New dosing regimens available for saquinavir (Invirase and Fortovase)
SSRI Lexapro approved for treatment of generalized anxiety disorder
FDA expands indication of palivizumab to include children with hemodynamically significant CHD
Factive approved for treating multidrug-resistant pneumococcal infection
FDA converts Gleevec in second-line setting to regular approval
FDA Guidance Stresses Importance of Genetic Differences in Drug Development
U.S. FDA okays Glaxo's Valtrex to prevent herpes transmission
U.S. clears Humatrope for treatment of short stature in children
Lescol approved for secondary prevention of cardiovascular events
FDA gives Alcon approval to sell new antibiotic solution for conjunctivitis
FDA approves Remicade for expanded Crohn's disease indication
Lamictal approved by FDA for treating partial seizures in children
December 30, 2003
ST. LOUIS (MD Consult) - On December 24, 2003, the U.S. Food and Drug Administration approved new dosing regimens for the 2 available formulations of saquinavir, Invirase and Fortovase. The newly approved dosing regimen for saquinavir (both Invirase and Fortovase) is 1000 mg twice a day co-administered with ritonavir 100 mg twice a day.
For Invirase, the new, ritonavir-boosted regimen replaces the previously approved regimen. As stated in the revised label, Invirase should never be used without ritonavir.
For Fortovase, the ritonavir-boosted regimen allows a reduced pill burden and ease of administration compared with the previously approved regimen. However, unboosted Fortovase remains a dosage option for patients who are unable to tolerate ritonavir.
The approval of the new dosing regimens were based on pharmacokinetic and safety data. Both boosted regimens of saquinavir provide plasma concentrations exceeding that of unboosted Fortovase.
Important changes in the Invirase and Fortovase labels include drug interaction information relevant to the co-administration of ritonavir.
The revised labeling will be available in the coming weeks through the index at fda.gov/cder/approval/index.htm.
December 22, 2003
ST. LOUIS (MD Consult) - On December 15, 2003, Roche Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved labeling for use of the prescription weight-loss medication Xenical (orlistat) in the management of obesity in adolescents aged 12 to 16 years.
"This is very good news for adolescents struggling with overweight and obesity," said Marc S. Jacobson, M.D., attending physician and director of the Center for Atherosclerosis Prevention in the Division of Adolescent Medicine at Schneider Children's Hospital of North Shore-Long Island Jewish Health System. "Obesity is an epidemic, with the number of obese adolescents doubling over the last 20 years. Physicians and parents of overweight and obese adolescents now have a safe and effective treatment option available that will help manage their child's weight."
The safety and efficacy of Xenical in adolescents with obesity was assessed in a randomized, double-blind, placebo-controlled study that lasted 54 weeks and involved 539 patients aged 12 to 16 years. Patients were treated with either 120 mg of Xenical 3 times/d with meals and a reduced-calorie diet containing no more than 30% of calories from fat (n=357) or matching placebo and diet (n=182). The Xenical dose used in the study is consistent with the currently approved dose for adults.
The average age of participants was 13.5 years with an average weight of approximately 210 lbs., putting them in the 99th percentile for their age. Body mass index (BMI) was the primary efficacy parameter because it takes into account changes in height and body weight, which occur in growing children. At the end of treatment, study results demonstrated the following:
A second study showed that the balance of calcium, magnesium, phosphorus, zinc, or copper was not decreased and was similar in those receiving Xenical compared with those receiving placebo. Iron balance was decreased in both Xenical-treated patients and placebo-treated patients.
Xenical is the only available weight-loss medication that works locally in the gut to prevent dietary fat absorption by around 30% to effectively promote weight loss. Xenical is well tolerated. Since it was first marketed in 1998, there have been more than 16.7 million patient treatments with Xenical worldwide. Xenical is approved for weight management in over 140 countries around the world.
The long-term effects of Xenical on morbidity and mortality associated with obesity have not been established. Because Xenical prevents about one third of the fat in the food consumed from being absorbed, patients may experience gas with oily discharge, increased bowel movements, an urgent need to have them, and an inability to control them, particularly after meals containing more fat than recommended. Xenical should not be taken if patients are pregnant, nursing, have food absorption problems, or reduced bile flow. If taking cyclosporine, patients should speak to their doctors before taking Xenical. Xenical reduces the absorption of some vitamins. Therefore, a daily multivitamin is strongly recommended.
For more information about Xenical, visit the web site at www.xenical.com.
December 19, 2003
ST. LOUIS (MD Consult) - On December 18, 2003, Forest Laboratories, Inc, announced that the U.S. Food and Drug Administration (FDA) had approved Lexapro (escitalopram oxalate), a selective serotonin reuptake inhibitor (SSRI), for the treatment of generalized anxiety disorder (GAD).
According to Forest, GAD affects approximately 4 million Americans annually. The new indication is based on 3 studies, all of which were positive and support the efficacy and safety of Lexapro in the treatment of GAD. GAD is characterized by excessive anxiety and worry that significantly affect an individual's daily functioning. Lexapro is also indicated for the initial treatment and maintenance of major depressive disorder.
"One of the biggest challenges in treating GAD patients is finding a treatment that is not only effective, but also one that patients will be able to tolerate for the long term," said Philip Ninan, MD, professor of Psychiatry and Behavioral Sciences and director of the Mood and Anxiety Disorders Program at Emory University School of Medicine. "Lexapro is a first-line treatment option, which has proven to be effective with a favorable side effect profile."
All 3 studies that support the indication approval were randomized, double-blind, placebo-controlled, and 8 weeks in duration. The studies involved approximately 850 patients, 18 to 80 years of age, diagnosed with GAD. Patients in the Lexapro arm were administered a fixed dose of 10 mg/d for the first 4 weeks and then flexibly dosed to a maximum of 20 mg/d. The Hamilton Anxiety Scale (HAMA) total score was the primary efficacy variable, and secondary efficacy measures included changes in HAMA psychic anxiety subscale and Clinical Global Impressions (CGI) scores. In each of the 3 studies, Lexapro 10 to 20 mg/d significantly improved GAD symptoms in patients compared with placebo, as measured by change from baseline in HAMA score. By-visit analyses of data pooled across the 3 studies revealed significantly greater improvement in the Lexapro group beginning at week 1 or 2 and continuing through week 8 for all primary and secondary efficacy variables.
Further analysis of 1 of the 3 placebo-controlled studies showed that Lexapro-treated patients experienced a significant improvement in quality of life compared with patients treated with placebo as measured by the Quality of Life (QOL) scale. Sixty-eight percent of Lexapro-treated patients in the study demonstrated a significant response rate compared with 41% of placebo-treated patients. In addition, more than twice as many patients in the Lexapro 10 to 20 mg/d group were in remission at week 8 than in the placebo group (36% and 16%, respectively).
Lexapro was well tolerated in the pooled analysis of the 3 studies, with 8% of patients discontinuing treatment due to adverse events compared with 4% of patients in the placebo group. The most commonly reported adverse events in the Lexapro group versus placebo were nausea (18.2% vs 7.5 %), ejaculation disorder (14.3% vs 1.5%), insomnia (11.9% vs 5.6%), fatigue (7.7% vs 2.1%), decreased libido (6.8% vs 2.1%), and anorgasmia (5.7% vs 0.4%).
According to Forest Laboratories, anxiety disorders are the most common mental illness in the United States, affecting 19.1 million adults. The United States spends more than $42 billion a year treating these conditions. The prevalence of GAD is estimated to be 4 million, or 2.8%, of the U.S. population, and it affects women twice as often as men.
According to The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), the essential feature of GAD is excessive anxiety and worry (apprehensive expectations) about everyday events or activities for 6 months or more. This constant worry affects daily functioning and can cause physical symptoms. For a diagnosis to be made, worry must be present more days than not for at least 6 consecutive months. GAD frequently co-occurs with mood disorders, including depression. Additionally, up to 80% of people suffering from depression also experience symptoms of anxiety.
Lexapro was first approved by the FDA in August 2002 for both the initial and maintenance treatment of major depressive disorder. Lexapro is available in tablet form and as an oral solution.
As with all SSRIs, Lexapro should not be taken with monoamine oxidase inhibitors (MAOIs). For more information about Lexapro, visit lexapro.com.
December 9, 2003
ST. LOUIS (MD Consult) - On December 8, 2003, the U.S. Food and Drug Administration (FDA) granted Gleevec regular approval as a second-line treatment for refractory chronic myeloid leukemia (CML), a rare, life-threatening form of cancer that affects about 40,000 people in the United States.
Regular approval means that the FDA has determined that Gleevec has demonstrated a long-term clinical benefit for refractory CML patients. When Gleevec was originally approved under the accelerated approval program in May 2001, available evidence indicated that a long-term clinical benefit was highly likely but further studies were necessary to confirm it.
"Our experience with Gleevec demonstrates the value of making promising drugs available early to patients with life threatening diseases based upon valid surrogate endpoints, such as short term tumor response rate, that are reasonably likely to predict that the drug can improve their lives," said Mark B. McClellan, M.D., Ph.D., Commissioner of the FDA. "Our experience also demonstrates the importance of follow-up studies after approval to confirm the drug provides a clinical benefit, just as the sponsor has done in this case."
The accelerated approval program helps make products for serious or life-threatening diseases available earlier in the development process by allowing approval to be based on a promising effect of the drug that can be observed significantly sooner than a long-term clinical benefit. For Gleevec, these promising effects included a normalization of blood cell counts and a reduction in the percent of abnormal chromosomes in bone marrow white blood cells.
As part of the original approval, the sponsor, Novartis Pharmaceuticals, was required to continue to study patients in their initial studies to confirm long-term benefit for this particular indication. Data presented to the FDA showed that 95% of patients achieved normal blood cell counts. Further, favorable treatment responses were sustained. An estimated 88% of patients who achieved a reduction in the percent of abnormal chromosomes in bone marrow white blood cells maintained that response for at least 2 years. After 2 years of treatment, an estimated 85% of patients were free of disease worsening. The estimated overall survival was 91%.
As a result of this additional data, the FDA was presented with enough information to convert Gleevec, in this particular treatment setting, to regular approval.
Since May 2001, Gleevec has been approved for use in the first-line treatment CML, for use in pediatric leukemia, and for a gastrointestinal stromal cancer, a rare form of stomach/intestinal cancer.
The drug is manufactured by Novartis Pharma AG for Novartis Pharmaceuticals Corporation, East Hanover, N.J.
November 26, 2003
ST. LOUIS (MD Consult) - On November 19, 2003, the U.S. Food and Drug Administration (FDA) approved the first-ever indication for the over-the-counter (OTC) relief of hives, a common skin condition. Schering-Plough Corporation announced that new Claritin Hives Relief tablets are the first and only FDA-approved, non-drowsy antihistamine to offer OTC itch relief to adults and children 6 years of age and older who suffer from hives. The once-daily formulation will begin shipping in February 2004 in 10- and 30-count packages.
Hives, also known as urticaria, affects approximately 25% of the U.S. population at least once in their lives. Hives are raised, itchy welts on the surface of the skin that are triggered by many factors, such as food, medicines, temperature, and stress. The welts, which can last from a few hours to several weeks, are pink or red and appear as bumps, blotches, or streaks. The triggers cause the release of histamine that, in turn, causes the symptoms of hives.
"Before this approval, many hives sufferers treated their condition with an OTC antihistamine that wasn't FDA-approved for the treatment of hives. If they used an OTC antihistamine for hives relief, they also had to cope with the negative side effects, such as drowsiness or medicine haze, that some medications can cause," said Dr. Leonard Fromer, a California-based, board-certified family practitioner, with a subspecialty in allergies, and a fellow of the American Academy of Family Physicians. "Claritin Hives Relief now offers people with hives a non-drowsy alternative that is clinically proven to safely and effectively relieve itching due to hives, without a prescription."
The FDA approved Claritin Hives Relief tablets for the relief of "itching due to hives," which is the most common indicator and most bothersome symptom of the condition. This is an important advancement because no other OTC medication has ever been approved by the FDA for the relief of hives symptoms. The FDA's decision was contingent upon the results of label comprehension studies fielded by Schering-Plough to demonstrate that the label could be properly understood by consumers.
Claritin Hives Relief effectively relieves severe itching due to hives. Multiple clinical studies in the United States, Canada, and other countries around the world have shown that Claritin Hives Relief is safe and well tolerated for the treatment of hives.
November 25, 2003
ST. LOUIS (MD Consult) - On November 24, 2003, Germany-based Schering AG announced it had received approval from the U.S. Food and Drug Administration (FDA) to market Climara Pro (estradiol/levonorgestrel transdermal system) for the treatment of moderate to severe vasomotor symptoms associated with menopause, such as hot flashes and night sweats. According to a statement from Schering, Climara Pro, a thin, translucent patch, is the first once-a-week combined hormone therapy approved in the United States.
"Hormone treatment is one of the most effective ways to alleviate menopausal symptoms," said Dr. Philip Smits, Head of Schering AG's Gynecology & Andrology division.
Climara Pro is a transdermal hormone therapy (HT) that uses levonorgestrel, a progestin that has been used worldwide in a variety of women's health care products for more than 20 years with millions of patient-years of experience. This patch also contains estradiol, an estrogen that is identical to the estrogen a woman's body produces before menopause. Transdermal (patch) technology allows for continuous delivery of hormones at doses much lower than in pills. Climara Pro delivers 0.015 mg/d of levonorgestrel and 0.045 mg/d of estradiol. Estradiol is the most active estrogen produced by the ovary.
Climara Pro is indicated for use by women with an intact uterus, wheras Climara-Schering's once-a-week estrogen-only patch-is appropriate for women who have had a hysterectomy.
Climara Pro is expected to be available in January 2004.
November 24, 2003
ST. LOUIS (MD Consult) - On November 17, 2003, pharmaceutical company Pfizer Inc announced it had received U.S. Food and Drug Administration (FDA) approval to market Vfend (voriconazole), a broad-spectrum antifungal medicine, for the treatment of esophageal candidiasis.
Candida organisms are normally found on skin and mucous membranes in healthy individuals, but in persons whose immune systems are weakened or compromised by cancer chemotherapy, organ transplants, or HIV/AIDS, candidae can multiply causing potentially serious infections. In immunocompromised patients, esophageal candidiasis may coat much of the surface of the mouth, resulting in pain and difficulty swallowing, and may ultimately progress to more serious, invasive disease.
The basis for the approval of Vfend to treat esophageal candidiasis was a clinical trial with immunocompromised patients conducted at study sites in 15 countries. All patients had a proven diagnosis of esophageal candidiasis, and most of the patients also had additional underlying diseases, such as hematologic malignancies, chronic obstructive pulmonary disease (COPD), and AIDS.
Patients in the trial received either Vfend or fluconazole. Those treated with Vfend had success rates of 98% compared with 95% for fluconazole. Both Vfend and fluconazole had acceptable tolerability and safety.
Vfend was discovered by Pfizer researchers and was developed to address the unmet medical need for more effective and better-tolerated options for patients with invasive aspergillosis and other serious fungal infections.
Vfend was first approved in the United States in 2002 and was initially prescribed for the primary treatment of acute invasive aspergillosis and salvage therapy for rare but serious fungal infections caused by the pathogens Scedosporium apiospermum and Fusarium species. Vfend can be administered both orally and intravenously. Pfizer is continuing to study Vfend for the treatment of serious fungal infections.
In clinical trials, the most common adverse events (all causalities) were rash, fever, vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, visual disturbances, and respiratory disorders. The treatment-related adverse events that most often led to discontinuation in clinical trials were rash, elevated liver function tests, and visual disturbances.
November 24, 2003
ST. LOUIS (MD Consult) - On November 19, 2003, TAP Pharmaceutical Products Inc announced that the U.S. Food and Drug Administration (FDA) had approved Prevacid NapraPAC (lansoprazole delayed-release capsules and naproxen tablets kit), a combination package containing two medications in one prescription.
Prevacid NapraPAC contains the nonsteroidal anti-inflammatory drug (NSAID) Syntex Pharmaceuticals' Naprosyn (naproxen tablets) and the acid suppressor Prevacid (lansoprazole), a commonly prescribed proton-pump inhibitor (PPI) marketed by TAP Pharmaceuticals, in one package. Prevacid NapraPAC is indicated for reducing the risk of NSAID-associated gastric ulcers in patients with a history of a documented gastric ulcer who also require the use of an NSAID for treatment of the signs and symptoms of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.
According to Lake Forest, Ill-based TAP, approximately 20 million people in the United States have osteoarthritis (OA) and 2.1 million adults have rheumatoid arthritis (RA). NSAIDs are commonly prescribed for the relief of pain and inflammation in these patients.
"Naprosyn, like most NSAIDs, is very effective at relieving pain associated with arthritis, but it has been recognized as being associated with serious gastrointestinal side effects, like stomach ulcers," said A. Mark Fendrick, MD, associate professor of Internal Medicine in the School of Medicine at the University of Michigan Health System. "Prevacid NapraPAC represents an easy-to-use option in one prescription for arthritis patients who must take anti-inflammatory agents to relieve their pain, but who also need to reduce the risk of recurrence of stomach ulcers."
NSAIDs can cause ulcers by interfering with the stomach's ability to protect itself from gastric irritants, such as acid. Gastric ulcers are round or oval sores where the lining of the stomach has been eaten away by stomach acid and digestive juices. NSAIDs, such as aspirin and naproxen, can irritate the stomach lining and cause ulcers.
In the United States, it is estimated that 14 million people take an NSAID on a daily basis. Approximately 100,000 patients are hospitalized and between 10,000 to 20,000 patients die each year from NSAID-related ulcer complications. The risk of NSAID-induced gastrointestinal events is increased two- to fourfold in patients with a history of prior ulcer disease or complications. This is the most significant risk factor for NSAID-induced complications.
A multicenter, double-blind placebo- and misoprostol-controlled study examined more than 500 patients who required chronic use of NSAIDs and who had a history of a documented gastric ulcer. Patients were randomly assigned to receive 15 mg or 30 mg Prevacid once daily, 200 mcg misoprostol four times a day, or placebo for 12 weeks. Data from this study demonstrated that significantly more patients remained ulcer free with Prevacid compared with placebo. In fact, after 12 weeks of the study, 80% of patients taking Prevacid 15 mg, 82% taking Prevacid 30 mg, and 93% taking misoprostol 200 mcg remained ulcer free compared with only 51% taking placebo.
Furthermore, in a subset analysis of study data from 119 patients, 89% of patients taking Prevacid 15 mg plus naproxen, with or without aspirin, remained free of recurrent stomach ulcers after 12 weeks versus 83% of patients taking misoprostol and 33% taking placebo plus naproxen. Concomitant aspirin was used in 15% of patients. The controlled studies did not extend beyond 12 weeks.
Prevacid NapraPAC is available as a daily dose of one Prevacid 15 mg delayed release capsule and two Naprosyn tablets of either 375 mg or 500 mg. Naprosyn is an NSAID with analgesic and antipyretic properties that has been prescribed for over 25 years for relief from pain associated with conditions such as rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis.
A monthly course of Prevacid NapraPAC is conveniently supplied in weekly blister cards. The easy-to-use blister card indicates which pills to take on which days, an important convenience for patients.
Prevacid NapraPAC is contraindicated in patients with known hypersensitivity to any component of the formulations of lansoprazole or naproxen.
Naproxen is also contraindicated in patients in whom aspirin or other NSAIDs/analgesic drugs induce the syndrome of asthma, rhinitis, and nasal polyps. Both types of reactions have the potential to be fatal. Other naproxen-containing products should not be used concomitantly.
Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation can occur with or without warning symptoms with chronic NSAID therapy.
In the risk-reduction study of Prevacid for NSAID-associated ulcers, the incidence of diarrhea was 5% and 3% for the Prevacid and placebo groups, respectively. Symptomatic response to Prevacid does not preclude the presence of gastric malignancy.
For complete prescribing information on Prevacid NapraPAC, visit prevacid.com/naprapac/pi or call 800-622-2011.
November 19, 2003
ST. LOUIS (MD Consult) - On November 17, 2003, the U.S. Food and Drug Administration (FDA) approved Advair Diskus 250/50 (fluticasone propionate 250 mcg and salmeterol inhalation powder 50 mcg) for treatment of chronic obstructive pulmonary disease (COPD) in patients with chronic bronchitis.
COPD is a serious and debilitating lung disease that, according to a statement from the Advair's manufacturer, GlaxoSmithKline, affects an estimated 20 million Americans. Many people with COPD have associated chronic bronchitis.
Advair Diskus 250/50 is indicated for the maintenance treatment of airflow obstruction in patients with COPD associated with chronic bronchitis. The drug was first approved in August 2000 for the treatment of asthma in patients aged 12 years and older.
Although no adverse effects on the cardiovascular system are usually seen with the administration of Advair Diskus in recommended doses, the cardiovascular and central nervous system effects seen with all sympathomemetic drugs (eg, increased blood pressure, heart rate, excitement) can occur after use of salmeterol, a component of Advair Diskus. These effects may require discontinuation of the regimen.
According to the FDA, Advair Diskus, like all medications containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Patients with convulsive disorders or thyrotoxicosis and those who are unusually responsive to sympathomimetic amines should also confer with their physicians before taking Advair Diskus.
Clinically significant changes in blood glucose or serum potassium were seen rarely during clinical studies with Advair Diskus given at recommended doses.
For more information, contact GlaxoSmithKline at 215-751-7709 or gsk.com.
November 12, 2003
ST. LOUIS (MD Consult) - On November 3, 2002, the U.S. Food and Drug Administration (FDA) issued a new document, "Draft Guidance for Industry: Pharmacogenomic Data Submissions," that encourages drug and biologic developers to conduct pharmacogenomic tests during drug development and clarifies how the FDA will evaluate the resulting data.
"Pharmacogenomics holds great promise to shed scientific light on the often risky and costly process of drug development, and to provide greater confidence about the risks and benefits of drugs in specific populations," said FDA Commissioner Mark B. McClellan, MD, PhD. "Pharmacogenomics is a new field, but we intend to do all we can to use it to promote the development of medicines. By providing practical guidance on how to turn the explosion of pharmacogenomic information into real evidence on new drugs, we are taking an important step toward that goal."
Pharmacogenomics deals with the small genetic differences that help explain why some people respond positively to a drug, and others don't respond or may experience an adverse effect. Genetic differences also can predict variations in drug metabolism—how quickly or slowly a drug is eliminated from the body. In the draft guidance, the FDA said that the promise of pharmacogenomics lies in its potential ability to individualize therapy by predicting which individuals have a greater chance of benefit or risk—thus helping to maximize the effectiveness and safety of drugs. The FDA believes that pharmacogenomic testing can be smoothly integrated into drug development processes.
This is the FDA's first step toward integration of this new field into the process of demonstrating that new drugs are safe and effective, and thus the regulatory guidance is intended to facilitate this integration. This guidance is intended to ensure that evolving regulatory policies and study designs are based on the best science; provide public confidence in this new field where scientifically appropriate; facilitate the use of such tests during drug development; and clarify for industry what types of pharmacogenomic data to submit to the FDA.
"Using genomic testing to guide drug therapy will constitute a significant shift from the current practice of population-based treatment towards 'fine-tuning' individual therapy," said Janet Woodcock, the FDA's Director of the Center for Drug Evaluation and Research.
Currently, scientific understanding of phamacogenomics is most advanced in the drug metabolism area, and early results are expected in this field. However, the FDA anticipates rapid evolution of additional uses. For example, it is hoped that pharmacogenomic testing will help identify cancers that have a high probability of responding to a particular medication or regimen. Pharmacogenomics may also be used to help track down the cause of certain rare and serious drug adverse effects.
The guidance provides specific criteria and recommendations on submission of pharmacogenomic data to investigational new drug applications (INDs), and New Drug Applications (NDAs), and Biological License Applications (BLAs). This includes information on what data is needed and how the FDA will or will not use such data in regulatory decisions.
Because there is a need for scientific exchange, the agency is asking for voluntary submissions of research information. This data will help the FDA gain experience as the field evolves. In these cases, the FDA advises sponsors to clearly label voluntary submissions, and the agency advises that it will not use information from voluntary reports for regulatory decisions. If a sponsor subsequently develops additional data that meet the criteria for submission for regulatory purposes, the Agency advises sponsors that such data should be submitted as explained in the guidance.
The FDA's Science Board recently (April 2003) endorsed FDA proposals to move forward with this guidance on assisting industry in deciding whether a submission is needed. In addition, the FDA held public meetings and workshops in which the key issues for drug development were identified.
The FDA plans to issue further guidance on co-development of pharmacogenomic tests and pharmaceuticals in the near future. The draft guidance is available on the FDA's Web site at fda.gov/cder/guidance/5900dft.pdf.
October 31, 2003
ST. LOUIS (MD Consult) - On October 29, 2003, the U.S. Food and Drug Administration (FDA) approved a long-acting injectable form of Risperdal (risperidone) for the treatment of schizophrenia. The treatment uses advanced technology to deliver and maintain therapeutic medication levels in the body through one injection every 2 weeks.
According to a press release from New Jersey-based Johnson & Johnson, as many as 75% of patients with schizophrenia have difficulty taking their oral medication on a regular basis. Interruption of the medication regimen can lead to worsening of symptoms. The new long-acting formula of risperidone, called Risperdal Consta, addresses this problem.
"By providing consistent levels of medication during a 2-week period, Risperdal Consta eliminates many of the peaks and valleys that you get with medication that you have to take daily. Patients also don't have to remember to take a pill every single day, which is difficult for anyone with a chronic disease," said John Kane, MD, executive director of The Zucker Hillside Hospital and professor of psychiatry at the Albert Einstein College of Medicine in New York.
Schizophrenia is a brain disorder that impairs a person's ability to think clearly, relate to others, and distinguish between reality and imagination. According to the National Institutes of Health (NIH), it is estimated that more than 2 million Americans suffer from the condition. Atypical antipsychotic medications have become the most commonly prescribed treatments for schizophrenia, and many experts believe these medications have advantages over older medications. However, until now, these treatments have been available only in short-acting formulations.
The effectiveness of Risperdal Consta was established in a 12-week, placebo-controlled study in 400 adults with schizophrenia, both in inpatient and outpatient settings. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), a common measure of the total severity of positive symptoms (psychological disturbances "added" as a result of the disorder, such as hallucinations, delusions, suspiciousness and paranoia) and negative symptoms (normal functioning the patient has "lost," resulting in lack of initiative and loss of normal enjoyment).
Patients who received Risperdal Consta experienced significantly greater improvements in both positive and negative symptoms than did those who were administered placebo. Forty-seven percent of patients treated with a 25-mg dosage of Risperdal Consta experienced clinical improvement compared with 17% of those who received placebo. Clinical improvement is defined as 20% or more reduction in PANSS total score.
