses.
In a long-term (26-week), double-blind study, adult patients who had responded to Effexor XR (75-225 mg/d) during an initial 12-week open-label phase were randomly assigned to continue the same Effexor XR dose (75, 150, or 225 mg) or switch to placebo for a 6-month double-blind treatment phase. Patients who continued to receive Effexor XR experienced a significantly longer time to relapse compared with those patients who were switched to placebo.
Panic disorder may be associated with conditions such as depression or other anxiety disorders. Effexor XR, a serotonin-norepinephrine reuptake inhibitor, is indicated not only for panic disorder but also for the treatment of major depressive disorder, generalized anxiety disorder, or social anxiety disorder in adults.
Antidepressants increased the risk of suicidal thinking and behavior in short-term studies in children and adolescents with major depressive disorder and other psychiatric disorders. Anyone considering the use of Effexor XR or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Effexor XR is not approved for use in pediatric patients.
Effexor XR is contraindicated in patients taking monoamine oxidase inhibitors. Adult and pediatric patients taking antidepressants can experience worsening of their depression or the emergence of suicidality. Patients should be observed closely for clinical worsening and suicidality, especially at the beginning of drug therapy or at the time of increases or decreases in dose. Anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania have been reported and may represent precursors to emerging suicidality. Stopping or modifying therapy should be considered especially when symptoms are severe, abrupt in onset, or not part of presenting symptoms.
Treatment with venlafaxine is associated with sustained increases in blood pressure in some patients. Preexisting hypertension should be controlled. Regular blood pressure monitoring is recommended. Abrupt discontinuation or dose reduction has been associated with discontinuation symptoms. Patients should be counseled on possible discontinuation symptoms and should be monitored while discontinuing the drug; the dose should be tapered gradually.
The most common adverse events reported in Effexor XR short-term placebo-controlled depression, generalized anxiety disorder, or social anxiety disorder trials (incidence, ≥10% and at least twice that of placebo) were anorexia, asthenia, constipation, dizziness, dry mouth, ejaculation problems, impotence, insomnia, nausea, nervousness, somnolence, and sweating.
Full prescribing information for Effexor XR is available at effexorxr.com.
November 9, 2005
ST. LOUIS (MD Consult) - On November 2, 2005, OSI Pharmaceuticals, Inc, and Genentech, Inc, announced that the US Food and Drug Administration (FDA) has approved Tarceva (erlotinib) in combination with gemcitabine chemotherapy for the treatment of advanced pancreatic cancer in patients who have not received previous chemotherapy. Tarceva is the first drug in a phase III trial to have shown a significant improvement in overall survival when added to gemcitabine chemotherapy as initial treatment for pancreatic cancer.
The FDA based its decision for Tarceva on results from a randomized double-blind, placebo-controlled phase III clinical study of Tarceva, in combination with gemcitabine chemotherapy, in patients with unresectable locally advanced or metastatic pancreatic cancer. The study met its primary end point of improving overall survival rates. Compared with gemcitabine plus placebo, those patients receiving gemcitabine plus 100 mg/d of Tarceva demonstrated a statistically significant (23%) improvement in overall survival rates (hazard ratio, 0.81; P = .028). After 1 year, 24% of patients receiving Tarceva plus gemcitabine were alive compared with 19% of patients receiving gemcitabine plus placebo. A statistically significant improvement in progression-free survival (hazard ratio, 0.76; P = .006) also was demonstrated. Although no difference in tumor response was observed (8.6% in patients receiving Tarceva plus gemcitabine vs 7.9% in the gemcitabine plus placebo arm), the disease control rate (complete response + partial response + stable disease) was significantly improved (59% in patients receiving Tarceva plus gemcitabine vs 49% in the gemcitabine plus placebo arm, P = .036). The global study was conducted by the National Cancer Institute of Canada in collaboration with OSI Pharmaceuticals.
Gabe Leung, President of Oncology at OSI Pharmaceuticals, stated that Tarceva is the first therapy approved by the FDA in the last 9 years that demonstrates an improvement in overall survival of pancreatic cancer.
The drugmakers boast a well-established safety profile for Tarceva. In the phase III study in pancreatic cancer, the most common adverse events reported were fatigue, rash, nausea, anorexia, and diarrhea. Rash was reported in 69% of patients who received Tarceva plus gemcitabine and in 30% of patients who received gemcitabine plus placebo. Diarrhea was reported in 48% of patients who received Tarceva plus gemcitabine and in 36% of patients who received gemcitabine plus placebo. Two percent of the patients discontinued use of Tarceva because of rash and 2% because of diarrhea. In addition, severe and potential fatal adverse events included interstitial lung disease–like complications, myocardial infarction or ischemia, cerebrovascular accident, and microangiopathic hemolytic anemia with thrombocytopenia.
Tarceva is a once-daily oral tablet already approved for use in the treatment of non–small cell lung cancer for those patients whose disease has progressed after 1 or more courses of chemotherapy. The drug is a small molecule designed to target the human epidermal growth factor receptor 1 (EGFR/HER1) pathway, which is one of the factors critical to cell growth in a number of different cancer types. EGFR/HER1 is a component of the HER signaling pathway, which plays a role in the formation and growth of numerous cancers. The medication is designed to inhibit the tyrosine kinase activity of the HER1 signaling pathway inside the cell, which may block tumor cell growth. Tarceva is the only EGFR therapy to show in a phase III trial improved survival for patients with advanced non–small cell lung cancer. Additional early-stage trials of the drug are being conducted in other solid tumors.
Pancreatic cancer has the highest 1-year mortality rate of any cancer. The average life expectancy for a patient diagnosed with metastatic pancreatic cancer is 3 to 6 months, according to The Pancreatic Cancer Action Network (PanCAN), a national patient advocacy organization for the pancreatic cancer community.
According to the World Health Organization, more than 216,000 people worldwide are diagnosed each year with pancreatic cancer. The American Cancer Society predicts that in 2005 about 32,180 people in the United States will be diagnosed with pancreatic cancer and about 31,800 will die of the disease. Although pancreatic cancer accounts for 2% of new cancer cases in the United States, it is the fourth leading cause of all cancer deaths. Most pancreatic tumors originate in the exocrine duct cells or in the cells that produce digestive enzymes. Adenocarcinomas account for nearly 95% of pancreatic cancers.
For full prescribing information on Tarceva, call 1-877-TARCEVA or visit tarceva.com.
November 1, 2005
ST. LOUIS (MD Consult) - The US Food and Drug Administration announced on October 28, 2005, that it has approved a new formulation of Kaletra (lopinavir/ritonavir). The drug is now available as a film-coated tablet (200 mg/50 mg) that provides advantages over the currently marketed capsule formulation for HIV-1–infected patients.
Specifically, the tablet formulation:
Additions and revisions were made to the Kaletra package insert to reflect the new approval. The Clinical Pharmacology section contains the following additions:
| Pharmacokinetics
Plasma concentrations of lopinavir and ritonavir after administration of two 200/50-mg Kaletra tablets are similar to three 133.3/33.3-mg Kaletra capsules under fed conditions with less pharmacokinetic variability. Effects of Food on Oral Absorption Kaletra Tablets No clinically significant changes in Cmax [peak concentration] and AUC [area under the curve] were observed following administration of Kaletra tablets under fed conditions compared to fasted conditions. Relative to fasting, administration of Kaletra tablets with a moderate-fat meal (500-682 Kcal, 23% to 25% calories from fat) increased lopinavir AUC and Cmax by 26.9% and 17.6%, respectively. Relative to fasting, administration of Kaletra tablets with a high-fat meal (872 Kcal, 56% from fat) increased lopinavir AUC by 18.9%, but not Cmax. Therefore, Kaletra tablets may be taken with or without food. |
In addition, under the Drug-drug Interactions heading of the Clinical Pharmacology section, Tables 2 and 3 were updated to clarify which formulations of Kaletra (capsule, oral solution, or tablets) were used in the drug-drug interaction studies. Results of the drug-drug interaction study between efavirenz and Kaletra tablets were included.
The following text was added or revised in the Precaution: Information for Patients section:
| Kaletra tablets can be taken at the same time as didanosine without food. Patients taking didanosine should take didanosine 1 hour before or 2 hours after Kaletra oral solution.
Kaletra tablets may be taken with or without food. Kaletra oral solution should be taken with food to enhance absorption. |
Also in the Precaution section, Table 10 ("Established and Other Potentially Significant Drug Interactions") was revised to include the following:
|
The Dosage and Administration sections of the Kaletra package insert was revised to include the following information regarding the new tablet formulation:
The recommended oral dose of Kaletra is as follows (please refer also to Indications and Usage and Adverse Reactions): Adults Therapy-Naive Patients
Therapy-Experienced Patients
Once-daily administration of Kaletra is not recommended in therapy-experienced patients. Concomitant Therapy: Efavirenz, Nevirapine, Fosamprenavir, or Nelfinavir
Increasing the dose of Kaletra tablets to 600/150 mg (3 tablets) twice daily coadministered with efavirenz significantly increased the lopinavir plasma concentrations approximately 35% and ritonavir concentrations approximately 56% to 92% compared to Kaletra tablets 400/100 mg twice daily without efavirenz (see Clinical Pharmacology: Drug-drug Interactions, Table 2 and/or Precautions, Table 10). Kaletra tablets and oral solution should not be administered as a once-daily regimen in combination with efavirenz, nevirapine, amprenavir, or nelfinavir. |
Finally, the How Supplied section was revised to include storage information for the Kaletra tablets as follows:
| Recommended storage: Store Kaletra film-coated tablets at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP controlled room temperature]. Dispense in original container. For patient use: exposure of this product to high humidity outside the original container for longer than 2 weeks is not recommended. |
Kaletra is a product of Abbott Laboratories. The capsule formulation will be phased out over time by the company. The original formulation was approved on September 15, 2000.
October 17, 2005
ST. LOUIS (MD Consult) - On September 15, 2005, biotechnology company Amgen announced that the US Food and Drug Administration (FDA) has approved an update to the Neulasta (pegfilgrastim) prescribing information to include data from a landmark phase 3 study. This trial demonstrated that the white blood cell booster helps protect patients with most types of cancer undergoing moderately myelosuppressive chemotherapy from infection, as manifested by febrile neutropenia, one of the most serious adverse effects of chemotherapy.
Previously, first- and subsequent-cycle administration of Neulasta to stimulate production of infection-fighting white blood cells was indicated for patients receiving myelosuppressive chemotherapy associated with a more than 30% to 40% risk of febrile neutropenia. Administration of Neulasta beginning in the first cycle of chemotherapy is now approved for patients receiving myelosuppressive chemotherapy associated with at least a 17% risk of febrile neutropenia. Myelosuppressive chemotherapy is toxic to the bone marrow where white blood cells, red blood cells, and platelets are produced.
The expanded label was based on a randomized, placebo-controlled study of 928 patients with metastatic or nonmetastatic breast cancer that was published in Journal of Clinical Oncology earlier this year. Compared with placebo, first- and subsequent-cycle administration of Neulasta resulted in a 94% reduction in the incidence of febrile neutropenia (1% vs 17% with placebo), a 93% reduction in the incidence of hospitalization (1% vs 14%), and an 80% reduction in the incidence of intravenous anti-infective use (2% vs 10%) in patients receiving moderately myelosuppressive chemotherapy.
"Approximately two thirds of neutropenic complications happen in the first cycle of chemotherapy," said study lead investigator Charles Vogel, MD, Cancer Research Network, Plantation, Fla. "This study demonstrates that administering Neulasta beginning in the first cycle of chemotherapy reduces the chance of patients developing an infection."
Neutropenia is an abnormally low level of neutrophils, important infection-fighting white blood cells, in the bloodstream. Neutropenia can put some patients at risk for severe infections and interruptions in cancer treatment. In fact, complications associated with a low white blood cell count are a common cause of dose reductions or delays in chemotherapy.
Febrile neutropenia is the most common presentation of infection in patients receiving chemotherapy. Infection in this setting can be serious and even life threatening because chemotherapy can compromise the patient's ability to fight infection.
Although white blood cell boosters have been available for more than a decade, only 17% of patients receiving myelosuppressive chemotherapy currently receive proactive first-cycle protection from neutropenic complications, which include infection, hospitalization, and anti-infective use. Approximately half of the 1.3 million patients receiving chemotherapy are at risk for developing neutropenia.
Neulasta was approved by the FDA in 2002 for decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.
Rare cases of splenic rupture and sickle cell crises have been reported in postmarketing experience. Allergic reactions, including anaphylaxis, have also been reported. The majority of these reactions occurred upon initial exposure. However, in rare cases, allergic reactions, including anaphylaxis, recurred within days after discontinuing antiallergic treatment.
In a placebo-controlled trial, bone pain occurred at a higher incidence in Neulasta-treated patients compared with placebo-treated patients (31% vs 26%). The most common adverse events reported in either active or placebo-controlled trials were consistent with the underlying cancer diagnosis and its treatment with chemotherapy, with the exception of bone pain. Although not reported in patients receiving Neulasta, rare events of adult respiratory distress syndrome have been reported in patients receiving the parent compound, filgrastim.
Full prescribing information for Neulasta is available at NEULASTA.com or via fax by calling 1-800-772-6436. Consumers can call 1-866-611-3784 for more information.
October 17, 2005
ST. LOUIS (MD Consult) - Centocor, Inc, announced on September 16, 2005, that Remicade (infliximab) has been approved by the US Food and Drug Administration for the treatment of ulcerative colitis. This approval makes the drug the first and only biologic agent approved to treat ulcerative colitis, a chronic inflammatory bowel disease (IBD).
Remicade is now indicated for reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy. Before this approval, no therapy had ever been indicated for mucosal healing and eliminating the use of corticosteroids.
"Not only did many patients in clinical trials experience a significant reduction in the occurrence of symptom flare-ups with Remicade, some achieved clinical remission and mucosal healing as well," said William J. Sandborn, MD, professor of medicine, Mayo Clinic College of Medicine and head of the IBD Interest Group and director of the IBD Clinical Research Unit at Mayo Medical Center. "This is welcome news for these patients whose only option otherwise may have been surgery to remove their colons."
Remicade's efficacy in the treatment of IBD is well established. First approved in the United States for the treatment of Crohn's disease in 1998, Remicade remains the only anti–tumor necrosis factor alpha (TNF-alpha) therapy indicated for the treatment of Crohn's disease. With this new approval for the treatment of ulcerative colitis, Remicade is now the only biologic agent indicated for the treatment of both types of IBDs, Crohn's disease and ulcerative colitis.
In addition to ulcerative colitis and Crohn's disease, Remicade is indicated for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis.
Ulcerative colitis is an incurable, debilitating chronic disease affecting more than 500,000 Americans. But although ulcerative colitis affects more persons in the United States than multiple sclerosis or cystic fibrosis, general awareness of this disease is lower. Characterized by inflammation and ulceration of the inner lining of the colon, ulcerative colitis symptoms can often include unwanted weight loss, severe and sometimes uncontrollable bloody diarrhea, fatigue, and frequent abdominal pain. For some patients, symptoms may lead to surgical removal of the colon or to secondary complications such as colorectal cancer.
"Results from a recent patient survey revealed that ulcerative colitis affects many aspects of people's lives, from their relationships with families and employers to the ability to participate in social activities," said Rodger DeRose, president and CEO of the Crohn's & Colitis Foundation of America.
The new approval of Remicade is based on positive results seen in 2 randomized, placebo-controlled pivotal phase 3 clinical trials, ACT 1 and ACT 2, which were conducted to evaluate the safety and efficacy of Remicade in people with active, moderate to severe ulcerative colitis. Each trial enrolled 364 patients with active ulcerative colitis who were unresponsive to at least 1 standard therapy, including corticosteroids, immunosuppressants, or 5-aminosalicylic acids. Patients in ACT 1 and ACT 2 had evidence of moderate or severe ulcerative colitis (total Mayo score of 6 to 12 and an endoscopy score > 2). In both trials, patients were randomly assigned to receive placebo or Remicade (5 or 10 mg/kg). ACT 1 patients received the study agent at weeks 0, 2, and 6 and then every 8 weeks through week 46 and had their last evaluations at week 54. Patients in the ACT 2 study received the study agent at weeks 0, 2, and 6 and then every 8 weeks through week 22 and had their last evaluations at week 30.
In ACT 1, significantly higher proportions of patients receiving 5 mg/kg (69%) and 10 mg/kg (62%) of Remicade achieved clinical response at week 8 versus placebo-treated patients (37%; P < .001 for both). In addition, at week 30, 52% of patients in the group receiving 5 mg/kg of Remicade and 51% of patients in the group receiving 10 mg/kg were in clinical response versus 30% of placebo-treated patients (P < .001 and P < .01, respectively). At week 8, 39% and 32% of patients treated with Remicade 5 and 10 mg/kg, respectively, were in clinical remission compared with 15% of placebo-treated patients (P < .001 and P < .01, respectively). These differences in remission rates persisted at week 30 (34% for 5 mg/kg and 37% for 10 mg/kg versus 16% for placebo; P < .001 for both). Mucosal healing was achieved at week 8 in 62% and 59% of patients receiving Remicade 5 and 10 mg/kg, respectively, versus 34% of placebo-treated patients (P < .001). This difference in mucosal healing was maintained at week 30 (50% for 5 mg/kg and 49% for 10 mg/kg versus 25% for placebo; P < .001 for both). The proportion of patients who were able to discontinue treatment with corticosteroids while in clinical remission at week 30 was greater in both Remicade groups compared with the placebo group (24% for 5 mg/kg, 19% for 10 mg/kg, 10% for placebo; P = .030 and P = .125, respectively).
In ACT 2, significantly higher proportions of patients receiving 5 mg/kg (65%) and 10 mg/kg (69%) of Remicade were in clinical response at week 8 versus 29% who received placebo (P < .001 for both). At week 30, 47% of patients receiving Remicade 5 mg/kg and 60% receiving 10 mg/kg were in clinical response versus 26% of patients receiving placebo (P < .001 for both). Clinical remission was achieved at week 8 in 34% and 28% of Remicade 5 and 10 mg/kg patients, respectively, compared with 6% of placebo-treated patients (P < .001 for both). Differences in remission rates persisted at week 30 (26%, 5 mg/kg; 36%, 10 mg/kg; 11%, placebo; P < .01 and P < .001). Mucosal healing was achieved at week 8 in 60% and 62% of patients receiving Remicade 5 mg/kg and 10 mg/kg, respectively, compared with 31% of placebo-treated patients (P < .001 for both). Mucosal healing at week 30 was achieved in 46% and 57% of patients receiving Remicade 5 and 10 mg/kg, respectively, compared with 30% of placebo-treated patients (P < .01 and P < .001). The proportion of patients who were able to discontinue taking corticosteroids while in clinical remission at week 30 was significantly greater in both Remicade groups compared with the placebo group (18%, 5 mg/kg; 27%, 10 mg/kg; 3%, placebo; P = .010 and P < .001, respectively).
