The FDA has issued letters to eight pharmaceutical manufacturers and 12 distributors warming them to stop marketing and distributing 20 unapproved ergotamine tartrate medications used to treat Migraine attacks and vascular headaches.
Steven Galson, M.D., director of the FDA’s Center for Drug Evaluation and Research (CDER) said,
“Unapproved drugs pose real risks to the American public… Because they have not been subject to FDA review, the safety, effectiveness, and quality of such products are unknown. We remain dedicated to tackling this problem through education and outreach, as well as enforcement actions like these. It is central to our mission to ensure a safe and effective drug supply for the American public.”
If you’re using ergotamine medications and have questions, contact your doctor or pharmacist about your concerns. This action does not affect the following FDA-approved products containing ergotamine, which will remain on the market:
- Cafergot - caffeine and ergotamine tartrate tablets (brand name and
- D.H.E. 45 - dihydroergotamine mesylate (injectable, brand name and
- Ergomar - ergotamine tartrate sublingual tablets
- Migergot - caffeine, ergotamine tartrate suppositories
- Migranal - dihydroergotamine nasal spray
In addition to marketing these products without FDA approval, most of the companies receiving warning letters have omitted from their drugs’ labeling critical warnings regarding the potential for serious, possibly fatal, interactions with certain other drugs. Based on recent scientific information, the five marketed, approved versions of ergotamine-containing products have updated their labeling to include a box warning (the strongest agency warning) against using such products when also taking potent CYP 3A4 inhibitors, including some antifungal agents, protease inhibitors, and certain antibiotics. CYP 3A4 is a metabolic enzyme that helps the body eliminate drugs or other chemicals. Serious and life-threatening ischemia (a restriction in blood supply), including death and gangrene, have resulted when such products are used together. Most unapproved versions of the drug do not carry these warnings.
CDER’s Director of Compliance, Deborah M. Autor, commented,
“The warning letters we issued are another example of our commitment to the Unapproved Drugs Initiative. We are taking a sensible, risk-based approach to the problem, and remain dedicated to the goal of getting unapproved drugs off the market… Doctors and patients often do not realize that not all drugs that are available on the market are backed by FDA approval. We estimate that less than 2% of prescribed drugs are unapproved. This lack of approval undermines FDA’s drug safety efforts. Drugs that skirt the approval process may be unsafe, may not work, and in our experience, often have inadequate labeling.”
I asked Migraine and headache specialist Dr. John Claude Krusz his opinion on this matter. He stated,
“In addition to the reasons stated by the FDA, it’s probably a good thing as ergotamine can lead to medication overuse headache.”
Companies have 15 days to respond to the FDA with a discontinuation plan for their products. Manufacturers have 60 days to cease manufacturing of new product, and distributors have 180 days to cease further shipment of existing products. Previously manufactured unapproved ergotamine products may still be found on pharmacy shelves for a short period of time.
Warning letters for ergotamine-containing medications were issued to the following companies for the products listed:
- Actavis Totowa LLC: Bellamine S Tablets, Belladonna Alka Ergotamine and PB Tablets, Bel-Phen-Ergot S Tablets, Bellaspas Tablets, Phenobarbital, Ergotamine, and Belladonna Tablets, and Bellamine Tablets
- Anabolic Laboratories: Bel Phen Ergot S Tablets, Bel-Tabs tablets, Cafatine PB Tabs tablets, Bellamine Tablets, Spastrin Tablets, and Urkaf-PB Tablets
- Bio Pharm Inc.: Migracet-PB Suppositories and Ergocaff PB Suppositories
- Breckenridge Pharmaceutical Inc.: Spastrin Tablets and Bellcomp-PB Suppositories
- Centrix Pharmaceutical Inc.: Ergocaff PB Suppositories
- DRX Pharmaceutical Consultants Inc.: Bellamine S tablets
- DSC Laboratories: Bellcomp PB suppositories
- Excellium Pharmaceutical Inc.: Eperbel S Tablets
- Ferndale Laboratories Inc.: phenobarbital, ergotamine, and belladonna tablets; Bellamine Tablets; and Spastrin Tablets
- IVAX Pharmaceuticals Inc. (formerly Goldline Laboratories Inc.): Bel-Phen-Ergot S Tablets
- Kaiser Foundation Hospitals: Belladonna Alka/Ergotamine and PB (Bellamine S) Tablets
- Lini Inc.: Bell Phen Ergot S Tablets, Bellaspas Tablets, and Bellamine Tablets
- Murfreesboro Pharmaceutical Nursing Supply: Bellamine S Tablets and Eperbel S Tablets
- Nucare Pharmaceuticals Inc.: Bellamine S Tablets
- Qualitest Pharmaceuticals, Inc.: Bellaspas Tablets
- Sandoz Inc.: phenobarbital, ergotamine, and belladonna tablets
- The Harvard Drug Group LLC (formerly Major Pharmaceuticals Inc.): Bellamine Tablets; Cafatine PB Tabs tablets; and caffeine, ergotamine, and pentobarbital suppositories
- United Research Laboratories Inc. and Mutual Pharmaceutical Company: Bel-Tabs tablets
- Vintage Pharmaceuticals Inc.: Bellaspas Tablets
Bridges, Andrew. “FDA warns migraine medicine makers.” Associated Press. March 1, 2007.
Interview. Dr. John Claude Krusz. March 5, 2007.
Teri Robert is a leading patient educator and advocate and the author of Living Well with Migraine Disease and Headaches. A co-founder of the Alliance for Headache Disorders Advocacy and the American Headache and Migraine Association, she received the National Headache Foundation’s Patient Partners Award and a Distinguished Service Award from the American Headache Society. Teri can be found on her website, and blog, Facebook, Twitter, StumbleUpon, Pinterest, LinkedIn, and Google+.