Eye drop approved for first-line treatment to reduce intraocular pressure in glaucoma
FDA approves oral contraceptive for 24-day active hormonal therapy
Avandament granted approval as inital treatment of type 2 diabetes
FDA approves orally disintegrating formulation of Parkinson’s treatment
First treatment approved in US for seasonal affective disorder
Higher dosage strengths approved for antihypertensive Lotrel
Marketing of Tysabri may resume under special program, FDA announces
Cubicin approved as once-daily therapy for certain Staphylococcus infections
Centocor wins approval for pediatric Crohn’s disease treatment
Janssen releases new dosages of antipsychotic drug Risperdal
Extended dosing of Aranesp approved to combat chemotherapy-induced anemia
FDA approves drug to prevent organ rejection in heart transplant
Vanos cream now approved as primary agent for all inflammatory skin conditions
Rituxan combination approved for first-line B-cell non-Hodgkin's lymphoma treatment
FDA approves intravenous osteoporosis treatment for postmenopausal women
Oncaspar wins new indication, approved for newly diagnosed acute lymphoblastic leukemia
Merck’s antiemetic drug approved to prevent postoperative nausea and vomiting
Celgene drug wins approval for treatment of multiple myeloma
FDA approves the first treatment for dementia of Parkinson’s disease
First drug combo to treat late-stage cervical cancer approved in US
Zetia combination therapy approved to reduce cholesterol in patients with mixed hyperlipidemia
Bayer granted orphan drug status for hepatocellular carcinoma treatment
Thalomid approved for the treatment of newly diagnosed multiple myeloma
Chemotherapy regimen including Taxotere now approved for treatment of advanced stomach cancer
FDA approves inhalation aerosol for 4- to 11-year-olds with asthma
Rituxan ok'd to treat moderate to severe rheumatoid arthritis
FDA approves combination antihistamine/decongestant, Clarinex-D 12 Hour
Erbitux approved for use in unresectable squamous cell cancer of the head and neck
Nausea treatment approved for use with more types of chemotherapy
Femara approved in US as initial breast cancer therapy after surgery
August 3, 2006
ST. LOUIS (MD Consult) - On August 2, 2006, Belgian pharmaceutical company UCB announced that the US Food and Drug Administration has approved Keppra (levetiracetam) injection 500 mg/5 mL (100 mg/mL) for use as adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy. Keppra injection is an alternative for patients when oral administration is temporarily not feasible. It must be diluted before use and administered as a 15-minute intravenous infusion.
The adverse events that may result from Keppra injection use include all those associated with the oral solution and tablet formulations of the drug. Keppra is associated with the occurrence of central nervous system adverse events including somnolence and fatigue, behavioral abnormalities, and hematologic abnormalities. In adults, this medication is also associated with coordination difficulties. In pediatric patients 4 to 16 years of age, the most common adverse events associated with Keppra in combination with other antiepileptic drugs were somnolence, accidental injury, hostility, nervousness, and asthenia. In adults, this combination may cause somnolence, asthenia, infection, and dizziness.
Keppra is indicated as adjunctive therapy in the treatment of partial-onset seizures in adults and children 4 years of age and older with epilepsy. US prescribing information and other details are available at keppra.com.
August 2, 2006
ST. LOUIS (MD Consult) - On June 23, 2006, Allergan, Inc, announced that the US Food and Drug Administration (FDA) has approved Allergan’s once-daily prescription eye drop Lumigan (bimatoprost ophthalmic solution) 0.03% as a first-line treatment for elevated intraocular pressure (IOP) associated with open-angle glaucoma or ocular hypertension.
Elevated IOP represents a major risk factor for vision loss associated with open-angle glaucoma; the higher the IOP, the greater the likelihood of optic nerve damage, which can lead to vision loss and potential blindness. Lumigan monotherapy reportedly delivers effective and sustained lowering of IOP, which is significant because elevated IOP is a leading risk factor for glaucoma and the only risk factor that can currently be treated. Glaucoma currently affects approximately 3 million persons in the United States and 67 million persons worldwide and is the leading cause of preventable blindness in the United States, according to the Glaucoma Foundation. An estimated 3 to 6 million persons in the United States have elevated IOP.
Lumigan has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased growth of eyelashes and pigmentation of the iris, periorbital tissue, and eyelashes. Pigmentation is expected to increase as long as Lumigan is administered. After discontinuation of the drug, pigmentation of the iris is likely to be permanent, whereas pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment with Lumigan should be informed of the possibility of increased pigmentation. The effects of increased pigmentation beyond 5 years are not known. In clinical trials, the most frequent events associated with the use of Lumigan, occurring in approximately 15% to 45% of patients, in descending order of incidence, included conjunctival hyperemia, growth of eyelashes, and ocular pruritus.
The FDA approved Lumigan in 2001 as an IOP-lowering medication for second-line use in patients who were intolerant of other IOP-lowering medications or who did not have a sufficient reduction in IOP in multiple measurements using another medication. Additional details, including full prescribing information, are available at lumigan.com.
August 1, 2006
ST. LOUIS (MD Consult) - Illinois-based health care company Abbott announced on July 31, 2006, that the US Food and Drug Administration (FDA) has approved Humira (adalimumab) for reducing signs and symptoms in patients with active ankylosing spondylitis (AS). AS is an autoimmune disease affecting the spine and large peripheral joints that causes inflammatory back pain and stiffness and also can be associated with other inflammatory diseases of the skin, eyes, and intestines. In its severe form, AS can result in complete spinal fusion, causing extreme physical limitation and reduction in health-related quality of life.
Ankylosing spondylitis affects young adults and commonly develops during the second and third decades of life. Because the pain and stiffness of AS are hard to distinguish from other common causes of back pain, patients may go undiagnosed for many years from the onset of their symptoms. Ankylosing spondylitis is one of the most overlooked causes of persistent back pain in young adults.
The recommended dose of Humira for AS is 40 mg (administered subcutaneously) every other week; this is also the usual dose recommended for Humira in the treatment of moderate to severe rheumatoid arthritis and psoriatic arthritis. Humira is available to patients with AS in the United States in a prefilled syringe. Beginning in August 2006, the medication will also be available in the Humira Pen, a new delivery device for the self-administration of this drug. The Humira Pen was approved by the FDA on June 23, 2006, and medication administration with the device is reportedly easier and less painful than administration using the Humira prefilled syringe.
The approval of Humira for the treatment of patients with active AS resulted from data from the Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS). This randomized, placebo-controlled, double-blind, phase III study was conducted in Europe and the United States. Results showed that Humira was successful in reducing pain and inflammation in patients with AS after 12 weeks of treatment, the study's primary end point. Other findings demonstrated significant improvement in measures of disease activity for many patients treated with Humira that were first observed at week 2 and were maintained through 24 weeks.
ATLAS also explored the impact of Humira on enthesitis, a condition in AS characterized by inflammation of the ligaments that attach to the bone. At week 24, the mean change in the enthesitis symptom score, as measured by Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) in patients treated with Humira, showed significant reduction. MASES is an index that assesses enthesitis in certain locations, such as the rib cage, lower back, and Achilles tendons.
In the ATLAS trial, a similar rate of treatment-emergent adverse events leading to discontinuation of study drug was observed among placebo-treated (1.9%) and Humira-treated (1.4%) patients. The overall incidence of adverse events reported by patients treated with Humira was higher than that of the placebo-treated patients. The most common adverse events included nasopharyngitis, injection site reactions, and headache.
Cases of tuberculosis have been observed in patients receiving Humira. Serious infections and sepsis, including fatalities, have been reported with the use of tumor necrosis factor (TNF)-blocking agents, including Humira. Many of these infections occurred in patients also taking other immunosuppressive agents that, in addition to their underlying disease, could predispose them to infections. Treatment with Humira should not be initiated in patients with active infections. TNF-blocking agents, including Humira, have been associated with reactivation of hepatitis B virus (HBV) infection in patients who are chronic carriers of this virus. Some cases have been fatal. Patients at risk for HBV infections should be evaluated for prior evidence of HBV infections before initiating treatment with Humira. The combination of Humira and anakinra is not recommended.
TNF-blocking agents, including Humira, have been associated in rare cases with demyelinating disease and severe allergic reactions. Infrequent cases 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. An approximately 4-fold higher rate of lymphoma occurred 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. As with any treatment program, the benefits and risks of Humira should be carefully considered before initiating therapy.
In Humira clinical trials for AS and psoriatic arthritis, the safety profile for patients treated with Humira was similar to the safety profile seen in patients with rheumatoid arthritis.
For more information, including full US prescribing information, visit humira.com.
July 27, 2006
ST. LOUIS (MD Consult) - Warner Chilcott announced on February 20, 2006, that the US Food and Drug Administration approved its 24-day oral contraceptive, Loestrin 24 Fe (24 norethindrone acetate and ethinyl estradiol tablets, and 4 ferrous fumarate tablets), for the prevention of pregnancy.
Loestrin 24 Fe provides 24 days of active hormonal therapy and 4 days of iron-containing placebo pills. Each active pill contains 1 mg of norethindrone acetate and 20 mcg of ethinyl estradiol. Each placebo pill contains 75 mg of ferrous fumarate.
In a clinical study, 743 women (aged 18 to 45 years) were treated with Loestrin 24 Fe for up to six 28-day cycles, providing a total of 3,823 treatment-cycles of exposure. A total of 583 women completed 6 cycles of treatment. A total of 5 on-treatment pregnancies occurred in 3,565 treatment cycles during which no backup contraception was used.
Oral contraceptives should not be used in women who have the following conditions:
Cigarette smoking increases the risk of serous cardiovascular adverse effects from oral contraceptive use. The risk increases with age and with the extent of smoking and is quite marked in women older than 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke.
For more information, including full prescribing information, visit loestrin24.com.
July 25, 2006
ST. LOUIS (MD Consult) - On July 24, 2006, the US Food and Drug Administration (FDA) expanded the approved use of Oncaspar (pegaspargase) to include treating newly diagnosed acute lymphoblastic leukemia (ALL) as part of a multiple-drug chemotherapy regimen in children and adults. The FDA approved Oncaspar in 1994 only for patients with ALL who were unable to receive the cancer drug L-asparaginase because of drug allergy.
Leukemia is a cancer of the white blood cells; patients with acute leukemia have ineffective white blood cells that cannot help the body fight infections. An estimated 25,000 new cases of leukemia will be diagnosed in the United States during 2006. Of these new leukemia cases, approximately 6,500 will be ALL, of which approximately 2,500 will occur in children and 4,000 will occur in adults.
The use of Oncaspar in place of the currently used drug, L-asparaginase, markedly reduces the number of drug injections required, from 21 injections of Elspar (L-asparaginase), which has been the standard of care, to 3 injections with Oncaspar over the 20-week course of treatment.
The approval was granted because of data from a randomized multicenter trial conducted by the Children’s Cancer Group, a National Cancer Institute–funded cooperative oncology group, in 118 pediatric patients. In the trial, researchers demonstrated that Oncaspar could be safely and effectively substituted for Elspar as part of a multidrug cancer regimen.
Serious adverse effects associated with Oncaspar include anaphylaxis, other serious allergic reactions, blood clots, stroke, pancreatitis, glucose intolerance, and bleeding problems.
