Six-month formulation of prostate cancer drug approved in U.S.
Abbott's lipid disorder treatment approved in new formulation
FDA approves Bristol-Myers Squibb antipsychotic to treat bipolar mania
Purdue Pharma L.P.'s Palladone Capsules approved for pain management
Lilly's drug approved for diabetic peripheral neuropathic pain
Pfizer wins FDA approval for drug to treat acute bipolar mania
FDA approves TNF blocker to improve physical function in RA patients
Merck wins approval for initial treatment of severe hypertension
Topical cream approved for treatment of superficial basal cell carcinoma
FDA approves hyperparathyroidism medication for children and teens
FDA approves Bayer's antibiotic to fight multidrug-resistant S pneumoniae
Combination of Proscar and doxazosin approved for treatment of benign prostatic hyperplasia symptoms
FDA approves Biovail's Cardizem LA for the treatment of angina
New dosage of medication for diarrhea-predominant IBS available
Intermittent dosing of SSRI approved for the treatment of pMDD
New formulation of Imitrex available for treatment of migrane
Expanded indications of provigil for those with excessive sleepiness associated with OSAHS and SWSD
GlaxoSmithKline's Lamictal approved for adults with partial seizures
New formulation of Roche's protease inhibitor Invirase approved
FDA approves more environmentally friendly inhaler from Boehringer Ingelheim
Merck wins approval for fungal infection treatment in febrile neutropenic patients
Remicade approved for first-line treatment of rheumatoid arthritis in the U.S.
Biologic approved to induce major clinical response in RA patients
Novartis drug approved to treat chronic idiopathic constipation
Boehringer Ingelheim's NSAID approved for rheumatoid arthritis
FDA approves Pfizer’s Lipitor to lower risk of heart attacks
Combined with paclitaxel, Gemzar wins U.S. approval for treatment of metastatic breast cancer
Taxotere, combined with prednisone, approved for prostate cancer
FDA approves Vitrase for increased dispersion of other drugs
New formulation of Protonix IV stomach acid suppressant wins FDA approval
Merck's arthritis and pain medicine approved for treatment of migraine
pfizer wins FDA approval for 3-day treatment for acute bacterial sinusitis
FDA approves schizophrenia drug for treatment of bipolar disorder
Eloxatin wins FDA approval for first-line treatment of colon cancer
December 28, 2004
ST. LOUIS (MD Consult) - Barr Pharmaceuticals Inc announced on December 21, 2004, that its subsidiary, Duramed Pharmaceuticals, Inc, has received U.S. Food and Drug Administration (FDA) approval for Enjuvia (synthetic conjugated estrogens, B) 0.3-mg and 0.45-mg tablets. The company's 0.625- and 1.25-mg doses of the drug received FDA approval in May 2004.
Enjuvia is the lowest-dose plant-derived, synthetic conjugated estrogen product approved for the treatment of vasomotor symptoms. The tablets contain a blend of 10 synthetic estrogenic substances, including the component delta 8,9-dehydroestrone sulfate. The patent on Enjuvia expires in 2020.
Barr hopes to launch a 0.9-mg tablet of Enjuvia as well; this dose is awaiting FDA approval.
Estrogen use that is unopposed by progestin is associated with an increased risk of endometrial cancer in postmenopausal women with intact uteri. Estrogens should not be used in women with undiagnosed abnormal genital bleeding, known or suspected breast cancer, estrogen-dependent neoplasia, active deep vein thrombosis, thromboembolic disorders, active or recent arterial thromboembolic disease, or pregnancy. Estrogens should not be used for the prevention of cardiovascular disease. The Women's Health Initiative study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis associated with estrogen. Due to these risks, estrogen with or without progestins should be prescribed at the lowest effective dose for the shortest duration, while maintaining consistency with treatment goals and risks for each individual woman; periodic clinical reevaluation of such therapy is also advised.
December 20, 2004
ST. LOUIS (MD Consult) - On December 17, 2004, the U.S. Food and Drug Administration approved a new 500-mg tablet formulation of the HIV protease inhibitor, Invirase (saquinavir mesylate). The dosage and administration for Invirase in adults (older than the age of 16 years) is 1,000 mg twice a day (taken as either two 500-mg tablets or five 200-mg capsules) in combination with ritonavir 100 mg twice a day, to be taken after a meal. The new tablet formulation reduces the pill burden compared with the capsule formulation.
Below is the Dosage and Administration section as it appears in the package insert.
| Dosage and Administration Invirase capsules and Fortovase (saquinavir) soft gelatin capsules are not bioequivalent and cannot be used interchangeably. Invirase may be used only if it is combined with ritonavir because it significantly inhibits saquinavir's metabolism to provide plasma saquinavir levels at least equal to those achieved with Fortovase at the recommended dose of 1,200 mg tid. When using saquinavir as the sole protease inhibitor in an antiretroviral regimen, Fortovase is the recommended formulation (see Clinical Pharmacology: Drug Interactions). Adults (Over the Age of 16 Years)
|
In combination with ritonavir and other antiretroviral agents, Invirase is inicated for the treatment of HIV infection. The efficacy of Invirase with ritonavir or Fortovase (with or without ritonavir coadministration) has not been compared against the efficacy of antiretroviral regimens currently considered standard of care.
Invirase is contraindicated in patients with clinically significant hypersensitivity to saquinavir or to any of the components contained in the capsule. When administered with ritonavir, Invirase is contraindicated in patients with severe hepatic impairment.
Invirase/ritonavir should not be administered concurrently with terfenadine, cisapride, astemizole, pimozide, triazolam, midazolam, or ergot derivatives. Inhibition of CYP3A4 by saquinavir could result in elevated plasma concentrations of these drugs, potentially causing serious life-threatening reactions such as cardiac arrhythmias or prolonged sedation.
Invirase is a product of Roche Laboratories, Inc, of Nutley, New Jersey. Complete product information is available at rocheusa.com/products/invirase/pi.pdf.
December 16, 2004
ST. LOUIS (MD Consult) - Canadian pharmaceutical company QLT Inc announced on December 15, 2004, it has received approval from the U.S. Food and Drug Administration (FDA) for a 6-month formulation of Eligard 45 mg (leuprolide acetate for injectable suspension). The medication is indicated for the palliative treatment of advanced prostate cancer.
Eligard is a luteinizing hormone-releasing hormone (LHRH) agonist. It works by lowering the levels of testosterone in the body, which may result in a reduction of symptoms related to prostate cancer. According to QLT, about 220,000 new cases of prostate cancer are diagnosed each year.
The 6-month Eligard product is the first of its kind to be approved for prostate cancer by the FDA. Eligard is already approved for 1-month (7.5 mg), 3-month (22.5 mg), and 4-month (30 mg) dosages.
Sustained levels of leuprolide decrease testosterone levels to suppress tumor growth in patients with hormone-responsive prostate cancer. Liquid Eligard products are injected subcutaneously with a small-gauge needle, forming a solid implant in the body that slowly releases leuprolide as the implant is bioabsorbed.
Eligard 45 mg, like other hormonal treatments for prostate cancer, causes a transient increase in serum concentrations of testosterone during the first week of treatment. Patients may experience worsening of symptoms or onset of new signs and symptoms during the first few weeks of treatment. Response to Eligard 45 mg should be monitored by measuring serum concentrations of testosterone and prostate-specific antigen periodically.
Eligard is a registered trademark of Sanofi-Aventis and was developed by Vancouver, BC–based QLT's subsidiary QLT USA, Inc. For more information, visit qltinc.com.
November 30, 2004
ST. LOUIS (MD Consult) - Boehringer Ingelheim Pharmaceuticals, Inc, announced on November 18, 2004, that the U.S. Food and Drug Administration had approved Atrovent HFA (ipratropium bromide HFA) Inhalation Aerosol as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Atrovent HFA is a new drug formulation that was developed to provide COPD patients a therapeutic benefit comparable to Atrovent Inhalation Aerosol, a leading treatment for COPD that contained chlorofluorocarbons (CFCs). New Atrovent HFA is formulated with a non-CFC propellant called hydrofluoroalkane (HFA) that was developed in response to the Montreal Protocol on Substances that Deplete the Ozone Layer. The Montreal Protocol, a global agreement to protect the ozone layer, requires the removal of ozone-depleting substances including CFC propellants. The agreement recognizes the special needs of persons throughout the world who have respiratory ailments and require inhalation therapy, as well as the essential role of the pressurized metered-dose inhaler, and therefore grants these products an exemption until they can be replaced by non-CFC alternatives. Boehringer Ingelheim supports the Montreal Protocol and will replace the company's CFC inhalers as the replacement products become available.
In 2005, Boehringer Ingelheim will distribute educational materials about new Atrovent HFA to patients through doctors and pharmacies, while it begins phasing out the Atrovent (CFC) metered-dose inhalers.
A 12-week, double-blind, placebo- and active-controlled trial established the comparable safety and efficacy of Atrovent HFA to Atrovent (CFC). The data were confirmed in a 1-year randomized, open-label, parallel-group multicenter trial comparing Atrovent HFA to Atrovent (CFC). Both products were shown to be safe and effective with no statistically significant differences between them. Both products significantly improved lung function in patients with COPD. The most common drug-related adverse events in clinical trials with Atrovent HFA were dry mouth (1.6%) and taste perversion (bitter taste) (0.9%).
Atrovent HFA is contraindicated in patients with a history of hypersensitivity to ipratropium bromide or other Atrovent HFA components and should also not be taken by patients hypersensitive to atropine or its derivatives.
Atrovent HFA is not indicated for the initial treatment of acute episodes of bronchospasm for which rapid response is required. Immediate hypersensitivity reactions may occur after administration of ipratropium bromide, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.
COPD, the fourth leading cause of death in the United States, is a respiratory disease primarily caused by smoking that is more commonly known as chronic bronchitis or emphysema. There are an estimated 24 million Americans who currently have COPD; however, only 10 million have been diagnosed with the illness and approximately 6 million are receiving therapy. Most people with COPD are at least 40 years old when they begin to notice symptoms, which may include shortness of breath after exertion, chronic cough, excess mucus production, and wheezing.
Boehringer Ingelheim Pharmaceuticals, Inc, based in Ridgefield, Conn, is a member of the Boehringer Ingelheim group of companies, which are headquartered in Ingelheim, Germany.
November 30, 2004
ST. LOUIS (MD Consult) - AstraZeneca announced on November 29, 2004, that a new indication for its prescription proton pump inhibitor Nexium (esomeprazole magnesium) had been approved by the U.S. Food and Drug Administration (FDA). Nexium is now indicated for reducing the risk of gastric ulcers developing among at-risk patients on continuous therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). The FDA also issued an approvable letter for the indication of the healing of gastric ulcers associated with NSAID therapy.