The most common adverse effects experienced by patients taking Risperdal Consta during the 12-week study were headache, agitation, psychosis, insomnia, dizziness, rhinitis, and pain. Overall, similar proportions of patients reported adverse events in the placebo and Risperdal Consta groups (80% vs 83%), and serious adverse events were more common in the placebo group (23.5%) than in the Risperdal Consta groups (13% in the 25-mg group and 14% in the 50-mg group). The incidence of spontaneously reported adverse events related to extrapyramidal symptoms (reversible movement disorders or muscle disturbances such as restlessness, tremors, and muscle stiffness) in the 25-mg Risperdal Consta group was similar to placebo (10% vs 13%). The rate of adverse events related to extrapyramidal symptoms in the 50-mg group was 24%. Treatment was discontinued due to side effects by 12% of patients receiving Risperdal Consta (37/302) and 12% of patients (12/98) receiving placebo.
As with oral Risperdal, originally approved by the FDA in 1993, patients taking Risperdal Consta experienced low weight gain over 12 weeks (1.1 lbs [0.5 kg] in the 25-mg group and 2.6 lbs [1.2 kg] in the 50-mg group). In addition, patients reported that injection-site pain was low at the first injection and decreased further as the study progressed. On a 100-point rating scale, where 0 represented no pain and 100 represented unbearable pain, patients receiving the 25-mg dose reported pain at a level of 9 after their sixth dose. Further, in all groups, less than 5% of patients experienced redness, swelling, or indurations after injection.
Risperdal Consta uses the proprietary Medisorb drug-delivery technology developed by Cambridge, MA-based Alkermes, Inc. The technology encapsulates active medication into polymer-based microspheres that are injected into the body, where they degrade slowly, gradually releasing the drug at a carefully controlled rate.
Risperdal has been marketed in tablet form in the United States by Janssen Pharmaceutica Products since 1994, and also is available in oral solution and quick-desolving tablet forms.
October 29, 2003
ST. LOUIS (MD Consult) - According to a statement dated October 29, 2003, the U.S. Food and Drug Administration (FDA) has recently been made aware of a substance called tetrahydrogestrinone (THG), which is reportedly used by athletes to improve their performance. Based on the agency's analysis of this product, the FDA has determined that THG is an unapproved new drug. As such, it cannot be legally marketed without FDA approval under the agency's rigorous approval standards that are meant to ensure that drugs that are sold to American consumers are safe and effective.
The FDA is concerned about the marketing and use of this unapproved product and is working with other federal law enforcement agencies to aggressively engage, enforce, and prosecute those firms or individuals who manufacture, distribute, or market THG. "Our mission is to protect the American public from this potentially harmful product," said John Taylor, the FDA's Associate Commissioner for Regulatory Affairs.
In the meantime, the FDA is warning consumers that although little is formally known about the safety of this drug, its structure and relationship to better known products leads the FDA to believe that its use may pose considerable risks to health.
Although purveyors of THG may represent it as a dietary supplement, in fact it does not meet the dietary supplement definition. Rather, it is a purely synthetic "designer" steroid derived by simple chemical modification from another anabolic steroid that is explicitly banned by the U.S. Anti-Doping Agency.
The use of THG by athletes as an alternative to other banned anabolic steroids was recently disclosed by the U.S. Anti-Doping Agency. This substance is closely and structurally related to two other synthetic anabolic steroids, gestrinone and trenbolone. Anabolic steroids, which build muscle mass, can have serious long-term health consequences in men, women, and children.
October 22, 2003
ST. LOUIS (MD Consult) - On October 20, 2003, Amgen and Wyeth Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) had approved a 50-mg once-weekly dosage of Enbrel (etanercept) for adult patients across all indications, including moderately to severely active rheumatoid arthritis (RA), active arthritis in patients with psoriatic arthritis, and active ankylosing spondylitis (AS). In addition, a 0.8-mg/kg once-weekly dosage (maximum 50 mg/wk) for patients aged 4 to 17 years with moderately to severely active juvenile rheumatoid arthritis (JRA) has also been approved.
Instead of taking two 25-mg injections 3 to 4 days apart, patients can now take both injections on the same day.
Data supporting the efficacy and tolerability of the Enbrel once-weekly dosage are from a phase 3 double-blind, placebo-controlled study of 420 patients with active RA. In a 16-week study, patients either were treated with Enbrel (50 mg) once weekly (administered in two 25-mg injections), Enbrel (25 mg) twice weekly, or placebo for 8 weeks followed by Enbrel (25 mg) twice weekly for another 8 weeks.
After 8 (the primary end point) and 16 weeks, there were no significant differences in ACR 20 response scores (a 20% improvement in signs and symptoms) between the two Enbrel groups. The tolerability profile for once-weekly dosing was comparable to that of twice-weekly dosing.
Adverse events were similar to those reported in previous clinical trials of Enbrel, with injection site reactions occurring more frequently than in the placebo group.
Enbrel is the only fully human tumor necrosis factor (TNF) receptor approved to reduce signs and symptoms, to improve physical function, to inhibit the progression of structural damage in patients with moderately to severely active RA, and to reduce the signs and symptoms and inhibit the progression of structural damage of active arthritis in patients with psoriatic arthritis. Enbrel is the only biologic therapy approved for first-line treatment of RA and can be used alone or in combination with methotrexate. It is approved to reduce the signs and syptoms of moderately to severely active polyarticular-course JRA in patients who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). It is also the first biologic agent approved to treat the signs and symptoms in patients with active ankylosing spondylitis (AS).
Enbrel has been used by more than 200,000 patients worldwide across indications since becoming commercially available nearly 5 years ago.
Enbrel acts by binding TNF, one of the dominant inflammatory cytokines or regulatory proteins that play an important role in both normal immmune function and cascade of reactions that causes the inflammatory process of RA, JRA, psoriatic arthritis, and AS. The binding of Enbrel to TNF renders the bound TNF biologically inactive, resulting in a significant reduction in inflammatory activity.
Since the product was first introduced, serious infections have been reported in patients using Enbrel. Many occurred in people prone to infection, such as those with advanced or poorly controlled diabetes. Some serious infections were fatal and included rare cases of tuberculosis.
Patients should not take Enbrel if they have infections or are allergic to Enbrel or its components. Patients who are prone to infection should notify their doctors. If a serious infection occurs, the administration of Enbrel should be halted. Enbrel can also cause injection site reactions.
Serious nervous system disorders such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes have also been reported in perons taking Enbrel. Patients having any of these disorders or developing them after starting Enbrel should notify their doctors.
There have been rare reports of serious blood disorders (some fatal) among patients taking Enbrel. Patients should contact their doctors immediately if they develop symptoms such as persistent fever, bruising, bleeding, or paleness.
In medical studies of all TNF-inhibitors, a higher rate of lymphoma was seen compared with the general population; however, the risk of lymphoma may be up to several-fold higher in patients with RA. The role of TNF-inhibitors in the development of lymphoma is unknown. The incidence of other cancers has not increased with extended exposure to Enbrel and is similar to the expected rate.
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, including serious infections (2%) and depression/personality disorder (1%).
For additional information about Enbrel, including full prescribing information, visit enbrel.com or call 888-4ENBREL (888-436-2735).
October 20, 2003
ST. LOUIS (MD Consult) - On October 17, 2003, British pharmaceutical manufacturer GlaxoSmithKline announced the U.S. Food and Drug Administration (FDA) had approved a new application for its antidepressant medication, Paxil CR (paroxetine hydrochloride). The tablets can now be used to treat social anxiety disorder.
Paxil CR is the first controlled-release selective serotonin reuptake inhibitor (SSRI) approved for treatment of social anxiety disorder, a highly debilitating condition that affects more than 10 million Americans. The medication is also indicated for the treatment of depression, panic disorder, and premenstrual dysphoric disorder (PMDD).
According to GlaxoSmithKline, Paxil CR was generally well tolerated during testing, with a low patient drop-out rate due to adverse events that was comparable to placebo (3% and 2%, respectively).
"Adverse events and poor compliance are often stumbling blocks in treating disorders like social anxiety disorder. As a result, many patients continue to suffer the debilitating symptoms of their condition, which often severely limits their social, home and work relationships," said Dr. Murray Stein, Professor of Psychiatry, University of California San Diego. "The low rate of drop outs due to adverse events seen with the Paxil CR social anxiety disorder study may offer new hope to patients."
The tolerability and efficacy of Paxil CR tablets in the treatment of social anxiety disorder were established in a 12-week, multicenter, placebo-controlled study of 370 patients with social anxiety disorder. Patients were randomly assigned to receive either a flexible dose regimen of Paxil CR (12.5-37.5 mg/d) or placebo. Patients given Paxil CR showed statistically significant and clinically meaningful differences versus placebo in the two primary efficacy variables: mean change from baseline in the Liebowitz Social Anxiety Scale (LSAS) and percent of responders defined by a CGI-Global Improvement score of one (very much improved) or two (much improved).
Social anxiety disorder, also known as social phobia, is the most common type of anxiety disorder, with more sufferers than general anxiety disorder, which currently ranks second. People with social anxiety disorder have an intense fear of being scrutinized by other people in social or performance situations. When exposed to "everyday" social situations such as meetings, classes, parties, speaking in public, and talking to strangers or authority figures, people with social anxiety disorder literally become "sick with fear" and often develop symptoms including rapid heartbeat, sweating, shaking, and upset stomach. Some people with social anxiety disorder avoid these situations altogether, severely limiting their life, work, and social relationships.
Social anxiety disorder is considered one of the most underdiagnosed anxiety disorders with only a small percentage of patients receiving treatment. Often people recognize that they have a life-impairing condition, but do not realize they suffer from an actual medical disorder that can be treated.
Paxil CR tablets contain a multilayered formulation that controls dissolution and absorption of the drug in the body. The drug offers flexible dosing with three dosing strengths: 12.5 mg, 25 mg, and 37.5 mg.
The most common adverse events (incidence of 5% or greater for Paxil CR and at least twice that for placebo) in studies for major depressive disorder, panic disorder, PMDD, and social anxiety disorder include infection, trauma, nausea, diarrhea, dry mouth, constipation, decreased appetite, somnolence, dizziness, decreased libido, tremor, yawn, sweating, abnormal vision, asthenia, insomnia, abnormal ejaculation, female genital disorders, and impotence. Patients should not be abruptly discontinued from any antidepressant medication, including Paxil CR. Concomitant use of this medication in patients taking monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated.
For more information on Paxil CR, visit paxilcr.com or CRBalance.com.
October 21, 2003
ST. LOUIS (MD Consult) - On October 13, 2003, Schering-Plough Corporation announced that the U.S. Food and Drug Administration (FDA) had granted marketing approval for Peg-Intron Redipen, a pre-filled pen for administering Peg-Intron (peginterferon alfa-2b) powder for injection used in the treatment of patients with chronic hepatitis C.
Peg-Intron Redipen is the first pen delivery system approved for administering pegylated interferon therapy. Pegylated interferon, in combination with ribavirin, is the standard of care in treating chronic hepatitis C. The Redipen is designed to be simpler for patients to use than a traditional vial and syringe method of administration.
The Peg-Intron Redipen is a disposable, single-dose delivery system that allows patients to administer Peg-Intron in three steps. First the patient mixes the powdered drug with sterile water, both of which are stored in the pen, by pushing down on the pen; next, the patient sets a dial on the Redipen to select his or her predetermined weight-based dose; then, the patient injects the individualized dose of the medication.
The Redipen will be available in four different strengths: 50, 80, 120, and 150 mcg, each indicated by a color-coded label and dosing button. An instructional videotape and brochure for use by patients and health care professionals will also be made available.
"The Redipen is a high-tech pen delivery system for injecting peginterferon therapy and offers an easy-to-use alternative for people who may be put off by using a traditional vial and syringe," said Alan P. Brownstein, president and chief executive officer of the American Liver Foundation.
The Peg-Intron Redipen is expected to be available in the United States in early 2004. It is currently available in the European Union and several other international markets.
October 9, 2003
ST. LOUIS (MD Consult) - On October 8, 2003, Swiss biotechnology company Serono announced that the U.S. Food and Drug Administration (FDA) approved its new pre-filled syringe for Ovidrel (choriogonadotropin alfa injection) for treatment of infertility.
Designed to make infertility treatment easier for patients, the new Ovidrel pre-filled syringe is the only liquid infertility treatment approved by the FDA that patients can administer in one step. Unlike other infertility treatments, the Ovidrel syringe does not require patients to mix medication before injection. It is also the only available recombinant version of human chorionic gonadotropin (hCG), one of three hormones required to treat infertility.
"Having Ovidrel in a pre-filled syringe will make that step easier for patients and may alleviate some of the difficulties and stresses associated with infertility treatment," said Raymond W. Ke, MD, Associate Professor of Obstetrics and Gynecology at the University of Tennessee and Director of IVF for Fertility Associates of Memphis, Tennessee.
The new pre-filled syringe for Ovidrel will carry the same indication as the currently marketed product for triggering ovulation in women undergoing infertility treatment.
Side effects of Ovidrel may include nausea, headache, tiredness, abdominal pain, and injection-site bruising, pain, or inflammation. As with all methods of assisted reproduction, there is a risk of ovarian hyperstimulation syndrome, multiple pregnancy, or miscarriage.
Infertility is defined as the inability of a couple to achieve pregnancy after 1 year of regular, unprotected intercourse, or after 6 months if the woman is older than 35 years. Serono noted that infertility affects about 6.1 million Americans, representing about 10% of couples in their childbearing years. Infertility is just as likely to be related to male factors as female factors, which each account for about a third of infertility problems. The remaining third are either a combination of male and female factors or are unexplained.
The manufacturer expects the syringe to be available in November 2003, replacing the currently available powder form of the medication.
For more information on infertility and full prescribing information on Ovidrel, visit seronofertility.com.
October 9, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) announced on October 8, 2003, the approval of Inspra (eplerenone) tablets for improving the survival of congestive heart failure patients after an acute heart attack.
Inspra is the first member of the aldosterone receptor blocker class of drugs to receive approval for this indication. The use of Inspra in the placebo-controlled clinical trial supporting its approval resulted in a significant (15%) reduction in the risk of death. The reduction in the risk of death and improved survival with Inspra occurred in patients who were typically receiving other appropriate therapy.
According to the National Heart, Lung and Blood Institute, part of the National Institutes of Health, more than 1 million persons in the United States have a heart attack annually, and about half (515,000) die. More than one third of heart attack survivors will develop heart failure and an increased risk of death. Half of the patients who develop heart failure will be dead within 5 years.
Pfizer Inc. is the sponsor of the approved New Drug Application (NDA) for Inspra. The FDA first approved Inspra in 2002 for the treatment of hypertension. The FDA reviewed the sponsor's application for the new use of Inspra on a priority basis, approving it within 6 months of receipt.
Inspra, an aldosterone blocker, works by inhibiting the effects of aldosterone, a hormone that may contribute to the development and progression of hypertension and congestive heart failure, including damage to blood vessels, kidney, and the heart. The medication will be available in December 2003.
September 23, 2003
ST. LOUIS (MD Consult) - On September 16, 2003, MedImmune, Inc. announced that the U.S. Food and Drug Administration (FDA) approved the addition of new safety and efficacy data to the prescribing information of its drug Synagis (palivizumab).
In a large study conducted in children with complex congenital heart disease (CHD), investigators' findings supported the drug's use in young children with hemodynamically significant CHD to prevent hospitalization caused by respiratory syncytial virus (RSV). According to Gaithersburg, Maryland–based MedImmune, RSV is the most common cause of lower tract respiratory infections in infants and children worldwide, typically occurring during the fall and winter months.
Congenital heart defects are structural problems of the heart that are present at birth, having occurred during development. Approximately 32,000 children are born in the U.S. each year with CHD. Children born with serious CHD who have decreased cardiac or pulmonary reserve appear to be at highest risk of serious RSV infection. These children have been shown to require intensive care and use mechanical ventilation with RSV infection more frequently than children who do not have CHD. Furthermore, children with CHD who are hospitalized with RSV have a fatality rate that is 2 to 6 times greater than those without CHD.
Synagis is a humanized monoclonal antibody that was licensed by the FDA in 1998 to prevent serious lower respiratory tract disease caused by RSV in pediatric patients at high risk of RSV disease. MedImmune submitted data to the FDA in November 2002 from its multinational phase 3 clinical study indicating that Synagis was safe and effective in preventing RSV-related hospitalizations in young children with hemodynamically significant CHD.
Dr. Henry M. Sondheimer, professor of pediatrics at University of Colorado Health Sciences Center and clinical director of Pediatric Cardiology at The Children's Hospital, Denver, said, "Children with CHD who are hospitalized with RSV have substantially higher rates of morbidity and mortality than those children who do not have CHD. With the FDA's approval of CHD information in the Synagis label, pediatricians and pediatric cardiologists will have a better understanding of those vulnerable children who will most benefit from RSV prophylaxis with Synagis."
The regulatory submission was based on a 4-year, double-blind, placebo-controlled study assessing 1,287 children younger than 2 years of age with serious CHD. In the study, children were randomly assigned to receive monthly intramuscular injections (15 mg/kg) of either Synagis (n = 639) or placebo (n = 648) during 4 consecutive RSV seasons. The study was conducted at 76 centers in North America, France, Germany, Poland, Sweden, and the United Kingdom and was completed in 2002. The Synagis group had 45% relative reduction in hospitalizations due to RSV (P = .003) compared with the placebo group, with a total of 34 versus 63 patients requiring hospitalization. The adverse events reported in the 2 treatment groups were similar.
For children with chronic lung disease, premature infants who are younger than 36 weeks' gestational age, and children with significant CHD, clinical studies have now demonstrated that palivizumab is safe and effective at preventing serious RSV-related hospitalizations.
For more information on Synagis, contact MedImmune at 240-632-4035 or medimmune.com.
September 10, 2003
ST. LOUIS (MD Consult) - On September 9, 2003, Illinois-based Abbott Laboratories announced that the U.S. Food and Drug Administration (FDA) has approved its anti-epilepsy drug Depakote ER (divalproex sodium, extended release) tablets for the treatment of seizures in children, aged 10 and older.
Depakote ER is the once-daily formulation of Depakote (divalproex sodium, delayed release) tablets, which has been used in the treatment of epilepsy since its initial approval in 1983. Depakote ER was approved for migraine prevention in adults in 2000 and for epilepsy in adults in 2002.