Oncaspar is marketed by Enzon Pharmaceuticals of Bridgewater, NJ. For more information, visit enzon.com.
July 18, 2006
ST. LOUIS (MD Consult) - On July 17, 2006, Eli Lilly and Company announced that the US Food and Drug Administration (FDA) has approved Gemzar (gemcitabine hydrochloride) for use in the treatment of recurrent ovarian cancer. The approval specifies that Gemzar be used in combination with carboplatin, a widely used platinum-based chemotherapy agent, in women with advanced ovarian cancer that has relapsed at least 6 months after initial therapy.
Clinical data submitted to the FDA showed that patients treated with a combination of Gemzar and carboplatin experienced a significant improvement in progression-free survival and response rates compared with carboplatin alone. Ovarian cancer, which is the eighth most common cancer among women, recurs in approximately 90% of those who are diagnosed and treated for the first time. According to the American Cancer Society, there will be an estimated 20,180 new cases of ovarian cancer in America in 2006.
"Ovarian cancer is marked by one of the highest recurrence rates of all women’s cancers, and when it does progress, it is frequently accompanied by significant symptoms that impede daily activities," said Robert Ozols, MD, PhD, of the Fox Chase Cancer Center in Philadelphia. "The Gemzar combination can help us aggressively address this recurrent disease with increased clinical efficacy and generally manageable side effects."
A randomized phase III study compared Gemzar plus carboplatin against carboplatin alone in locally advanced or metastatic disease in patients previously treated with platinum-based therapy such as carboplatin or cisplatin. The primary end point of this 356-patient trial was progression-free survival. Many patients with ovarian cancer will receive additional treatments each time their disease recurs. Progression-free survival as an end point is a meaningful measurement because it is not influenced by subsequent treatments. Response rate, safety, and survival were secondary end points.
Results showed a median progression-free survival increase of 48% (a statistically significant finding) in the Gemzar-and-carboplatin arm compared with the carboplatin-alone arm (8.6 months vs 5.8 months; P = .0038). The Gemzar combination demonstrated a 2-fold increase in complete response rate (ie, disappearance of tumor) over carboplatin alone (14.6% vs 6.2%). The overall response rate for the Gemzar combination was significantly higher than carboplatin alone, with 47% and 31% of the patients responding, respectively (P = .0016).
The most commonly observed adverse effect of the Gemzar and carboplatin combination therapy in this study was neutropenia; the rate of serious infection was limited (<3%). As anticipated, when cytotoxic combination therapy is compared with a cytotoxic single agent, toxicity was observed more frequently in the combination arm. Grade 3 and 4 toxicities were primarily hematologic laboratory toxicities, such as anemia and thrombocytopenia. However, these laboratory toxicities infrequently resulted in meaningful adverse effects such as febrile neutropenia and grade 3 hemorrhage.
In clinical studies, adverse effects were generally manageable. There have been rare reports of serious kidney, lung, or liver toxicity with Gemzar treatment. Gemzar treatment will likely not be appropriate for women who are pregnant, may be pregnant, or are nursing.
Gemzar was first approved by the FDA in 1996. Previously approved indications for this medication are carcinoma of the breast, lung, and pancreas. For complete safety and prescribing information, visit gemzar.com.
July 12, 2006
ST. LOUIS (MD Consult) - Merck & Co, Inc, announced on July 11, 2006, that the US Food and Drug Administration (FDA) has approved Emend (aprepitant) for the prevention of postoperative nausea and vomiting (PONV), one of the most common adverse effects associated with surgical procedures. The recommended dose of Emend for PONV is a single, oral, 40-mg dose administered up to 3 hours before the induction of anesthesia.
Emend is a substance P/neurokinin-1 receptor antagonist and is believed to work through a novel mechanism that primarily blocks nausea and vomiting signals to the brain. This mechanism is distinct from how current anti-vomiting therapies work, including 5-HT3 receptor antagonists (eg, Zofran [ondansetron hydrochloride]). The 5-HT3 receptor antagonists primarily target nausea and vomiting signals in the gut.
The FDA approval for Emend was granted on the basis of 2 multicenter, randomized, double-blind, active comparator–controlled, parallel-group studies of 1,658 patients undergoing open abdominal surgery. Patients were randomly assigned to receive 40 mg of Emend 1 to 3 hours before anesthesia or 4 mg of Zofran given intravenously (IV) immediately before anesthesia. A single 125-mg dose of Emend was also studied; however, no additional clinical benefit was seen compared with the 40-mg dose. Of the patients receiving 40 mg of Emend, 92% were women and 8% were men, and the age of patients in the group ranged from 19 to 84 years with a mean age of 46 years.
In study 1, (N = 573), Emend 40 mg was superior to Zofran 4 mg IV for the prevention of vomiting from 0 to 24 hours after surgery. "Prevention of vomiting" was defined as no emetic episodes and was 1 of 2 primary end points in the study. Of patients taking Emend 40 mg, 84% of patients (246 of 293) did not experience vomiting through 24 hours compared with 71% of patients taking Zofran 4 mg IV (200 of 280; P < .001).
In a pre-specified noninferiority analysis in study 1, patients taking Emend 40 mg had a complete response in the 0 to 24 hours after surgery comparable to that experienced with Zofran 4 mg IV. "Complete response" was defined as no emetic episodes and no use of rescue therapy, and was the other primary end point in the study. In this analysis, 64% of patients (187 of 293) taking Emend 40 mg had a complete response compared with 55% of patients (154 of 280) taking Zofran 4 mg IV. Complete response in the 24 hours after surgery was also evaluated using a pre-specified superiority analysis in this study, which found that Emend was not superior to Zofran on this end point.
Furthermore, in study 1 Emend 40 mg was superior to Zofran 4 mg IV in the prevention of vomiting from 0 to 48 hours after surgery, a secondary end point. Of patients taking Emend 40 mg, 82% (238 of 292) did not experience vomiting through 48 hours compared with 66% of patients taking Zofran 4 mg IV (185 of 279; P < .001). That is, in this study almost twice as many patients taking Zofran 4 mg IV experienced vomiting (34%; 94 of 279 patients) compared with patients taking Emend 40 mg (18%; 54 of 292 patients) in the 48 hours after surgery.
Study 2 (N = 494) did not satisfy its primary hypothesis that Emend 40 mg is superior to Zofran 4 mg IV in the prevention of PONV as measured by the proportion of patients with a complete response in the 24 hours after the end of surgery. In the second study, Emend 40 mg demonstrated a clinically meaningful effect with respect to the secondary end point of "no vomiting" during the first 24 hours after surgery. Emend 40 mg was associated with a 16% improvement over Zofran 4 mg IV in the prevention of vomiting.
In these 2 well-controlled clinical studies, 564 patients received Emend 40 mg orally and 538 patients received Zofran 4 mg IV. Emend was generally well tolerated. Clinical adverse experiences were reported in approximately 60% of patients treated with Emend compared with roughly 64% of persons receiving Zofran. In the PONV studies, the most common adverse events reported with Emend versus Zofran were constipation (8.5% vs 7.6%), nausea (8.5% vs 8.6%), itching (7.6% vs 8.4%), fever (5.9% vs 10.6%), low blood pressure (5.7% vs 4.6%), headache (5.0% vs 6.5%), and bradycardia (4.4% vs 3.9%).
Emend is only used to help prevent nausea and vomiting after surgery or, when used in combination with other antiemetics, to help prevent nausea and vomiting caused by chemotherapy. It is not used to end nausea and vomiting after they start.
Patients should be instructed to report all medications they are taking, pregnancy or plans to become pregnant, and any liver problems to their physicians. Emend should not be taken with Orap (pimozide), Seldane (terfenadine), Hismanal (astemizole), or Propulsid (cisapride) because, when administered in conjuction with these drugs, Emend can cause serious or life-threatening problems. Emend may also affect the action of some medicines. Chronic continuous use of Emend for prevention of nausea and vomiting is not recommended because this use has not been studied. To avoid pregnancy, women using birth control medication during treatment with Emend should also use a back-up method of contraception for the duration of treatment and for up to 1 month after treatment ends.
Studies show that nausea and vomiting may affect up to 30% of all patients undergoing surgery and as many as 70% of high-risk patients. One study shows that nearly 80% of PONV occurs within 48 hours after surgery. A study has also shown that patients find vomiting to be the most undesirable consequence of surgery, even ranking above surgical pain.
For more information, visit emend.com.
July 12, 2006
ST. LOUIS (MD Consult) - GlaxoSmithKline announced on July 11, 2006, that the US Food and Drug Administration has granted approval of Avandamet (rosiglitazone maleate and metformin hydrochloride) for use as initial treatment of type 2 diabetes as an adjunct to diet and exercise. Avandamet was previously approved as a second-line therapy for use in patients whose conditions were uncontrolled with metformin monotherapy.
Avandamet is the only combination of a thiazolidinedione (ie, rosiglitazone maleate) and metformin hydrochloride with approved use as initial therapy of type 2 diabetes. Avandamet is indicated to improve glycemic control in patients with type 2 diabetes mellitus when treatment with dual rosiglitazone and metformin therapy is appropriate.
"Rosiglitazone targets insulin resistance, an underlying cause of type 2 diabetes, whereas metformin primarily works to reduce the amount of blood sugar produced by the liver," said Barry Goldstein, MD, PhD, director, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University, Philadelphia. He went on to say that a clinical trial comparing Avandamet to both rosiglitazone alone and metformin alone showed significantly lower blood sugar levels among patients taking Avandamet.
Nearly 18 million Americans have type 2 diabetes, the most common form of diabetes. Type 2 diabetes is characterized by high blood sugar levels that occur when the body does not produce enough insulin or when insulin resistance is present. Blood sugar control is measured by the HbA1C test, or A1C, which reflects a person’s average blood sugar levels over the previous 2 to 3 months. The American Association of Clinical Endocrinologists recommends an A1C of 6.5% or lower. The American Diabetes Association recommends an A1C of less than 7%. Lowering blood sugar levels can help reduce the risk of diabetes-related complications such as heart disease, stroke, blindness, loss of limbs, and kidney disease.
Avandamet was originally approved in the United States in 2002 and is available in 4 tablet strengths of rosiglitazone/metformin: 2 mg/500 mg, 4 mg/500 mg, 2 mg/1,000 mg, and 4 mg/1,000 mg.
A small number of persons who have taken metformin have developed lactic acidosis. This rare yet serious condition occurs most often in persons with kidney problems and can be fatal in up to one half of cases. Patients who have kidney problems should not take Avandamet. Tests should be used to check the kidneys before and during therapy with Avandamet. Patients should not drink alcohol excessively when taking this drug.
Furthermore, patients taking medicines for heart failure may be at increased risk of lactic acidosis. Patients should be questioned about their cardiac history and current cardiac status. Avandamet can cause fluid retention, a condition which can lead to or exacerbate some cardiac problems, including heart failure. Patients should be instructed to immediately report the occurrence of swelling or fluid retention, shortness of breath or difficulty breathing, an unusually rapid increase in weight, or unusual tiredness while taking Avandamet.
Patients with liver problems should not take Avandamet. Blood tests should be used to check for liver problems before initation and during treatment with this medication. Patients should notify their doctors if they have liver disease or if they experience unexplained tiredness, stomach problems, dark urine, or yellowing of skin while taking Avandamet.
