Conflict of Interest: Dr. Tepper receives grants/research support from Allergan, ATI, BristolMyerSquibb, GSK, MAP, Merck, NuPathe, Valkee, and Zogenix. These grants do not go to him personally, and do not count toward his salary at Cleveland Clinic. All amounts received are <$10,000/year per Cleveland Clinic Policy and are listed on the Cleveland Clinic website. In the last 12 months, he has served as a consultant for Allergan, ATI, MAP, Nautilus, NuPathe, Pfizer, and Zogenix. In the last 12 months, he has served on the speakers bureau for Allergan, MAP, Nautilus, and Zogenix. In the last 12 months, he served on advisory boards for Allergan, ATI, MAP, Nautilus, NuPathe, USWorldMeds, and Zogenix. He has stock options in ATI.
Orally Inhaled Dihydroergotamine: A Review
Article first published online: 11 SEP 2013
© 2013 American Headache Society
Headache: The Journal of Head and Face Pain
Special Issue: New Delivery Systems
Volume 53, Issue Supplement S2, pages 43–53, September 2013
How to Cite
Tepper, S. J. (2013), Orally Inhaled Dihydroergotamine: A Review. Headache: The Journal of Head and Face Pain, 53: 43–53. doi: 10.1111/head.12184
This supplement to HEADACHE was supported by MAP Pharmaceuticals, a wholly owned subsidiary of Allergan, Inc. MAP Pharmaceuticals did not provide suggestions for topic ideas nor for authors of this manuscript to HEADACHE. MAP Pharmaceuticals was not involved in the development of the manuscript with the authors or the journal/vendor. The authors determined final content, and all authors read and approved the final manuscript. Neither honoraria nor payments were made for authorship by the journal or MAP Pharmaceuticals.
- Issue published online: 11 SEP 2013
- Article first published online: 11 SEP 2013
- Manuscript Accepted: 22 APR 2013
- central sensitization;
- acute treatment;
Orally inhalable dihydroergotamine (iDHE), before the US Food and Drug Administration in 2013 for consideration for approval for acute treatment of episodic migraine in adults, is a user-friendly formulation of an older medication. Dihydroergotamine (DHE) has a heterogeneous receptor profile, central penetration, and persistent receptor binding that may account for its clinical prolonged benefits in acute treatment of migraine. The same features may result in the ability of DHE to reverse central sensitization and allodynia and to maintain efficacy deep into attacks. These characteristics make DHE particularly useful in treating migraine upon awakening, prolonged migraine and status migrainosus, menstrually related migraine, and for bridging patients out of medication-overuse headache/chronic migraine. The inhalable formulation has helpful pharmacokinetics, with a lower maximal serum concentration than intravenous DHE which may account for minimal nausea, and less binding to the potentially toxic serotonin2B receptor. The inhaler itself is designed for delivery of reproducible aliquots of intrapulmonary DHE with only nominal need for patient coordination. The inhalable form allows for bypassing the gastrointestinal tract in the setting of migraine nausea or vomiting, and greatly reduces first-pass effect. No drug-related serious adverse events were reported during the Phase 3 study of iDHE. Product taste and nausea were the most common side effects in both the Phase 3 regulatory trial and in the safety extension trial. Limitations for use of iDHE are those for any ergot or triptan, ie, contraindication in the setting of vascular disease. In addition, iDHE is metabolized by the cytochrome P450 3A4 liver enzymatic system. Inhalable DHE provides the promise of a new formulation of a valued medication with important clinical features, useful deep into attacks in a variety of situations.