"NSAIDs play a crucial role in providing relief to many pain sufferers. However, potentially serious gastrointestinal side effects are often a deterrent to continue long-term treatment," says James Scheiman, MD, gastroenterologist at University of Michigan Health System. "Health care professionals now can offer their patients on NSAID therapy, who may be at risk for developing gastric ulcers, a therapeutic option that may lessen possibility of such stomach injury occurring."
A total of 1,429 patients (aged 19-89 years) were evaluated in 2 separate multicenter, double-blind, placebo-controlled clinical studies. Patients included in both studies had a chronic condition requiring daily NSAID treatment (including cyclo-oxygenase 2–selective NSAIDs). They were randomly assigned to receive treatment with Nexium (40 or 20 mg once daily) or placebo for up to 6 months. Nexium 20 mg and 40 mg demonstrated comparable benefits in providing risk reduction, with the proportion of NSAID patients remaining free of gastric ulcers ranging from 95.4% to 96.7% in one study and 94.7% to 95.3% in the other.
It is estimated that over 100 million prescriptions are written for NSAIDs each year in the United States. Every day, approximately 30 million people worldwide take NSAIDs. NSAIDs, which include such popular pain medications as aspirin, ibuprofen, and naproxen, are a common cause of stomach ulcers and have been associated with adverse effects ranging from stomach upset to potentially life-threatening stomach bleeding. In fact, NSAID use leads to more than 103,000 hospitalizations and 16,500 deaths each year in the United States.
Beyond its newest indication in the United States for the reduction in the occurrence of gastric ulcers associated with continuous NSAIDs therapy in patients at risk for developing gastric ulcers, Nexium is also approved for healing erosive esophagitis. Studies show that up to 94% of patients were healed with Nexium. Most erosions heal in 4 to 8 weeks. Individual results may vary, and only a doctor using endoscopy can determine whether erosions to the esophagus have occurred. The drug is also indicated for treating heartburn and other symptoms associated with acid reflux disease.
November 15, 2004
ST. LOUIS (MD Consult) - Sanofi-Synthelabo announced on November 5, 2004, that the U.S. Food and Drug Administration (FDA) had approved Eloxatin (oxaliplatin for injection), in combination with conventional chemotherapy (infusional 5-fluorouracil/leucovorin [5-FU/LV]), for the adjuvant (postsurgical) treatment of patients with stage III colon cancer who have undergone complete resection of the primary tumor.
The American Cancer Society (ACS) estimates that, by the end of 2004, 106,370 new cases of colon cancer will have been diagnosed in the United States. According to the ACS, colorectal cancer is the second leading cause of malignancy-related death in the United States, accounting for 10% to 15% of all cancer deaths. Over a lifetime, about 1 in 18 people develops colorectal cancer, and, each year, more than 56,000 people die from it in the United States. Most patients undergo surgery to remove the primary tumor, but many of these patients will still be at risk for recurrence. This latest approval of Eloxatin helps to decrease the risk of cancer recurrence and spread.
The FDA based its decision on results from the MOSAIC study, a large, international, randomized phase III trial involving 2,246 patients in 146 centers. At a median follow-up of 4 years, there was a statistically significant improvement in the primary end point, disease-free survival (DFS), for the Eloxatin combination compared with infusional 5-FU/LV, both in the overall study population (4-year DFS: 76% vs 69%; P = .0008) and in the subgroup with stage III disease (4-year DFS: 70% vs 61%; P = .002). Survival data were not mature at the time of the analysis. No statistical difference in overall survival was shown between the treatment arms in the overall study population or in stage III patients. No statistical difference was observed either in DFS or survival in stage II patients.
These results demonstrated that the addition of Eloxatin to conventional adjuvant chemotherapy for colon cancer (5-FU/LV) reduced the risk of recurrence of cancer by 24% in the overall patient population who had undergone surgery to remove a primary tumor.
In the United States, Eloxatin received approval on January 9, 2004, for the first-line treatment of advanced carcinoma of the colon or rectum in combination with infusional 5-FU/LV. This combination had had previously (August 2002) received approval for second-line treatment of this patient population.
Eloxatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.
Anaphylactic-like reactions to Eloxatin have been reported, and may occur within minutes of Eloxatin administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms.
Adjuvant Colon Cancer Setting
In the context of adjuvant treatment of colon cancer, the incidence of grade 3 or 4 events was 70% and 31% on the Eloxatin combination arm and infusional 5-FU/LV arm, respectively. Granulocytopenia, paresthesia, diarrhea, vomiting, and nausea were the most common grade 3 or 4 adverse events. Paresthesia was seen in 92% of patients taking the Eloxatin combination; 21% had residual paresthesia at 18-month follow-up. Three percent and 0.5% had grade 2 or 3 paresthesias, respectively, at 18-month follow-up. Grade 3 or 4 hypersensitivity was noted in 3% and may require discontinuation of therapy. Hepatotoxicity, evidenced by increase in transaminases (57% vs 34%) and alkaline phosphates (42% vs 20%), was observed more commonly in the Eloxatin arm. The incidence of increased bilirubin was similar on both arms. Hepatic vascular disorders should be considered and investigated if abnormal liver function tests or portal hypertension are present and cannot be explained by liver metastases or other known etiologies.
Advanced Colorectal Cancer Setting
Fatigue, neuropathy, nausea, vomiting, diarrhea, stomatitis, neutropenia, and thrombocytopenia were the more common adverse events in the setting of advanced colorectal cancer. Neither febrile neutropenia nor requirement for platelet transfusion was increased as compared with treatment with irinotecan plus bolus 5-FU/LV. Eloxatin has been associated with pulmonary fibrosis (<1% of study patients), which may be fatal. There have been reports from clinical trials and postmarketing surveillance of prolonged prothrombin time and international normalized ratio occasionally associated with hemorrhage in patients who received Eloxatin plus 5-FU/LV while taking anticoagulants. Patients requiring oral anticoagulants may require closer monitoring. Hypersensitivity has been observed (<2% grade 3/4) in clinical studies and trials. It was usually managed with standard epinephrine, corticosteroid, and antihistamine therapy and may require discontinuation of Eloxatin therapy.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions, and contraindications, is available at fda.gov/cder/foi/label/2004/021492s004lbl.pdf.
November 9, 2004
ST. LOUIS (MD Consult) - On November 5, 2004, Illinois-based health care company Abbott announced it had received U.S. Food and Drug Administration approval to market a new formulation of TriCor (fenofibrate) tablets for the treatment of lipid disorders such as mixed dyslipidemia. The new formulation of TriCor can be taken with or without food.
Until now, TriCor had to be taken with food to enable optimal absorption of TriCor in the body. Taking the previous version of TriCor with food (compared with taking it on an empty stomach) could result in a difference of approximately 35% in the body's absorption of the medicine. New TriCor 145- and 48-mg tablets offer the same effectiveness at a lower dose than the previous 160- and 54-mg tablets, but the medication can now be taken with or without food. TriCor remains a once-daily treatment
Nanoparticle technology was applied in the development of the new formulation of TriCor to allow the drug to dissolve faster and more completely in the gastrointestinal tract, which makes the drug more easily absorbed by the body.
TriCor, in addition to appropriate diet, is used to treat adults with high cholesterol or mixed dyslipidemia, with or without elevated triglycerides, after results of lifestyle changes are unsuccessful. TriCor reduces elevated low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and apolipoprotein B and increases high-density lipoprotein (HDL) cholesterol.
A recent report published in Circulation, which proposes changes to the National Cholesterol Education Program Adult Treatment Panel III Guidelines, stated that one class of drugs that modestly raises HDL cholesterol is the fibrate class. The report also suggests that treatment with fibrates, a class of drugs that includes fenofibrate, may have a complementary role in the treatment of patients with high triglyceride and low-HDL cholesterol levels.
Cholesterol is a natural, waxy, fat-like substance found in the body. There are 2 sources of cholesterol in the body: some cholesterol is made in the liver, and the rest comes primarily from animal products that are eaten, such as meats, poultry, eggs, and cheese.
Elevated LDL cholesterol can lead to heart attacks and other cardiovascular-related problems. Unlike high-LDL cholesterol, a high-HDL cholesterol level is considered good because it can often help reduce the risks for heart disease. Triglycerides are another type of fat in the bloodstream. It is not clear whether high triglyceride levels alone increase the risk of heart disease. However, an excessive amount of triglycerides can be a medical concern. The independent effect of raising HDL cholesterol or lowering triglycerides on the risk of cardiovascular morbidity and mortality has not been determined with TriCor.
TriCor should not be taken by people with serious liver, kidney, or gallbladder disease or by those who may be allergic or sensitive to the drug.
The combined use of TriCor and statin drugs is not advised because it can produce potentially serious adverse effects that could lead to acute renal failure. Therefore, it is important for health care professionals to determine whether the benefits of the combined use of these drugs are likely to outweigh the increased risks of the drug combination.
TriCor tablets may cause changes in laboratory reports, especially in liver chemistry results. Regular periodic liver tests should be performed while patients are taking TriCor. Patients should contact their doctors if they feel pain in the stomach area while taking TriCor; this can be a sign of gallstones or inflammation of the pancreas. TriCor can cause muscle pain or serious muscle disease, allergic-type reactions, and possible changes in blood chemistry. If patients experience unexpected muscle pain, tenderness, or weakness while taking TriCor, a health care provider should be contacted immediately.
Patients should notify a doctor if they are taking any other drugs while taking TriCor, including any other cholesterol-lowering medications. TriCor may have an effect on drugs that help prevent blood clotting, such as the blood thinner warfarin sodium, and doctors should monitor blood-clotting tests more frequently during administration of this medication.
Patients should tell their doctors about any adverse effects they experience, including breathing problems, back pain, and headaches.
For more information about TriCor tablets, including full prescribing information, visit TriCortablets.com.
November 4, 2004
ST. LOUIS (MD Consult) - On October 26, 2004, Johnson & Johnson announced the U.S. Food and Drug Administration (FDA) had approved Concerta (methylphenidate hydrochloride) Extended-release Tablets CII for use in adolescents with attention deficit–hyperactivity disorder (ADHD), expanding the product's labeling to include a 72-mg dosing regimen.
The administration of Concerta 72 mg may be warranted when symptoms of ADHD are not responding to lower doses of the medication. Previous clinical research demonstrates that a few weeks after taking an initial dose of Concerta, 8 of 10 patients were given higher doses of the medication to achieve effective symptom management. In a clinical study of adolescents aged 13 to 18 years, Concerta 72 mg significantly reduced ADHD symptoms.
Concerta tablets are currently available in 18-, 27-, 36-, and 54-mg strengths. There is no 72-mg tablet. Although physicians will determine how the medication should best be taken by adolescents for whom it is prescribed, it is believed Concerta 72 mg will most often be taken as a once-a-day morning dose of two 36-mg Concerta tablets.
Symptoms of ADHD generally first occur before the age of 7 years. The classic ADHD symptoms include inattention, distractibility, impulsivity, and hyperactivity. Some experts focus on deficits in "executive functions" in the brain to understand and describe ADHD behaviors. Such impaired executive functions in ADHD children can cause problems such as an inability to hold information in short-term memory, impaired organization and planning skills, and an inability to keep emotions from becoming overpowering.
Concerta CII is a once-daily extended-release formulation of methylphenidate approved to treat ADHD. The efficacy of Concerta has been demonstrated in studies conducted in children and adolescents. Only a doctor can determine whether medication is the right treatment for individuals with ADHD.
Concerta uses an extended-release delivery system to deliver a controlled rate of medication throughout the day. One advantage of this system is the minimization of the ups and downs within blood levels experienced with stimulant medications taken several times a day.
Concerta should not be taken by patients with significant anxiety, tension, or agitation; allergies to methylphenidate or other ingredients in Concerta; glaucoma, Tourette's syndrome, tics, or family history of Tourette's syndrome; or current/recent use of monoamine oxidase inhibitors. Abuse of methylphenidate can lead to dependence. Concerta should not be taken by children younger than 6 years of age.
In clinical studies with children using Concerta, the most common adverse effects were headache, stomach pain, sleeplessness, and decreased appetite. In clinical studies with adolescents using Concerta, the most common adverse effects were headache, accidental injury, and sleeplessness.
For more information about Concerta, including full U.S. prescribing information, visit concerta.net.
November 4, 2004
ST. LOUIS (MD Consult) - Ortho-McNeil Pharmaceutical, Inc, announced on October 28, 2004, that the U.S. Food and Drug Administration had approved a new, once-a-day formulation of Levaquin (levofloxacin) Oral Solution, 25 mg/mL. The new liquid formulation provides a convenient option for adult patients who have trouble swallowing tablets. According to published data, as many as 1 in 17 people may experience trouble swallowing; this includes 25% of all hospitalized patients and up to 40% of patients in nursing homes.
Levaquin Oral Solution is indicated to treat infections currently approved for the tablet and intravenous formulations and is effective against Staphylococcus aureus, Streptococcus pneumoniae (including all multiple drug–resistant strains), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae. The new oral solution has the same efficacy as the tablet formulation and continues to provide the flexible dosing required for renally impaired patients. Levaquin oral solution should be taken 1 hour before or 2 hours after eating.
Levaquin has demonstrated safety and a low incidence of gastrointestinal and central nervous system adverse events, including nausea (1.2%), diarrhea (1.0%), insomnia (0.4%), and dizziness (0.3%).
The safety and efficacy of levofloxacin in pediatric patients, adolescents (younger than 18 years), pregnant women, and nursing mothers have not been established. Levofloxacin is contraindicated in persons with a history of hypersensitivity to levofloxacin, quinolone antimicrobial agents, or any other components of this product. Serious and occasionally fatal hypersensitivity or anaphylactic reactions have been reported in patients receiving therapy with quinolones, including levofloxacin. These reactions often occur after the first dose is taken. The drug should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity.
As with other quinolones, levofloxacin should be used with caution in patients with known or suspected central nervous system disorders or peripheral neuropathy or in patients who have a predisposition to seizures.
Antacids containing magnesium, aluminum, or sucralfate; metal cations such as iron; and multivitamin preparations with zinc or didanosine (Videx; Bristol-Myers Squibb) chewable/buffered tablets or the pediatric powder for oral solution should be taken at least 2 hours before or 2 hours after levofloxacin administration. For the full U.S. prescribing information, including warnings, precautions, and additional adverse reactions associated with Levaquin, visit levaquin.com.
Levaquin Oral Solution is marketed in the United States by Ortho-McNeil Pharmaceutical, Inc, which is a Johnson & Johnson company based in Raritan, NJ.
November 2, 2004
ST. LOUIS (MD Consult) - On October 25, 2004, Connetics Corporation, a pharmaceutical company specializing in dermatology products, announced that the U.S. Food and Drug Administration had approved Evoclin (clindamycin) Foam 1% for the treatment of acne vulgaris. Evoclin (formerly referred to as "Actiza") will be available in the fourth quarter of 2004 in 50-g and 100-g unit sizes.
According to an Evoclin study investigator, the once-a-day medication leaves minimal residue, dissolves rapidly on contact with skin, and is easy to apply. Evoclin is indicated for topical application in the treatment of acne vulgaris. Treatment with this drug is contraindicated in persons with a history of hypersensitivity to preparations containing clindamycin or lincomycin, a history of regional enteritis or ulcerative colitis, or a history of antibiotic-associated colitis.
Approximately 17 million people in the United States have acne, resulting in approximately 5.5 million office visits per year.
Connetics Corporation is based in Palo Alto, California. For more information about the company and its products, visit connetics.com.
November 2, 2004
ST. LOUIS (MD Consult) - In a press release dated October 29, 2004, Swiss pharmaceutical company Novartis announced its medication Femara (letrozole) had won approval by the U.S. Food and Drug Administration (FDA) for the extended adjuvant treatment of postmenopausal women with early breast cancer who have received adjuvant (postsurgery) tamoxifen therapy for 5 years.
The term extended adjuvant describes the period after adjuvant (postsurgery) treatment with tamoxifen. Even years after breast cancer diagnosis and primary treatment, the ongoing risk of breast cancer recurrence remains significant for all patients. Globally, approximately one third of women with estrogen receptor–positive early breast cancer experience a recurrence, and over half of those recurrences occur more than 5 years after surgery. Although tamoxifen is beneficial for 5 years after surgery, if used beyond that period, the risks associated with it outweigh the benefits. Extended adjuvant treatment with Femara is the first therapy to effectively reduce the ongoing risk of breast cancer recurrence.
The approval for the extended adjuvant indication was based on results from the landmark, international, independent MA-17 study, which included more than 5,100 postmenopausal women and was coordinated by the National Cancer Institute of Canada Clinical Trials Group at Queens University in Kingston, Ontario, Canada, and supported by Novartis. Initial results were published in The New England Journal of Medicine in October 2003.
The study showed that Femara reduced the risk of cancer coming back by 38% and significantly increased a woman's chance of staying cancer-free. This is particularly important because when breast cancer recurs, it has very often metastasized beyond the breast, which can have serious consequences. Femara also greatly reduced the chance of breast cancer returning to another part of the body by 39%.
Femara is a once-a-day oral aromatase inhibitor that is also indicated for first-line treatment of postmenopausal women with hormone receptor–positive or hormone receptor–unknown locally advanced or metastatic breast cancer and for the treatment of advanced breast cancer in postmenopausal women with disease progression after antiestrogen therapy, and as neo-adjuvant (preoperative) therapy. Not all indications are available in every country.
The most common adverse events experienced with Femara are hot flashes, arthralgia/arthritis, and myalgia. Other commonly reported adverse reactions include nausea, fatigue, anorexia, appetite increase, peripheral edema, headache, dizziness, vomiting, dyspepsia, constipation, diarrhea, alopecia, increased sweating, rash, myalgia, bone pain, arthritis/arthralgia, and weight increase.
Femara is contraindicated in women who are pregnant or breast-feeding as well as in women with premenopausal endocrine hormone receptor status. Femara is contraindicated in patients with known hypersensitivity to letrozole or any of its excipients.
Additional information regarding Femara or Novartis Oncology can be found by visiting femara.com or novartisoncology.com.
October 27, 2004
ST. LOUIS (MD Consult) - Eisai Global Clinical Development announced on October 21, 2004, that the U.S. Food and Drug Administration (FDA) had approved Aricept (donepezil hydrochloride) orally disintegrating tablets (ODT), the first such medication approved by the FDA to treat the symptoms of mild to moderate Alzheimer's disease.
The new dosage form was designed to make administration easier for patients. Studies have shown that patients with Alzheimer's disease may develop difficulty with swallowing.
Aricept ODT will be available in the United States in 5- and 10-mg tablets in blister packaging and will provide the same dosage strength as Aricept tablets. It will be available in the second quarter of 2005 and will be copromoted by Eisai Inc and Pfizer Inc.
Although there is no cure for Alzheimer's disease, medical treatments are available to manage symptoms of the disease. Once-a-day prescription Aricept is indicated for mild to moderate Alzheimer's disease.
Aricept is generally well tolerated, but people at risk for stomach ulcers should inform their doctors before beginning treatment because serious stomach problems, such as bleeding, could be exacerbated by this medication.
According to Eisai, some persons taking Aricept may vomit, have nausea or diarrhea, or experience troubled sleep. Some may experience fainting, fatigue, muscle cramps, or loss of appetite. In studies, these adverse effects were usually mild and went away over time.
For full prescribing information, visit aricept.com.
October 13, 2004
ST. LOUIS (MD Consult) - Merck & Co, Inc, announced on October 12, 2004, that the U.S. Food and Drug Administration had approved the once-daily antifungal medicine Cancidas (caspofungin acetate) as empirical therapy for presumed fungal infections in febrile neutropenic patients.
Approval was based on results from the largest prospective antifungal empirical therapy trial published to date involving treatment of neutropenic patients with persistent fever. This study, recently published in The New England Journal of Medicine, showed that Cancidas was as effective as AmBisome (amphotericin B) for empiric therapy of presumed fungal infections in these patients.
"Invasive fungal infections are particularly life-threatening in neutropenic patients undergoing chemotherapy for malignancies such as acute myelogenous leukemia and non-Hodgkin's lymphoma and those who undergo hematopoietic stem cell transplantation," said Issam Raad, professor of medicine, and chairman of infectious diseases, infection control, and employee health at the University of Texas M.D. Anderson Cancer Center, Houston. "When clinical signs, such as persistent fever despite the presence of broad spectrum antibiotics, suggest the possible presence of a fungal infection in this population, it is important to intervene with an effective treatment."
Cancidas is the first in a class of antifungal drugs called echinocandins that inhibit fungal cell wall synthesis of β (1,3)-D-glucan, an integral component of the fungal cell wall. Cancidas is contraindicated in patients with hypersensitivity to any component of the product. Concomitant use of Cancidas with cyclosporine is not recommended unless the potential benefit outweighs the potential risk to the patient.
The multicenter, double-blind trial showed that Cancidas (n = 556) was as effective as AmBisome (n = 539), a frequently used antifungal agent, in treating presumed fungal infections in neutropenic patients with persistent fever.
The study enrolled patients who had received chemotherapy or undergone hematopoietic stem-cell transplantation (HSCT, such as bone marrow transplantation) and presented with neutropenia (<500 cells/mm3 for 96 hours) and fever (>38.0°C [100.4°F]) that did not respond to antibacterial therapy. An overall favorable response required meeting each of the following 5 criteria: (1) survival for 7 days after completion of study therapy; (2) no breakthrough fungal infections during treatment or within 7 days after the end of therapy; (3) no discontinuation of study drug because of drug-related toxicity or lack of efficacy; (4) resolution of fever during the period of neutropenia; and (5) successful treatment of any baseline fungal infection (identified on days 1 and 2).