Avandamet may increase female patients’ risk of pregnancy. Women who could become pregant or are pregnant should discuss this with their physicians before initiating therapy with this drug. Persons who are nursing should not take Avandamet.
Very rarely, some persons have experienced vision changes caused by swelling in the back of the eye while taking rosiglitazone, a component of Avandamet. Patients taking this drug should have their eyes checked regularly by a health care professional.
The announcement of the FDA approval coincides with GlaxoSmithKline’s announcement that its supply of Avandamet has been reestablished. For additional details, including full prescribing information, visit avandamet.com.
July 11, 2006
ST. LOUIS (MD Consult) - Celgene Corporation announced on June 29, 2006, that the US Food and Drug Administration (FDA) has granted approval for an additional indication for Revlimid (lenalidomide), for use in combination with dexamethasone as a treatment for patients with multiple myeloma who have received at least 1 prior therapy. Revlimid is also approved for use in the treatment of patients with transfusion-dependent anemia caused by low- or intermediate-1-risk myelodysplastic syndromes (MDSs) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.
Revlimid, a thalidomide analog, is an immunomodulatory agent with antiangiogenic and antineoplastic properties. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is taken during pregnancy, it may cause birth defects or death to an unborn baby. Women should be advised to avoid pregnancy while taking Revlimid.
Multiple myeloma, also known as myeloma or plasma cell myeloma, is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. It is the second most common blood cancer in the United States, affecting approximately 50,000 persons. Approximately 200,000 persons worldwide had multiple myeloma in 2005. An estimated 74,000 new cases of multiple myeloma are expected in 2006. The estimated number of deaths from multiple myeloma expected in 2006 is approximately 60,000 worldwide. The average survival time for a patient diagnosed with multiple myeloma is about 3 to 4 years.
This drug is associated with significant neutropenia and thrombocytopenia. Eighty percent of patients with deletion 5q MDS had to have a dose delay or reduction during the major study. Thirty-four percent of patients had to have a second dose delay or reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in a study. Patients receiving therapy for deletion 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption, reduction, or both. In addition, patients may require use of blood product support or growth factors.
In a clinical trial, 151 patients (45%) in a treatment group receiving Revlimid and dexamethasone underwent at least 1 dose interruption with or without a dose reduction of Revlimid compared with 21% in the placebo/dexamethasone treatment group. Most adverse events and grade 3 or 4 adverse events were more frequent in patients who received the combination of Revlimid/dexamethasone compared with placebo/dexamethasone.
It is not known whether Revlimid is excreted in human milk. Because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
Revlimid has demonstrated a significantly increased risk of deep venous thrombosis and pulmonary embolism in patients with multiple myeloma who were treated with Revlimid combination therapy. Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. It is not known whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with Revlimid may lessen the potential for venous thromboembolic events. The decision to take prophylactic measures should be done carefully after an assessment of a patient's underlying risk factors.
Revlimid is substantially excreted by the kidney, so the risk of toxic reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it would be prudent to monitor renal function. In addition, Revlimid is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components.
Adverse events demonstrated in trials among persons with multiple myeloma taking the Revlimid/dexamethasone combination were as follows: constipation (39%), fatigue (38%), insomnia (32%), muscle cramp (30%), diarrhea (29%), neutropenia (28%), anemia (24%), asthenia (23%), pyrexia (23%), nausea (22%), headache ((21%), peripheal edema (21%), dizziness (21%), dyspnea (20%), tremor (20%), decreased weight (18%), thrombocytopenia (17%), rash (16%), back pain (15%), hyperglycemia (15%), and muscle weakness (15%).
Because of the potential toxicity and to avoid fetal exposure to Revlimid, Revlimid is only available under a special restricted distribution program called RevAssist. Under this program, only prescribers and pharmacists registered with the program can prescribe and dispense the product. In addition, Revlimid must only be dispensed to patients who are registered and who meet all the conditions of the RevAssist program.
Revlimid will be available in 5-, 10-, 15-, and 25-mg capsules. For more details on this medication, including full prescribing information and data on the RevAssist program, visit revlimid.com or call the manufacturer's toll-free number at 1-888-423-5436.
June 26, 2006
ST. LOUIS (MD Consult) - Endo Pharmaceuticals Inc announced on June 23, 2006, that the US Food and Drug Administration (FDA) has approved the company’s new drug applications for its extended-release and immediate-release formulations of oxymorphone hydrochloride. These products are now known under the trade names Opana ER tablets and Opana tablets, respectively.
A new oral opioid analgesic option for patients, Opana ER is indicated for the relief of moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for an extended period of time and is not intended to be used on an as-needed basis. This is the first time oxymorphone will be available in an oral, extended-release formulation. Opana ER is not indicated for pain in the immediate postoperative period (12-24 hours after surgery) nor if pain is mild or not expected to persist for an extended period of time.
Opana ER will be available in 5-, 10-, 20-, and 40-mg tablets. The immediate-release version, Opana, is indicated for the relief of moderate to severe acute pain in cases when the use of an opioid is appropriate and will be available in 5- and 10-mg tablets. Both products are expected to be commercially available in the United States in the summer of 2006. Endo also plans to relaunch its oxymorphone hydrochloride injection under the new trade name in the hospital setting.
The clinical profile of Opana ER demonstrates it can be dosed consistently on a twice-daily basis and is well tolerated when titrated effectively. Opana ER has also demonstrated maintenance of effective pain control at a stable dose over the 3-month period of the pivotal clinical trials, which the company believes highlights the durability of its analgesic effect. Experts agree that patients with moderate to severe chronic pain that is present much or all of the day need around-the-clock coverage with an analgesic agent to sustain pain relief. Opana ER uses a patented delivery system that was specifically developed to provide continuous delivery of medication over a 12-hour period, helping patients maintain a steady level of pain relief. Before the formulation of Opana ER and Opana occurred, oxymorphone hydrochloride had been available only as an injectable formulation. Both products have been proven to achieve effective relief in multiple moderate to severe pain models, in both opioid-naďve and opioid-experienced patients.
Peter A. Lankau, President and Chief Executive Officer, said, "The clinical program for Opana ER and Opana represents one of the most comprehensive ever conducted for an opioid analgesic, with more than 15 clinical trials enrolling over 3,000 patients." Among these phase II and III trials were the first phase III, placebo-controlled, double-blind studies ever conducted with an oral opioid for 12 weeks in chronic moderate to severe low back pain. These 2 studies—one trial in opioid-naďve patients and the other in opioid-experienced patients—involved titrating patients to an effective and well-tolerated dose of Opana ER and then randomly assigning them to receive either placebo or Opana ER. The studies showed that patients could have their pain level maintained effectively at that same dose level of Opana ER for a period of 12 weeks. These patients achieved a statistically significant reduction in average pain intensity compared with placebo (P < .0001). The data confirm that, in patients titrated effectively to an appropriate dose, Opana ER offered a durable analgesic effect in a broad base of patient types.
A multiple-dose study of immediate-release Opana assessed time to discontinuation for any reason and pain intensity in patients with moderate to severe pain after abdominal surgery. Results showed a statistically significant decrease in the primary end point (time to discontinuation for any reason) when comparing Opana with placebo (P < .0001).
Opana ER has been studied in a wide range of chronic pain conditions, including low back pain, osteoarthritis pain, and cancer pain. Opana has been studied as a treatment for acute pain conditions, such as postsurgical pain. Endo developed Opana ER using Penwest Pharmaceuticals’ proprietary time-release technology, TIMERx. The two companies provided funding for the Opana ER studies.
Opana ER and Opana are opioid agonists and schedule II controlled substances with an abuse liability similar to morphine. Opana ER and Opana can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Opana ER in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
Endo has worked with the FDA and outside experts to develop a comprehensive program focused on the proper prescribing and clinical use of opioid analgesics. As the launch of the Opana product line approaches, Endo also will launch its Partnership for Responsible Opioid Management through Information, Support, and Education (PROMISE) initiative. For more information on this program, visit endopromise.com.
Opana ER tablets are to be swallowed whole and are not to be broken, chewed, dissolved, or crushed. Taking broken, chewed, dissolved, or crushed Opana ER tablets leads to rapid release and absorption of a potentially fatal dose of oxymorphone.
Patients must not consume alcoholic beverages, or prescription or nonprescription medications containing alcohol, while receiving Opana ER therapy. The coingestion of alcohol with Opana ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone.
Opana ER and Opana are contraindicated in patients with a known hypersensitivity to oxymorphone hydrochloride, morphine analogs such as codeine, or any of the other ingredients of Opana ER and Opana. In addition, these drugs are contraindicated in patients with moderate or severe hepatic impairment or in any situation where opioids are contraindicated.
Respiratory depression is the chief hazard of Opana ER and Opana, particularly in elderly or debilitated patients. The most common adverse drug reactions (0.10%) in clinical trials for Opana ER were nausea, constipation, dizziness, vomiting, pruritus, somnolence, headache, increased sweating, and sedation. The most common adverse drug reactions (0.10%) reported in clinical trials for Opana were nausea and pyrexia.
For full prescribing information, visit opana.com. To learn more about the manufacturer, visit endo.com.
June 28, 2006
ST. LOUIS (MD Consult) - On June 27, 2006, the US Food and Drug Administration (FDA) approved Exelon (rivastigmine tartrate) for the treatment of mild to moderate dementia associated with Parkinson’s disease. Exelon was previously approved for the treatment of mild to moderate dementia of the Alzheimer’s type.
"It’s been recognized for almost a decade that the dementia of patients with Parkinson’s disease differs from the dementia of patients with Alzheimer’s," said Dr Steven Galson, director of the FDA's Center for Drug Evaluation and Research, "but until now, there has been no treatment that has been shown to be effective specifically for the dementia associated with Parkinson’s disease. Today’s approval of Exelon helps to fill this medical need."
It is estimated that about 0.2% to 0.5% of persons older than 65 years are affected by Parkinson’s dementia and experience such symptoms as impairments in executive function, memory, and attention. The approval of Exelon for the treatment of Parkinson’s dementia is based on the results of a randomized, placebo-controlled clinical study of 541 patients who showed symptoms of mild to moderate dementia 2 years or later after their diagnosis of Parkinson’s disease. At the end of the 24-week trial, the condition of the Exelon-treated patients, as shown on a scale that measures mental processes, was significantly better than the condition of the patients taking placebo.
The use of Exelon has been associated with significant gastrointestinal adverse reactions. In clinical trials, nausea developed in 47% of the patients treated with the drug, and 26% of women and 18% of men taking high doses of Exelon experienced significant weight loss. Other common adverse events reported by patients taking Exelon include vomiting, anorexia, dyspepsia, and asthenia. In some patients with Parkinson’s disease, treatment with Exelon was associated with a worsening of tremor.
Exelon is manufactured by Novartis Pharmaceutical Corp in East Hanover, NY.
June 20, 2006
ST. LOUIS (MD Consult) - Valeant Pharmaceuticals International announced on June 15, 2006, that the US Food and Drug Administration has approved Zelapar (selegiline hydrochloride) Orally Disintegrating Tablets. This form of Zelapar was created using an oral delivery system called Zydis Technology, which allows the tablets to dissolve within seconds in the mouth and deliver more active drug at a lower dose. The drug is indicated as once-daily adjunct therapy for Parkinson’s disease patients being treated with levodopa/carbidopa who exhibit deterioration in the quality of their response to this therapy.
