FDA orders halt to manufacture of unapproved ergotamine drugs.

The Food and Drug Administration has told eight manufacturers and 12 distributors of unapproved ergotamine-containing drugs to stop marketing these products because of concerns about inadequate safety labeling.

On Feb. 27, the FDA issued warning letters to 20 firms that market unapproved prescription drugs containing ergotamine tartrate. The firms have 60 days to stop manufacturing the products and 180 days to stop distribution. Drugs containing ergotamine tartrate are used to treat vascular headaches, including migraines.

"Consumers and physicians may wrongly assume that these widely marketed and available drugs are approved and have been found to be safe and effective by the FDA," said Michael Levy, director of the agency's division of new drugs and labeling compliance in the Center for Drug Evaluation and Research, during a telephone news conference.

"This action is the next step in an aggressive FDA initiative to ensure that all marketed U.S. drugs have required FDA approval," Mr. Levy said.

There are currently five approved ergotamine-containing drugs: Migergot suppositories (marketed by G & W Laboratories Inc.), ergotamine tartrate and caffeine tablets (marketed by West-Ward Pharmaceutical Corporation and Mikart), Cafergot tablets (marketed by Sandoz), and Ergo-mar sublingual tablets (marketed by Rosedale Therapeutics).

The approved drugs' labels include a black box warning regarding the use of these products with CYP 3A4 inhibitors, including some antifungal drugs, protease inhibitors, and certain antibiotics. CYP 3A4 is a metabolic enzyme that helps the body eliminate drugs and other chemicals. When ergotamine-containing drugs are used in combination with CYP 3A4 inhibitors, serious and life-threatening ischemia can occur, possibly resulting in gangrene and death.

The approximately 40 unapproved ergotamine-containing drugs singled out in this action pose a safety threat because the labels do not bear these warnings. It's not known if any deaths or serious adverse events have occurred with the use of these unapproved products.

The letters are part of an FDA initiative to curb unapproved drug marketing. In June 2006, the agency published a compliance policy guide, which describes FDA's risk-based enforcement approach to marketed unapproved drugs. The highest priority is given to those drugs that present safety risks.

"Unapproved drugs have not been through the rigorous new drug application approval process. They may not be safe, effective, and adequately labeled," Mr. Levy said. Some of these drugs are listed in the Physicians' Desk Reference and are advertised in medical journals, he added.

These drugs have bypassed the agency approval process, in part because of changes in federal regulations. The drug manufacturers have the option to seek approvals for their individual products, the FDA said.

To see a list of the affected companies, visit www.fda.gov/cder/drug/unapproved_drugs/ergotamine_WL.htm.

BY KERRI WACHTER

Senior Writer