The article was updated May 27, 2021.

Over 10% of people worldwide experience migraines, including about 12% of Americans.^1,2 Women tend to have them more than men, and people with a family history of migraines or those who are experiencing hormonal changes have a higher risk as well.^1,2,3 Migraines can be disabling and, by some estimates, have accounted for billions of dollars in lost productivity in the U.S.⁴

Many people who experience chronic migraines have been prescribed products containing isometheptene mucate along with dichloralphenazone and acetaminophen, commonly known by the brand name Midrin^™. However, the manufacturer discontinued Midrin several years ago. Recently, the FDA ordered manufacturers of all other isometheptene mucate-containing products to stop distributing them as well.⁵ Drug products approved by the FDA between 1938 and 1962 were only required to be proven safe. Isometheptene mucate was approved prior to 1962 and fell into this group of drugs only tested for safety. The 1962 Amendments to the Federal Food, Drug and Cosmetic (FD&C) Act established that a manufacturer had to prove both the safety of its product and the drug’s efficacy for its intended purpose.⁶ Because it was already on the market and deemed safe, isometheptene mucate was exempted from the efficacy requirement until the FDA’s recent order that stopped all distribution.

This presents a challenge for prescribers and the patients previously helped by medications that are no longer available. Commercially manufactured products containing isometheptene mucate now need to go through the FDA’s new drug approval process before they can be distributed. Fortunately, isometheptene mucate and acetaminophen have drug substance monographs in the United States Pharmacopeia and National Formulary (USP-NF). Therefore, compounding pharmacies can still compound with these ingredients in compliance with section 503A of the FD&C Act.⁷ (For more information about this, read our blog post about compounding with bulk drug substances .) Though dichloralphenazone is no longer available for pharmacy compounding, we have a blog post about two potential alternatives to dichloralphenazone where pharmacists can learn about some options.

To support compounding pharmacies in meeting the needs of practitioners and patients, PCCA offers isometheptene mucate and acetaminophen that are USP grade, and that meet The PCCA Standard ^™ above and beyond industry requirements.

As always, compounders should consult with the prescriber and the patient to find a solution tailored to the patient’s unique needs. If PCCA member pharmacies with Clinical Services support have questions about compounding for these patients, they can contact our clinical compounding pharmacists for more information at 800.331.2498.

References

1. National Institute of Neurological Disorders and Stroke. (2019). Migraine information page. Retrieved from https://www.ninds.nih.gov/Disorders/All-Disorders/Migraine-Information-Page

2. U.S. National Library of Medicine. (2019). Migraine. Retrieved from https://medlineplus.gov/migraine.html

3. Mayo Clinic. (2018). Migraine. Retrieved from https://www.mayoclinic.org/diseases-conditions/migraine-headache/symptoms-causes/syc-20360201

4. Burton, W. N., Landy, S. H., Downs, K. E., & Runken, M. C. (2009). The impact of migraine and the effect of migraine treatment on workplace productivity in the United States and suggestions for future research. Mayo Clinic Proceedings, 84(5), 436–445. https://dx.doi.org/10.1016%2FS0025-6196(11)60562-4

5. U.S. Food & Drug Administration. (2018). FDA notification regarding isometheptene-containing drug products. Retrieved from https://www.fda.gov/drugs/unapproved-prescription-drugs-drugs-marketed-united-states-do-not-have-required-fda-approval/fda-notification-regarding-isometheptene-containing-drug-products

6. U.S. Food & Drug Administration. (2012). Kefauver-Harris Amendments revolutionized drug development. Retrieved from https://www.fda.gov/consumers/consumer-updates/kefauver-harris-amendments-revolutionized-drug-development

7. U.S. Food & Drug Administration. (2018). Section 503A of the Federal Food, Drug, And Cosmetic Act. Retreived from https://www.fda.gov/drugs/human-drug-compounding/section-503a-federal-food-drug-and-cosmetic-act

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The references cited did not necessarily evaluate PCCA products or formulas included in these statements. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment.