Med Check
Regulatory and Legal Briefs
Noven Pharmaceuticals' methylphenidate transdermal system (MTS) was deemed approvable last month by the Food and Drug Administration (FDA) after a public advisory committee hearing resulted in an approval recommendation earlier in December. The tentative approval would allow for once-daily use by children aged 6 to 12 years for attention-deficit/hyperactivity disorder (ADHD). | |||||
The MTS will be marketed by Shire Pharmaceuticals globally. In the United States Shire will market the skin patch under the trade name Daytrana.
The FDA's approvable letter to Shire contained “proposed labeling, as well as requests for data clarification, postmarketing surveillance, and postmarketing studies,” according to a company press release. Shire said it was “initiating dialogue with the FDA to address these issues.” The company said it hopes to launch the MTS “during the first half of 2006.”
The FDA has granted varenicline a six-month priority review. The agency designates new drug applications (NDA) for priority handling when the drug under review “may provide a significant therapeutic advance over existing therapies.” Pfizer submitted an NDA for varenicline in December 2005, and the designation should shave off about four months from the average FDA review time of 10 months. | |||||
Varenicline, developed by Pfizer for smoking cessation, is a selective nicotinic-acetylcholine receptor partial agonist and is designed to bind to the same receptor sites as nicotine. By activating nicotinic receptors, the drug is believed to reduce both the severity of a smoker's craving and the withdrawal symptoms from nicotine addiction. At the same time, the drug blocks the rewarding effects of nicotine. In placebo-controlled clinical trials that included bupropion as an active comparator, 44 percent of those treated with varenicline quit smoking by the end of 12 weeks compared with 30 percent of those taking bupropion. Only 18 percent of those who received placebo quit smoking.
Pfizer has proposed the trade name Champix for the new product.
Naltrexone–extended release for injection was deemed approvable by the FDA for the treatment of alcohol dependence in combination with a treatment program that includes psychosocial support. An NDA for the drug was submitted in March 2005 by Alkermes Inc. and Cephalon Inc. Alkermes developed the injectable formulation, which Cephalon will market under the trade name Vivitrol. | |||||
The FDA's approvable letter requested “preclinical pharmacokinetic data to support reference to existing oral naltrexone preclinical data,” according to a press release that the two companies issued jointly. Final approval is also contingent upon approval of labeling. The companies said they are “on track” to launch the product in the second quarter of 2006.
Research Briefs
Testosterone gel, applied daily to the skin, may improve overall quality of life in elderly men with Alzheimer's disease but has minimal effects on preserving cognitive function. A pilot study involving 16 men with Alzheimer's and 22 healthy control subjects compared testosterone gel with placebo gel over the course of a 24-week, double-blind, parallel-group study. Outcome measures included the Alzhiemer's Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), a battery of learning, memory, and motor function tests, as well as the Neuropsychiatric Inventory, Clinical Global Impression of Change, and the Quality of Life-Alzheimer's Disease Scale. | |||||
Alzheimer's patients who received testosterone had significantly greater improvements in caregiver-rated quality of life; however, no significant differences were seen between those on testosterone and those on placebo in any of the cognitive assessments. In the healthy control group, a nonsignificant trend toward greater improvement in self-rated quality of life was observed with those on testosterone compared with those on placebo. No significant differences were observed in side effects between those on testosterone and those on placebo.
Arch Neurol 2006; 63:1-9
Clozapine, quetiapine, risperidone, and olanzapine are all associated with a significantly increased risk of venous thromboembolism (VTE) in the elderly. Researchers conducted a retrospective cohort study of nursing home residents in five states. Using the Systematic Assessment of Geriatric Drug Use via Epidemiology (SAGE) database, which contains data from the Centers for Medicare and Medicaid Services required Minimum Data Set, they identified 19,940 new users of antipsychotic agents and 112,078 nonusers. | |||||
Overall, the rate of hospitalization for VTE was 0.91 per 100 person years. Peripheral venous thrombosis accounted for 77.6 percent of hospitalizations, while 22.4 percent were for pulmonary embolisms. After adjusting for other known risk factors that may influence susceptibility to VTE, the rate of hospitalization for those taking atypical antipsychotics was 1.24 per 100 person years compared with 0.87 for nonusers. In addition, those taking risperidone were 1.98 times more likely to suffer a VTE, while those taking olanzapine were 1.89 times more likely. Patients taking clozapine or quetiapine were 2.68 times more likely than nonusers to suffer a VTE. No increased rate of VTE was associated with phenothiazine antipsychotics or other typical or first-generation drugs.