Levodopa/carbidopa is commonly used early in the treatment of Parkinson’s disease, but as the disease progresses, it becomes increasingly difficult to adequately control symptoms with this medication. Parkinson’s disease patients may endure many hours of "off" time each day in which their symptoms return as a result of levodopa/carbidopa wearing off. The use of Zelapar as adjunctive therapy to levodopa/carbidopa has been shown to reduce "off" time, on average, by 2.2 h/d.
The effectiveness of Zelapar as an adjunct to levodopa/carbidopa in the treatment of Parkinson’s disease in patients who exhibit deterioration in the quality of their response to this therapy was established in a 12-week multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients received either 1.25 mg of the drug or placebo each day for the first 6 weeks and then 2.5 mg of the drug or placebo once daily for the following 6 weeks. Zelapar was shown to significantly reduce "off" time after 1 week of treatment. At the end of 12 weeks, Zelapar-treated patients had, on average, 2.2 h/d less "off" time compared with baseline, and placebo-treated patients had 0.6 h/d less "off" time. The observed reduction in "off" time between the 2 treatment groups compared with baseline was statistically significant (P < .001).
The most common adverse events reported by patients treated with Zelapar were comparable to placebo and included nausea (11%), dizziness (11%), pain (8%), headache (7%), insomnia (7%), rhinitis (7%), dyskinesia (6%), skin disorders (6%), stomatitis (5%), back pain, (5%) and dyspepsia (5%).
Selegiline, the active ingredient in Zelapar, is a monoamine oxidase (MAO)-B inhibitor that prevents the breakdown of dopamine, the key neurotransmitter in the brain controlling movement. MAO inhibitors have been used as an adjunct therapy in Parkinson’s disease since the first clinical trials of levodopa therapy in the early 1960s.
Because of the fast disintegration of Zelapar Orally Disintegrating Tablets, the drug significantly bypasses the gut and first-pass hepatic metabolism. It is primarily absorbed into the systemic circulation through the oral mucosa, thereby potentially enhancing the therapeutic effect and reducing adverse effects.
Zelapar is contraindicated in patients with a known hypersensitivity to any formulation of selegiline or any of the inactive ingredients of Zelapar. Serious, sometimes fatal reactions have been precipitated with the concomitant use of meperidine (eg, Demerol and other trade names) and MAO inhibitors including selective MAO-B inhibitors. These reactions have been characterized by coma, severe hypertension or hypotension, severe respiratory depression, convulsions, malignant hyperpyrexia, excitation, peripheral vascular collapse, and death. In addition, the combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. Severe toxicity has also been reported in patients receiving the combination of tricyclic antidepressants and conventional selegiline and selective serotonin reuptake inhibitors and conventional selegiline. Zelapar should not be administered along with other selegiline products.
Zelapar may potentiate the dopaminergic adverse effects of levodopa and may cause or worsen preexisting dyskinesia. Decreasing the dose of levodopa may reduce this phenomenon.
Adverse events prompted 5.2% of patients to discontinue Zelapar therapy (vs 1% with placebo). This medication should be taken during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
Parkinson’s disease is a chronic, progressive motor system disorder. The symptoms of Parkinson’s disease appear when approximately 80% of neurons in the substantia nigra become impaired. In the United States, 1.5 million persons currently have Parkinson’s disease. It is estimated that 60,000 new patients are diagnosed each year. Although the condition usually develops after the age of 65 years, 40% of diagnosed persons are younger than 60 years. Parkinson’s disease affects nearly equal numbers of men and women, with no obvious social, ethnic, economic, or geographic boundaries. Presently, no cure for the disease exists, and the cause is unknown.
For more details, including full prescribing information, visit zelapar.com or call Valeant Pharmaceuticals International at 1-877-361-2719.
June 16, 2006
ST. LOUIS (MD Consult) - On June 15, 2006, the US Food and Drug Administration (FDA) announced that it has approved a combination of Hycamtin (topotecan hydrochloride) and cisplatin for use as the first drug treatment for women with late-stage cancer of the cervix when a physician determines that surgery or radiation therapy are unlikely to be effective. The approval includes a new indication for GlaxoSmithKline’s Hycamtin, which was approved in 1996 for treating ovarian cancer and in 1998 for treating small-cell lung cancer.
In the United States, an estimated 10,000 new cases of cervical cancer and about 3,700 related deaths occur each year, according to the FDA. The combination of Hycamtin and cisplatin is specifically indicated for women with stage IVB, recurrent, or persistent cancer of the cervix that metastasizes and is not likely respond to treatment with surgery or radiation.
In clinical trials involving this patient population, 293 patients were randomly assigned to receive Hycamtin plus cisplatin or cisplatin alone. Most of the participants had received prior radiation therapy as the standard treatment, whereas some may have undergone prior surgery. The combination therapy significantly improved survival compared with the use of cisplatin alone. Patients receiving combined therapy survived an average 9.4 months, about 3 months longer than patients receiving cisplatin alone (6.5 months).
Hycamtin is associated with a significant risk of neutropenia. Serious adverse effects also include thrombocytopenia, which can lead to excessive bleeding and anemia. Less serious effects include nausea and vomiting. The incidences of neutropenia, anemia, and thrombocytopenia were significantly increased among patients receiving the combination treatment compared with those receiving cisplatin alone, as were the occurrences of nausea and vomiting, mucositis, rash, and liver toxicity.
For more information and full prescribing information, visit hycamtin.com.
June 13, 2006
ST. LOUIS (MD Consult) - The US Food and Drug Administration (FDA) announced on June 12, 2006, that is has approved Wellbutrin XL (bupropion hydrochloride extended-release tablets) for the prevention of major depressive episodes in patients with a history of seasonal affective disorder (SAD). The first drug approved for this indication, Wellbutrin XL was previously approved for the treatment of major depressive disorder.
SAD is characterized by recurrent major depressive episodes that usually coincide with the seasonal decrease of daylight during autumn and winter. The depressive episodes can last up to 6 months. Although patients with SAD may have depressive episodes during other times of the year, the diagnosis of SAD requires that the number of seasonal episodes substantially outnumber the nonseasonal episodes during the person's lifetime.
A major depressive episode is defined as the presence of 5 or more of the 9 core symptoms of major depression for at least 2 weeks. The symptoms include:
To qualify as a major depressive episode, one of the 5 symptoms present must be either depressed mood or loss of interest in activities.
Another essential feature of major depression is the presence of significant distress or impairment in social, occupational, or other important areas of functioning. A seasonal major depressive episode is defined by the identical features.
The effectiveness of GlaxoSmithKline's Wellbutrin XL for the prevention of SAD episodes was established in 3 double-blind, placebo-controlled trials in adults with a history of major depressive disorder in autumn and winter. Treatment was initiated before the onset of symptoms in the autumn (ie, September to November) and was discontinued after a 2-week taper that began the first week of spring (ie, the fourth week of March). In these trials, the percentage of patients who were depression free at the end of treatment was significantly higher for those taking Wellbutrin XL than for those taking placebo; for all 3 studies combined, the overall rate of patients who were depression free at the end of treatment was 84% for persons taking Wellbutrin XL compared with 72% among those in the placebo group.
Wellbutrin XL's labeling includes a black box warning concerning the increased risk of suicidal thoughts and behavior in pediatric patients treated with antidepressant medications. As with all antidepressants, Wellbutrin XL labeling includes a medication guide advising that pediatric patients taking antidepressants should be watched closely for these serious symptoms. Other important adverse effects to watch for with Wellbutrin XL, especially shortly after the initiation of the treatment, include agitation, anxiety, and insomnia. Wellbutrin was safe and well tolerated by patients in the SAD trials.
In the treatment of SAD, Wellbutrin XL is indicated only for patients who meet strict diagnostic criteria of seasonal major depressive episodes. Such patients have a pattern of recurrent, clinically significant depressive symptoms with associated impairment of functioning. The clinician and patient should carefully assess the potential risks and benefits when considering treatment with Wellbutrin XL for SAD.
For more information about Wellbutrin XL, including full prescribing information, visit wellbutrin-xl.com.
June 12, 2006
ST. LOUIS (MD Consult) - Merck/Schering-Plough Pharmaceuticals announced on June 9, 2006, that the US Food and Drug Administration has approved Zetia (ezetimibe) for use, along with diet, in combination with fenofibrate for the reduction of elevated total cholesterol and low-density lipoprotein (LDL) cholesterol in patients with mixed hyperlipidemia, when diet alone is not enough. Zetia is the first in a class of cholesterol-lowering agents that inhibits the intestinal absorption of cholesterol.
With this new indication, Zetia offers patients with mixed hyperlipidemia another treatment option when it is prescribed in combination with fenofibrate. Fenofibrate is commonly used along with diet to treat hyperlipidemia and has proven efficacy in lowering triglyceride levels and increasing high-density lipoprotein (HDL) cholesterol. The use of Zetia with fibrates other than fenofibrate is not recommended until use in patients is studied.
Mixed hyperlipidemia is a metabolic disorder characterized by elevated LDL cholesterol, elevated triglycerides, and reduced levels of HDL cholesterol.
FDA approval was granted on the basis of the results from a clinical trial that showed combination therapy of 10 mg of Zetia coadministered with 160 mg of fenofibrate significantly reduced LDL cholesterol levels compared with either treatment alone (P <.001). Patients in a 12-week study who were coadministered Zetia 10 mg and fenofibrate 160 mg (n = 183) showed a 20% reduction in LDL cholesterol levels compared with a 6% reduction in LDL cholesterol levels with 160 mg fenofibrate as monotherapy (n = 188) and a 13% reduction in LDL cholesterol levels with 10 mg Zetia as monotherapy (n = 185).
The study consisted of patients with mixed hyperlipidemia; 625 patients were treated for up to 12 weeks, and 576 of these patients continued treatment for up to an additional 48 weeks. The changes in lipid end points after an additional 48 weeks of treatment with Zetia coadministered with fenofibrate or with fenofibrate alone were consistent with the 12-week data.
In this study, Zetia coadministered with fenofibrate appeared to be well tolerated. For patients taking Zetia and fenofibrate in whom cholelithiasis is suspected, physicians should perform gallbladder studies and consider alternative lipid-lowering therapy. Although this study was not designed to compare how often infrequent events occurred, the rates for cholecystectomy were 0.6% for fenofibrate alone and 1.7% for Zetia and fenofibrate together.
Zetia, along with diet, is indicated for use either by itself or together with statins or fenofibrate in patients with high cholesterol to reduce LDL cholesterol and total cholesterol when the response to diet and exercise has been inadequate. Zetia, which works in the digestive tract, is complementary to the class of cholesterol-lowering agents known as statins, which work in the liver to reduce the production of cholesterol. Alone or in combination with statins, Zetia has been proven to significantly improve LDL cholesterol levels. The drug has not been shown to prevent heart disease or heart attacks when used either alone or in addition to a statin or fenofibrate.
Zetia should not be taken by persons who are allergic to any of its ingredients. When prescribed with a statin, the medication should not be taken by women who are nursing or pregnant or who may become pregnant, nor by anyone with active liver disease. Statins should not be taken by anyone with these conditions. Blood tests may be required to check a patient's liver before therapy with Zetia and a statin is initiated. To date, no adequate and well-controlled studies of Zetia in pregnant women have been performed.