Overall favorable response rates showed Cancidas to be as effective as AmBisome with 33.9% and 33.7% of patients, respectively, meeting all 5 criteria in each group. Favorable response rates for Cancidas and AmBisome on each of the following strictly defined components of the primary end point were:
The safety profile of Cancidas was superior to AmBisome with regard to several prespecified safety measures. Among patients with normal to moderately impaired renal function, the occurrence of nephrotoxicity was significantly lower for patients treated with Cancidas versus AmBisome (2.6% vs 11.5%). The percentage of patients with either a drug-related clinical or drug-related laboratory adverse experience was significantly lower among patients receiving Cancidas versus AmBisome (54.4% vs 69.3%). The percentage of patients who discontinued therapy due to a drug-related clinical or laboratory adverse experience was significantly lower among patients receiving Cancidas versus AmBisome (5.0% vs 8.0%). The proportion of patients who experienced an infusion-related adverse event was significantly lower in patients treated with Cancidas versus AmBisome (35.1% vs 51.6%).
In this study, the most common drug-related clinical adverse experiences in patients treated with Cancidas were fever (17%), chills (13.8%), rash (6.2%), headache (4.3%), hypokalemia (3.7%), and vomiting and nausea (3.5%).
Laboratory abnormalities in liver function test results have been seen in healthy volunteers and in patients treated with Cancidas. In some patients with serious underlying conditions who were receiving multiple concomitant medications along with Cancidas, clinical hepatic abnormalities have also occurred. Isolated cases of significant hepatic dysfunction, hepatitis, or worsening hepatic failure have been reported in patients; a causal relationship to Cancidas has not been established. Patients who develop abnormal liver function tests during Cancidas therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing Cancidas therapy.
For patients receiving Cancidas and tacrolimus, standard monitoring of tacrolimus blood concentrations and appropriate tacrolimus dosage adjustments are recommended. Patients taking rifampin should receive 70 mg of Cancidas daily. When Cancidas is coadministered with inducers of drug clearance, such as efavirenz, nevirapine, phenytoin, dexamethasone, or carbamazepine, a daily dose of 70 mg of Cancidas should be considered.
Cancidas should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether caspofungin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Cancidas is administered to a nursing woman.
Possible histamine-mediated symptoms have been reported, including isolated reports of rash, facial swelling, pruritus, sensation of warmth, and bronchospasm.
The Caspofungin versus Liposomal Amphotericin B for Empirical Antifungal Therapy in Persistently Febrile Neutropenic Patients study was a prospective, double-blind study conducted from January 2000 through August 2002 at 116 sites in the United States and 25 other countries. An independent Data and Safety Monitoring Board monitored all blinded safety data and, at a predefined point (after 512 patients completed the study), reviewed the unblinded efficacy and safety data to assess whether the study should continue. No changes to the study conduct were made based on this review. An Adjudication Committee reviewed blinded data from all cases of suspected fungal infection to determine, according to international criteria, whether an invasive fungal infection was present.
Patients enrolled were men and women older than age 16 years who had received chemotherapy for malignancy or undergone HSCT, had documented neutropenia (absolute neutrophil count, <500/µL) for at least 96 hours that was not expected to dissipate within 48 hours, had fever higher than 38.0°C at randomization, and had received more than 96 hours of parenteral systemic antibacterial therapy before enrollment. Patients received either intravenous caspofungin (70 mg once on day 1 and 50 mg once daily thereafter) plus placebo to liposomal amphotericin B or liposomal amphotericin B (3.0 mg/kg once daily) plus placebo to caspofungin.
Cancidas is an intravenous antifungal medicine that was first approved in 2001 for the treatment of invasive aspergillosis in patients who do not respond to or cannot tolerate other antifungal treatments. Cancidas is indicated for the first-line treatment of candidemia and other Candida infections—intra-abdominal abscesses, peritonitis, and pleural space infections—and is also approved for the treatment of esophageal candidiasis.
For more information, visit merck.com.
October 4, 2004
ST. LOUIS (MD Consult) - On October 1, 2004, Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co, Ltd, announced that the U.S. Food and Drug Administration (FDA) had approved Abilify (aripiprazole) for the treatment of acute bipolar mania, including manic and mixed episodes associated with bipolar disorder.
The FDA approval is based on positive results from 2 placebo-controlled, 3-week trials of 516 hospitalized patients with bipolar I disorder who were experiencing an acute manic or mixed episode. In these studies, Abilify demonstrated significant improvement in the symptoms of acute manic or mixed episodes. The most common adverse effects reported in clinical trials (=5% incidence and occurring at least twice as frequently in the Abilify-treated group compared with the placebo group) were akathisia, constipation, and accidental injury. The rate of discontinuation due to adverse effect was low (aripiprazole-treated, 11%; placebo-treated, 9%). In these clinical trials with Abilify, there was no significant difference from placebo with respect to weight gain, blood sugar levels, or lipids. The proportion of patients meeting a weight gain criterion of =7% of body weight was 3% for Abilify compared with 2% for placebo.
In short-term, placebo-controlled trials of bipolar mania, somnolence was reported in 14% of patients taking Abilify compared with 7% of patients receiving placebo.
According to Bristol-Myers Squibb, bipolar I disorder affects more than 2 million Americans, and onset generally occurs before the age of 30 years. Bipolar I disorder can include manic, depressive, or mixed phases or episodes. During the manic phase of the illness, patients experience elation of mood and impairment of judgment, and they are likely to deny that they are ill and need help. During the depressive phase, patients may feel so hopeless that they are incapable of seeking or accepting help, and they may believe that they cannot be helped. Mixed episodes involve the simultaneous occurrence of depressive and manic symptoms. People with bipolar I disorder may also experience some psychotic symptoms, including hallucinations and paranoia. The duration of mood episodes range from hours or days to many months. Bipolar I disorder can be difficult to recognize, and even after a diagnosis is made it is often extremely challenging to convince a person with bipolar I disorder to seek and maintain treatment.
A rare but potentially fatal complex of symptoms referred to as neuroleptic malignant syndrome has been reported with antipsychotic medicines, including Abilify. Another condition associated with these medicines is tardive dyskinesia.
Hyperglycemia, in some cases extreme and associated with coma or death, has been reported in patients treated with atypical antipsychotics, including Abilify. It is important that patients tell their health care providers if they are diabetic, have risk factors for diabetes (eg, obesity, family history of diabetes), or are experiencing unexpected increases in thirst, urination, or hunger. Before starting treatment with atypical antipsychotics, patients should have their glucose levels tested; they should also be monitored during treatment.
Orthostatic hypotension has also been reported with these medicines. Abilify should be used cautiously if a patient has a history of seizures.
Patients should not drive or operate heavy machinery until they know how Abilify affects them.
Patients should talk to their health care providers if they are pregnant or intend to become pregnant. Patients should also discuss with their health care providers all prescription and non-prescription medicines they are taking or plan to take.
Other common adverse effects associated with Abilify are headache, agitation, anxiety, insomnia, nausea, upset stomach, sleepiness, akathisia, lightheadedness, vomiting, constipation, and tremors.
Abilify was approved by the FDA in 2002 for the treatment of schizophrenia. The efficacy and tolerability of Abilify in schizophrenia was established by short-term and longer-term controlled trials.
For more details including full prescribing information, visit ABILIFY.com.
October 1, 2004
ST. LOUIS (MD Consult) - On September 30, 2004, Centocor, Inc, announced that the U.S. Food and Drug Administration (FDA) had approved an expanded label for Remicade (infliximab) in combination with methotrexate (Remicade regimen), as a first-line regimen to treat patients with moderate to severe rheumatoid arthritis (RA). The expanded label eliminates the requirement that patients must fail to respond to methotrexate, the current standard of treatment for RA, before starting on the Remicade regimen. This regimen has been shown to reduce signs and symptoms, inhibit further joint destruction, and improve physical function.
Early intervention is critical to change the course of joint destruction in this debilitating disease. In the Active Controlled Study of Patients Receiving Infliximab for Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) study, more than 80% of patients had evidence of erosive joint damage despite the fact that the median disease duration was only 7 months. This study demonstrated that the Remicade regimen was superior to methotrexate alone in changing the course of the disease when given early. The majority of patients treated with the Remicade regimen experienced no progression of structural damage, whereas the majority of patients treated with methotrexate alone progressed significantly despite titration to high doses of methotrexate.
"The ASPIRE trial demonstrated that with early, intensive intervention patients can achieve substantial symptomatic improvement," said David E. Yocum, MD, director, Arizona Arthritis Center, the University of Arizona College of Medicine, and ASPIRE investigator. "Moreover, in a subset of patients without joint damage at baseline, Remicade plus methotrexate provided greater benefit than methotrexate alone in maintaining an erosion-free state."
The FDA approval is based on the results of ASPIRE, the largest controlled trial ever conducted exclusively in RA patients with early disease, (< 3 years' duration), which found Remicade plus methotrexate to be superior to methotrexate alone in patients with moderately to severely active disease. ASPIRE was a 54-week, randomized, double blind, active control study involving 1,004 patients with early disease enrolled in 125 centers in North America and Europe. At randomization, all patients received methotrexate and either placebo, 3 mg/kg of Remicade, or 6 mg/kg of Remicade at weeks 0, 2, and 6 and then every 8 weeks thereafter. The ASPIRE trial demonstrated superiority of the Remicade regimen over methotrexate alone on all 3 primary end points, including reduction of signs and symptoms, inhibition of the progression of structural damage, and improvement in physical function.
The most commonly reported adverse events were upper respiratory infection, nausea, and headache. Serious infections included pneumonia, tuberculosis (TB), and sepsis.
As Centocor states, RA is a chronic, progressive disease, and research suggests that a critical therapeutic window may exist within the first 2 years of disease onset when the rate of radiographic progression of the disease can be "reset." Radiographic changes occur within 2 years of disease onset in 50% to 70% of pateints with RA. The American College of Rheumatology (ACR) suggests control of disease progression should start early to limit joint damage in RA. RA is associated with substantial disability and economic losses, and one study showed that one third of patients in the United Kingdom who were employed became work-disabled within 2 years of disease onset. Rheumatologic disorders also account for 25% of Social Security disability payments.
Many people with heart failure should not take Remicade; before treatment, patients should discuss any heart condition with their doctors. Patients developing new or worsening symptoms of heart failure (such as shortness of breath or swelling of ankles or feet), should alert their doctors.
There are reports of serious infections, including TB and sepsis. Some of these infections have been fatal. Patients who have had recent or past exposure to people with TB should tell their doctors, who will then evaluate for TB and perform a skin test. If a patient has latent (inactive) TB, the doctor should begin TB treatment before beginning the administration of Remicade. Remicade can lower the ability to fight infections, so patients who are prone to or have a history of infections, or who develop any signs of an infection such as fever, fatigue, cough, or influenza while taking Remicade should inform their doctors immediately. It should also be mentioned if a patient lives in a region where histoplasmosis or coccidioimycosis is common. Blood disorders have been reported, and some have been fatal. Patients developing possible signs of blood disorders such as persistent fever, bruising, bleeding, or paleness while taking Remicade should alert their physicians. Nervous system disorders have also been reported, therefore any disease that affects the nervous system should be pointed out to a patient's doctor, as should any numbness, weakness, tingling, or visual disturbances experienced during treatment with Remicade.