In the United States, Remicade, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. Remicade is the only biologic agent indicated for the treatment of patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. Remicade is also indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in patients with fistulizing Crohn's disease. In December 2004, Remicade was approved for the treatment of active ankylosing spondylitis in the United States. On May 13, 2005, Remicade was approved for the treatment of psoriatic arthritis.
Unlike self-administered therapies that require patients to inject themselves frequently, Remicade is the only anti-TNF biologic agent administered directly by caregivers in the clinic or office setting. In cases of rheumatoid arthritis and Crohn's disease, Remicade is administered as a 2-hour infusion given every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2, and 6. As a result, patients taking Remicade may require as few as 6 treatments each year. When used in the treatment of ankylosing spondylitis, Remicade is given as a 2-hour infusion (5 mg/kg) administered every 6 weeks, following a standard induction regimen that requires treatment at weeks 0, 2, and 6. The safety and efficacy of Remicade have been well established in clinical trials over the past 12 years.
Many persons with heart failure should not take Remicade; before treatment, patients should discuss any heart conditions they have with their doctors. Patients should notify their physicians immediately if new or worsening symptoms of heart failure (eg, shortness of breath or swelling of the ankles or feet) are experienced.
There have been reports of serious infections, including tuberculosis, sepsis, and pneumonia among persons taking Remicade. Some of these infections have been fatal. Patients should notify their doctors of recent or past exposure to persons with tuberculosis, and a skin test and evaluation for tuberculosis will be administered. If a patient has latent tuberculosis, his or her doctor should begin tuberculosis treatment before beginning the administration of Remicade. Remicade can lower a person's ability to fight infections, so if a patient is prone to or has a history of infections or develops any signs of an infection such as fever, fatigue, cough, or influenza while taking Remicade, he or she should notify a physician immediately. Also, patients should tell their doctors if they have lived in a region where histoplasmosis or coccidioidomycosis is common.
There have been rare cases of serious liver injury in persons taking Remicade, some of which have been fatal. Symptoms such as jaundice, dark brown urine, right-sided abdominal pain, fever, or severe fatigue should be reported to a physician.
Blood disorders have been reported among persons taking this medication, and some of these have been fatal. Possible signs of blood disorders include persistent fever, bruising, bleeding, or paleness, and these should be reported to a physician if experienced while taking Remicade. Nervous system disorders have also been reported; patients should tell their doctors if they have or have had a disease that affects the nervous system or if they experience any numbness, weakness, tingling, or visual disturbances while taking Remicade.
Reports of lymphoma in patients taking Remicade and other TNF blockers are rare but occur more often than in the general population. Patients should notify their doctors if they have or have had cancer. Persons who have been treated for rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, or psoriatic arthritis for a long time, particularly those with highly active disease, may be more prone to develop lymphoma. Cancers other than lymphoma have also been reported. Patients should be informed that their risk of developing lymphoma or other cancers may increase if they take Remicade or other TNF blockers.
Serious infusion reactions have been reported in association with Remicade, including hives, difficulty breathing, and low blood pressure. Reactions have occurred during or after infusions. In clinical studies, some persons experienced the following common side effects: respiratory infections (that may include sinus infections and sore throat), coughing, stomach pain, or mild reactions to infusion such as rash or itchy skin.
More details about Remicade, including full prescribing information, is available at remicade.com.
October 6, 2005
ST. LOUIS (MD Consult) - Pfizer Inc announced on October 5, 2005, that it has received approval from the US Food and Drug Administration to market its aromatase inhibitor Aromasin (exemestane tablets) to postmenopausal women with early breast cancer. The drug is now indicated for use as adjuvant treatment of breast cancer after the completion of 2 to 3 years of tamoxifen therapy, leading to a total of 5 consecutive years of adjuvant hormonal therapy. Aromasin was previously approved in the United States late in 1999 for the treatment of advanced breast cancer in postmenopausal women whose tumors have stopped responding to tamoxifen.
The approval was based on the results of the Intergroup Exemestane Study. In this study, patients who switched to Aromasin after 2 to 3 years of treatment with tamoxifen, for a combined total of 5 years of therapy, had 31% more protection from cancer recurrence than those who contined to take tamoxifen for 5 years.
This landmark study, published in The New England Journal of Medicine, established the superiority of switching to Aromasin rather than remaining on tamoxifen. After its publication, the American Society of Clinical Oncologists and the National Comprehensive Cancer Network updated their guidelines to support the use of a new switch-regimen using Aromasin adjuvant treatment.
The Intergroup Exemestane Study trial involved over 4,700 postmenopausal women with estrogen-receptor–positive breast cancer who were followed up for an average of 35 months. Patients receiving Aromasin experienced a significant reduction in the risk for recurrence of the disease, compared with those continuing to take tamoxifen. This reduction includes fewer local and distant tumors as well as new cancers in the other breast.
The most common adverse effects associated with Aromasin, which were mild to moderate, include hot flashes (21.2%), fatigue (16.1%), and arthalgia/bone pain (14.6%). Aromasin should not be administered to premenopausal women or women who are pregnant. Dose modifications should be considered for patients taking concomitant CYP3A4 inducers.
Breast cancer is one of the most common cancers occurring in women and the second leading cause of death from cancer in women, after lung cancer.
More information on this medication is available at aromasin.com. For full prescribing information, visit pfizer.com/pfizer/download/uspi_aromasin.pdf.
October 5, 2005
ST. LOUIS (MD Consult) - On October 4, 2005, Abbott announced that the US Food and Drug Administration (FDA) has approved Humira (adalimumab) for two new indications: (1) for first-line treatment of recent-onset moderate to severe rheumatoid arthritis (RA), and (2) for reducing signs and symptoms of active arthritis in patients with psoriatic arthritis.
Rheumatoid Arthritis
The approval for the expanded RA indication is based on clinical and radiographic data from the 2-year PREMIER study of 799 methotrexate (MTX)-naive patients with active recent-onset moderate to severe RA (defined as disease of less than 3 years' duration). On average, patients had less than 9 months of disease duration from the time of diagnosis. The trial compared 3 arms—Humira monotherapy, MTX monotherapy, and the 2 drugs combined. The study showed Humira in combination with MTX was superior to MTX alone on several efficacy end points, including the 2 primary end points (inhibition of joint damage and improvement in signs and symptoms at 1 year) and a secondary end point (achievement of clinical remission measure of Disease Activity Score [DAS] 28 < 2.6 at 1 year). The DAS measures disease activity responses in RA by assessing tender and swollen joint count, general health status, and an inflammatory marker.
The PREMIER study showed patients taking Humira in combination with MTX experienced significantly less joint damage than those taking MTX alone, as measured by the change in modified Total Sharp Score (mTSS). The mTSS assesses bone erosion and joint space narrowing on radiographs. A smaller change in mTSS reflects less progression of joint damage. Also, approximately twice as many patients taking the Humira-MTX regimen experienced no further joint destruction compared with those taking MTX alone (61% vs 34%) after 2 years. No joint destruction was defined as ≤0.5 units change from baseline in mTSS. After 1 year, patients taking MTX alone had 4 times the disease progression as those taking the Humira-MTX regimen, with mean changes in mTSS of 5.7 and 1.3, respectively, and after 2 years the patients taking MTX alone had 5 times more disease progression than those taking the Humira-MTX regimen, with mean changes in mTSS of 10.4 and 1.9, respectively.
PREMIER is the first RA trial to include, as a primary end point, the measurement of ACR50 (a 50% or greater improvement in signs and symptoms of RA, as defined by the American College of Rheumatology [ACR]). ACR scores measure the percentage of improvement in tender and swollen joint count and several other clinical measures. In this trial, Humira in combination with MTX significantly improved the signs and symptoms of RA. After 1 year, 62% of patients taking the Humira-MTX regimen achieved ACR50 compared with 46% of those taking MTX alone and 41% taking Humira alone. After 2 years, 59% of patients taking the Humira-MTX regimen achieved ACR50 compared with 43% taking MTX alone and 37% taking Humira alone.
Forty-three percent of patients taking the Humira-MTX regimen achieved a measure of clinical remission as defined by DAS28 < 2.6 at 1 year versus 21% of patients taking MTX only, and nearly 1 in 2 patients receiving the combination therapy achieved clinical remission at 2 years compared with 1 in 4 patients taking MTX alone (49% vs 25%). Additionally, almost half of patients receiving the Humira-MTX regimen achieved major clinical response, defined as achieving and maintaining an ACR70 response for 6 or more continuous months, compared with MTX alone (49% vs 28%). Also, 27% of patients on the Humira-MTX regimen achieved ACR90 at 2 years, a 90% or greater improvement in signs and symptoms, compared with 13% of those taking MTX alone.
In the PREMIER trial, all treatment arms had a comparable overall rate of adverse events. Among patients taking Humira, the most common adverse events were nasopharyngitis, headache, nausea, diarrhea, joint pain, and pharyngitis.
More than 5 million persons worldwide have 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, potentially resulting in destruction of the joints' interior and the surrounding bone.
