FDA Approves First Autoinjector Form of DHE for Acute Migraine and Cluster Headache

Joe Renda

(Credit: Amneal Pharmaceuticals)

According to a new announcement, the FDA has granted approval to Amneal Pharmaceuticals’ dihydroergotamine mesylate injection, marketed as Brekiya, as the first dihydroergotamine (DHE) autoinjector for the acute treatment of migraine with or without aura and cluster headache in adults.¹

The company noted that the therapy contains the same DHE used in hospitals but in a ready-to-use, subcutaneous autoinjector form that can be self-adminstered.² The device delivers 1 mg dose into the thigh and does not require refrigeration, assembly, or priming. The hope is that the formulation may provide sustained pain relief and is intended for patients who experience issues with oral therapies, such as inefficacy, nausea, vomiting, or delayed dosing.³

“The DHE autoinjector is a really important milestone for patients living with acute migraines and cluster headaches. For the first time, it puts this type of treatment into a ready-to-use autoinjector that patients can administer themselves—giving them more control and the ability to act quickly during these painful attacks," Joe Renda, senior vice president and chief commercial officer – specialty at Amneal Pharmaceuticals, told NeurologyLive^®. "This approval is especially meaningful to me, having seen my sibling struggle with cluster headaches for many years and the toll it can take. Making treatment more accessible and actionable is a step forward for so many families."

DHE is typically administered intravenously in emergency settings or headache clinics. With the newly approved therapy, patients now have access to a single-dose device designed for at-home use, potentially reducing the need for emergency department visits. Amneal noted in its release that the treatment can be used at any point during a migraine attack and may help prevent recurrence as observed from previous research.^4,5

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The company noted that in its label patients are advised not to use the therapy with strong CYP3A4 inhibitors as this has been associated with rare but serious reductions in blood flow to the brain or extremities. Furthermore, the treatment was recommended to not be used by patients with certain cardiovascular conditions, peripheral vascular disease, severe liver or kidney impairment, a history of vascular surgery or sepsis, or known allergies to DHE, ergot alkaloids, latex, or any component of the autoinjector.

Amneal Pharmaceuticals announced in the release that the autoinjector could interact with other prescription and over-the-counter medications, including certain migraine therapies, antidepressants, antifungals, beta blockers, and substances such as grapefruit juice and nicotine. Moreover, the company reported that if needed, up to 2 additional doses of the original 1 mg single dose may be administered, with at least 1 hour between each but total use should not exceed 3 doses in 24 hours or 6 doses in 1 week.

Possible adverse effects (AEs) of the autoinjector include cardiovascular events such as heart attack or stroke, as well as increased blood pressure and gastrointestinal symptoms. Other AEs may include changes in sensation or color in the fingers or toes, and in rare cases, fibrotic tissue changes. Additionally, overuse of the treatment could lead to increased headache frequency.

REFERENCES
1. Amneal Receives U.S. FDA Approval for Brekiya® (dihydroergotamine mesylate) injection for the Acute Treatment of Migraine and Cluster Headaches in Adults. News Release. Amneal Pharmaceuticals. Published May 15, 2025. Accessed May 16, 2025. https://investors.amneal.com/news/press-releases/press-release-details/2025/Amneal-Receives-U-S--FDA-Approval-for-Brekiya-dihydroergotamine-mesylate-injection-for-the-Acute-Treatment-of-Migraine-and-Cluster-Headaches-in-Adults/default.aspx
2. Silberstein SD, Shrewsbury SB, Hoekman J. Dihydroergotamine (DHE) - Then and Now: A Narrative Review. Headache. 2020;60(1):40-57. doi:10.1111/head.13700
3. Aurora SK, Papapetropoulos S, Kori SH, Kedar A, Abell TL. Gastric stasis in migraineurs: etiology, characteristics, and clinical and therapeutic implications. Cephalalgia. 2013;33(6):408-415. doi:10.1177/0333102412473371
4. Winner P, Ricalde O, Le Force B, Saper J, Margul B. A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine. Arch Neurol. 1996;53(2):180-184. doi:10.1001/archneur.1996.00550020092020
5. Mather PJ, Silberstein SD, Schulman EA, Hopkins MM. The treatment of cluster headache with repetitive intravenous dihydroergotamine. Headache. 1991;31(8):525-532. doi:10.1111/j.1526-4610.1991.hed3108525.x