"In a pharmacokinetic study of Depakote ER in pediatric patients, the clinical researchers found that Depakote ER produces consistent, therapeutic concentrations of medication throughout an entire 24-hour cycle. I have also found that once-a-day dosing is much more convenient for children and their parents," said John Pellock, MD, professor of pediatrics and neurology, Virginia Commonwealth University, Medical College of Virginia.
Approximately 2 million Americans have some form of epilepsy, with approximately 50% of newly diagnosed cases of epilepsy reported in children under age 18. Epilepsy is a chronic neurologic condition that can result in periodic disturbances in the normal electrical functions of the brain, resulting in seizures, which are caused by unusually intense and intermittent electrical energy in the brain. Seizures can affect a person's consciousness, body movements, or sensations for short periods of time.
The pharmacokinetic profile and safety of Depakote ER was studied in a 1-week open-label trial involving subjects between 8 and 17 years of age. Subjects enrolled in the study were already taking Depakote delayed-release tablets or Depakote ER tablets. All subjects were given doses of Depakote ER equivalent to their previous doses and were divided into two groups, one age 8 to 11 (n = 14), and the other age 12 to 17 (n = 12). The pharmacokinetic profiles were compared with the profiles of a healthy adult historical control group.
The concentration-time profiles of Depakote ER were similar among the 8- to 11-year-olds and the 12- to 17-year-olds, and the profiles did not differ significantly from the profile observed in the historical adult control group. The Depakote ER once-daily regimens were generally well tolerated. Adverse events reported by three or more subjects were flu syndrome (17%) and headache (10%).
In addition, Depakote ER once daily produced 40% to 50% lower peak-to-trough fluctuations compared to other valproate formulations requiring more frequent dosing. This behavior of Depakote ER in pediatric patients is similar to the performance of Depakote ER in adults.
Depakote, Depakote ER (in adults and children), Depakote Sprinkle Capsules, and Depacon (all manufactured by Abbott) are indicated for the treatment of complex partial seizures and simple and complex absence seizures. Depakote and Depakote ER are also indicated for the prevention of migraine headaches in adults. Valproate products should not be administered to patients with hepatic disease or significant hepatic dysfunction. Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives, usually during the first 6 months of treatment. Valproate may produce teratogenic effects in the offspring of women receiving the drug during pregnancy.
Benefits of using Depakote and Depakote ER in migraine treatment should be weighed against the risk of injury to the fetus in women of childbearing potential. Cases of life-threatening pancreatitis, some rapidly progressing to death, have been reported in both adults and children receiving valproate. Valproate administration is contraindicated in patients with known urea cycle disorders, a group of uncommon genetic abnormalities, due to reports of sometimes-fatal cases of hyperammonemic encephalopathy. The frequency of adverse effects, particularly elevated liver enzymes and thrombocytopenia, may be dose related.
In a clinical trial of valproate in elderly patients with dementia, some patients taking valproate experienced somnolence, sometimes requiring discontinuation. The safety and effectiveness of Depakote and Depakote ER for the prevention of migraine patients older than 65 years have not been established.
The safety and effectiveness of Depakote ER for the prophylaxis of migraine headaches in pediatric patients has not been established. The safety and effectiveness of Depakote ER for the treatment of epilepsy has not been established in pediatric patients younger than the age of 10.
September 3, 2003
ST. LOUIS (MD Consult) - On September 2, 2003, the U.S. Food and Drug Administration announced it had granted approval of Paxil CR (paroxetine hydrochloride) for the treatment of premenstrual dysphoric disorder (PMDD).
The drug's manufacturer, Great Britain-based GlaxoSmithKline, stated that the condition affects 3% to 8% of women of reproductive age in the United States.
PMDD is characterized by intense emotional symptoms including irritability, tension, anxiety, and depressed mood as well as physical symptoms associated with the menstrual cycle. Paxil CR is also indicated for the treatment of depression and panic disorder.
The tolerability and efficacy of Paxil CR for the treatment of PMDD was established in placebo-controlled studies. In these studies, the lowest dose of Paxil CR performed significantly better than placebo in reducing the emotional and physical symptoms of PMDD. Similar results were seen with the 25 mg/d dose. Patients reported significant improvements in social functioning. Compared with women taking placebo, patients taking Paxil CR reported fewer symptoms that interfered with regular daily activities.
Paxil CR is a multi-layered formulation that controls dissolution and absorption of the drug in the body. The tablets are available in three dosing strengths: 12.5, 25, and 37.5 mg.
Most common adverse events (incidence of 5% or greater and incidence for Paxil CR) in studies for major depressive disorder, panic disorder, and premenstrual dysphoric disorder included infection, trauma, nausea, diarrhea, impotence, tremor, sweating, drowsiness, dizziness, constipation, dry mouth, decreased appetite, decreased libido, abnormal vision, asthenia, insomnia, abnormal ejaculation, and female genital disorders. Patients should not be abruptly discontinued from antidepressant medication, including Paxil CR. Concomitant use of Paxil CR in patients taking monoamine oxidase inhibitors (MAOIs) or thioridazine is contraindicated.
For more information on Paxil CR, contact GlaxoSmithKline at 919-483-2839.
September 2, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) approved a new indication for Valtrex (valacyclovir hydrochloride) Caplets on August 29, 2003. Valtrex reduces the risk of heterosexual transmission of genital herpes to susceptible partners with healthy immune systems when used as suppressive therapy in combination with safer sex practices.
Genital herpes is a common sexually transmitted infection caused by herpes simplex virus (HSV). Many individuals have no or only minimal signs or symptoms from genital HSV infection and may transmit the virus during sexual contact when they show no signs of active infection (i.e., genital lesions).
Safer sex practices can also lower the chances of passing genital herpes to a partner. The practices include: (1) using a condom made of latex or polyurethane when having sexual contact, and (2) not having sexual contact with a partner while exhibiting any symptoms or outbreak of genital herpes.
The FDA based its decision to revise the labeling for Valtrex on the results of an international, double-blind, placebo-controlled clinical trial conducted by the manufacturer, GlaxoSmithKline (GSK) of Research Triangle Park, NC. The study was conducted among about 1,500 monogamous, heterosexual couples and lasted 8 months. At the beginning of the study, only 1 member in each couple had evidence of genital herpes. The results of the GSK study showed a 48% reduction in HSV acquisition; individual results may vary based on the consistency of safer sex practices.
Valtrex may cause kidney problems in some people. In addition, Valtrex may cause nervous system problems; these include confusion, hallucinations, aggressive behavior, speech problems, unsteady or shaky movements, seizures, and coma. Kidney and nervous system problems have occurred in patients who already have kidney disease and in elderly patients whose kidneys do not work well due to age. Therefore, it is important for patients to tell their health care providers if they have kidney problems or other medical conditions before taking Valtrex.
Today's action follows the recommendation of the FDA's Antiviral Drugs Advisory Committee, which met on May 14, 2003, to discuss GSK's then-proposed use of Valtrex for reduction of the risk of transmission of genital herpes with the use of suppressive therapy. The FDA first approved Valtrex in 1995.
August 8, 2003
ST. LOUIS (MD Consult) - On August 7, 2003, the U.S. Food and Drug Administration approved usage of anti-epilepsy medication Trileptal (oxcarbazepine) for use as a stand-alone treatment in children 4 years of age and older.
Trileptal, manufactured by Novartis, was first approved in the United States in January, 2000. The drug was previously only approved for pediatric use in conjunction with other medicines for treating epilepsy, as well as alone or with other therapies in adults.
Side effects that can accompany use of Trileptal include dizziness, drowsiness, depression, difficulty concentrating, speech or language problems, and difficulty with coordination or walking. Alcohol consumption while taking the drug can increase the incidence of side effects.
Trileptal can cause low levels of sodium in the blood. Signs of low levels of blood sodium, which can be dangerous, include nausea, extreme drowsiness and discomfort, headache, confusion, or dullness. Patients should tell their health care providers if they are taking any other medications that may lower the level of sodium in their blood. Such medications include carbamazepine (Tegretol), chlorpropamide (Diabinese), cyclophosphamide, diuretics (water pills), octreotide, and vincristine.
Trileptal can cause allergic reactions. If a patient has had an allergic reaction to other anti-seizure medicines, especially carbamazepine (Tegretol), he or she should notify his or her health care provider.
Because certain other medications can interact with Trileptal, all medications taken in conjunction should be reviewed, including those taken without a prescription. Trileptal may reduce the effectiveness of birth control pills, some medications used to lower blood pressure (eg, calcium channel blockers), and other anti-seizure medications.
Trileptal may cause birth defects. Patients who are pregnant, nursing, or plan to become pregnant or nurse should notify their health care providers before taking Trileptal.
August 5, 2003
ST. LOUIS (MD Consult) - On August 4, 2003, the U.S. Food and Drug Administration (FDA) announced the approval of Photofrin (porfimer sodium) injection for the ablation of precancerous lesions (high-grade dysplasia) in patients with Barrett's esophagus who do not undergo surgery to remove the esophagus (esophagectomy). Axcan Scandipharm Inc., of Birmingham, Alabama, is the sponsor of the new application for Photofrin.
Barrett's esophagus is estimated to affect about 700,000 adults in the United States. It is associated with the very common condition gastroesophageal reflux disease (GERD).