Serious infusion reactions have been reported with Remicade, including hives, difficulty breathing, and low blood pressure. Reactions have occurred during or after infusions. In clinical studies, some people experienced the following common adverse effects: respiratory infections (that may include sinus infections and sore throat), coughing, and stomach pain or mild reactions to infusion such as rash or itchy skin.
Remicade is a monoclonal antibody that specifically targets and irreversibly binds to tumor necrosis factor a (TNF-α) on the cell membrane and in the blood. Overproduction of TNF-α is believed to play a role in RA, ankylosing spondylitis (AS), Crohn's disease (CD), and psoriatic arthritis (PSA), in addition to a wide range of immune-mediated inflammatory disorders (IMID) in which Remicade is currently being studied.
Remicade is unique among available anti-TNF biologic therapies. Unlike self-administered therapies that require patients to inject themselves frequently, Remicade can be administered directly by caregivers in the clinic or office setting. In RA and CD patients, Remicade is a 2-hour infusion administered every 8 weeks, following a standard induction regimen that requires treatment at weeks 0, 2, and 6. As a result, Remicade patients may require as few as 6 treatments each year.
More details regarding Remicade, including full prescribing information, are available at remicade.com.
September 9, 2004
ST. LOUIS (MD Consult) - On September 28, 2004, Illinois-based Abbott Laboratories announced the U.S. Food and Drug Administration (FDA) had approved a 250 mg/5 mL dosing option of the antibiotic Omnicef (cefdinir) Oral Suspension (OS) for use in pediatric patients aged 6 months to 12 years old. The more concentrated formulation allows parents to administer fewer teaspoons per dose of the antibiotic to their children. When using the 250 mg/5 mL formula, parents administer half of the volume used in the standard formula (125 mg/5 mL).
Omnicef OS is proven to effectively treat mild to moderate bacterial infections such as ear infections, sinus infections, strep throat, and skin infections.
The FDA based its approval on the supplemental New Drug Application filed by Abbott on March 26, 2004. Omnicef OS was originally approved in 1997 at 125 mg/5 mL to treat bacterial infections in children. Omnicef is included in many treatment guidelines, such as those published by the American Academy of Pediatrics.
The new formulation was approved based on a bioequivalence study of the Omnicef OS new 250 mg/5 mL dosage compared with the original 125 mg/5 mL. To be considered bioequivalent, the two dosage formulations must perform in the same ways when given under similar conditions in clinical studies.
Omnicef Oral Suspension is indicated for pediatric patients (ages 6 months to 12 years) for the treatment of mild to moderate infections, including acute bacterial otitis media due to Haemophilus influenzae (including beta-lactamase–producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), and Moraxella catarrhalis (including beta-lactamase–producing strains); and pharyngitis/tonsillitis due to Streptococcus pyogenes. Omnicef is also effective in the eradication of S. pyogenes from the oropharynx.
Omnicef has not, however, been studied for the prevention of rheumatic fever after S. pyogenes–induced pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Omnicef OS is also indicated for the treatment of uncomplicated skin and skin structure infections due to Staphylococcus aureus (including beta-lactamase–producing strains) and S. pyogenes.
To reduce the development of drug-resistant bacteria and to maintain the effectiveness of Omnicef and other antibacterial drugs, Omnicef should be used only to treat or prevent infections that are strongly suspected to be caused by susceptible bacteria.
Omnicef is contraindicated in patients with known allergy to the cephalosporin class of antibiotics. Patients with previous hypersensitivity to penicillins should be closely monitored when taking Omnicef. If allergic reaction to Omnicef occurs, the drug should be discontinued.
In clinical studies, Omnicef was well tolerated. In pediatric trials, the most common adverse events were diarrhea (8%), rash (3%) and vomiting (1%).
For complete details including full prescribing information, please visit omnicef.com or omnicefforkids.com.
September 29, 2004
ST. LOUIS (MD Consult) - On September 28, 2004, Amgen Inc and Wyeth Pharmaceuticals announced that Enbrel (etanercept) became the first biologic agent to receive an indication by the U.S. Food and Drug Administration (FDA) to induce a major clinical response in patients with rheumatoid arthritis (RA). In addition, the FDA approved updated radiographic data in the Enbrel label, which demonstrated that more than half of Enbrel patients observed in an open-label long-term study experienced no progression of joint damage for up to 5 years.
Major clinical response is defined as achieving an American College of Rheumatology 70 response (ACR 70) for 6 consecutive months. ACR response scores are categorized as ACR 20, ACR 50, and ACR 70; ACR 70 is the highest level of sign and symptom control in this evaluation system. ACR response scores measure improvement in RA disease activity, including joint swelling and tenderness, pain, level of disability, and overall patient and physician assessment.
In addition to the major clinical response indication, the Enbrel label was updated to include data that showed that at 5 years' follow-up patients with early, active RA continued to demonstrate inhibition of joint damage and more than half (55%) had no progression of joint damage.
More than 2 million Americans have RA, which is a chronic and progressive disease that causes stiffness, swelling, and limitation in the motion and function of multiple joints. If RA is left untreated, patients can become disabled from progressive joint damage caused by the disease, limiting their ability to function.
Enbrel is the only fully human tumor necrosis factor (TNF) receptor approved to reduce signs and symptoms, induce major clinical response, to inhibit the progression of structural damage, and to improve the physical function in patients with moderately to severely active RA. Enbrel is also indicated to reduce the signs and symptoms and to inhibit the progression of structural damage of active arthritis in patients with psoriatic arthritis. Enbrel is the only biologic therapy approved in the United States for first-line treatment of RA patients and can be used alone or in combination with methotrexate.
Enbrel is approved to reduce the signs and symptoms of moderately to severely active polyarticular-course juvenile RA (JRA) in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs. It is also the only biologic agent approved in the United States to treat the signs and symptoms in patients with active ankylosing spondylitis (AS). Enbrel is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
Enbrel acts by binding TNF, one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immune function and the cascade of reactions involved in the inflammatory process of RA, JRA, psoriasis, psoriatic arthritis, and AS. The binding of Enbrel to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory activity.
Since the product was first introduced, some serious infections have been reported in patients using Enbrel. Many occurred in people prone to infection, such as those with advanced or poorly controlled diabetes, and some serious infections were fatal. There were rare cases of tuberculosis.
Patients with an infection or those who are allergic to Enbrel or its components should not take Enbrel. Those prone to infection should alert their doctors, as should those who have ever been treated for heart failure. If serious infection occurs, use of the drug should be discontinued.
Serious nervous system disorders such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes are contraindications to Enbrel use. Patients who have ever had any of these disorders or who develop them after beginning treatment with Enbrel should alert their doctors.
Rare reports of serious blood disorders (some fatal) have occurred with this medication. Patients experiencing symptoms such as persistent fever, bruising, bleeding, or paleness should contact their physicians. In medical studies of all TNF blockers, a higher rate of lymphoma was seen compared with the general population; however, the risk of lymphoma may be up to several-fold higher in RA and psoriasis patients. The role of TNF blockers in the development of lymphoma is unknown. The incidence of other cancers has not increased with exposure to Enbrel and is similar to the expected rate.
Enbrel can also cause injection site reactions. In a medical study of patients with JRA, infections, headaches, abdominal pain, vomiting, and nausea occurred more frequently than in adults. The kinds of infections reported were generally mild and similar to those usually seen in children. Other serious adverse reactions were reported rarely and included serious infections (2%) and depression/personality disorder (1%).
Additional information about Enbrel, including full prescribing information, can be found at enbrel.com or by calling 888-4ENBREL (888-436-2735).
September 29, 2004
ST. LOUIS (MD Consult) - On September 24, 2004, Purdue Pharma L.P. announced that the U.S. Food and Drug Administration (FDA) had approved Palladone (hydromorphone HCl extended-release) Capsules (CII) for the management of persistent, moderate to severe pain in patients requiring continuous, around-the-clock analgesia with a high potency opioid for an extended period of time (weeks to months or longer). The painful conditions may arise from either cancer or non-cancer conditions.
The efficacy of Palladone Capsules was established in a 4-week, double-blind, randomized trial. The multicenter placebo-controlled trial used a parallel-group model to evaluate patients aged 18 years and older with pain that was present for at least 1 month. The majority of these patients had moderate to severe pain due to musculoskeletal disorders while maintained on one or more opioid analgesics, often in addition to non-opioid analgesics.
Two hundred twenty-one patients with persistent moderate to severe pain were randomly assigned to receive once-daily 12-mg Palladone Capsules or placebo after they had demonstrated they needed approximately 12 mg of immediate-release hydromorphone (in addition to non-opioid medication) around the clock for control of their pain. Patients taking Palladone Capsules maintained adequate analgesia for a significantly longer time compared with patients in the placebo group.
Palladone Capsules should be administered once every 24 hours.
Palladone Capsules should only be used in patients who are already receiving opioid therapy, who have demonstrated opioid tolerance, and who require a minimum total daily dose of opioid medication equivalent to 12 mg of oral hydromorphone. Palladone Capsules should not be used as the first opioid product prescribed for a patient, nor in patients who require opioid analgesia for a short period of time. Patients considered opioid tolerant are those taking any of the following for a week or longer: at least 60 mg oral morphine/day, at least 30 mg oral oxycodone/day, at least 8 mg oral hydromorphone/day, or an equianalgesic dose of another opioid. Use in non–opioid-tolerant patients may lead to fatal respiratory depression.
Palladone Capsules are contraindicated for use on an as-needed (i.e., p.r.n.) basis and in situations of significant respiratory depression, especially in unmonitored settings where there is a lack of resuscitative equipment. They also are contraindicated in patients who have acute or severe bronchial asthma, in patients who have or are suspected of having paralytic ileus, and in patients with known hypersensitivity to any of its components or to the active ingredient, hydromorphone.
The most common adverse events reported in clinical trials with Palladone Capsules include constipation, nausea, infection, headache, and somnolence. Serious adverse reactions that may be associated with Palladone Capsules therapy in clinical use are similar to those of other opioid analgesics, including respiratory depression, apnea, respiratory arrest, and to a lesser degree, circulatory depression, hypotension, shock, or cardiac arrest. Acute overdosage with hydromorphone can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, bradycardia, hypotension, and death. Patients who receive an overdose will require an extended period of monitoring and treatment that may go beyond 18 hours.
Palladone Capsules are to be swallowed whole and are not to be broken, chewed, opened, dissolved, or crushed. Taking broken, chewed, dissolved, or crushed Palladone Capsules or their contents can lead to the rapid release and absorption of a potentially fatal dose of hydromorphone.
