Razadyne generic wins FDA approval

November 10, 2008

Barr Pharmaceuticals has received final FDA approval for galantamine, its generic version of Ortho McNeil Janssen's Razadyne ER, for the treatment of mild to moderate dementia of the Alzheimer's type.

Key Points

Barr Pharmaceuticals Inc., recently announced that its subsidiary, Barr Laboratories Inc., received final approval from the U.S. Food and Drug Administration for a generic version of Razadyne ER, Ortho McNeilJanssen's galantamine hydrobromide extended release capsules. Galantamine, a tertiary alkaloid, is a competitive and reversible acetylcholinesterase inhibitor.

Barr also announced it is the first company to file an Abbreviated New Drug Application (ANDA) with the FDA containing a Paragraph IV certification for a generic version of Razadyne ER capsules, and therefore it is entitled to 180 days of marketing exclusivity, as provided for under the Hatch-Waxman Act. Barr filed its ANDA with the FDA containing a Paragraph IV certification for the 8 mg capsule strength of Razadyne ER on March 1, 2006, and amended its ANDA on March 10, 2006, to include the 16 mg and 24 mg capsule strengths.

"Assuming the price is less than any of the branded drugs in this class, generic Razadyne ER will be a more cost-effective option for most patients who respond to cholinesterase inhibitors. Having a less expensive cholinesterase inhibitor available likely will make it the first-choice agent in the class for patients just being started on cognitive therapy, since there is no way to tell which drug in this class the patient is most likely to respond to," Robert J. Cluxton Jr., PharmD, MBA, CGP, said. Cluxton is Professor of Pharmacy Practice and Family Medicine at the James L. Winkle College of Pharmacy, University of Cincinnati.

Treating Alzheimer's disease can be challenging, as the pathology of the disease is not fully understood. The FDA-approved drugs may slow the progression of Alzheimer's disease for a few months or even a few years. They may help some patients perform activities of daily living and decrease behavioral symptoms such as delusions and agitation. They may even improve memory and speaking skills. But they are not a cure.

While the precise mechanism of galantamine's action is unknown, it is postulated that it exerts its therapeutic effect by enhancing cholinergic function. If this is the case, galantamine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. Cluxton said that as with all agents in this class, galantamine has no impact on the underlying disease and effects only modest and temporary improvement in cognition.

Galantamine extended-release (ER) is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. The efficacy of galantamine's ER capsules was studied in a randomized, double-blind, placebo-controlled trial that was six months in duration, with an initial four-week dose-escalation phase. In this trial, patients were assigned to one of three treatment groups: galantamine ER in a flexible dose of 16 to 24 mg once daily, galantamine ER in a flexible dose of 8 to 12 mg twice daily, and placebo. The primary efficacy measures in this study were the Alzheimer's Disease Assessment Scale (ADAS-cog) and Alzheimer's Disease Assessment Scale (ADAS-cog) Clinician's Interview-Based Impression of Change plus the Caregiver Interview (CIBIC-plus). On the protocol-specified primary efficacy analysis at month six, a statistically significant improvement favoring galantamine ER over placebo was seen for the ADAS-cog, but not for the CIBIC-plus. Galantamine ER showed a statistically significant improvement when compared with placebo on the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, a measure of function, and a secondary efficacy measure in this study.

Per the product labeling, the recommended starting dose of Galantamine ER is 8 mg/day and increasing to the initial maintenance dose of 16 mg/day after a minimum of four weeks. A further increase to 24 mg/day should be attempted after a minimum period of four weeks at 16 mg per day. The manufacturer recommends administering Galantamine ER once daily in the morning, preferably with food. Patients and caregivers should be advised to ensure adequate fluid intake during treatment. If therapy has been interrupted for several days or longer, the manufacturer recommends the patient be restarted at the lowest dose and the dose escalated until the patient is again taking the desired dose.