Psoriatic Arthritis
The FDA approval of Humira for patients with psoriatic arthritis is based on results of the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), which is the largest biologic trial in psoriatic arthritis. ADEPT studied 313 adult patients with moderately to severely active psoriatic arthritis who had an inadequate response to nonsteroidal anti-inflammatory drug therapy. Patients taking Humira experienced significantly greater improvement in both joint and skin disease symptoms than placebo-treated patients at 24 weeks. Improvements in both skin lesions and joint symptoms were seen as early as 2 weeks after initiation of treatment and continued to improve over time.
Patients' arthritic symptoms also responded to Humira, with nearly 60% of patients achieving ACR20 at week 12, 1 of the study's primary end points, and with a sustained response through week 24. ACR70, a more stringent response criterion, was achieved by nearly 25% of patients treated with Humira versus 1% of patients treated with placebo at week 24.
Clinical trial data from ADEPT showed the ability of Humira to improve both the skin and joint symptoms associated with psoriatic arthritis. Among the 69 patients in the trial who had skin lesions involving more than 3% body surface area and were treated with Humira, 3 of 4 (75%) achieved a Psoriasis Area and Severity Index (PASI) score of 50, approximately 3 of 5 (59%) achieved a PASI score of 75, and approximately 2 of 5 (42%) achieved a PASI score of 90 at 24 weeks, which reflects at least 50%, 75%, or 90% improvement, respectively, in skin symptoms assessed by the PASI.
The recommended dose of Humira for psoriatic arthritis is 40 mg taken every other week by subcutaneous injection; this is also the usual dose used for Humira in the treatment of moderate to severe RA.
The rates of adverse events and serious adverse events in the ADEPT trial were comparable with other Humira RA clinical trials. Among patients taking Humira, the most common adverse events (affecting at least 5% of patients) were upper respiratory infection, nasopharyngitis, injection site reaction, headache, and hypertension. The safety profile of Humira in the ADEPT clinical trial was similar to that observed in the Humira RA clinical trials.
Abbott simultaneously submitted applications with the FDA and the European Medicines Agency seeking approval to market Humira to treat psoriatic arthritis and early moderate to severe RA in December 2004.
Psoriatic arthritis is a chronic disease that combines the symptoms of arthritis, including joint pain and inflammation, with those of psoriatic skin disease, such as dry, scaly skin. Psoriatic arthritis is a serious autoimmune disease, and few available treatment options address the combination of symptoms affecting both the skin and joints. Common symptoms of psoriatic arthritis include varying degrees of skin involvement along with stiffness, pain, swelling, and tenderness of the joints that can lead to a reduced range of motion and potential severe joint destruction.
Left untreated, psoriatic arthritis can be a progressively disabling disease. The arthritic manifestations often include debilitating disease of the hands and feet, as seen in RA, as well as painful inflammation of the tendon insertions and arthritis of the spine. Psoriatic arthritis is most often found in patients who have psoriasis, a chronic skin disease that affects nearly 3% of the world's population. It is estimated that up to 30% of persons with psoriasis also develop psoriatic arthritis.
Like RA, psoriatic arthritis is an autoimmune disorder in which a human protein, tumor necrosis factor-alpha (TNF-α), has been suggested to play a role in disease development. Humira, which is a fully human monoclonal antibody that resembles antibodies normally found in the body, works by specifically blocking TNF-α.
Important Safety Information
Cases of tuberculosis have been observed in patients taking Humira. Serious infections and sepsis, including fatalities, have been reported with the use of 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. Treatment with Humira should not be initiated in patients with active infections. The combination of Humira and anakinra is not recommended.
TNF-blocking agents, including Humira, have been associated with rare cases with demyelinating disease and severe allergic reactions. Infrequent reports of serious blood disorders have been reported with TNF-blocking agents. More cases of malignancies have been observed among patients receiving TNF blockers, including Humira, compared with control patients in clinical trials. These malignancies, other than lymphoma and nonmelanoma skin cancer, were similar in type and number to what would be expected in the general population. There was an approximately 4-fold higher rate of lymphoma in combined controlled and uncontrolled open-label portions of Humira clinical trials. 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 in 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 occurred in 7% of patients taking Humira and 4% of those taking placebo. As with any treatment program, the benefits and risks of Humira should be carefully considered before initiating therapy.
The safety profile for patients with psoriatic arthritis treated with Humira in the clinical trials has been similar to the safety profile seen in patients with RA.
Humira is the first fully human monoclonal antibody to be approved by the FDA for reducing the signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adults with moderately to severely active RA. In 2002, HUMIRA was approved to treat patients with moderately to severely active RA, who have had insufficient response to one or more disease-modifying anti-rheumatic drugs (DMARDs). With the new FDA approval, Humira can be used alone or in combination with methotrexate or other DMARDs.
More information about Abbott Immunology and Humira, including full prescribing information, is available at rxabbott.com.
October 5, 2005
ST. LOUIS (MD Consult) - On September 28, 2005, the US Food and Drug Administration (FDA) approved a new indication for Emtriva (emtricitabine). The medication, in combination with other antiretroviral agents, is now approved for the treatment of human immunodeficiency virus-1 infection in patients older than 3 months.
In addition, the FDA also approved Emtriva oral solution 10 mg/mL. The approval of this new formulation allows for dosing recommendations in pediatric patients.
The following changes to the label were made to reflect this new information:
To review the new label, please visit fda.gov/cder/foi/label/2005/021896lbl.pdf
September 28, 2005
ST. LOUIS (MD Consult) - On September 27, 2005, Pfizer Inc announced that the US Food and Drug Administration (FDA) has approved its cholesterol-lowering medicine Lipitor (atorvastatin calcium) to reduce the risk of stroke and heart attack in persons with type 2 diabetes without evidence of heart disease but with other risk factors. Lipitor also received approval to reduce the risk of stroke in persons without evidence of heart disease but with multiple risk factors other than diabetes. Common risk factors for heart disease include high cholesterol, high blood pressure, family history, age older than 55 years, smoking, diabetes, and obesity.
The FDA's decision was based on the findings of the Collaborative Atorvastatin Diabetes Study (CARDS), a landmark trial of more than 2,800 patients with type 2 diabetes, near normal cholesterol levels, and at least 1 other risk factor, such as high blood pressure or smoking. The study showed that patients taking Lipitor experienced nearly 50% fewer strokes than those taking placebo. The CARDS trial was stopped nearly 2 years earlier than planned by the study's Steering Committee because of the strong benefits among patients who took Lipitor.
The additional approval of Lipitor to reduce the risk of stroke in patients with multiple risk factors reflects findings from The Anglo-Scandinavian Cardiac Outcomes Trial: Lipid-Lowering Arm (ASCOT-LLA), another landmark trial that was also halted nearly 2 years earlier than planned. The trial found that Lipitor reduced the relative risk of stroke by 26% compared with placebo. The study involved more than 10,300 persons with normal or borderline cholesterol levels and no prior history of heart disease, but with controlled high blood pressure and at least 3 other risk factors for heart disease, such as family history, age older than 55 years, smoking, diabetes, and obesity.
Lipitor is used in patients with type 2 diabetes and one other risk factor such as high blood pressure, smoking, or other complications of diabetes, including eye disease and protein in urine, to reduce the risk of stroke and heart attack. The medication is not indicated for persons with liver problems, nor for women who are nursing, pregnant, or may become pregnant.
Patients taking Lipitor should notify their doctors if they feel any unusual muscle pain or weakness. This could be a sign of serious muscle side effects. Patients should tell their doctors about all of the medications they take; this may help avoid serious drug interactions. The most commonly encountered side effects are gas, constipation, stomach pain, and heartburn, and these tend to be mild and often of limited duration.
The American Heart Association (AHA) estimates that 700,000 Americans—or 1 person every 45 seconds—will experience a stroke in 2005. Stroke is more prevalent in adults age 65 and older, and the incidence of stroke continues to rise as age increases. According to the AHA, stroke is a leading cause of major disability in the United States. Direct (medical) and indirect (disability) costs related to stroke are anticipated to reach $57 billion in 2005.
The 2004 update to guidelines issued by the National Cholesterol Education Program confirms the added benefit of prescribing cholesterol-lowering medication, along with diet modification and exercise, to patients at risk for cardiovascular disease.
More than 18 million Americans have diabetes, which is a leading risk factor for cardiovascular disease. The majority of persons with diabetes (roughly 65%) will suffer a heart attack or stroke, a rate that is up to 4 times higher than in adults without diabetes. According to the American Diabetes Association–recommended treatment guidelines, adults with type 2 diabetes should be considered for statin therapy regardless of their low-density lipoprotein levels.
For additional information about Lipitor, visit lipitor.com or call 1-888-LIPITOR.
September 7, 2005
ST. LOUIS (MD Consult) - On September 6, 2005, Paris-based pharmaceutical company Sanofi-aventis announced that the US Food and Drug Administration has approved Ambien CR (zolpidem tartrate extended-release tablets) C(IV), a new formulation of the prescription sleep aid Ambien (zolpidem tartrate) CIV, for the treatment of insomnia. Ambien CR is a non-narcotic non-benzodiazepine and is formulated to offer a similar safety profile to Ambien with a new indication for sleep maintenance, in addition to sleep induction.
According to its manufacturer, Ambien CR is the first extended-release prescription sleep medication to help persons with insomnia fall asleep fast and maintain sleep with no significant decrease in next-day performance. Ambien CR, a bi-layered tablet, is delivered in 2 stages. The first layer dissolves quickly to induce sleep, and the second layer is released more gradually into the body to help provide more continuous sleep.