Overestimating the Palladone dose when converting the patient from another opioid medication can result in fatal overdose with the first dose. With the long half-life of Palladone (18 hours), patients who receive the wrong dose will require an extended period of monitoring and treatment that may go beyond 18 hours. Even in the face of improvement, continued medical monitoring is required because of the possibility of extended effects.
When prescribing any opioid medication, patients should be assessed for their clinical risks for opioid abuse or addiction and should be closely monitored for signs of misuse, abuse, and addiction throughout the course of therapy.
Palladone Capsules contain the potent Schedule II opioid agonist hydromorphone. Schedule II opioid agonists (which include hydromorphone, fentanyl, methadone, morphine, oxycodone, and oxymorphone) have the highest risk of fatal overdoses due to respiratory depression, as well as the highest potential for abuse. These risks should be considered when administering, prescribing, or dispensing Palladone in situations where the health care professional is concerned about increased risk of misuse, abuse, or diversion.
Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients should be assessed for their clinical risks for opioid abuse or addiction before they are prescribed opioids. All patients receiving opioids should be routinely monitored for signs of misuse, abuse, and addiction. Patients at increased risk of opioid abuse may still be appropriately treated with modified-release opioid formulations; however, these patients will require intensive monitoring for signs of misuse, abuse, or addiction.
Purdue Pharma has designed a comprehensive Risk Management Program (RMP) that is intended to facilitate proper patient selection, reduce abuse, minimize diversion, and avoid pediatric exposure and other improper uses of Palladone Capsules. The RMP includes extensive medical education, detailed prescribing information, surveillance of medication use and drug diversion, and appropriate interventions when merited.
For the first 18 months following the launch of Palladone, the company will market the product to a limited number of medical practitioners experienced in prescribing opioid analgesics. During this 18-month period, the company will monitor and collect data on medication use and drug diversion and will report these data to the FDA.
Palladone will be available in 12-mg, 16-mg, 24-mg, and 32-mg dosage strengths. Palladone Capsules are expected to be available in retail pharmacies in the first half of 2005.
Full prescribing information for Palladone Capsules is available at purduepharma.com/PI/Prescription/Palladone.pdf.
September 9, 2004
ST. LOUIS (MD Consult) - Merck & Co Inc announced on September 8, 2004, that its arthritis and pain medicine Vioxx (rofecoxib) had received approval from the U.S. Food and Drug Administration (FDA) for a new indication. The medication is now approved for the treatment of the signs and symptoms of the most common forms of juvenile rheumatoid arthritis (JRA), pauciarticular or polyarticular, in children 2 years and older and who weigh at least 22 pounds. Vioxx is the only cyclooxygenase 2 (COX-2)-specific inhibitor approved for the treatment of JRA.
The approval of Vioxx for the relief of the signs and symptoms of JRA follows the approval of this drug in March 2004 for the acute treatment of migraine in adults. In addition, the medication is also approved for the relief of the signs and symptoms of osteoarthritis and rheumatoid arthritis in adults, management of acute pain in adults, treatment of primary dysmenorrhea, and acute treatment of migraine attacks with or without aura in adults. The drug's safety and effectiveness have not been established for cluster headache, which is present in an older, predominantly male population.
JRA is the most common form of arthritis in children, affecting an estimated 30,000 to 50,000 children in the United States. It can occur in children of any age, but girls are more likely to be affected than boys. In March 2004, Merck was granted orphan drug designation for Vioxx for the treatment of JRA, a designation given to medicines that have been researched for the treatment of medical conditions that affect 200,000 people or fewer in the United States.
JRA is known to cause persistent joint inflammation and stiffness that can affect any joint in the body. There are 3 major types of JRA: pauciarticular, which affects 4 or fewer joints; polyarticular, which affects 5 or more joints; and systemic onset, which affects at least 1 joint but also causes inflammation of internal organs. The drug's new indication for JRA is only for patients with pauciarticular or polyarticular JRA.
The FDA approval of Vioxx for JRA was based on the largest JRA study ever conducted, which included 310 pediatric and adolescent patients aged 2 to 17 years with active pauciarticular or polyarticular JRA. Results from the pivotal 12-week, multinational, double-blind study showed once-daily Vioxx provided measurable improvement in reducing joint symptoms. Improvement was evaluated based on JRA "Definition of Improvement = 30%" (DOI 30) criterion, a core set of standardized criteria used to measure arthritis impact. A 1-year open-label extension to the pivotal study also was conducted to evaluate the long-term safety of Vioxx.
Vioxx was generally well tolerated among pediatric and adolescent patients in the study. The most commonly reported adverse events in patients taking Vioxx over the 12-week period were upper abdominal pain, nasopharyngitis, diarrhea, upper respiratory tract infection, abdominal pain, headache, and rhinitis.
Vioxx is available in once-daily dosing in both tablet and strawberry-flavored liquid (oral suspension) formulations. For adolescents 12 to 17 years of age, the recommended dose of Vioxx is 25 mg once daily. For children and adolescents 2 to 11 years of age, dosing is dependent on weight: for children weighing 22 to 88 pounds, the recommended dose is 0.6 mg/kg to a maximum of 25 mg once daily, and for those over 88 pounds, 25 mg once daily is recommended. To improve dosing accuracy among young children, use of Vioxx 12.5 mg/5 mL oral suspension is recommended.
People with allergic reactions (such as asthma) to aspirin or other arthritis medicines should not take Vioxx. In rare cases, serious stomach problems such as bleeding can occur without warning. Patients should inform their physicians if they have or have had liver or kidney disease, angina, a heart attack, or a blocked artery in the heart. Vioxx cannot take the place of aspirin for the prevention of heart attack or stroke, and it should not be used by women in late pregnancy.
Commonly reported adverse effects in clinical trials with Vioxx in adults have included upper-respiratory infections, diarrhea, nausea, and high blood pressure.
The recommended starting dose of Vioxx for the treatment of osteoarthritis is 12.5 mg once daily, although some patients may receive additional benefit by increasing the dose to 25 mg once daily. For rheumatoid arthritis, the recommended dose is 25 mg once daily. The maximum recommended daily dose for osteoarthritis and rheumatoid arthritis is a once-daily dose of 25 mg.
Vioxx 50 mg given once daily is the recommended dose for acute pain and primary dysmenorrhea. Use of Vioxx for more than 5 days in the management of pain has not been studied. Chronic use of this dosage is not recommended.
For the treatment of migraine attacks, the recommended starting dose is 25 mg once daily. Some patients may receive additional benefit with 50 mg, which is the maximum recommended daily dose. The safety of treating more than 5 migraine attacks in any given month has not been established. Chronic daily use of Vioxx for the acute treatment of migraine is not recommended.
For full prescribing information and patient package insert, visit vioxx.com.
September 8, 2004
ST. LOUIS (MD Consult) - On September 7, 2004, Eli Lilly and Co. announced that the U.S. Food and Drug Administration (FDA) had approved the antidepressant Cymbalta (duloxetine hydrochloride), judging it safe and effective for the management of diabetic peripheral neuropathic pain. This symptom of nerve damage affects up to 5 million Americans, according to the Indianapolis-based drug maker.
Cymbalta, a balanced and potent serotonin and norepinephrine reuptake inhibitor, is the first FDA-approved treatment for pain elicited by this disorder. The approval came after a 6-month priority review. More than 18 million Americans have diabetes and are at risk for developing persistent pain as a result of nerve damage believed to be caused by high blood sugar levels.
Cymbalta's safety and efficacy in the treatment of pain caused by diabetic peripheral neuropathy at doses of 60 and 120 mg/day was proved in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose studies in nondepressed adults who had the disorder for at least 6 months. However, doses of 120 mg/day, although safe and effective, were not as well tolerated as 60 mg/day. On average, patients in the studies were 60 years old, suffered from diabetes for 11 years and from related diabetic neuropathy for 4 years, and at the beginning of the studies, rated their pain as moderate to moderately severe.
In both studies, Cymbalta significantly reduced 24-hour average pain compared with placebo. Improvements were noted as early as the first week of treatment and continued for the duration of the studies. In addition, the medication showed rapid onset of action and sustained effect in reducing pain caused by diabetic neuropathy at both 60 and 120 mg/day and was effective in relieving pain at night. Nighttime pain is especially troublesome to many patients with diabetic neuropathy because it can interfere with sleep.
Although Cymbalta does not change the underlying nerve damage caused by diabetic peripheral neuropathy, it does help relieve the stabbing, burning, and shooting pain often associated with the disorder. Scientists believe it does this by increasing levels of serotonin and norepinephrine, 2 neurotransmitters believed to be important in regulating a person's emotions as well as sensitivity to pain. Increasing these levels in a balanced way is thought to improve the body's natural ability to regulate pain. Relatedly, on August 3, 2004, the FDA approved Cymbalta for the treatment of major depression in adults.
Cymbalta is available in 20-, 30-, and 60-mg capsules and can be taken once a day. The recommended daily dose is 60 mg. The effects of the drug have not been studied in children, and therefore Lilly discourages its use in those younger than 18 years of age.
According to the National Institute of Diabetes & Digestive & Kidney Diseases, approximately half of those with diabetes have some form of neuropathy, but not all will develop symptoms. While nerve problems can occur at any time, the highest rates are among those who have had diabetes for at least 25 years. People who have had problems controlling their blood sugar levels, have high blood pressure, are overweight, have high levels of blood fat, or are over the age of 40 years may also have a greater risk of developing diabetic peripheral neuropathy.
Symptoms can include numbness, tingling, or pain and weakness in the toes, feet, legs, hands, arms, and fingers. These symptoms are often worse at night.
People who are allergic to duloxetine hydrochloride or the other ingredients in Cymbalta should not take it. If a patient has recently taken a monoamine oxidase inhibitor, is taking thioridazine, or has uncontrolled narrow-angle glaucoma, he or she should not take Cymbalta. Patients should talk with their doctors before taking this medication if they have serious liver or kidney problems, have glaucoma, or consume large quantities of alcohol, as should women who are pregnant or breast-feeding.
In clinical studies of Cymbalta for pain caused by diabetic neuropathy, the most common adverse effects were nausea, sleepiness, dizziness, constipation, dry mouth, increased sweating, decreased appetite, and fatigue. Most people were not bothered enough by the adverse effects to stop taking Cymbalta. Physicians administering this drug should periodically check their patients' blood pressure. Patients should not stop taking Cymbalta without discussing the cessation with their doctors.
For full prescribing information, visit Cymbalta.com.
September 3, 2004
ST. LOUIS (MD Consult) - Schering-Plough Corporation announced on September 1, 2004, that the U.S. Food and Drug Administration (FDA) had approved the use of Clarinex (desloratadine) Syrup for the relief of symptoms associated with seasonal allergic rhinitis in children 2 years and older as well as perennial allergic rhinitis and chronic idiopathic urticaria in children as young as 6 months. The new Clarinex Syrup is expected to be available in the United States during the first half of 2005.