Because of the unknown effects of increased exposure to Zetia in patients with moderate or severe hepatic insufficiency, the medication is not recommended in these patients. In clinical trials, an increased incidence of myopathy or rhabdomyolysis was not found in association with Zetia; however, myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-lowering drugs.
When Zetia was coadministered with a statin, consecutive elevations in liver enzymes (more than 3 times the upper limit of normal) were slightly higher than those with the statin alone (1.3% vs 0.4%). These elevations were generally asymptomatic and returned to baseline after discontinuation of therapy or with continued treatment. When Zetia was coadministered with fenofibrate, consecutive elevations in liver enzyme levels were 2.7% (more than 3 times the upper limit of normal), and elevations were 4.5% in patients treated with fenofibrate alone. Caution should be exercised when initiating therapy with Zetia in patients treated with cyclosporine, particularly in patients with severe renal insufficiency, because blood levels of Zetia in these patients may be increased.
In clinical trials, the most frequent adverse effects for Zetia alone versus placebo included back pain (4.1% vs 3.9%), arthralgia (3.8% vs 3.4%), and fatigue (2.2% vs 1.8%). For Zetia plus statin versus statin or placebo alone, adverse effects were back pain (4.3% vs 3.7% vs 3.5%), abdominal pain (3.5% vs 3.1% vs 2.3%), and fatigue (2.8% vs 1.4% vs 1.9%).
For more information on Zetia, which is marketed as Ezetrol in countries outside the United States, visit zetia.com.
June 12, 2006
ST. LOUIS (MD Consult) - Novartis Pharmaceuticals Corporation announced on June 9, 2006, that it has received marketing approval from the US Food and Drug Administration for 2 new dosing strengths of Lotrel (amlodipine besylate/benazepril hydrochloride), 5/40 mg and 10/40 mg. The new doses combine the calcium channel blocker amlodipine with the highest available dose of the angiotensin-converting enzyme (ACE) inhibitor benazepril.
The addition of the new higher strengths offers expanded dosing flexibility and treatment options for patients whose hypertension has previously been uncontrolled and who may need more powerful antihypertension medication. Lotrel is not indicated for the initial treatment of hypertension. It may, however, be beneficial to a patient if other blood pressure medicines have been ineffective or have caused excessive edema.
Novartis continues to explore Lotrel's clinical potential in the landmark large-scale clinical trial ACCOMPLISH, which is designed to determine whether Lotrel is more effective in preventing cardiovascular disease and death than an ACE/diuretic combination. Results are expected in 2009.
More than 65 million Americans have high blood pressure, according to Novartis. However, nearly 70% of these persons do not have their blood pressure controlled to the recommended level of less than 140/90 mm Hg. According to national guidelines, most patients will require a combination of medications to lower their blood pressure to goal levels.
If pregnancy is detected in a patient receiving Lotrel, the drug should be discontinued because it may cause harm or even death to an unborn child. Furthermore, Lotrel should not be taken by patients who are allergic to any of the ingredients in the product nor to any ACE inhibitor.
Lotrel has been associated with the rare occurrence of potentially dangerous swelling of the mouth and throat. Other associated rarely reported events include angina or myocardial infarction, which have occurred particularly in patients with preexisting severe cardiac disease. Serious adverse effects such as hypotension and kidney problems could occur. The most common adverse effects include cough, headache, edema, and dizziness.
The additional 5/40- and 10/40-mg doses will be available in June 2006, in addition to the already approved dosage strengths 2.5/10, 5/10, 5/20, and 10/20 mg. For important product information, including complete drug labeling, visit lotrel.com.
June 7, 2006
ST. LOUIS (MD Consult) - On June 5, 2006, the US Food and Drug Administration (FDA) approved an application for resumed marketing of Tysabri (natalizumab) subject to a special restricted distribution program. Tysabri is a monoclonal antibody used to treat relapsing forms of multiple sclerosis (MS) to reduce the frequency of exacerbations. The drug is indicated for use as monotherapy because not enough is known about its potential risks when used with other immune-modifying drugs. Tysabri is also indicated for patients who have not responded adequately to, or cannot tolerate, other treatments for MS.
Tysabri was initially approved by the FDA in November 2004 but was withdrawn by the manufacturer, Biogen-Idec, in February 2005, after 3 patients in the drug's clinical trials developed progressive multifocal leukoencephalopathy (PML), a serious and rare viral infection of the brain. Two of the cases were fatal. On the basis of this information, the FDA put clinical trials of the drug on hold in February 2005. The FDA allowed a clinical trial of Tysabri to resume in February 2006 after a reexamination of the patients who had participated in the previous clinical trials, confirming that there were no additional cases of PML.
In March 2006, the FDA consulted with its Peripheral and Central Nervous Systems Drugs Advisory Committee. The committee recommended the creation of a risk-minimization program with mandatory patient registration and periodic follow-up for use with appropriate patients with MS who were potential candidates for Tysabri therapy. The program's purpose was to provide a means to identify, as early as possible, any cases of PML that may occur, and to try to determine the reason the infection occurs. In response, Biogen-Idec submitted to the FDA a risk management plan called the TOUCH Prescribing Program to help ensure safe use of the product.
After a thorough review of the risk management plan and proposed changes to its original marketing application, the FDA determined that Tysabri can be made available under the TOUCH Program with the following main features:
Biogen Idec is the manufacturer and Elan the distributor for Tysabri. Additional information on the TOUCH Prescribing Program is available from the companies by calling 1-800-456-2255.
To read more about natalizumab, including a detailed product history, the updated Tysabri drug label, and a patient information sheet, visit fda.gov/cder/drug/infopage/natalizumab/default.htm.
June 5, 2006
ST. LOUIS (MD Consult) - Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc, announced on April 26, 2006, that Nexavar (sorafenib) tablets have been granted orphan drug status for the treatment of hepatocellular carcinoma (HCC) by the US Food and Drug Administration (FDA).
In the United States, the FDA's orphan drug designation aims to encourage the development of drugs involved in the diagnosis, prevention, or treatment of a medical condition affecting fewer than 200,000 people in the country. The designation grants US market exclusivity to a drug for a particular indication for a 7-year period if the sponsor complies with certain FDA specifications. The designation does not shorten the duration of the regulatory review and approval process.
In a phase II single-agent study, 43% of patients treated with Nexavar experienced stable disease for at least 4 months and an additional 9% of patients experienced tumor shrinkage. The most common grade-3 or -4 drug-related toxicities were fatigue (9.5%), diarrhea (8%), and hand-foot skin reaction (5%). The toxicity profile of Nexavar was similar to that previously reported in a safety analysis in patients with renal cell carcinoma.
A phase III trial of Nexavar administered as a single agent is ongoing. It is designed to measure differences in overall survival, time-to-symptom progression, and time-to-tumor progression of Nexavar versus placebo in patients with HCC. A randomized phase II trial for patients with liver cancer designed to evaluate the efficacy of Nexavar in combination with the chemotherapeutic agent doxorubicin is also ongoing.
Nexavar is the first oral multi-kinase inhibitor that targets both the tumor cell and tumor vasculature. In preclinical models, Nexavar targeted members of 2 classes of kinases known to be involved in both tumor cell proliferation and tumor angiogenesis. These kinases included RAF kinase, VEGFR-2, VEGFR-3, PDGFR-ß, KIT, and FLT-3.
Nexavar is currently in phase III clinical trials for the treatment of liver cancer, metastatic melanoma, and non–small cell lung cancer and has been studied in more than 20 tumor types and in more than 8,000 patients in clinical trials. In December 2005, Nexavar received approval from the FDA to treat patients with advanced renal cell carcinoma.
HCC, also known as primary liver cancer, is the most common form of liver cancer and is responsible for 80% of the primary malignant liver tumors in adults. It is the fifth most common cancer in the world. HCC disproportionately affects men, with 4 times as many men developing the disease as women. In 2002, approximately 626,000 cases of HCC were reported worldwide (15,000 in the United States and 53,600 in Europe), and more than 600,000 deaths caused by HCC (about 13,000 Americans and 57,000 Europeans) were reported. The 5-year relative survival rate is about 7%.
Hypertension may occur early in the course of therapy with Nexavar, and the blood pressure of persons taking this medication should be monitored weekly during the first 6 weeks of therapy and treated as needed. Incidence of bleeding regardless of causality was 15% for Nexavar versus 8% for placebo, and the incidence of treatment-emergent cardiac ischemia/infarction was 2.9% for Nexavar versus 0.4% for placebo. The most common treatment-emergent adverse events with Nexavar were diarrhea, rash/desquamation, fatigue, hand-foot skin reaction, alopecia, and nausea. Grade-3 and -4 adverse events were 38% for Nexavar versus 28% for placebo.
Women of child-bearing potential who are taking this drug should be advised to avoid becoming pregnant and advised against breast-feeding during the course of therapy. In cases of any severe or persistent adverse effects, temporary treatment interruption, dose modification, or permanent discontinuation should be considered.
For full US prescribing information for Nexavar, visit nexavar.com or call 1-866-NEXAVAR (1-866-639-2827).
May 31, 2006
ST. LOUIS (MD Consult) - On May 25, 2006, Cubist Pharmaceuticals, Inc, announced that the US Food and Drug Administration (FDA) has approved the supplemental new drug application for Cubicin (daptomycin for injection) as once-daily therapy at 6 mg/kg for the treatment of Staphylococcus aureus bacteremia, including right-sided endocarditis caused by methicillin-susceptible S aureus (MSSA) and methicillin-resistant S aureus (MRSA). Cubist estimates that these infections account for 30,000 deaths in the United States alone each year.
Cubicin will be the only intravenous antibiotic approved for this indication, which was granted on the basis of the results of a prospective, randomized, controlled registration trial.
The FDA decision follows the positive recommendations of the Anti-infective Drugs Advisory Committee, which at its March 6, 2006, meeting reviewed data from a landmark phase 3 trial that studied the efficacy and safety of Cubicin at 6 mg/kg once a day as monotherapy versus dual-therapy standard of care therapy (ie, semi-synthetic penicillin plus initial gentamicin for infections caused by MSSA or vancomycin plus initial gentamicin for infections caused by MRSA) for the treatment of S aureus bacteremia and endocarditis.
Cubicin was originally approved on September 12, 2003, at 4 mg/kg intravenously once daily for the treatment of complicated skin and skin structure infections caused by gram-positive organisms, including both MSSA and MRSA.
Cubicin is not indicated for the treatment of pneumonia. Patients with persisting or relapsing S aureus infection or poor clinical response should be tested with repeated blood cultures. If a culture has positive test results for S aureus, minimum inhibitory concentration susceptibility testing of the isolate should be performed using a standardized procedure, and a diagnostic evaluation should be performed to rule out sequestered foci of infection.
Most adverse events reported in clinical trials were mild to moderate in intensity. The most common were anemia, constipation, diarrhea, nausea, vomiting, injection site reactions, and headache.
For more details, including full prescribing information, visit cubicin.com.