"Insomnia is a significant public health problem, affecting millions of Americans. Insomnia impacts daily activities and is associated with increased health care costs," said James K. Walsh, PhD, Executive Director and Senior Scientist, Sleep Medicine and Research Center at St Luke's Hospital in St Louis, Mo. "Helping patients stay asleep is recognized as being as important as helping them fall asleep."
According to a recent National Sleep Foundation poll, more than one half (54%) of Americans said they experience at least 1 symptom of insomnia at least a few nights a week. Additionally, 1 in 5 adults experienced difficulty falling asleep and 1 in 3 reported waking often during the night at least a few nights a week.
For important safety and prescribing information, please view the FDA-approved product label at fda.gov/cder/foi/label/2005/021774lbl.pdf.
Ambien CR will be available in a 12.5-mg dose recommended for adults and a 6.25-mg dose recommended for elderly persons.
Sanofi-aventis Group subsidiaries in the United States include Sanofi-Synthelabo Inc, Aventis Pharmacuticals Inc, and Sanofi Pasteur Inc.
August 29, 2005
ST. LOUIS (MD Consult) - On August 19, 2005, pharmaceutical company Allergan, Inc, announced it has received approval from the US Food and Drug Administration (FDA) to market Alphagan P (brimonidine tartrate ophthalmic solution) 0.1%, indicated for the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.
The new product is an optimized formulation of Alphagan 0.2% and was developed to further minimize drug exposure while maintaining the drug's favorable efficacy profile.
In a clinical trial, Alphagan P ophthalmic solution 0.1% was proved to have IOP-lowering efficacy equivalent to Alphagan 0.2%, effectively lowering IOP in patients with open-angle glaucoma or ocular hypertension by approximately 2 to 6 mm Hg. Alphagan P 0.1% is contraindicated in patients receiving monoamine oxidase inhibitor therapy. The most frequently reported adverse events included allergic conjunctivitis, conjunctival hyperemia, and eye pruritus.
Full prescribing information for Alphagan P 0.1% can be found at Allergan.com.
Allergan, Inc, is headquartered in Irvine, Calif.
August 25, 2005
ST. LOUIS (MD Consult) - Solvay Pharmaceuticals, Inc, and CV Therapeutics, Inc, announced on August 23, 2005, that the US Food and Drug Administration has approved Aceon (perindopril erbumine) Tablets for patients with stable coronary artery disease to reduce the risk of cardiovascular mortality or nonfatal myocardial infarction (MI). Aceon, an angiotensin-converting enzyme (ACE) inhibitor, is currently indicated for the treatment of essential hypertension.
ACE inhibitors act to reduce hypertension by interfering with the conversion of angiotensin I to artery-constricting angiotensin II. Blocking the production of angiotensin II results in arterial vasodilation and an accompanying reduction in blood pressure. ACE inhibitors are currently recommended as first-line therapy for the treatment of hypertension in certain patient populations because of their safety and efficacy. Most recently, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure has recommended ACE inhibitors as one of the initial therapy choices for compelling comorbidities such as heart failure, postmyocardial infarction, high coronary disease risk, diabetes, chronic kidney disease, and recurrent stroke prevention.
Certain ACE inhibitors, including Aceon, have been shown to have an enhanced affinity for the tissues and are known as tissue-ACEs.
The new indication is based on the EUropean trial on Reduction Of cardiac events with Perindopril in patients with stable coronary Artery disease (EUROPA). EUROPA was a multicenter, randomized, double-blind, placebo-controlled trial involving 12,218 patients with stable coronary disease and without heart failure, which assessed the ability of perindopril to reduce cardiovascular death, nonfatal MI, or cardiac arrest. Patients underwent a mean follow-up of 4.2 years.
In this study, in a broad population of patients with stable coronary artery disease, there was a 20% reduction in the combined end point of cardiovascular mortality, nonfatal MI, and cardiac arrest compared with placebo. This significant (P = .0003) reduction in relative risk was seen in patients receiving a treatment regimen of 8 mg of perindopril, including patients treated with conventional cardiovascular preventive therapy, such as aspirin, other anticoagulants, beta-blockers, and other antihypertensive therapy and lipid-lowering therapy, such as statins. Patients not randomly assigned to receive perindopril received placebo in addition to their conventional therapy.
In the EUROPA study, the 20% reduction in the risk of cardiovascular events with Aceon 8 mg was observed in a broad range of older and younger stable coronary artery disease patients with or without hypertension or previous MI, and including patients treated with a background of conventional therapies for the management of coronary artery disease.
Aceon offers continuous 24-hour blood pressure control with once-daily dosing. The medication may be used alone or with other classes of antihypertensive agents.
Aceon is contraindicated in patients known to be hypersensitive to this product or to any other ACE inhibitor and in patients with a history of angioedema related to previous treatment with an ACE inhibitor. When used in pregnant patients during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, Aceon should be discontinued as soon as possible.
In the EUROPA study, the overall rate of discontinuation was about 22% on drug and placebo. The most common medical reasons for discontinuation that were more frequent among patients taking perindopril than those taking placebo were cough, drug intolerance, and hypotension.
Aceon prescribing information is available at solvaypharmaceuticals-us.com/products.
In the United States, perindopril is co-promoted under the brand name Aceon by CV Therapeutics and Solvay Pharmaceuticals. CV Therapeutics is headquartered in Palo Alto, Calif, and Solvay Pharmaceuticals is based in Marietta, Ga, and is a subsidiary of Solvay Group, which is headquartered in Brussels, Belgium.
August 19, 2005
ST. LOUIS (MD Consult) - Merck & Co, Inc, announced on August 18, 2005, that the US Food and Drug Administration (FDA) has approved Singulair (montelukast sodium) for the relief of symptoms of perennial allergic rhinitis (PAR), also known as indoor allergies, in adults and children 6 months of age and older. A once-a-day tablet, Singulair has been proved to help relieve a broad range of indoor and outdoor allergy symptoms for up to 24 hours.
Allergic rhinitis, an inflammation of the mucous membranes of the nose due to allergens, is one of the most common allergic conditions in the United States, affecting approximately 50 million Americans. Allergic rhinitis is classified as either seasonal or perennial, depending on the type of trigger and the duration of symptoms. SAR symptoms occur in the spring, summer, and early fall and are triggered by outdoor allergens such as airborne tree, grass, and weed pollens, whereas PAR is usually persistent and chronic with symptoms occurring year-round and is commonly associated with indoor allergens such as dust mites, animal dander, and mold spores. Symptoms of allergic rhinitis may include runny nose, nasal itching, sneezing, watery eyes, and nasal congestion.
Approved for the treatment of the symptoms of seasonal allergic rhinitis (SAR) in 2003, Singulair is different from most oral allergy medications, which block histamine, in that it blocks leukotrienes. Leukotrienes are an important contributor to allergy symptoms, and Singulair is the only medication indicated for the treatment of allergic rhinitis that specifically targets this particular underlying contributor to allergy symptoms. The medication is approved to treat SAR in adults and children 2 years and older and for PAR in adults and children 6 months and older. For treatment of symptoms of allergic rhinitis, Singulair is available in tablet form for adults (10 mg), as a cherry-chewable tablet (4 or 5 mg) for children aged 2 to 14 years, and in oral granules (4 mg) for children aged 6 months to 5 years.
In separate clinical trials of PAR and SAR, Singulair (10 mg) has provided significantly greater symptom relief compared with placebo. The efficacy of Singulair for the treatment of PAR was evaluated in 2 randomized, double-blind, placebo-controlled studies in patients aged 15 to 82 years with PAR. In one of these studies, the drug demonstrated effectiveness in improving daytime nasal symptoms score, the primary end point, measured as the average of individual scores for nasal congestion, runny nose, and sneezing.
The efficacy of Singulair for the treatment of symptoms of SAR was previously established in placebo- and active-controlled clinical studies of patients aged 15 to 82 years. In these studies, the drug demonstrated effectiveness in improving daytime nasal symptoms score, the primary end point, measured as the average of individual scores for nasal congestion, runny nose, nasal itching, and sneezing.
In clinical studies for both SAR and PAR, Singulair was generally well tolerated with a safety profile similar to that of placebo for both children and adults. The incidence of sleepiness was similar to placebo in all studies for adults and adolescents 15 years of age and older with SAR and PAR. In these studies, the most frequently reported adverse effects included headache, ear infection, sore throat, and upper respiratory infection. These events varied by age and were reported at a frequency greater than or equal to 2%, and at an incidence greater than placebo in either the SAR or PAR studies.
Singulair is also indicated for the prevention and chronic treatment of asthma in adults and pediatric patients 12 months and older. The use of Singulair for asthma may not eliminate the need for inhaled or oral corticosteroids. Patients should be advised to take Singulair daily as prescribed even when they have no symptoms, as well as during periods of worsening asthma, and to contact their health care providers if their asthma is not well controlled. This medication should not be used for the fast relief of acute asthma attacks nor used alone to treat and manage asthma made worse by exercise. Patients with known aspirin sensitivity should continue avoidance of aspirin or nonsteroidal anti-inflammatory agents while taking Singulair.
In clinical studies for asthma, adverse effects in adults and children taking Singulair were usually mild and generally did not cause patients to discontinue therapy. The most commonly reported adverse effects varied by age and included headache, ear infection, sore throat, and upper respiratory infection.
For more information on Singulair and its manufacturer, visit merck.com.