The FDA approval of this prescription non-sedating antihistamine syrup results from 3 double-blind, placebo-controlled safety studies involving 246 pediatric subjects 6 months to 11 years of age with a documented history of allergic rhinitis or chronic idiopathic urticaria, or subjects who were candidates for antihistamine therapy. The results of these studies demonstrated the safety of Clarinex Syrup in pediatric subjects 6 months to 11 years of age.
In clinical trials, the overall incidence of adverse events in children between the ages of 6 and 11 years was similar for the group taking desloratadine syrup and the placebo groups. In pediatric patients 6 months to 5 years of age, the most frequently seen adverse events were upper respiratory tract infection, diarrhea, fever, urinary tract infection, varicella, irritability, and coughing.
Full prescribing information is available at www.spfiles.com/piclarinex.pdf.
August 24, 2004
ST. LOUIS (MD Consult) - In an announcement made August 23, 2004, Pfizer Inc announced that the U.S. Food and Drug Administration (FDA) had approved the use of its atypical antipsychotic medication Geodon (ziprasidone hydrochloride) for the treatment of acute bipolar mania including manic and mixed episodes.
Prompt and effective control of acute mania is an important goal because patients affected by this disorder are at an increased risk for impulsive and dangerous behaviors, often requiring psychiatric hospitalization. Geodon was shown to rapidly improve acute manic symptoms and to sustain these improvements over a 3-week study period. Consistent with Geodon's overall clinical profile, no significant adverse effects on weight gain or lipids were seen.
In 2 randomized double-blind trials involving 416 hospitalized patients with acute bipolar mania, Geodon-treated patients showed greater improvement compared with placebo from day 2 through the end of the trial (day 21). Patients treated with Geodon were initially given a dose of 80 mg/d with an increase permitted to 160 mg on day 2 in the first study and day 3 in the second study.
Efficacy was measured using standardized psychiatric assessment scales. The most common adverse effects in the studies were somnolence, dizziness, and extrapyramidal symptoms.
According to a survey conducted by Harris Interactive of 554 bipolar patients in the United States older than 30 years, 7 of 10 have gained weight—on average, 50 pounds, with 1 in 10 gaining an alarming 100 pounds or more—while taking bipolar medications. This medication-induced weight gain caused almost half of patients surveyed to stop taking or change their medication.
More than one third of patients (39%) surveyed who had gained weight while taking bipolar medications reported developing high cholesterol, and 3 of 10 developed high triglyceride levels. Some even reported having other serious conditions including diabetes (13%) and abnormal lipid levels (18%).
As Pfizer reports, despite the serious consequences that bipolar patients may experience when not properly treated, the majority (67%) say that they are unwilling to take a medication that controls symptoms but could cause them to gain 10 pounds or more. Patient compliance in taking prescribed medication is key to reducing physician office visits and expenses of hospitalization as well as providing best outcomes of the treatment.
Weight gain may be one reason that the patients surveyed have tried, on average, 6 medications to satisfactorily treat their bipolar disorder. In fact, 1 in 6 bipolar patients has taken 11 or more medications seeking relief from their troubling condition that affects their ability to function in daily life.
It is important to note that patients should not discontinue their medication without first consulting their physician. With appropriate diagnosis and treatment, most patients can improve substantially and even resume normal functioning.
Bipolar disorder, also referred to as manic-depressive illness, is a common and persistent psychiatric condition. Patients suffer from profound mood swings ranging from severe depression to unnatural "highs." During manic periods, which can last for a week or more, patients may appear to be overly energetic, irritable, extremely talkative, or excessively happy.
Geodon was approved in the United States in February of 2001 for the treatment of schizophrenia and in 2004 for acute bipolar mania. The drug is contraindicated in patients with a known history of QT prolongation, recent acute myocardial infarction, or uncompensated heart failure, and it should not be used with other QT-prolonging drugs. Geodon has a greater capacity to prolong the QTc interval than several antipsychotic agents. With some drugs, QT prolongation has been associated with torsades de pointes, a potentially fatal arrhythmia.
Hyperglycemia-related adverse events, sometimes serious, have been reported in patients treated with atypical antipsychotic drugs. There have been few reports of hyperglycemia or diabetes in patients treated with Geodon, and it is not known whether Geodon is associated with these events. Patients treated with an atypical antipsychotic medication should be monitored for symptoms of hyperglycemia.
Full Geodon prescribing information is available at pfizer.com/download/uspi_geodon.pdf.
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August 24, 2004
ST. LOUIS (MD Consult) - On August 23, 2004, Novartis Pharma AG announced that the U.S. Food and Drug Administration had approved a supplemental indication for its promotility agent Zelnorm (tegaserod maleate) for the treatment of chronic idiopathic constipation in male and female patients younger than 65 years of age.
The effectiveness of Zelnorm in patients 65 years or older with chronic idiopathic constipation has not been established.
The new indication is supported by safety and efficacy data from the 2 largest and longest randomized, double-blind, placebo-controlled, multinational phase III clinical trials ever conducted in chronic constipation. The two 3-month trials included more than 2,600 patients. In addition, one of the studies included a 13-month extension safety study of 840 patients. Zelnorm was found to significantly increase the frequency of complete spontaneous bowel movements as well as to provide relief of the multiple symptoms of chronic constiptation that patients complain about most, including straining, hard stool, incomplete evacuation, infrequent defecation, bloating, and abdominal discomfort.
Zelnorm has been available since July 2002 to treat abdominal discomfort or pain, bloating, and constipation associated with irritable bowel syndrome (IBS) in women. IBS with constipation and chronic idiopathic constipation are both lower gastrointestinal (GI) dysmotility disorders.
Constipation, including that due to other diseases or drugs, is one of the leading GI complaints in the United States, affecting nearly 18% of the population, or 37 million people. More than 4.5 million Americans report they are constipated most of the time. Chronic constipation, as a whole, accounts for more than 5.7 million constipation-related outpatient visits each year, with 990,994 to emergency rooms and 586,868 to hospital outpatient facilities. More than 282,000 in-patient hospitalizations carry constipation as the primary diagnosis. Diagnosed cases of chronic constipation are evenly distributed across age groups and in both genders, although it is slightly more frequent in women.
Zelnorm is indicated for the short-term treatment of women with IBS whose primary bowel symptom is constipation. The safety and effectiveness of Zelnorm in men with IBS with constipation have not been established.
In chronic constipation studies, the incidence of adverse events with Zelnorm was similar to that of placebo. The only adverse event reported more often with Zelnorm (6 mg twice a day) than placebo was diarrhea (6.6% vs 3%). Diarrhea rarely led to discontinuation of the study (0.9%). Typically, diarrhea was transient, lasting 2 days, and generally resolved without rescue medication or interruption of treatment. Data from the trial that incorporated a 13-month extension study showed Zelnorm to be generally safe and well tolerated in the long term.
In clinical trials involving IBS with constipation, tolerability to Zelnorm was similar to placebo. The only adverse event reported notably more often with Zelnorm than with placebo was diarrhea (9% vs 4%). The majority of patients reporting diarrhea had a single episode and, in most cases, diarrhea occurred in the first week of treatment. Typically, it resolved with continued therapy. Serious consequences of diarrhea, including hypovolemia, hypotension, and syncope, have been reported in the clinical studies (0.04%) and during marketed use of Zelnorm. In some cases, these complications have required hospitalization for rehydration.
Novartis AG is headquartered in Basel, Switzerland. For more information, visit novartis.com.
August 20, 2004
ST. LOUIS (MD Consult) - Eli Lilly and Company announced on August 19, 2004, that the anti-cancer drug Alimta (pemetrexed) had received its second U.S. approval in 2004. The U.S. Food and Drug Administration (FDA) granted accelerated approval for Alimta for the treatment of locally advanced or metastatic non–small cell lung cancer in previously treated patients. In February 2004, Alimta was approved, in combination with cisplatin, for the treatment of malignant pleural mesothelioma, a cancer often associated with asbestos exposure.
Over the past decade, lung cancer rates have continued to rise, and now the disease is the leading cause of cancer death in men and women. According to the American Cancer Society, approximately 174,000 individuals in the United States are diagnosed with lung cancer each year.
Due to the aggressive nature of lung cancer, the disease recurs in the majority of patients and only 40,000 to 50,000 are well enough to tolerate treatment in the second-line setting. Patients treated with the current standard of care in the second-line setting, Taxotere (docetaxel), usually experience severe toxic adverse effects such as diarrhea, hair loss, neutropenia, and neutropenia with fever.
Alimta is an antifolate that simultaneously blocks 3 separate enzyme targets vital to the survival of cancer cells. Alimta's administration includes vitamin supplementation with folic acid and vitamin B12. A team of researchers led by Lilly discovered that this vitamin regimen significantly reduces the drug's adverse effects without negatively affecting its ability to kill cancer cells. The administration cycle for Alimta is a 10-minute infusion, once every 3 weeks.
The FDA-accelerated approval is based on Alimta's efficacy and safety profile as evidenced in one of the largest phase III studies to date in the second-line setting. The study compared Alimta directly to Taxotere. In July, the study was the basis for a unanimous recommendation for accelerated approval by the FDA's Oncologic Drug Advisory Committee.
Alimta's approval was based on the drug's ability to reduce tumor size (response rate) in patients with advanced non–small cell lung cancer.
The FDA also cited Alimta's significantly improved safety profile compared with Taxotere as a supporting basis for approval. Patients taking Alimta also experienced less grade 3 or 4 neutropenia, less neutropenia with fever, less diarrhea, fewer hospitalizations due to adverse events, and less hair loss. As with all chemotherapy agents, patients taking Alimta and Taxotere experienced low blood cell counts. Patients treated with Alimta experienced higher rates of grade 3 or 4 alanine transaminase. Some of the most common grade 3 or 4 toxicities associated with Alimta (regardless of causality) include anemia (8% vs 7% for Taxotere), fatigue (16% vs 17%), anorexia (5% vs 8%), and infection without neutropenia (6% vs 4%).
In accordance with the FDA's accelerated approval, Lilly will continue to gather data for Alimta in non–small cell cancer.
For full prescribing information about Alimta, visit lillyoncology.com.
August 20, 2004
ST. LOUIS (MD Consult) - French pharmaceutical company Aventis announced on August 19, 2004, that the U.S. Food and Drug Administration (FDA) has approved Taxotere (docetaxel) Injection Concentrate in combination with doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) for the adjuvant (post-surgery) treatment of patients with operable, node-positive breast cancer. The supplemental New Drug Application received a Priority Review designation by the FDA, which is assigned to those applications that have the potential for providing a significant therapeutic advance. The additional indication is also under review by the European regulatory authorities.