May 30, 2006
ST. LOUIS (MD Consult) - Celgene Corporation announced on May 25, 2006, that the US Food and Drug Administration (FDA) has granted accelerated approval to its supplemental new drug application for Thalomid (thalidomide) in combination with dexamethasone for the treatment of newly diagnosed multiple myeloma. The effectiveness of Thalomid is established on the basis of response rates; there are no controlled trials demonstrating a clinical benefit, such as an improvement in survival.
Multiple myeloma is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. The malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors. The cause of the disease remains unknown.
Multiple myeloma is the second most common blood cancer in the United States, affecting approximately 50,000 persons. About 14,600 new cases of multiple myeloma are diagnosed each year, and it is thought that about 12,000 Americans will die of this disease in 2006.
The manufacturer states that thalidomide can cause severe birth defects or death to an unborn baby if taken during pregnancy. Thalidomide should not be used by women who are pregnant or who could become pregnant while taking the drug. Even a single dose, one capsule (50, 100, or 200 mg), taken by a pregnant woman can cause severe birth defects. Because thalidomide is present in the semen of male patients, any male taking thalidomide must always use a latex condom during sexual contact with women of childbearing potential, even if he has undergone a successful vasectomy.
This safety concern prompted the formation of a special restricted distribution program, the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.). Thalidomide can only be marketed under this program, and only registered prescribers and pharmacists may dispense the drug. In addition, patients must be advised of, agree to, and comply with the requirements of S.T.E.P.S.
The use of Thalomid in multiple myeloma results in an increased risk of venous thromboembolic events, such as deep venous thrombosis and pulmonary embolus. This risk increases significantly when thalidomide is used in combination with standard chemotherapeutic agents including dexamethasone. In one controlled trial, the rate of venous thromboembolic events was 22.5% in patients receiving thalidomide in combination with dexamethasone compared with 4.9% in patients receiving dexamethasone alone (P = .002). Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Preliminary data suggest that patients who are appropriate candidates may benefit from concurrent prophylactic anticoagulation or aspirin treatment.
Thalidomide is contraindicated in patients who have demonstrated hypersensitivity to the drug and its components. It is not known whether Thalomid is excreted in human milk. Because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or taking the drug, considering the importance of the drug to the mother.
Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common, potentially severe, adverse effect of treatment with thalidomide that may be irreversible. Decreased white blood cell counts, including neutropenia, have been reported in the clinical use of thalidomide. In placebo-controlled clinical trials of HIV-seropositive patient populations, there have been reports of increased plasma HIV RNA levels associated with thalidomide therapy.
The most frequently reported adverse events were constipation (55%), sensory neuropathy (54%), confusion (28%), hypocalcemia (72%), edema (57%), dyspnea (42%), thrombosis/embolism (23%), and rash/desquamation (30%). These events occurred in more than 20% of patients and with a frequency more than 10% in patients treated with Thalomid/dexamethasone compared with dexamethasone alone. Patients should be advised about these associated adverse events and should be routinely monitored by a physician during treatment with thalidomide. Patients should not extensively handle or open thalidomide capsules, and storage of capsules in blister packs should be maintained until ingestion.
Thalomid received FDA clearance on July 16, 1998, for the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) and as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.
For more information, including full prescribing information, visit thalomid.com.
May 22, 2006
ST. LOUIS (MD Consult) - On May 19, 2006, the US Food and Drug Administration (FDA) approved Remicade (infliximab) to treat children with active Crohn’s disease. Remicade is a genetically engineered monoclonal antibody that reduces inflammation by blocking the action of tumor necrosis factor alpha (TNF-α). The drug was initially approved in 1998 to treat Crohn’s disease in adults.
Dr Steven Galson, director of the FDA's Center for Drug Evaluation and Research, noted that there have been no satisfactory treatments for children with Crohn’s disease who have moderate to severe disease activity despite traditional or conventional therapies. Crohn’s disease can cause diarrhea, cramping, abdominal pain, and gastrointestinal bleeding, and in some cases creates fistulas leading from the intestine to the skin.
"Remicade is not a cure, but it provides a much-needed option for reducing the symptoms and inducing and maintaining disease remission in children who have no other safe and effective therapy," Galson said. "We believe that the potential benefits of this product outweigh the risks that are known and have been carefully evaluated."
The approval was based on data from the phase 3 REACH (a Randomized, Multicenter, Open-label Study to Evaluate the Safety and Efficacy of Anti-TNF Monoclonal Antibody Remicade in Pediatric Subjects with Moderate to Severe Crohn’s Disease) trial involving 112 children aged 6 to 17 years. This study demonstrated that 88.4% of pediatric patients with moderately to severely active Crohn’s disease who had an inadequate response to conventional therapy achieved clinical response at week 10 when treated with Remicade. Additionally, the patients who responded to Remicade therapy were then randomly assigned to receive maintenance therapy every 8 weeks or every 12 weeks. In the every-8-weeks maintenance treatment group, nearly two thirds (64%) of the patients were in clinical response at 1 year and more than half were in clinical remission at the end of 1 year (56%).
The proportion of these patients who achieved clinical response compared favorably with the proportion of adults in an earlier Remicade study in adult Crohn’s disease, and the pediatric trial’s results showed no new safety concerns not already expressed in the product's current label.
In general, the safety profile for Remicade in the pediatric trial was similar to the data that was presented at an FDA Arthritis Advisory Committee meeting in March 2003, and that dealt with the extent to which anti-TNF therapies may increase the risk of serious infections and malignancies, such as sepsis and pneumonia in certain patients.
These risks, which are described in a study in the May 17, 2006, issue of The Journal of the American Medical Association, are included in the current labels for all approved TNF-α–blocking agents, including Remicade.
More recently, the FDA has received rare postmarketing reports of an aggressive and often fatal type of T-cell lymphoma (hepatosplenic T-cell lymphoma) in adolescent and young adult patients with the Crohn’s disease. In most but not all cases, these patients were treated with standard immunosuppressive therapies (ie, azathioprine or 6-mercaptopurine) in combination with Remicade. The FDA is working with the manufacturer to address this risk by updating the Warnings sections of the Remicade label.
The FDA has declared that it continues to actively and carefully monitor the safety experience with Remicade and similar therapies in an effort to maximize their benefits yet limit, to the degree possible, the potential for very serious toxicities.
The complete drug label for Remicade, updated May 19, 2006, is available at fda.gov/cder/foi/label/2006/103772s5138lbl.pdf. The medication is manufactured by Centocor.
May 18, 2006
ST. LOUIS (MD Consult) - Barr Pharmaceuticals, Inc, announced on May 12, 2006, that its subsidiary, Barr Laboratories, Inc, received approval from the US Food and Drug Administration (FDA) to manufacture and market Claravis (isotretinoin capsules USP), 30 mg. The company’s full line of isotretinoin product strengths now includes Claravis in doses of 10, 20, 30, and 40 mg.
Claravis is indicated for the treatment of severe recalcitrant nodular acne. Because of the significant adverse effects associated with its use, Claravis should be reserved for patients with severe nodular acne that is unresponsive to conventional therapy, including systemic antibiotics.
In addition, for female patients of childbearing potential, Claravis is indicated only for those persons who are not pregnant and will not become pregnant. There is an extremely high risk that severe birth defects will result if pregnancy occurs while a patient is taking isotretinoin in any amount, even for a short period of time. Any fetus exposed to the drug during pregnancy can potentially be affected. There are no accurate means of determining whether an exposed fetus has been affected.
Because of this toxicity, isotretinoin can only be marketed under a special restricted distribution program called iPLEDGE. Under this program, prescribers must be registered and activated with the iPLEDGE program and can prescribe isotretinoin only to registered patients who meet all the requirements of the program. Isotretinoin can be dispensed only by pharmacies registered and activated with iPLEDGE, and these pharmacies can only receive isotretinoin from wholesalers who are likewise registered.
Patients taking isotretinoin have been known to become depressed or to develop other serious mental health problems. Some persons taking the drug have had thoughts of self-harm or suicidal ideation. Some have attempted or committed suicide. There have been reports that persons taking isotretinoin were aggressive or violent. It has not been determined whether isotretinoin caused these problems or behaviors. Isotretinoin use has been associated with pseudotumor cerebri (benign intracranial hypertension), which is caused by increased pressure on the brain. This condition may occur more often in patients also taking tetracycline.
Patients should be aware of other serious adverse effects, including problems with the pancreas, liver, stomach, bones, muscles, hearing, vision, lipids, allergic reactions, blood sugar, or red and white blood cells. The most common, less serious adverse events include dry skin, chapped lips, dry eyes, and dry nose that may lead to nosebleeds. Patients should be advised about these adverse events and should be routinely monitored by a doctor during treatment with isotretinoin.
For more information, contact Barr Laboratories at barrlabs.com or 1-800-222-0190.
May 9, 2006
ST. LOUIS (MD Consult) - On March 24, 2006, two additional dosages (3 and 4 mg) of Risperdal M-Tab (risperidone), the fast-dissolving form of the antipsychotic medication Risperdal, are now available by prescription. Risperdal is indicated for the treatment of schizophrenia and for the short-term treatment of bipolar mania in acute manic or mixed episodes of bipolar I disorder (ie, manic depression).
Risperdal M-Tabs dissolve in seconds when placed on the tongue. This is a prescribing option for health care professionals with patients who hide medication in their mouths to avoid taking it or patients who have difficulty swallowing pills.
Schizophrenia affects more than 2 million Americans and is characterized by symptoms such as hallucinations, delusions, social withdrawal, and a diminished capacity for organized thought.
Bipolar mania is one aspect of bipolar disorder. Persons with bipolar mania may experience high levels of energy, unrealistic thoughts or ideas, and reckless or impulsive behavior. Of the more than 3 million Americans believed to have bipolar disorder, two thirds may go underdiagnosed and undertreated, according to the National Alliance for the Mentally Ill.
Risperdal has been marketed in tablet form in the United States since 1994. It is available as a standard, oral tablet in doses of 0.25, 0.5, 1, 2, 3, and 4 mg; as a quick-dissolving tablet (Risperdal M-Tab) in doses of 0.5, 1, and 2 mg (plus the new 3- and 4-mg doses); and as an oral solution in a 1.0-mg/mL dose. Risperdal Consta (risperidone) Long-Acting Injection is available in 25-, 37.5-, and 50-mg strengths and is given by intramuscular injection every 2 weeks.
As with all other psychotropic medications, Risperdal is associated with adverse effects. Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared with placebo. Neither Risperdal nor Risperdal Consta is approved for the treatment of patients with dementia-related psychosis.
The most common adverse effects that occurred with Risperdal in the treatment of schizophrenia were anxiety, sleepiness, restlessness, tremors and muscle stiffness, dizziness, constipation, nausea, indigestion, runny nose, rash, and rapid heartbeat. In the treatment of bipolar mania either alone or in combination with a mood stabilizer (lithium or valproate), the most common adverse effects were sleepiness, muscle stiffness, restlessness, tremor, indigestion, nausea, abnormal vision, muscle aches, dizziness, runny nose, diarrhea, increased saliva, stomach pain, and urinary incontinence. In a study of persons taking Risperdal Consta, the most common adverse effects were sleepiness, restlessness, tremors and muscle stiffness, nausea, constipation, dry mouth, fatigue, and weight increase. In addition, tardive dyskinesia can be caused by all medications of this type.
Another rare but serious adverse effect that has been reported with this kind of medicine, including Risperdal, is neuroleptic malignant syndrome (NMS). NMS is characterized by muscle rigidity and fever and can be serious.
Studies suggest an increased risk of elevated blood sugar–related adverse effects, sometimes potentially fatal, in patients treated with this class of medications, including Risperdal. Some persons taking this medication may require regular blood sugar testing.
Another rare but serious adverse effect that has been reported with this kind of medicine, including Risperdal, is neuroleptic malignant syndrome (NMS). NMS is characterized by muscle rigidity and fever and can be serious.
Complete US prescribing information and other information about Risperdal is available at janssen.com.
April 20, 2006
ST. LOUIS (MD Consult) - Sanofi-aventis announced on March 23, 2006, that the US Food and Drug Administration (FDA) has approved Taxotere (docetaxel) Injection Concentrate, in combination with cisplatin and 5-fluorouracil, for the treatment of advanced gastric cancer, including cancer of the gastroesophageal junction, in patients who have not received prior chemotherapy for advanced disease.
The FDA based its decision on results from the Tax 325 study, the largest international phase III clinical trial in previously untreated advanced stomach cancer, involving 445 patients. Patients treated with the Taxotere-based chemotherapy regimen (Taxotere, cisplatin, and 5-fluorouracil; TCF) experienced a significant 23% reduction in the risk of death compared with patients who received a current standard treatment of cisplatin and 5-fluorouracil (CF) (median follow-up, 23 months). The median overall survival was significantly longer with the TCF regimen (9.2 vs 8.6 months; P < .02), with a hazard ratio of 1.29 (95% confidence interval [CI], 1.04-1.61). In addition, the time to disease progression was nearly 2 months longer in the TCF arm (5.6 vs 3.7 months; P = .0004), with a hazard ratio of 1.47 (CF/TCF 95% CI, 1.19-1.83).
Locally advanced or metastatic stomach cancer has a poor prognosis with a low long-term survival rate of only 11.5%. This study was undertaken to evaluate the benefits of adding Taxotere to a standard chemotherapy regimen. The primary study end point was time to tumor progression, which was significantly improved with TCF therapy (5.6 months) compared with standard treatment (3.7 months) with a 32% reduction in the risk of progression (log-rank test, P = .0004). The main secondary end point was to detect a statistically significant increase in overall survival. Other secondary objectives included response rate, time to treatment failure, duration of response, safety profiles, quality of life, and disease-related symptoms.
In total, 81.4% of the patients experienced at least one grade-3 to -4 (severe) adverse effect with the Taxotere-based regimen versus 75.4% in the control arm, with neutropenia being the most common grade-3 to -4 adverse effect in the TCF regimen. The most common (all-grade) adverse effects associated with the Taxotere-based regimen were anemia, neutropenia, diarrhea, and nausea. The most common (all-grade) adverse effects associated with the cisplatin and 5-fluorouracil arm were anemia, neutropenia, nausea, and vomiting. Primary prophylactic use of growth factor support (ie, granulocyte-colony stimulating factor; G-CSF) was not allowed per the study protocol. G-CSF is a bone marrow growth factor that may be administered to reduce febrile neutropenia in patients receiving myelosuppressive chemotherapy. In the TCF arm of the study, febrile neutropenia and/or neutropenic infection occurred in 12% of patients receiving secondary prophylactic G-CSF compared with 28% who did not, which represents a 57% reduction.
With this new indication, Taxotere is now approved in the United States for 6 indications in 4 different tumor types. The 3 types of tumors other than gastric cancer for which the drug may be indicated include breast cancer, non-small cell lung cancer, and prostate cancer.
According to Donna Vining, President of Gastro Esophageal Cancer Foundation, Inc, stomach cancer accounts for more than 700,000 deaths globally each year. It is the fourth most common type of cancer worldwide, with more than 934,000 new patients every year. There were about 22,800 new cases of stomach cancer in the United States in 2005. In Europe, this number is over 143,000 patients. At diagnosis, most patients with stomach cancer have advanced disease with an expected 2-year survival rate of only 11.5%.
For more details on Taxotere, including full prescribing information, visit taxotere.com.
April 18, 2006
ST. LOUIS (MD Consult) - Amgen announced on March 27, 2006, that the US Food and Drug Administration (FDA) has approved every-3-week dosing of Aranesp (darbepoetin alfa) for the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies. Aranesp is the only erythropoiesis-stimulating agent approved by the FDA for administration every 3 weeks.
"In clinical studies, Aranesp has proven effective in reducing the incidence of red blood cell transfusions and boosting and maintaining target hemoglobin levels when administered every 3 weeks," said Ralph Boccia, MD, director of clinical research, Center for Cancer and Blood Disorders, Bethesda, Md.
The updated Aranesp label includes a recommended starting dose of 500 mcg once every 3 weeks in addition to the recommended starting dose of 2.25 mcg/kg once weekly. The new dosing recommendations are the result of a randomized, double-blind, phase III study that evaluated the safety and effectiveness of every-3-week administration of Aranesp. Patients with chemotherapy-induced anemia were randomly assigned to receive 500 mcg of Aranesp every 3 weeks (n = 353) or 2.25 mcg/kg (n = 352) administered weekly for up to 15 weeks. In both groups, the starting dose was reduced by 40% if hemoglobin levels increased by more than 1 g/dL in a 14-day period, and Aranesp was withheld if hemoglobin levels exceeded 13 g/dL. More than 70% of patients in the every-3-week group required dose reductions, resulting in an average weekly dose of 125 mcg for the patients in this group.
Aranesp was approved by the FDA in September 2001 for the treatment of anemia associated with chronic renal failure for patients both receiving and not receiving dialysis. In July 2002, Aranesp was approved by the FDA for the treatment of chemotherapy-induced anemia in patients with non-myeloid malignancies.
Use of Aranesp is contraindicated in patients with uncontrolled hypertension. Erythropoietic therapies may increase the risk of thrombotic events and other serious events. The target hemoglobin level should not exceed 12 g/dL. If the hemoglobin increase exceeds 1.0 g/dL in any 2-week period, dose reductions are recommended. In a study with another erythropoietic product, where the target hemoglobin was 12 to 14 g/dL, an increased incidence of thrombotic events, disease progression, and mortality was seen.
Cases of pure red cell aplasia and of severe anemia, with or without other cytopenias associated with neutralizing antibodies to erythropoietin, have been reported in patients treated with Aranesp. This has been reported predominantly in patients with chronic renal failure receiving Aranesp by subcutaneous administration. A sudden loss of response to Aranesp, accompanied by severe anemia and low reticulocyte count, should be evaluated. If anti-erythropoietin antibody-associated anemia is suspected, withhold Aranesp and other erythropoietic proteins. Use of Aranesp should be permanently discontinued in patients with antibody-mediated anemia. Patients should not be switched to other erythropoietic proteins.
The most commonly reported adverse effects in clinical trials were fatigue, edema, nausea, vomiting, diarrhea, fever, and dyspnea.
In 2006, an estimated 1.3 million cancer patients will undergo chemotherapy in the United States; approximately 800,000 (67%) will become anemic. Chemotherapy can reduce the bone marrow's ability to produce red blood cells. More than half of patients receiving chemotherapy report that fatigue, a common symptom of anemia, affects their daily lives more than any other adverse effect of treatment, including nausea, pain, and depression.
Although anemia is one of the most common side effects of chemotherapy, it is often not recognized and frequently under-treated, despite treatments that have been available for more than a decade. According to Amgen, approximately half of patients with a hemoglobin level less than the recommended target level of 11 to 12 g/dL in the National Comprehensive Cancer Network guidelines for "Cancer and Treatment-Related Anemia" are never treated with erythropoietic therapy.
Anemia can have a negative impact on patients and their daily activities. This can manifest as fatigue, trouble breathing or rapid heartbeat, chest pain, dizziness or lightheadedness, inability to concentrate, headache, inability to stay warm, loss of sex drive, or pale skin. Reducing the number of visits required for anemia treatment with less frequent dosing and trying to synchronize anemia treatment with other naturally occurring visits could reduce the amount of patient and caregiver time required for anemia treatment.
For more information on Aranesp, including full prescribing information, call 1-800-772-6436 or visit aranesp.com.
April 5, 2006
ST. LOUIS (MD Consult) - GlaxoSmithKline announced on March 23, 2006, that the US Food and Drug Administration (FDA) has approved the use of Flovent HFA (fluticasone propionate HFA) in children 4 to 11 years of age with asthma. Flovent HFA, now available in an environmentally friendly aerosol formulation, is an inhaled corticosteroid that helps prevent airway inflammation associated with asthma.
Flovent HFA is a reformulation of the asthma medication Flovent (fluticasone propionate) Inhalation Aerosol that uses hydrofluoroalkane (HFA-134a) to propel the medication out of the canister and into the lungs. Hydrofluoroalkane replaces the chlorofluorocarbon (CFC) propellant and is more ozone friendly.
In clinical trials, Flovent HFA, 88 µg twice daily, improved peak expiratory flow, reduced daily rescue albuterol use, and reduced nighttime awakenings caused by asthma compared with placebo over 12 weeks in children 4 to 11 years of age with persistent asthma. Adverse events associated with Flovent HFA were similar to those experienced with placebo. Additional safety and efficacy of Flovent HFA for children aged 4 to 11 years is supported by clinical studies in patients 12 years of age and older, pharmacokinetic studies in patients 4 to 11 years of age, and the established efficacy of fluticasone proprionate in other formulations for patients 4 to 11 years of age.
Flovent HFA was first approved by the FDA in May 2004 for patients 12 years and older. The drug is also indicated for patients requiring oral corticosteroid therapy for asthma. Flovent HFA does not replace fast-acting inhalers for sudden symptoms.
According to the US Centers for Disease Control and Prevention, 9 million children younger than 18 years have been diagnosed with asthma, and 3.6 million of those children are between the ages of 5 and 11 years. A recent survey of children with asthma in America showed that 42% of children with asthma had some form of urgent or emergency care visit for their asthma in the past year. More than half of children with asthma have experienced an asthma attack so severe that they had to seek immediate care in an emergency department or from a doctor. And more than one fourth of children with asthma have experienced an asthma attack severe enough so as to require hospitalization. Additionally, children with asthma miss more than 12 million school days every year, making asthma the number 1 cause of school absences attributed to chronic conditions.
For more information on GlaxoSmithKline, including full prescribing information for Flovent HFA, visit us.gsk.com/products/assets/us_flovent.pdf.
April 3, 2006
ST. LOUIS (MD Consult) - On March 31, 2006, Astellas Pharma US, Inc, announced that the US Food and Drug Administration (FDA) has granted approval for the use of Prograf (tacrolimus) as an immunosuppressant to prevent organ rejection in patients who have received a heart transplant. Prograf was previously approved for a similar indication involving kidney and liver transplants.
The FDA’s review of Prograf for use in patients undergoing heart transplant was based on 2 open-label, randomized, comparative clinical studies—1 based in the United States and one based in Europe. The studies represented a total of 645 heart transplant recipients and evaluated the safety and efficacy of Prograf-based versus cyclosporine-based immunosuppression in primary orthotopic heart transplantation. In a phase 3 study conducted in Europe, 314 patients received a regimen of antibody induction, corticosteroids, and azathioprine in combination with Prograf or cyclosporine modified for 18 months. In a 3-arm study conducted in the United States, 331 patients received corticosteroids and Prograf plus sirolimus, Prograf plus mycophenolate mofetil (MMF), or cyclosporine modified plus MMF for 1 year.