Arch Intern Med 2005; 165:2677-2682
SSRI antidepressants appear to be associated with a reduced risk of suicide in elderly depressed patients. Israeli researchers conducted a retrospective, matched case-controlled study over a 10-year period of patients aged 65 and older who had major depressive disorder and had been hospitalized at their facility within 30 days of a suicide attempt. The researchers identified 101 cases and compared them with a control group consisting of age- and sex-matched patients admitted for major depression but no suicide attempt. | |||||
Patients in the control group were 1.94 times more likely to have been taking an antidepressant compared with those in the suicide-attempt group. SSRIs were prescribed to 29 percent of those in the control group versus 21 percent of those in the suicide-attempt group.
Neuropsychopharmacology 2006; 31:178-181
Industry Briefs
The InstaRead Lithium System is said to provide an easy and accurate measure of blood lithium levels without patients' having to go to a lab to have blood drawn. Approved last year by the FDA, the finger-stick test has also received a CLIA waiver authorizing use of the test in physicians' offices. | |||||
The test, marketed by ReliaLAB, is similar to finger-stick blood glucose tests and, according to the company, is as accurate as laboratory tests on venous blood samples. A “starter kit” including the InstaRead workstation, reader, control kit, extra supplies, and 12 patient test packs retails for around $400, and a refill kit containing 24 patient test packets runs $264. More information is posted at<www.ReliaLAB.com>.
Johnson and Johnson's Janssen division has submitted an NDA to the FDA for paliperidone ER, a new, investigational antipsychotic medication. Paliperidone is an active metabolite of the company's second-generation antipsychotic, risperidone. Paliperidone ER utilizes the OROS technology for extended release of the medication into the bloodstream. The NDA includes data involving more than 1,600 patients studied in 23 countries, according to a company press release. The FDA has averaged about 10 months between submission and response. If approved by the end of this year, the new drug could be on pharmacy shelves by the second quarter of 2007. | |||||
Shire PLC and partner New River Pharmaceuticals Inc. filed an NDA for its investigational drug NRP104 for the treatment of children aged 6 to 12 for attention-deficit/hyperactivity disorder. NRP104 is a prodrug of amphetamine—that is, it is an amphetamine conjugated to a specific amino acid. By conjugating the pair, NRP104 is intended to provide better overdose protection and reduced potential for addiction than currently marketed stimulants. A preliminary review by the U.S. Drug Enforcement Administration last year indicated that the agency did not consider NRP104 to be an amphetamine; therefore, it would not be subject to controlled-substance scheduling. No proposed trade name for the drug has been announced. | |||||
The following medications appear in this edition of Med Check:
Bupropion (extended release): Wellbutrin XL; Zyban (GlaxoSmithKline) | |||||
Clozapine: Clozaril (Novartis); generics | |||||
Lithium: Lithobid (Solvay); Eskalith (GSK); generics | |||||
Methylphenidate transdermal system: Daytrana (Shire) (pending final FDA approval) | |||||
Naltrexone–extended release for injection: Vivitrol (Alkermes/Cephalon) (pending final FDA approval) | |||||
NRP104: Trade name pending (Shire) (submitted for FDA approval) | |||||
Olanzapine: Zyprexa (Lilly) | |||||
Paliperidone: Trade name pending (Janssen) (submitted for FDA approval) | |||||
Quetiapine: Seroquel (AstraZeneca) | |||||
Risperidone: Risperdal (Janssen) | |||||
Varenicline: Champix (Pfizer) (pending final FDA approval)▪ | |||||