August 17, 2005
ST. LOUIS (MD Consult) - On August 12, 2005, the US Food and Drug Administration (FDA) approved Actonel with Calcium (risedronate sodium tablets with calcium carbonate tablets), the first prescription osteoporosis therapy to include calcium.
Actonel with Calcium is a prescription therapy indicated for the prevention and treatment of postmenopausal osteoporosis. Both Actonel and Calcium decrease the elevated rate of bone turnover that is typically seen in postmenopausal osteoporosis. Each package contains a 28-day course of therapy. Each week contains 7 tablets (one 35-mg once-a-week Actonel tablet and 6 tablets that each provide 500 mg of calcium). This new treatment option comes in light of the recent Surgeon General's Report on Bone Health and Osteoporosis, which emphasizes the need for osteoporosis regimens to be simplified and organized.
Calcium is a basic building block of bone and is essential for maintaining bone health. Despite this, 2 new surveys suggest that many women may not take enough calcium or may take it incorrectly with a bisphosphonate therapy like Actonel. According to a study conducted by Information Resources, Inc. (IRI), 73% of women who filled a bisphosphonate prescription purchased less than the equivalent of 1 calcium tablet per day. A second survey conducted by Harris Interactive revealed that 1 in 4 US women aged 50 years and over (26%) take calcium within 30 minutes of their bisphosphonate, which decreases the effectiveness of the bisphosphonate. Both surveys were conducted on behalf of The Alliance for Better Bone Health, which was formed in 1997 by Procter & Gamble Pharmaceuticals and Aventis Pharmaceuticals to promote bone health and disease awareness.
Harris Interactive, a Rochester, NY–based global research company, conducted the online and telephone survey between February 9 and 18, 2005, among 1,004 US women aged 50 years and over, of which 372 were bisphosphonate users. Data were weighted to be representative of the total US adult female population aged 50 years and over on the basis of age, race/ethnicity, education, region, income, and propensity to be online. Although the online sample is not a probability sample, with probability samples of this size, Harris Interactive estimates with 95% certainty that the overall results have a sampling error of ±3 percentage points. Sampling error for the various sub-sample results, including bisphosphonate users (372); bisphosphonate users who also take calcium supplements (338); and calcium supplement users (755), is higher and varies.
The study conducted by IRI analyzed calcium purchasing practices of current bisphosphonate users over a 1-year period. Four hundred ninety-eight households of women who filled a prescription for a bisphosphonate 1 year before and at least once during the current 52-week period were included in this study. Households were part of IRI's RxPulse Patient Panel, a subset of IRI's Consumer Network Panel, a nationally representative set of 70,000 households that scan all of their bar-coded purchases at home. Households within the RxPulse Patient Panel used scanning devices to record prescription information, including name of drug, strength and dose frequency, for each person in their households. Data for supplement purchases included brand, calcium content (mg), and total tablet count.
The panel provided a single source of data for bisphosphonate usage as well as total number of calcium supplement tablets (including Tums) purchased. Panel data are weighted to match US demographics, and aggregate claimed purchases are verified through a comparison to store level scanner data. For this study, the supplement category was specifically examined and confirmed to fit within standard limits.
"Osteoporosis is a serious, widespread and growing public health threat," said Judith Cranford, Director, National Osteoporosis Foundation. Osteoporosis affects millions of postmenopausal women, making their bones weak and more likely to fracture over time. In fact, in the United States today, 8 million women are estimated to already have osteoporosis, and almost 27 million more are estimated to have low bone mass, placing them at increased risk for fracture. Each year the incidence of osteoporosis-related fractures is greater than the incidence of heart attacks, strokes, and breast cancer combined. However, there are prescription medications available that effectively reduce both vertebral and nonvertebral fracture risk
When the body does not get enough calcium, it breaks down bone to help meet its calcium needs. According to the Surgeon General's Report on Bone Health and Osteoporosis, the average adult intake of calcium is approximately 700 mg daily, which is below the US recommended daily allowance of 1,200 mg for women over the age of 50 years. Many women who are taking a bisphosphonate may be able to make up this difference by taking a 500-mg calcium tablet, which is the amount of calcium found in Actonel with Calcium.
Calcium, whether from diet or supplements, is absorbed best by the body when it is taken in doses of 500 mg or less of elemental calcium at one time. Calcium should not be taken at the same time as a bisphosphonate; bisphosphonate effectiveness decreases if calcium is taken within 30 minutes of its own administration. Women should talk with their doctors about the bone health regimen that's right for them.
Actonel with Calcium is contraindicated in patients with known hypersensitivity to any component of this product or an inability to stand or sit upright for at least 30 minutes. Actonel tablets and calcium are contraindicated, respectively, in patients with hypocalcemia and hypercalcemia. These and other disturbances of bone and mineral metabolism should be effectively treated before starting Actonel with Calcium therapy. Actonel with Calcium is not recommended for use in patients with severe renal impairment (creatinine clearance <30 mL/min). In patients with conditions causing or predisposing to hypercalcemia and in patients with a history of kidney stones, the administration of calcium should be assessed before prescribing and then should be monitored appropriately.
Bisphosphonates may cause upper gastrointestinal disorders such as dysphagia, esophagitis, and esophageal or gastric ulcer. Patients should pay particular attention to the dosing instructions because failure to take the drug according to instructions may compromise clinical benefits and may increase the risk of adverse events. Calcium may cause gastrointestinal adverse effects such as constipation, flatulence, nausea, abdominal pain, and bloating.
Among patients treated with bisphosphonates, there have been infrequent reports of severe and occasionally incapacitating bone, joint, or muscle pain. Rare occurrences of osteonecrosis, primarily of the jaw (ONJ), have been reported in patients receiving bisphosphonates. Most ONJ cases have occurred in patients with cancer who are undergoing dental procedures. In the majority of cases reported, patients had received intravenous bisphosphonate therapy.
In clinical trials, Actonel was generally well tolerated. The overall incidence of adverse events with Actonel 5 mg daily was comparable to placebo. The most commonly reported adverse events, regardless of causality, were infection (primarily upper respiratory; placebo 29.7% vs Actonel 5 mg 29.9%), back pain (23.6% vs 26.1%), and arthralgia (21.1% vs 23.7%).
In a 1-year clinical trial comparing Actonel 35 mg given once a week and Actonel 5 mg daily, the overall incidence of adverse events with the two dosing regimens was similar. The most commonly reported adverse events, regardless of causality, were infection (Actonel 35 mg 20.6% vs Actonel 5 mg 19.0%), arthralgia (14.2% vs 11.5%), and constipation (12.2% vs 12.5%).
For more information about Actonel with Calcium, visit actonel.com. The Actonel label, approved by the FDA on August 12, 2005, is available at fda.gov/cder/foi/label/2005/021823lbl.pdf.
August 16, 2005
ST. LOUIS (MD Consult) - Merck & Co, Inc, announced on August 15, 2005, that the US Food and Drug Administration has approved Vaqta (hepatitis A vaccine, inactivated) for use in children 12 months of age and older. Vaqta is the first hepatitis A vaccine indicated for use in children as young as 12 months of age. Previously, Vaqta was approved for use in persons 2 years of age and older.
"Surveillance data have shown that young children often transmit hepatitis A in the United States, but since they do not typically show symptoms, they unknowingly pass the infection on to older siblings and parents who can become very ill from hepatitis A," said Fernando Guerra, MD, MPH, director of Health, San Antonio Metropolitan Health District. The expanded indication for Vaqta provides an opportunity to guard against hepatitis A infection in children earlier in life.
Hepatitis A is a contagious disease caused by a virus that can result in an infection of the liver. Symptoms include jaundice, fever, abdominal pain, dark urine, and nausea. Signs and symptoms usually last less than 2 months, although 10% to 15% of symptomatic persons have prolonged or relapsing disease for up to 6 months. The virus is transmitted most frequently by the fecal-oral route through person-to-person contact and/or ingestion of contaminated food or water. The source of a case of hepatitis A is unknown in nearly half of all instances. There is no specific treatment available for the disease.
According to a Centers for Disease Control and Prevention report issued in September 2004, there were 8,795 reported cases of hepatitis A in 2002, down from an average of 28,000 cases per year from 1987 through 1997, before hepatitis A vaccines became widely used. Approximately 25% of hepatitis A cases reported in 2002 required hospitalization, and approximately 1 in 200 cases resulted in death.
The younger age indication for Vaqta is supported by the results of an open-label study of children with no evidence of hepatitis A infection. The study was designed to investigate the immunogenicity and safety of Vaqta in this age group when it was administered with and without other routinely used vaccines given at the same age.
In this study of 617 children 12 to 23 months of age, 343 children were evaluated for indicators of an immune response to Vaqta after the second dose of a 2-dose series. Of these children (n = 343), 100% developed protective immune responses. The study also showed that Vaqta may be given concomitantly with M-M-R II (measles, mumps, and rubella virus vaccine live), another Merck vaccine. The availability of data on concomitant use with other routinely recommended childhood vaccines is limited.
In combined clinical trials involving healthy children aged 12 to 23 months (n = 706) who received 1 or more doses (˜25 U) of Vaqta alone or in combination with other routinely recommended pediatric vaccines, the most commonly reported complaints (>2% of injections) after 1 or both of the doses of Vaqta included rash, cough, fever, diarrhea, vomiting, irritability, rhinorrhea, otitis media, upper respiratory infection, and localized injection-site reactions (eg, pain/tenderness/soreness).
Clinical trials involving healthy children 12 to 23 months of age and children and adolescents 2 to 18 years of age were also undertaken. In these studies, the most commonly reported complaints (>2% of injections) in one or both of these groups included rash, cough, warmth, fever, headache, diarrhea, vomiting, rhinorrhea, irritability, otitis media, upper respiratory infection, and localized injection-site reactions (eg, pain/tenderness/soreness, erythema, swelling).
In combined clinical trials involving healthy adults 19 years of age and older, the most commonly reported complaints (>2% of injections) were localized injection-site reactions (eg, tenderness, pain, warmth, swelling, and erythema), headache, asthenia/fatigue, fever, pharyngitis, upper respiratory infection, diarrhea, and nausea. As with any vaccine, there is the possibility that use of Vaqta in very large populations might reveal adverse experiences not observed in clinical trials.
Primary immunization with Vaqta should be given at least 2 weeks before expected exposure to hepatitis A virus. Persons 12 months through 18 years of age should receive a single 0.5-mL (˜25 U) dose of vaccine at an elected date and a booster dose of 0.5 mL (˜25 U) 6 to 18 months later. Adults older than 19 years of age should receive a single 1.0-mL (˜50 U) dose of vaccine at an elected date and a booster dose of 1.0 mL (˜50 U) 6 to 18 months later.
Vaqta is contraindicated in persons who are hypersensitive to any component of the vaccine. Hepatitis A vaccine should not be administered to persons with a history of a severe reaction to a prior dose of hepatitis A vaccine or to a vaccine component. As with any vaccine, vaccination with Vaqta may not result in a protective response in all people.
For details about the indications, contraindications, warnings, precautions, adverse reactions, and dosage and administration for Vaqta, please read the prescribing information available at merck.com/product/usa/pi_circulars/v/vaqta/vaqta_pi.pdf.
For more information about Merck, visit merck.com.
August 5, 2005
ST. LOUIS (MD Consult) - On August 1, 2005, Pfizer Inc announced that the US Food and Drug Administration has approved the company's selective cycloxygenase-2 inhibitor Celebrex (celecoxib) for the relief of the signs and symptoms associated with ankylosing spondylitis, a form of arthritis that affects the spine.
Ankylosing spondylitis, which affects over 400,000 Americans, is the sixth approved indication for Celebrex in the United States. Unlike other forms of arthritis that typically affect older persons, ankylosing spondylitis usually strikes between the ages of 17 and 35 years. Approximately as common as rheumatoid arthritis, ankylosing spondylitis also can cause inflammation, pain, and stiffness in other areas of the body such as the shoulders, knees, hips, ribs, and feet.
"With this new indication, Celebrex offers physicians a new treatment option for this difficult-to-treat patient population," said Dr Joseph Feczko, Pfizer's chief medical officer. "The inflammation associated with ankylosing spondylitis can cause such severe pain that people who suffer from this condition—often young men—cannot perform even simple, everyday activities like walking and may have trouble attending school or work."
For the management of the signs and symptoms of ankylosing spondylitis, the recommended dose of Celebrex is 200 mg daily in single or divided twice-per-day doses. If no effect is seen after 6 weeks, a trial of 400 mg daily may be worthwhile. If no effect is observed after 6 weeks on 400 mg daily, a response is not likely, and consideration should be given to alternate treatment options.
Celebrex may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. All nonsteroidal anti-inflammatory drugs (NSAIDs) may have a similar risk. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
Celebrex is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft surgery.
NSAIDs, including Celebrex, cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.
As with all NSAIDs, Celebrex can lead to the onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of cardiovascular events. NSAIDs should be used with caution in patients with hypertension.
Celebrex is a sulfonamide and can cause serious skin adverse events, which can be fatal. These serious events can occur without warning and in patients without prior known sulfa allergy.
The most common adverse effects in arthritis trials were dyspepsia, diarrhea, and abdominal pain and were generally mild to moderate. The types of adverse events reported in the ankylosing spondylitis studies were similar to those reported in the arthritis studies.
For complete prescribing information, please see www.celebrex.com.
July 29, 2005
ST. LOUIS (MD Consult) - Shire Pharmaceuticals Group PLC announced on July 22, 2005, that the US Food and Drug Administration (FDA) has approved Adderall XR (mixed salts of a single-entity amphetamine product) as a once-daily treatment for adolescents aged 13 to 17 years with attention-deficit/hyperactivity disorder (ADHD). Since October 2001, Adderall XR has been approved in the United States for treatment in children aged 6 to 12 years and since August 2004 in adults 18 years and older.
In support of this new approval, Dr Timothy Wilens of Massachusetts General Hospital stated, "The symptoms of ADHD often continue past childhood into adolescence and adulthood, where they can have a significant impact on an individual's family, academic performance, and overall quality of life. Stimulant therapies are effective and generally well tolerated, and have been used medically in patients for more than 60 years."
The FDA based its approval on data provided by Shire that included the results of a pharmacokinetic study and a placebo-controlled, fixed-dose clinical trial of a range of doses of once-daily Adderall XR in adolescents with ADHD.
In a randomized, double-blind, placebo-controlled clinical trial, Adderall XR was proved to be significantly more effective than placebo in the treatment of ADHD symptoms in adolescents. Adderall XR was generally safe and well tolerated, with adverse events similar to those seen in other populations. The most common adverse events were loss of appetite, insomnia, abdominal pain, and weight loss. The results of this study show that Adderall XR produces a positive clinical response in adolescents diagnosed with ADHD. The study showed Adderall XR at doses between 10 and 40 mg daily were statistically significantly superior to placebo (P < .0001) on the ADHD-RS-IV (investigator-rated with the parent and adolescent). Furthermore, 63% of investigators considered their subjects' ADHD symptoms to be much improved or very much improved with Adderall XR, compared with 27% for placebo (P < .0001).
Adderall XR may not be right for everyone. Adderall XR was generally well tolerated in clinical studies. The most common adverse events in pediatric trials included loss of appetite, insomnia, abdominal pain, and emotional lability; the most common adverse effects in the adolescent trial included loss of appetite, insomnia, abdominal pain, and weight loss; and the most common in the adult trial included dry mouth, loss of appetite, insomnia, headache, and weight loss.
The effectiveness of Adderall XR for long-term use has not been systematically evaluated in controlled trials. As with other psychostimulants indicated for ADHD, there is a potential for exacerbating motor and phonic tics and Tourette's syndrome. An adverse effect associated with use of drugs in the amphetamine class is psychosis. Caution also should be exercised in prescribing Adderall XR to patients with a history of psychosis.
Abuse of amphetamines can lead to dependence. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. Adderall XR generally should not be used in children or adults with structural cardiac abnormalities. Adderall XR is contraindicated in patients with symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism and glaucoma, known hypersensitivity to this class of compounds, agitated states, history of drug abuse, or current or recent use of monoamine oxidase inhibitors. Adderall XR should be prescribed with close physician supervision.
ADHD affects approximately 3% to 7% of all school-aged children, or approximately 2 million US children, and is considered the most commonly diagnosed psychiatric disorder in children and adolescents. ADHD is a neurologic brain disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in other persons at comparable age and maturity levels. ADHD can have a profound effect on a child's quality of life and can be serious enough to affect not only academics, but can lead to problems maintaining friendships, focusing on after-school activities, and relating well with family members. Untreated ADHD has long-term adverse effects on academic performance, vocational success, and social-emotional development. Evidence also suggests that many with untreated ADHD may be at risk for other problems, such as drug abuse, antisocial behavior, and poor self-esteem. As they age, up to 65% of adolescents with ADHD may still exhibit symptoms into adulthood.
To be properly diagnosed with ADHD, a child must demonstrate at least 6 of 9 symptoms determined to be representative of inattention; at least 6 of 9 symptoms of hyperactivity/impulsivity; the onset of such symptoms before age 7 years; that some impairment from the symptoms is present in 2 or more settings (eg, at school and at home); and that the symptoms continue for at least 6 months.
Although there is no cure for ADHD, there are accepted treatments that specifically target its symptoms. The most common standard treatments include educational approaches, psychological or behavioral modification, and medication.
For further information on Adderall XR, visit the product's Web site at AdderallXR.com.
July 18, 2005
ST. LOUIS (MD Consult) - On July 15, 2005, Schering-Plough Corporation announced that the US Food and Drug Administration has approved reformulated Clarinex (desloratadine 2.5 mg and 5 mg) Reditabs tablets for the treatment of allergy symptoms caused by both perennial indoor and seasonal outdoor allergens and chronic idiopathic urticaria (CIU) in adults and children aged 6 years and older. The tablet disintegrates orally and is taken once daily for 24-hour relief.
This new formulation will be available in both 2.5- and 5-mg doses. The tablet dissolves rapidly, allowing persons with allergies to take their medication when it is convenient for them, even when they do not have access to water. Patients who have active lifestyles or dislike swallowing pills may prefer this treatment option.
Seasonal allergies affect an estimated 36 million people in the United States. Symptoms, which include sneezing, runny nose, congestion, itchy throat, and itchy and watery eyes, can have a significant impact on everyday activities at work and school and during leisure time. According to Schering-Plough, there is also a growing body of evidence that points to an association between allergies and more serious conditions, such as asthma.
CIU refers to ongoing outbreaks of hives that last longer than 6 weeks and have no known cause. These outbreaks can develop anywhere on the body and are usually associated with itching. The itchy, red spots appear quickly, usually disappear within 24 hours, and may reappear elsewhere on the body.