In the European phase 3 study, patient/graft survival 18 months after transplant was similar between treatment arms: 91.7% in the tacrolimus group and 89.2% in the cyclosporine group. In the US study, patient and graft survival at 12 months was similar, with 93.5% survival in the Prograf plus MMF group and 86.1% survival in the cyclosporine modified plus MMF group.
Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should prescribe Prograf. Insulin-dependent posttransplant diabetes mellitus was reported in 13% and 22% of Prograf-treated heart transplant patients in the US and European studies, respectively, but was reversible in some patients. Black and Hispanic patients undergoing kidney transplant were at an increased risk for posttransplant diabetes mellitus. The more common adverse reactions in Prograf-treated heart transplant recipients were abnormal renal function, hypertension, diabetes mellitus, cytomegalovirus infection, tremor, hyperglycemia, leukopenia, infection, and hyperlipemia.
Prograf is contraindicated in patients with a hypersensitivity to tacrolimus. Prograf injection is contraindicated in patients with a hypersensitivity to castor oil. The safety and efficacy of the use of tacrolimus with sirolimus has not been established.
For more details, including full prescribing information for Prograf, visit prograf.com/Full_Prescribing_Information.htm.
April 3, 2006
ST. LOUIS (MD Consult) - Genentech, Inc, and Biogen Idec, Inc, announced on February 28, 2006, that the US Food and Drug Administration (FDA) has approved the therapeutic antibody Rituxan (rituximab) in combination with methotrexate (MTX) to reduce signs and symptoms in adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to 1 or more tumor necrosis factor antagonist therapies.
Rituxan is the first treatment for RA that selectively targets immune cells known as CD20-positive B cells. Through this mechanism of action, Rituxan may affect multiple pathways by which B cells are believed to contribute to the initiation and development of RA.
The FDA based its approval decision for Rituxan for RA on data from 3 randomized, double-blind, placebo-controlled studies of patients with active RA. Results of the pivotal phase III trial known as REFLEX showed that a significantly greater proportion of patients who received a single treatment course of 2 infusions of Rituxan (1,000 mg on days 1 and 15) with a stable dose of MTX achieved American College of Rheumatology (ACR) 20, 50, and 70 response rates compared with patients who received placebo and MTX. The study included patients with active RA who had an inadequate response or were intolerant to prior treatment with 1 or more tumor necrosis factor antagonist therapies and current MTX therapy.
ACR 20, ACR 50, and ACR 70 responses indicate a 20%, 50%, and 70% improvement in the number of swollen and tender joints, respectively, as well as a 20%, 50%, and 70% improvement compared with baseline in 3 of 5 disease-activity measures: patient assessment, physician assessment, pain scale, Health Assessment Questionnaire, and the value for 1 acute phase reactant (ie, erythrocyte sedimentation rate or C-reactive protein).
At 24 weeks, patients receiving Rituxan displayed clinically and statistically significant improvements in RA signs and symptoms, including pain and disability. In patients receiving Rituxan:
Rituxan was also shown to reduce biologic markers of inflammation.
In REFLEX, the most frequently reported adverse events that occurred with Rituxan were primarily associated with infusion. Serious adverse events occurred in 7% of patients receiving Rituxan and MTX compared with 10% in patients receiving placebo and MTX. Less than 1% of acute infusion reactions were serious. The incidence of serious infections was 2% in Rituxan-treated patients and 1% in placebo-treated patients. The companies are committed to monitoring long-term safety of Rituxan.
The safety profile of Rituxan has been established in more than 730,000 patient exposures over a period of 8 years. In general, the adverse events observed in patients with RA were similar in type to those seen in patients with non-Hodgkin's lymphoma. The most common adverse events observed in patients treated with Rituxan for RA in clinical trials were infusion reactions and infections. No significant change in average immunoglobulin levels was observed in Rituxan-treated patients in clinical trials. Over 24 weeks of treatment, no increases in hematologic malignancies, demyelinating events, or risk of opportunistic infections (including tuberculosis) were observed in Rituxan-treated patients. Although 5% of Rituxan-treated patients developed human anti-chimeric antibodies, this was not associated with loss of clinical response or additional safety observations.
The majority of patients experience infusion-related symptoms with their first Rituxan infusion. These symptoms include but are not limited to flulike illness, fever, chills/rigors, nausea, urticaria, headache, bronchospasm, angioedema, hypotension, and hypoxia. These symptoms vary in severity and generally are reversible with medical intervention.
Severe infusion reactions have been reported in patients treated with Rituxan, some with fatal outcomes in patients with non-Hodgkin's lymphoma. These severe reactions typically occur during the first infusion. The most severe manifestations and sequelae include pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic and anaphylactoid events. Patients who develop clinically significant infusion reactions should have their Rituxan infusion discontinued and receive medical treatment. Acute renal failure requiring dialysis with instances of fatal outcome has been reported in the setting of tumor lysis syndrome after treatment with Rituxan. Severe mucocutaneous skin reactions, some with fatal outcome, have been reported in association with Rituxan treatment. Patients experiencing a severe mucocutaneous reaction should not receive any further infusions and should seek prompt medical evaluation. Abdominal pain and bowel obstruction and perforation, in some cases leading to death, were observed in patients receiving Rituxan in combination with chemotherapy for diffuse large B-cell, CD20-positive, non-Hodgkin's lymphoma. Other serious or potentially life-threatening adverse reactions that have been reported after Rituxan therapy include hepatitis B reactivation with fulminant hepatitis, other viral infections, hypersensitivity reactions, and cardiac arrhythmias.
Rituxan is a therapeutic antibody that targets and selectively depletes CD20-positive B-cells without targeting stem cells or existing plasma cells. In patients with RA, Rituxan is given as two 1000-mg intravenous infusions separated by 2 weeks, in combination with MTX. It is recommended to administer the steroid methylprednisolone 100 mg intravenously 30 minutes before each infusion.
Rituxan was approved by the FDA in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma. In addition, Rituxan received FDA approval in February 2006 for the treatment of diffuse large B-cell lymphoma in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone or other anthracycline-based chemotherapy regimens in previously untreated patients.
For full Rituxan prescribing information, including the boxed warning, call 1-800-821-8590 or visit gene.com.
March 31, 2006
ST. LOUIS (MD Consult) - On March 29, 2006, the US Food and Drug Administration (FDA) approved the use of Relenza (zanamivir for inhalation) for prophylaxis of influenza in adults and children 5 years of age and older. Relenza, an antiviral medication, was previously approved for the treatment of influenza A and B virus infections in adults and children. This new approval of Relenza provides Americans with another option for the prevention of influenza A and B infections, in addition to the already available Tamiflu (oseltamivir phosphate).
The effectiveness of Relenza in preventing seasonal influenza has been demonstrated in 4 large-scale studies comparing the drug with placebo. In 2 of these trials, the use of the drug substantially reduced the spread of influenza in the participating households in which participants were aged 5 years or older. In both of these trials, the proportion of households that developed symptoms confirmed to be caused by influenza was 19.0% for the placebo group and 4.1% for the Relenza group.
In the other 2 trials, which were conducted in communities experiencing an influenza outbreak, Relenza reduced the incidence of the disease in both young and older populations. In the first study, with participants aged 18 years or older, the proportion of persons who developed symptoms confirmed to be caused by influenza was 6.1% for the placebo group and 2.0% for the Relenza group. The second community study enrolled persons 12 to 94 years of age (56% of whom were older than 65 years). In this trial, the percentage of persons who developed symptoms confirmed to be caused by influenza were reduced from 1.4% of the participants receiving placebo to 0.2% for those who used Relenza.
In all of these studies, the most common events during treatment with Relenza in adults and adolescents were cough, headaches, nausea, vomiting, bronchitis, dizziness, diarrhea, nasal irritation, sinus infections, and infections of the ear, nose, and throat. In children, the most common adverse effects were vomiting, diarrhea, and ear, nose, and throat infections. Less common reported events included rashes and allergic reactions, some of which were severe.
Episodes of bronchospasm, sometimes leading to death, were reported in some patients after the initial approval of Relenza. Most of these patients had asthma or chronic obstructive pulmonary disease. Relenza therefore is not recommended for treatment or prophylaxis of seasonal influenza in persons with underlying airway disease such as asthma or chronic obstructive pulmonary disease.
Relenza has not been proved effective for the treatment of influenza in persons with underlying airway disease, nor for prevention of influenza in nursing homes. The drug is also not a substitute for the influenza vaccine, which is the primary means for preventing influenza. Consumers should continue receiving an annual influenza vaccination according to guidelines on immunization practices.
Relenza is manufactured and distributed by GlaxoSmithKline Inc, based in Research Triangle Park, NC. For more details, including a patient safety leaflet and full prescribing information, visit relenza.com.
March 22, 2006
ST. LOUIS (MD Consult) - On February 1, 2006, Schering-Plough Corporation announced that the US Food and Drug Administration (FDA) has approved Clarinex-D 12 Hour (desloratadine 2.5 mg, pseudoephedrine sulfate USP 120 mg) Extended Release Tablets for the relief of nasal and non-nasal symptoms of seasonal allergic rhinitis, including nasal congestion, in patients 12 years and older.
Clarinex-D 12 Hour will be available nationwide in March 2006, according to the drug's manufacturer. The new formulation uses a bi-layer system that controls the release of the pseudoephedrine component for consistent delivery. The recommended twice-daily dosing of Clarinex-D 12 Hour will help patients control their nasal congestion, along with their sneezing, runny nose, itchy throat, or itchy and watery eyes. Clarinex-D 12 Hour Extended Release Tablets should be administered when the antihistaminic properties of desloratadine and the nasal decongestant properties of pseudoephedrine are desired.
According to the American Academy of Allergy, Asthma & Immunology, seasonal allergies affect an estimated 36 million persons in the United States. Symptoms can have a significant impact on everyday activities at work, school, and leisure. There also is a growing body of evidence that points to an association between allergies and more serious conditions, such as asthma.
The FDA approval made on the basis of results from 2 clinical trials involving 1,248 patients aged 12 to 78 years with seasonal allergic rhinitis, 414 of whom received Clarinex-D 12 Hour tablets. In both 2-week randomized, parallel group trials, the antihistaminic efficacy of Clarinex-D 12 Hour, when symptoms of allergic rhinitis excluding nasal congestion were examined, was significantly greater than that of pseudoephedrine alone during the treatment period. And the decongestant efficacy of Clarinex-D 12 Hour formulation was significantly greater than that of desloratadine alone during the treatment period, according to nasal congestion scores. The data show that Clarinex-D 12 Hour effectively treats nasal congestion and relieves other nasal and non-nasal symptoms of allergic rhinitis.
The most commonly reported adverse events for Clarinex-D 12 Hour Extended Release Tablets compared with desloratadine alone are insomnia (10% vs 3%), headache (8% vs 8%), dry mouth (8% vs 2%), fatigue (4% vs 2%), somnolence (3% vs 4%), pharyngitis (3% vs 3%), and dizzi