The Power of DHE

D.H.E. 45^®, an established migraine and cluster headache therapy, has 80 years of clinical use^1,2

DHE has the potential for a long duration of effect, so it’s usually  quite long and associated with low recurrence.

-DR. STEWART TEPPER

D.H.E. 45^® has a broad spectrum of bioactivity.^2,*

MECHANISM OF ACTION

	Serotonergic (5‑HT)	Noradrenergic	Dopaminergic	CGRP Receptor
D.H.E. 45^®2	1A, 1Dα, 1Dβ, 2A, 2C	α2A, α2B, α1	2L, 3	Indirect CGRP inhibition³
Triptans⁴	1B, 1D, 1F			Indirect CGRP inhibition
Gepants/Monoclonal Antibodies⁵				Downstream decrease in CGRP production

DHE can be effective at any point during a migraine or cluster headache attack.⁶

In addition, DHE^†:

DHE=dihydroergotamine

*The clinical significance of the receptor activity is unknown.⁹

^†Findings were reported using studies with varied forms of DHE administration including intranasal, IV, and SC.^1,2,6-8

Clinical studies of DHE have shown that it is effective in treating patients experiencing^‡,§:

^‡Findings were reported using studies with varied forms of DHE administration including intranasal, IV, and SC.^1,6,9-11

Brekiya autoinjector is bioequivalent to subcutaneous D.H.E. 45^®12,§

^§Bioequivalence demonstrated in a randomized, open-label, crossover bioavailability study in 27 healthy, fasting adults.¹²

Study showed subcutaneous D.H.E. 45^® effective in sustaining migraine pain relief⁸

PATIENTS WITH PAIN RELIEF BY TREATMENT GROUP^8,||

This data is based on a study of SC D.H.E. 45^® vs. SC sumatriptan. Not studied in Brekiya autoinjector. Brekiya autoinjector contains DHE, the same active ingredient as D.H.E. 45^®.^6,8

Significantly more patients experienced pain relief with SC D.H.E. 45® 24 hours post-dose (90% vs. 77%)(P=0.004)⁸

Of patients who reported headache relief, 82% in the SC D.H.E. 45^® group and 70% in the SC sumatriptan group reported no pain at all 24 hours post-dose⁸

Study showed subcutaneous D.H.E. 45^® reduced headache recurrence⁸

SIGNIFICANTLY MORE D.H.E. 45^® PATIENTS HAD NO HEADACHE RECURRENCE VS. SUMATRIPTAN^8,||

This data is based on a study of SC D.H.E. 45® vs. SC sumatriptan. Not studied in Brekiya autoinjector.
Brekiya autoinjector contains DHE, the same active ingredient as D.H.E. 45®.^6,8

In a double-blind, randomized trial of SC D.H.E. 45® vs. SC sumatriptan, the D.H.E. 45® group had 2.5 times less headache recurrence within 24 hours compared to the sumatriptan group.⁸

More than 8 in 10 patients taking SC D.H.E. 45® had no headache recurrence within 24 hours post-dose⁸

^||Data based on a randomized, double-blind trial of 295 adult patients with migraine with or without aura, experiencing moderate to severe head pain. Patients were given SC injections of either D.H.E. 45® (1 mg) or sumatriptan succinate (6 mg) into their lateral thigh and self-reported results from 0.5-24 hours after dose. Pain was rated on a 4 point scale as none, mild, moderate, or severe. Pain relief was defined as a change from moderate or severe at onset, to mild or none. 30% of patients in the D.H.E. 45® group and 15% of patients in the sumatriptan group received a second injection after 2 hours, with further rescue medication administered 1 hour after re-dose if needed. Main outcome measures were relief of head pain and recurrence of successfully treated headache.⁸

NS=not significant

Headache recurrence was defined as an increase in pain severity from none or mild at least 2 hours after achieving pain relief.⁸

Based on a review of hospital records

Intravenous D.H.E. 45^® has proven results in cluster headache^13,¶

of episodic cluster patients remained completely headache-free 3 months after IV DHE administration¹³

^¶Data based on a hospital record review of 54 adult cluster headache patients (episodic and chronic) admitted to hospital on 64 occasions. Patients were given an initial dose of intravenous DHE, and subsequent doses based on response. Patients whose headaches improved were given further doses of IV DHE every 8 hours until they were headache-free for 24 hours. Patients whose headaches persisted were given an additional IV dose 1 hour after the first, followed by additional, larger IV doses every 8 hours until they were headache-free for 24 hours. All patients were then given 2-3 additional IV doses every 12 hours. Patients with nausea were treated with smaller doses. Subsequent breakthrough headaches were treated with self-administered intramuscular injections of DHE. Patients were given metoclopramide throughout their hospital stay.¹³

DHE can be used deep in a migraine attack when patients have central sensitization, when they have sensitivity to light and sensitivity to noise and nausea and that they’re at the peak of the migraine.