Clarinex is the only prescription nonsedating antihistamine approved for patients as young as 6 months old and is available in different forms to accommodate patient preference and symptoms. Other available formulations of Clarinex include Clarinex (0.5 mg/1 mL) Syrup for children as young as 6 months old, and Clarinex (5 mg) Tablets and Clarinex-D 24-Hour (desloratadine 5 mg/pseudoephedrine 240 mg) Extended Release Tablets for patients 12 years of age and older. Clarinex-D 24-Hour combines an antihistamine with a decongestant for patients suffering from nasal congestion associated with seasonal allergic rhinitis.
Clarinex is also the only prescription nonsedating 24-hour antihistamine approved for the treatment of indoor and outdoor allergies and CIU. The efficacy and safety of Clarinex in outdoor allergies has been established in 4 double-blind, randomized, placebo-controlled studies involving more than 2,300 patients with seasonal allergies. Clarinex was also studied in indoor allergies in 2 double-blind, randomized, placebo-controlled studies involving more than 1,300 patients with perennial allergies. A single 5-mg dose of Clarinex taken once daily provides 24-hour nonsedating relief from nasal and non-nasal symptoms of indoor and outdoor allergies. The approval for Clarinex in CIU was based on 2 double-blind, randomized, placebo-controlled studies involving more than 400 patients.
In clinical trials, Clarinex provided significantly greater symptom relief than placebo. Also, Clarinex provided powerful morning symptom relief with significant improvement in morning symptom scores over placebo. Tablet side effects in patients 12 years of age and older with seasonal and year-round allergies were similar to placebo and included sore throat, dry mouth, and fatigue. Tablet side effects in patients 12 years of age and older with ongoing itching and rash from hives of unknown cause were headache, nausea, and fatigue. Syrup side effects in children aged 6 to 11 years were similar to placebo. For children 6 months to 5 years of age, syrup adverse effects varied by age and included fever, diarrhea, upper respiratory infection, irritability, and coughing.
Due to its pseudoephedrine component, Clarinex-D 24-Hour Extended Release Tablets should not be taken by patients with narrow-angle glaucoma, difficulty urinating, severe high blood pressure, or severe heart disease, nor by patients who have taken a monoamine oxidase inhibitor within the past 14 days. Patients with high blood pressure; diabetes; heart disease; increased intraocular pressure; thyroid, liver, or kidney problems; or enlarged prostate should check with their health care provider before taking Clarinex-D 24-Hour Extended Release Tablets. Care should be used if Clarinex-D 24-Hour Extended Release Tablets is taken with other antihistamines and decongestants because combined effects on the cardiovascular system may be harmful. The most commonly reported adverse events for Clarinex-D 24-Hour Extended Release Tablets were dry mouth, headache, insomnia, fatigue, sore throat, and drowsiness.
Full prescribing information for Clarinex is available at spfiles.com/piclarinex.pdf. The company expects the reformulated Clarinex Reditabs to be in pharmacies by September 2005.
Schering-Plough is based in Kenilworth, NJ. For more information about the company, visit schering-plough.com.
July 5, 2005
ST. LOUIS (MD Consult) - On June 30, 2005, Johnson & Johnson announced that the US Food and Drug Administration (FDA) has approved a new indication for Topamax (topiramate) Tablets and Topamax Sprinkle Capsules as initial monotherapy in patients 10 years of age and older with partial-onset or primary generalized tonic-clonic seizures.
Johnson & Johnson Pharmaceutical Research and Development, LLC, demonstrated the drug's effectiveness as a monotherapy in a controlled trial involving patients with epilepsy who had no more than 2 seizures in the 3 months before enrollment. Safety and effectiveness in patients who were converted to monotherapy from a previous regimen of other anticonvulsant drugs have not been established in controlled trials.
Epilepsy is one of the most common neurologic disorders, occurring in an estimated 2.7 million Americans. Each year in the United States, approximately 200,000 people are diagnosed with epilepsy for the first time. Epilepsy is characterized by seizures, which are abnormal electrical discharges in the brain that temporarily disrupt normal brain function. Seizures are classified as "generalized," originating in both sides of the brain simultaneously, or "partial-onset," starting in one area of the brain.
"Anti-epilepsy medications, or neuromodulators, are selected based on seizure type; however, the specific seizure type may not always be obvious at the time of diagnosis," said Tracy Glauser, MD, director of the Comprehensive Epilepsy Center at the Cincinnati Children's Hospital. By providing coverage for both partial-onset and primarily generalized tonic-clonic seizures, Dr Glauser continued, Topamax may serve as a treatment option when distinguishing between seizure types is problematic.
In a double-blind clinical trial, 470 patients with partial-onset or primary generalized tonic-clonic seizures were randomly assigned to receive 50 or 400 mg/d of Topamax. The primary efficacy assessment was a group comparison of time to first seizure during the double-blind phase of the study. Comparison of the Kaplan-Meier survival curves of time to first seizure favored the 400-mg/d group over the 50-mg/d group. The recommended dose for monotherapy in patients 10 years of age and older is 400 mg/d in 2 divided doses. Approximately 58% of patients assigned to receive 400 mg/d achieved this maximal dose in the monotherapy controlled trial; the mean dose achieved in the trial was 275 mg/d.
As monotherapy, the most common adverse effects of Topamax (in the 400-mg/d group and at a rate higher than the 50-mg/d group) in adults were paresthesia, weight decrease, somnolence, anorexia, dizziness, and difficulty with memory. The most common adverse effects experienced by children were weight decrease, upper respiratory tract infection, paresthesia, anorexia, diarrhea, and mood problems.
In addition, Topamax has been associated with serious adverse events such as hyperchloremic, nonanion gap metabolic acidosis; measurement of baseline and periodic serum bicarbonate levels is recommended. Some patients taking Topamax may experience acute myopia and secondary angle closure glaucoma; therefore, persons should seek medical attention if they experience blurred vision or ocular pain. Oligohidrosis and hyperthermia may also occur, most often in hot weather and in children. Also reported have been cognitive/psychiatric adverse effects, including somnolence and fatigue, cognitive dysfunction, and psychiatric/behavioral disturbances; hyperammonemia with or without encephalopathy (associated with the concomitant use of valproic acid); and kidney stones. Patients should maintain an adequate fluid intake to minimize the risk of renal stone formation.
In women taking oral contraceptives in combination with Topamax, a significant decrease in estrogen exposure has been shown in conjunction with Topamax doses greater than or equal to 200 mg/d. The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered.
For more details, including full US prescribing information, visit TOPAMAX-epilepsy.com or ortho-mcneilneurologics.com.
June 27, 2005
ST. LOUIS (MD Consult) - On June 24, 2005, Belgian pharmaceutical company UCB announced that the US Food and Drug Administration (FDA) has approved the company's anti-epilepsy drug Keppra (levetiracetam) as add-on therapy in the treatment of partial-onset seizures in children 4 years of age and older with epilepsy. The FDA approved this new pediatric indication for Keppra under priority review, a designation for products that address unmet medical needs and represent a significant improvement to therapies already available.
"More than 25% of children with epilepsy experience treatment-resistant seizures or intolerable side effects from medication," said Tracy Glauser, MD, director of the Comprehensive Epilepsy Program, Cincinnati Children's Hospital, and principal investigator of the well-controlled study reviewed for the pediatric indication. Dr. Glauser added, "Keppra was effective and well-tolerated by the children in the study, many of whom had failed on multiple anti-epileptic drugs (AEDs) prior to trying Keppra."
This approval of Keppra for children was based on findings from 1 multicenter, randomized, double-blind, placebo-controlled pivotal study conducted at 60 sites in North America, involving 198 children aged 4 to 16 years with partial-onset seizures with or without secondary generalization uncontrolled by standard AEDs. Study participants were taking 1 or 2 other AEDs at entry. The study consisted of an 8-week baseline period and a 4-week titration period, followed by a 10-week evaluation period.
In terms of efficacy, those taking Keppra had a significantly larger reduction (26.8%) in weekly seizure frequency over placebo, on average. Additionally, another measure of efficacy for patients taking Keppra—responder rates (ie, the portion of patients achieving a 50% or greater reduction in seizures)—were 44.6% versus 19.6% for placebo (both with a P = .0002 compared with placebo).
In pediatric patients 4 to 16 years of age, the most common adverse events associated with Keppra in combination with other AEDs were somnolence, accidental injury, hostility, nervousness, and asthenia. Keppra is associated with somnolence, fatigue, and behavioral abnormalities as well as hematologic abnormalities.
In the United States, Keppra is approved for adjunctive therapy in the treatment of partial-onset seizures in adults and children 4 years of age and older with epilepsy. Keppra is available in 250-, 500-, and 750-mg tablets and a grape-flavored (100 mg/mL) oral solution for patients who prefer a solution or have difficulty swallowing tablets. Keppra dosing must be individualized according to renal function status.
In adults, Keppra use is associated with the occurrence of central nervous system adverse events, including somnolence and fatigue, coordination difficulties, and behavioral abnormalities as well as hematologic abnormalities. In well-controlled adult clinical studies, the most frequently reported adverse events associated with the use of Keppra in combination with other AEDs that were not seen at an equivalent frequency among placebo-treated patients included somnolence, asthenia, infection, and dizziness.
Keppra was approved in 1999 as adjunctive therapy for adults with partial-onset seizures. For full prescribing information, visit www.keppra.com.
June 22, 2005
ST. LOUIS (MD Cons