Taxotere, a drug in the taxoid class of chemotherapeutic agents, inhibits cancer cell division by essentially "freezing" the cell's internal skeleton, which is comprised of microtubules. Microtubules assemble and disassemble during a cell cycle. Taxotere promotes their assembly and blocks their disassembly, thereby preventing many cancer cells from dividing and resulting in death in some cancer cells.
The FDA based its decision on results from a second interim analysis from the pivotal Breast Cancer International Research Group (BCIRG) 001/TAX 316 study, which demonstrated that women with node-positive, early-stage breast cancer who received a Taxotere-based chemotherapy regimen (TAC) after surgery experienced a significant 25.7% reduction in their risk of relapse compared with women treated with another adjuvant combination regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). Notably, with nearly 5 years of follow-up (55 months), the significant reduction in the risk of relapse of this Taxotere-based regimen was observed regardless of a woman's hormone receptor status.
Additionally, at the time of this interim analysis, based on a total of 219 deaths, overall survival was longer for TAC than FAC (hazard ratio, 0.69; 2-sided 95% confidence interval, 0.53, 0.90). There will be further analysis when survival data mature.
The primary end point of the BCIRG 001/TAX 316 multicenter study was to compare the disease-free survival after treatment with Taxotere in combination with doxorubicin and cyclophosphamide to a standard regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide. The nearly 5-year follow-up results of the study were presented at the San Antonio Breast Cancer Symposium on December 5, 2003.
The study enrolled 1,491 premenopausal and postmenopausal women with node-positive, early-stage breast cancer from 112 sites in 20 countries between June 1997 and June 1999. Women were randomly assigned to receive either TAC or FAC in the adjuvant setting.
Follow-up data (55 months) of women in the study did not identify unexpected safety concerns and confirmed the results already presented at the time of the first interim analysis (33 months). Specifically, the TAC regimen was associated with a higher rate of febrile neutropenia compared with FAC (24.7% vs 2.5%). However, incidence of severe infection were similar (3.9% vs 2.2%), and there were no treatment-related deaths due to infection in the study. Patients in the study were not treated with primary prophylactic granulocyte colony-stimulating factor (G-CSF), but G-CSF was required for subsequent cycles after the first episode of febrile neutropenia or infection.
Other severe adverse events occurring in 5% or more of patients treated with TAC included neutropenia, nausea, stomatitis, and asthenia, and with FAC included neutropenia, nausea, vomiting, and asthenia.
More than 90% of patients in both treatment groups received all 6 cycles of treatment.
Breast cancer is the most common cancer among women other than skin cancer. It is the second-leading cause of cancer death in women after lung cancer and is the leading cause of cancer death among women aged 40 to 59 years. More than 1,000,000 new cases of breast cancer are reported worldwide annually, and more than 400,000 women die each year from the disease. The risk of a woman developing breast cancer during her lifetime is approximately 11% (about 1 in 9 of all women worldwide). In the United States alone, breast cancer this year is expected to account for 32% (215,990) of all new cancer cases among women, and approximately 40,110 women will die from the disease.
It is estimated that more than 300,000 women per year worldwide will be diagnosed with node-positive, early-stage breast cancer. Most patients with early-stage breast cancer (cancer localized to the breast with or without invasion of the lymph nodes under the arm) undergo surgery to remove the tumor. After surgery, most patients receive additional treatments, which may include chemotherapy to reduce the probability of tumor recurrence. Earlier diagnosis of breast cancer results in earlier treatment and may offer a better chance for cure.
For more information on Taxotere, visit aventis.com or taxotere.com.
August 13, 2004
ST. LOUIS (MD Consult) - On August 12, 2004, the U.S. Food and Drug Administration (FDA) approved Topamax (topiramate) Tablets and Topamax Sprinkle Capsules for the prophylaxis of migraine headaches in adults. Clinical trials found that about half of all patients receiving the recommended daily dose of Topamax experienced a significant reduction in monthly migraine attacks, compared with placebo.
Migraines are a chronic, debilitating condition characterized by sharp throbbing pain on one side of the head, nausea or vomiting, visual disturbances, and/or sensitivity to noise and light. Approximately 14 million Americans suffer from frequent or severe migraines. Many prescription migraine medicines currently available are taken to treat migraines at the start of an attack. Patients with frequent or severe migraines may be candidates for treatment that may reduce the frequency of their migraine attacks.
According to the National Headache Foundation (NHF), a leading advocacy organization, people with migraines are often forced to cope with their attacks. Whereas some retreat to a quiet, dark room and wait out an attack, many attempt to endure them, struggling through even the simplest tasks such as completing household chores.
People with migraines should talk to their doctors about the treatment options that are right for them. Factors to discuss include the frequency and severity of the migraines, medications they are currently using, how often they are using their migraine medications, and how well their current migraine medications are working.
Topamax has been approved for migraine prophylaxis in 22 countries. The usefulness of Topamax in the acute treatment of migraine headaches has not been studied. Like most medicines, Topamax may cause adverse effects. The most common adverse effect is tingling in the extremities. Others include fatigue, loss of appetite, nausea, taste alteration, diarrhea, cognitive side effects, and weight loss. Serious, as well as minor, adverse effects have been reported with Topamax.
Ortho-McNeil Pharmaceutical, Inc, markets Topamax in the United States. Johnson & Johnson Pharmaceutical Research & Development, LLC, discovered Topamax and conducted the research for the new indication. For more information, or for full U.S. prescribing information, visit ortho-mcneil.com or topamax.com or call 1-800-682-6532.
August 13, 2004
ST. LOUIS (MD Consult) - Shire Pharmaceuticals Group, PLC, announced on August 12, 2004, that its treatment for attention deficit hyperactivity disorder (ADHD), Adderall XR (mixed salts of a single-entity amphetamine) has been approved by the U.S. Food and Drug Administration (FDA) as a once-daily treatment for adults.
Shire will begin promoting the adult indication in the United States immediately.
In addition, the FDA has confirmed to Shire that new 40-mg, 50-mg, and 60-mg dose strengths of Adderall XR will require additional clinical data for approval.
Adderall XR is a once-daily extended release, single-entity amphetamine product available in 5-mg, 10-mg, 15-mg, 20-mg, 25-mg, and 30-mg doses. The capsule contains 2 types of drug-containing beads designed to give a double-pulsed delivery of amphetamines, which prolongs the release of amphetamine from Adderall XR compared with the conventional Adderall (immediate-release) tablet formulation. The FDA approved Adderall XR in November 2001 for the treatment of ADHD in children.
Shire Chief Executive, Matthew Emmens, noted that physicians have been prescribing Adderall XR for adults in an off-label capacity for some time, stating that adults represent 15% to 20% of those currently receiving prescriptions of the drug.
According to Shire, studies have shown that up to 65% of children with ADHD continue to exhibit symptoms into adulthood, and an estimated 4.4% of the U.S. adult population is affected by ADHD. If left untreated, this disorder can lead to other psychological difficulties, such as depression and occupational and social disability. Appropriate diagnosis and treatment of ADHD in adults helps improve self-esteem, work performance and skills, educational attainment, and social competencies. Over 8 million adults in the U.S. may exhibit the symptoms of ADHD, and only an estimated 600,000 are being treated.
Shire Pharmaceuticals is a global company headquartered in London. For more information, visit shire.com.
August 12, 2004
ST. LOUIS (MD Consult) - Abbott Laboratories announced on August 10, 2004, that the U.S. Food and Drug Administration (FDA) had approved an expanded indication for its rheumatoid arthritis (RA) treatment, Humira (adalimumab), to include improvement in physical function for adult patients with moderately to severely active RA.
Improvement in physical function is an important goal of therapy for patients with RA, who often experience disability and loss of function that can greatly reduce quality of life. "It is not uncommon for RA patients to live with such debilitating pain and loss of function that they cannot perform simple activities such as bathing or even cutting up food," said Arthur Kavanaugh, MD, rheumatologist and professor of medicine at University of California, San Diego. Many people with RA are unable to groom or dress themselves, and some cannot walk due to the crippling effects of their disease.
The FDA based its approval on a supplemental Biologics Licensing Application (sBLA) filed by Abbott on September 30, 2003. In 2002, Humira was approved to reduce signs and symptoms and to inhibit the progression of structural damage in adult patients with moderately to severely active RA who have had an inadequate response to 1 or more disease-modifying antirheumatic drugs (DMARDs).
The physical function approval was based on a 52-week open-label continuation study of 457 RA patients with inadequate response to methotrexate who were previously enrolled in a double-blind, placebo-controlled, 52-week lead-in study. The continuation study was designed to assess the maintenance of improved physical function in patients treated with Humira.
Improvement in physical function was measured using the Health Assessment Questionnaire Disability Index (HAQ). HAQ is a measure of physical function that assesses a patient's ability to perform normal daily activities such as getting dressed, walking, and climbing stairs.
In this study, meaningful improvements in HAQ were achieved as soon as 2 weeks after the first Humira dose, and improvements in physical function were maintained with Humira through 2 years of treatment. Sustained improvement in HAQ scores beyond 2 years has also been seen in other trials with Humira: in one long-term open-label study presented previously in 2004, HAQ response was maintained for up to 5 years.
Improvement in physical function was also demonstrated using the Short Form 36-item Health Survey (SF-36), a broad questionnaire that examines the physical and mental impact of RA on patients. SF-36 assesses several quality-of-life factors, including vitality, mental health, bodily pain, general health perceptions, and limitations in physical, social, and emotional functioning. Data showed that clinically meaningful improvements in SF-36 measures for patients taking Humira were sustained for 2 years.
Cases of tuberculosis have been observed in patients receiving Humira. Serious infections and sepsis, including fatalities, have been reported with the use of tumor necrosis factor (TNF)-blocking agents, including Humira. Many of these infections occurred in patients also taking other immunosuppressive agents that, in addition to their underlying disease, could predispose them to infections. The combination of Humira and anakinra is not recommended.
TNF-blocking agents, including Humira, have been associated in rare cases with demyelinating disease and severe allergic reactions. Rare reports of serious blood disorders and lymphoma have been reported with TNF-blocking agents. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of TNF-blocking therapy in the development of malignancies is not known.
The most frequent adverse events seen in the placebo-controlled clinical trials of RA (Humira vs placebo) were injection site reactions (20% vs 14%), upper respiratory infection (17% vs 13%), injection site pain (12% vs 12%), headache (12% vs 8%), rash (12% vs 6%), and sinusitis (11% vs 9%). Discontinuations due to adverse events were 7% for Humira and 4% for placebo. As with any treatment program, the benefits and risks of Humira should be carefully considered before therapy is initiated.
More than 5 million people worldwide suffer from RA, a chronic autoimmune disease that causes pain, swelling, and stiffness in the joints of the hands, feet, and wrists and often leads to the destruction of joints. Unlike osteoarthritis, the most common form of arthritis, RA is an autoimmune disease in which joints are inflamed, resulting in the eventual destruction of the joints interior and the surrounding bone.
More information