-DR. STEWART TEPPER

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How to Prescribe

IMPORTANT SAFETY INFORMATION

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WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH STRONG CYP3A4 INHIBITORS

Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with strong CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of Brekiya with strong CYP3A4 inhibitors is contraindicated.

Indications

Brekiya is an ergotamine derivative indicated for the acute treatment of migraine with or without aura and the acute treatment of cluster headaches in adults.

Limitations of Use:

Brekiya is not indicated for the preventive treatment of migraine or for the management of hemiplegic migraine or migraine with brainstem aura.

Contraindications

Concomitant use of strong CYP3A4 inhibitors
Ischemic heart disease or coronary artery vasospasm
Uncontrolled hypertension, peripheral arterial diseases, sepsis, following vascular surgery, or severe hepatic or renal impairment
Concomitant use of other 5-HT₁ agonists or ergotamine-containing or ergot-type medications within 24 hours
Hypersensitivity to dihydroergotamine, ergot alkaloids, latex, or any of the ingredients in Brekiya
Concomitant use with peripheral and central vasoconstrictors

Warnings and Precautions

Myocardial Ischemia and/or Infarction, Other Cardiac Adverse Reactions, and Fatalities: In patients with risk factors predictive of coronary artery disease, consider first dose administration under medical supervision with an electrocardiogram.
Cerebrovascular Adverse Reactions and Fatalities: Cerebrovascular hemorrhage, subarachnoid hemorrhage, and stroke have been reported; discontinue Brekiya if suspected.
Other Vasospasm Related Adverse Reactions: Brekiya may cause vasospasm or elevation in blood pressure. Discontinue if signs or symptoms of vasoconstriction develop.
Medication Overuse Headache: Detoxification may be necessary.
Preterm Labor: Advise pregnant women of the risk.
Fibrotic Complications: Pleural and retroperitoneal fibrosis have been reported following prolonged daily use of dihydroergotamine mesylate. Do not exceed the Brekiya dosing guidelines or use for chronic daily administration.

ADVERSE REACTIONS

Serious cardiac events (including fatal) that have been reported with dihydroergotamine mesylate injection use include coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, ventricular fibrillation.

DOSAGE AND ADMINISTRATION

For subcutaneous injection only.
Recommended dosage is 1 mg administered subcutaneously as a single 1 mL autoinjector.
Do not exceed 3 mg (3 doses) in a 24-hour period.
Do not exceed 6 mg (6 doses) in a week.
Prior to initiation, a cardiovascular evaluation is recommended.

DRUG INTERACTIONS

Beta Blockers/Nicotine: May potentiate/provoke vasoconstriction.
Selective Serotonin Reuptake Inhibitors: Weakness, hyperreflexia, and incoordination may occur with coadministration.

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm.
Lactation: Advise not to use during breastfeeding and for 3 days after the last dose.

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Global Patient Safety at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References: 1. Silberstein SD, Shrewsbury SB, Hoekman J. Headache. 2020;60(1):40-57. doi:10.1111/head.13700 2. D.H.E. 45® [package insert]. Aliso Viejo, CA: Valeant Pharmaceuticals North America; 2008 3. Silberstein SD, McCrory DC. Headache. 2003;43(2):144-166. doi:10.1046/j.1526-4610.2003.03034.x 4. Neeb L, Meents J, Reuter U. Neurotherapeutics. 2010;7(2):176-182.doi:10.1016/j.nurt.2010.03.003 5. Deen M, Edvige C, Kamm K et al. J Headache Pain. 2017;18:96. doi:10.1186.s10194-017-0807-1. 6. Brekiya [package insert]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; 2025.  7. Burstein R, Jakubowski M, Rauch SD. J Vestib Res. 2011; 21(6) 305-314. doi:10.3233/VES-2012-0433. 8. Winner P, Ricalde O, Le Force B, Saper J, Margul B. Arch Neurol. 1996;53(2):180-184. doi:10.1001/archneur.1996.00550020092020 9. Shafqat R, Flores-Montanez Y, Delbono V, Nahas SJ. J Pain Res. 2020;13:859-864. doi:10.2147/JPR.S203650 10. Silberstein SD, Kori SH. CNS Drugs. 2013;27(5):385-394. doi:10.1007/s40263-013-0061-2 11. Tepper SJ. Headache. 2013; 53. Suppl 2:43-53. doi:10.1111/head.12184 12. Data on file, Amneal Pharmaceuticals LLC. 13. Mather PJ, Silberstein SD, Schulman EA, Hopkins MM. Headache. 1991;31(8):525-532. doi:10.1111/j.1526-4610.1991.hed3108525.x

Based on a review of hospital records

Intravenous D.H.E. 45® has proven results in cluster headache13,¶

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Intravenous D.H.E. 45^® has proven results in cluster headache^13,¶