Although Barrett's esophagus may cause no symptoms itself, a small number of people with this condition can have precancerous lesions that progress to an often deadly type of cancer of the esophagus called esophageal adenocarcinoma.
Photofrin is a photosensitizing agent used in photodynamic therapy (PDT), a treatment for some types of cancer. PDT is based on the discovery that photosensitizing agents can kill one-celled organisms when the organisms are exposed to a particular type of light. PDT destroys cancer cells through the use of a laser light in combination with a photosensitizing agent. The FDA first approved Photofrin in 1998.
The clinical study supporting this new use of Photofrin PDT showed that patients receiving Photofrin PDT were more likely to achieve complete reversal of their precancerous lesions in Barrett's esophagus compared with those who did not receive Photofrin PDT. Two-year follow-up data from this clinical study showed that patients receiving Photofrin PDT had an 80% chance of being cancer free. Patients who did not receive Photofrin PDT had a 50% chance of being cancer free. The effectiveness of Photofrin PDT in reducing the long-term risk of esophageal cancer has not been demonstrated.
Side effects of Photofrin PDT treatment include photosensitivity reactions and esophageal strictures. The drug's labeling includes information on precautions that should be taken to avoid exposure of skin and eyes to bright light.
This new approval follows the recommendations of the June 26, 2003, meeting of the FDA's Gastrointestinal and Coagulation Drugs Advisory Committee.
Photofrin PDT was recently approved in Canada for the ablation of high-grade dysplasia in patients with Barrett's esophagus. The drug is still under review in Europe for a similar indication.
For more information about Photofrin, contact David W. Mims, Executive Vice President and Chief Operating Officer of Axcan Pharma Inc., at 205-991-8085, ext. 223, or Isabelle Adjahi, Director of Investor Relations of Axcan Pharma Inc., at 450-467-2600, ext. 2000.
July 30, 2003
ST. LOUIS (MD Consult) - On July 29, 2003, Genesoft Pharmaceuticals Inc. announced that the U.S. Food and Drug Administration had approved its antibiotic, Factive (gemifloxacin mesylate), for treatment of mild-to-moderate community-acquired pneumonia caused by multidrug-resistant Streptococcus pneumoniae.
In April 2003, Factive was approved for the treatment of mild-to-moderate community-acquired pneumonia caused by other pathogens, as well as for acute bacterial exacerbations of chronic bronchitis.
As many as 4 million cases of community-aquired pneumonia are diagnosed each year. According to a Genesoft statement, approximately 1 in 4 S. pneumoniae isolates in the United States are currently resistant to multiple drugs.
According to the FDA, Factive should not be used in children younger than 18 years.
In some people, use of the antibiotic may cause prolongation of the QTc, a rare heart problem. This condition can cause an abnormal heartbeat and can result in sudden death. Patients with bradycardia or a history of recent heart attacks should notify their health care providers.
Factive can cause photoxicity, which makes the skin sunburn more easily. Persons taking Factive should not use a sunlamp or tanning bed, and should use a sunscreen and wear protective clothing if they must be exposed to the sun.
Factive should only be used to treat infections that are proved or strongly suspected to be caused by bacteria. It does not treat viral infections. Common side effects include rash, headache, nausea, diarrhea, dizziness, and stomach pain.
July 29, 2003
ST. LOUIS (MD Consult) - On July 25, 2003, the U.S. Food and Drug Administration (FDA) approved a new indication for Indianapolis-based Eli Lilly's Humatrope (Somatropin, rDNA origin, for injection), a brand of growth hormone, for the long-term treatment of children with idiopathic short stature, also called non–growth hormone deficient short stature.
Humatrope's new indication for idiopathic short stature is the first indication for growth hormone in children that specifies a height restriction. "Short stature" has been defined by the American Association of Clinical Endocrinologists and the Growth Hormone Research Society as height more than 2 standard deviations (SD) below the mean for age and sex. This corresponds to the shortest 2.3% of children. This new indication restricts therapy to children who are even shorter, specifically more than 2.25 SD below the mean for age and sex, or the shortest 1.2% of children. For example, for 10-year-old boys and girls, this would correspond to heights of less than 4'1" inch. This would further correspond to heights of less than 5'3" and 4'11" in adult men and women, respectively.
This approval was based on 2 randomized, multicenter trials, conducted in approximately 300 children with idiopathic short stature. The diagnosis of idiopathic short stature was made after excluding other causes of short stature, including growth hormone deficiency.
The pivotal trial was a randomized, double-blind study in 71 children aged 9 to 15 years. Patients received injections of either Humatrope or placebo 3 times weekly until adult height was reached. Thirty-three patients contributed final height measurements after a mean treatment duration of 4.4 years. The mean final height of the patients receiving Humatrope exceeded that of the placebo group by approximately 1.5 inches.
In a second study, patients received 1 of 3 increasing doses of Humatrope, in divided doses, 6 times weekly. The average duration of treatment to final height was 6.5 years. Final height exceeded that predicted at the time of enrollment in the majority of patients, and by up to nearly 4 inches in some. In the high-dose group, the mean final height exceeded the mean height predicted at baseline by nearly 3 inches.
The safety profile of Humatrope in children with idiopathic short stature did not differ from that in children with other conditions for which growth hormone is indicated. According to Lilly spokeswoman Judy Kay Moore, the most common side effects are usually mild and include joint aches.
Various growth hormone products are currently indicated in children for short stature associated with growth hormone deficiency, chronic renal insufficiency, Turner syndrome, and Prader-Willi syndrome, and in children born small for gestational age. However, this new approval will make Humatrope available for short children with normal levels of growth hormone and no evidence of a disease that stunts growth.
Eli Lilly has advised the FDA that it will not engage in direct-to-consumer advertising of Humatrope and will limit the marketing of this product for this new use to pediatric endocrinologists to better ensure the proper use of this product in the indicated pediatric population. In addition, the manufacturer intends to tightly control the distribution of Humatrope.
June 18, 2003
ST. LOUIS (MD Consult) - Aventis said the U.S. Food and Drug Administration (FDA) has approved an expanded indication for the rheumatoid arthritis treatment Arava (leflunomide) tablets for improvement in physical function.
The FDA based this approval on a supplemental new drug application submitted by Aventis in December 2002.
Arava (leflunomide), an oral disease-modifying antirheumatic drug (DMARD), is a first-line therapy to reduce signs and symptoms, inhibit structural damage and joint space narrowing and improve physical function in active rheumatoid arthritis in adults. Rheumatoid arthritis is one of the most common forms of arthritis, a potentially crippling autoimmune disease affecting approximately two million Americans, 70 percent of whom are women.
The FDA also approved revisions and additions to the Arava safety information, which include revised liver function and hematology monitoring recommendations. When used as directed, Arava is a safe and effective drug among the very limited therapies available to treat RA.
The FDA approval was based on data from three long-term, Phase III pivotal trials. Improvement in physical function was assessed through a series of validated and widely accepted tools measuring patients' ability to conduct daily activities (e.g., walking, eating, dressing and washing), their function in daily life, and their sense of well-being.
A marked, clinically meaningful improvement in physical function was demonstrated in the same three studies that previously had demonstrated improvement in signs and symptoms of rheumatoid arthritis and retardation of structural damage evidenced by X-ray erosions and joint space narrowing. The data showed that efficacy was sustained for two years in patients continuing treatment in the three multinational, multicenter, double-blind, parallel group studies.
Arava is contraindicated in pregnant women or women of childbearing potential who are not using reliable contraception. Before starting treatment with Arava, patients must be fully counseled on the potential for serious risks to the fetus. Men wishing to father a child should consider discontinuing use of Arava and taking cholestyramine eight grams three times daily for 11 days to minimize any possible risk to the fetus.
Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide. Most cases of severe liver injury occur within 6 months of therapy and in a setting of multiple risk factors for hepatotoxicity (liver disease, other hepatotoxins). Arava is not recommended in patients with significant hepatic impairment or evidence of infection with hepatitis B or C viruses given the risk of increased hepatotoxicity.
Arava is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. Rarely, severe infections including sepsis, which may be fatal, have been reported.
Adverse reactions associated with the use of Arava in clinical trials include diarrhea, elevated liver enzymes (ALT and AST), alopecia, and rash.
Prescribing information is available by visiting arava.com.
May 29, 2003
ST. LOUIS (MD Consult) - Novartis Pharmaceuticals Corp. has received supplementary approval from the US Food and Drug Administration (FDA) for Lescol (fluvastatin sodium) and Lescol XL (fluvastatin sodium) 80 mg extended-release tablets for secondary prevention of cardiovascular events in patients who have undergone percutaneous coronary intervention (PCI) procedures such as angioplasty.
Novartis, based in East Hanover, N.J., said the approval was based on the positive findings of the landmark Lescol Intervention Prevention Study (LIPS). LIPS assessed the effect of Lescol 80 mg daily in patients with coronary artery disease who had undergone a first PCI. This patient population has early stage coronary heart disease and is at high risk of a second major adverse cardiac event.
LIPS, a four-year study involving 1,677 patients in 10 countries, was the first prospective, randomized, placebo-controlled trial to evaluate the effects of a statin exclusively in patients who had a first PCI. The study examined the time to first major cardiac event, which was defined as cardiac death, nonfatal heart attack, coronary artery bypass grafting or repeat PCI.
Lescol and Lescol XL are indicated as an adjunct to diet to reduce patients' elevated total cholesterol, LDL-C, TG and apolipoprotein B (Apo B) levels and to increase HDL-C in patients with primary hypercholesterolemia and mixed dyslipidemia. Lescol and Lescol XL are also indicated to slow the progression of atherosclerosis in patients with coronary heart disease.
Lescol capsules and Lescol XL tablets should be used with changes in diet for treating high cholesterol. Physicians should perform blood tests before and during treatment to check for liver problems. Patients should not take Lescol or Lescol XL if they are nursing; are pregnant or may become pregnant; have liver problems; or are allergic to any of the ingredients.
Possible side effects may include upset stomach, insomnia, upper respiratory tract infections, flu-like symptoms, back pain or headache. Unexplained muscle pain, tenderness or weakness could be a sign of a serious side effect and should be reported to the patient's doctor immediately.
April 18, 2003
ST. LOUIS (MD Consult) - Merck & Co. Inc. has updated the labeling for its cholesterol-lowering drug Zocor (simvastatin) to reflect study results showing its cardiovascular benefits, U.S. regulators said.
The new labeling reflects research indicating Zocor reduces risks of fatal and non-fatal heart attacks and strokes and reduces the need for bypass surgery and angioplasty, the Food and Drug Administration said in a statement.
With the new label, Merck can promote the results of the Heart Protection Study, a trial involving approximately 20,000 patients treated with either Zocor or a placebo for an average of five years.
Zocor treatment reduced the risk of death from coronary heart disease by 18 percent, while the risk of having a non-fatal heart attack was reduced by 38 percent, the FDA said. Stroke risk fell 25 percent in patients using Zocor.
Zocor's effects in reducing cardiovascular events were seen in various patients, including diabetics and people with and without heart disease, the FDA said.
Patients with diabetes, peripheral vessel disease and cerebrovascular disease but no evidence of heart disease benefited from taking Zocor, the FDA statement said.
April 17, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has given approval to Alcon Inc. to market its Vigamox antibiotic solution (moxifloxacin 0.5%) for treating bacterial conjunctivitis.
Moxifloxacin is a fourth-generation fluoroquinolone antibiotic that is highly soluble and can be formulated at a high concentration, Alcon said. The company said Vigamox should be available within several weeks.
The drug dosage is three times a day for 1 week.
The FDA approval came after a 6-month review and was based on three major clinical trials showing that Vigamox is effective against many kinds of harmful bacteria that infect the eye, Alcon said.
The clinical testing showed enhanced coverage for difficult-to-treat Gram-positive bacteria, which account for about 80 percent of eye infections, plus emerging bacterial threats such as chlamydia, the company said.
The clinical trials also showed Vigamox is safe for adults and children over age 1, the company said. Vigamox may be particularly useful in children because it causes very little stinging, Alcon said.
Approximately 1,400 patients participated in the clinical testing, Alcon said.
April 4, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has given a supplemental approval to British drugmaker GlaxoSmithKline to market its antiviral valacyclovir HCl (Valtrex) as the first FDA-approved antiviral therapy for suppressing recurrent genital herpes in HIV-infected people.
The supplemental approval was based on a placebo-controlled study showing that 65% of those receiving Valtrex 500 mg twice daily remained recurrence-free compared with 26% of those receiving placebo over a 6-month period, GlaxoSmithKline said. A total of 293 HIV-seropositive patients, treated with antiretroviral therapy for at least 2 months before randomization, participated in the study, the company said.
Valtrex was first approved in 1995 for treating herpes zoster. GlaxoSmithKline has since earned supplemental FDA approvals to indicate the antiviral therapy for treating cold sores, recurrent herpes and suppressing genital herpes outbreaks in immunocompromised people.
April 4, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has given a supplemental approval to Centocor, a division of Johnson & Johnson, to market Remicade (infliximab) for reducing the number of draining fistulas and maintaining fistula closure in patients with fistulizing Crohn's disease.
The FDA previously approved Remicade in June 2002 as a maintenance therapy for inducing and maintaining clinical remission in patients with moderate-to-severe Crohn's disease.
The supplemental approval was based on a priority review of 54-week data from Centocor's ACCENT II trial, which was conducted at 45 sites in North America, Europe and Israel, the company said.
At the end of the study period, trial results showed, 38% of the patients randomized to Remicade maintenance had no draining fistulas compared with 22% of placebo-treated patients (p=0.02), Centocor said. The trial included 296 patients with draining enterocutaneous fistulas, and in some cases rectovaginal fistulas, who received 5 mg/kg Remicade at weeks 0, 2 and 6.
In the U.S., Remicade was first approved -- when used with methotrexate -- for reducing signs and symptoms and inhibiting the progression of structural damage in patients with moderately to severely active rheumatoid arthritis.
March 14, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration has approved Reliant Pharmaceuticals LLC's InnoPran XL, an extended-release form of propranolol hydrochloride, for treating hypertension.
InnoPran XL is a once-daily drug available in 80 mg to 120 mg doses. According to Liberty Corner, New Jersey-based Reliant, it is the only product available in its class approved for evening use. It is intended to counter the morning rise in blood pressure that has been associated with high risk for MI and stroke.
March 14, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration has given approval to Wyeth for its low-dose version of Prempro, the female hormone replacement product that was the focus of a public health controversy last year.
A large federally sponsored trial reported last July that long-term users of Prempro have an increased risk of breast cancer, heart attack and stroke.
The study spurred a significant reduction in the number of Prempro prescriptions, which contains the active ingredient of Wyeth's estrogen replacement drug Premarin plus a synthetic progestin intended to prevent uterine cancer in women taking estrogen products.
Wyeth said the new low-dose version of Prempro has 28 percent less estrogen and 40 percent less progestin than full-dose Prempro.
The Madison, New Jersey-based drugmaker said low-dose Prempro was approved for use by women with an intact uterus to treat severe menopause symptoms.
January 21, 2003
ST. LOUIS (MD Consult) - The US Food and Drug Administration has approved GlaxoSmithKline's Lamictal (lamotrigine) Tablets as add-on therapy for partial seizures in epileptic children ages two and up.
The new indication expands upon previous approvals of the drug for adjunctive use in adults with partial seizures and for treating generalized seizures of Lennox-Gastaut Syndrome in children two and older.
The approval was based upon data from a study in the November 1999 issue of Neurology.
The researchers, led by Dr. Michael Duchowny of Miami Children's Hospital in Florida, randomly assigned 199 children to receive either lamotrigine or placebo. Over six-weeks, the children took a gradually larger dose of medication or placebo. They then continued to take the same dose for 12 weeks.
The investigators measured the drug's effect on partial seizures and secondary generalized seizures.
The frequency of all partial seizures was reduced by at least one-half in 42 percent of children taking lamotrigine, but only in 16 percent of the placebo group
Lamotrigine and placebo caused a similar number of side effects, but two children taking lamotrigine were hospitalized for a rash, the researchers reported. This side effect can likely be avoided, Dr. Duchowny's team said, by not taking lamotrigine with another epilepsy drug or exceeding the recommended dose.
January 6, 2003
ST. LOUIS (MD Consult) - Eli Lilly & Co.'s Prozac (fluoxetine) for treating depression and obsessive compulsive disorder (OCD) in children and adolescents 7 to 17 years old has been approved by the US Food and Drug Administration.
Prozac is the first selective serotonin reuptake inhibitor (SSRI) to receive approval for treating depression in this patient population, according to the FDA. The approval was based on two studies of children and adolescents with depression, which showed the drug had a statistically significant effect compared with placebo.
The drug also had a statistically significant effect compared with placebo in studies of children and adolescents with OCD.
Figures from the National Institute of Mental Health indicate that depression affects up to 2.5 percent of children and 8 percent of adolescents in the US. OCD affects roughly 2 percent of the population and typically begins during adolescence or childhood.
January 3, 2003
ST. LOUIS (MD Consult) - The US Food and Drug Administration has given approval to Merck & Co. Inc. to market its asthma drug Singulair (montelukast) for treating seasonal allergic rhinitis.
The FDA approved Singulair for relief of seasonal allergic rhinitis symptoms in adults and children age 2 and older. The drug is sold in a 10-mg tablet form for adults and as a cherry chewable tablet in 4-mg or 5-mg strength for children ages 2 to 14.
Singulair was first approved by the FDA in February 1998 for treating asthma in adults and children.
Unlike other medicines currently marketed for treating seasonal allergic rhinitis, Singulair blocks leukotrienes instead of histamine.
In clinical studies, Singulair was effective in improving daytime nasal symptoms, including nasal congestion, itching and sneezing and runny nose, according to Merck.
Singulair will compete with a wide array of antihistamines including Aventis SA's prescription pill fexofenadine (Allegra) and loratadine, which is sold over the counter as Claritin by Schering-Plough Corp. and as Alavert by Wyeth. Singulair, like Allegra and loratadine, doesn't cause the sleepiness frequently seen with other allergy treatments.
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