Comprehensive medication guide to D.H.E. 45 including estimated pricing, availability information, side effects, and how to find it in stock at your local pharmacy.
Estimated Insurance Pricing
$10–$60 copay for generic injectable depending on plan tier (typically Tier 2–3); brand formulations like Trudhesa and Brekiya may require prior authorization and have higher copays. Medicare Part D covers generic DHE; $2,000 annual OOP cap applies as of 2025.
Estimated Cash Pricing
$335–$733 retail cash price for 5–10 mL ampules of generic injectable; as low as $262 with GoodRx or similar discount cards. Generic nasal spray has higher retail prices but comparable discount prices (~$262–$270 with GoodRx).
Medfinder Findability Score
42/100
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D.H.E. 45 is the brand name for dihydroergotamine mesylate injection — an ergot alkaloid used for the acute treatment of migraine headaches (with or without aura) and cluster headache episodes. It has been FDA-approved since 1946, making it one of the longest-used migraine medications in the United States.
The original brand D.H.E. 45 by Bausch Health was discontinued in 2022. Generic versions of dihydroergotamine mesylate injection (1 mg/mL ampules) are still available from Hikma and Provepharm, though the drug remains on the ASHP drug shortage list. Newer formulations include Trudhesa (nasal spray), Brekiya (subcutaneous autoinjector, FDA approved 2025), and Atzumi (nasal powder, FDA approved 2025).
D.H.E. 45 is not used for migraine prevention — it is an acute, episodic treatment only. It is particularly valuable for patients who have not responded to triptans, who need a parenteral option due to severe nausea and vomiting, or who require treatment for cluster headaches.
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Dihydroergotamine mesylate is an ergot alkaloid that works through a dual mechanism of action. It binds with high affinity to serotonin 5-HT1D receptors (as well as 5-HT1A, 5-HT2A, and 5-HT2C) and alpha-adrenergic receptors. This broad receptor activity distinguishes it from triptans, which are more selective.
The first mechanism involves vasoconstriction of intracranial blood vessels — particularly arteriovenous anastomoses — that are believed to dilate during migraine. DHE's activation of 5-HT1D receptors on these vessels causes them to narrow, reducing the throbbing pain of migraine. DHE is also a potent venoconstrictor, which may contribute to its lower headache recurrence rate compared to triptans.
The second mechanism involves the trigeminal nerve system. During migraine, trigeminal nerve fibers release pro-inflammatory neuropeptides around cranial blood vessels, causing neurogenic inflammation. DHE activates presynaptic 5-HT1D receptors on trigeminal nerve terminals, inhibiting this neuropeptide release and reducing neurogenic inflammation — treating migraine at both the vascular and neural level.
1 mg/mL — Injection (IV, IM, or SC)
Standard injectable formulation; 1 mL ampules; max 3 mg/day IM/SC or 2 mg/day IV; max 6 mg/week
0.5 mg/spray — Nasal spray (Migranal / generic)
1 spray per nostril initially; repeat after 15 min; max 2 mg/dose
0.725 mg/spray — Nasal spray (Trudhesa)
1 spray per nostril; may repeat after >1 hour; max 4 sprays/24h; available through specialty pharmacies
1 mg — Subcutaneous autoinjector (Brekiya)
FDA approved 2025; single-use pen; 1 mg SC; repeat q1h as needed; max 3 mg/day; no refrigeration required
Varies — Nasal powder (Atzumi)
FDA approved 2025; intranasal powder delivery system
D.H.E. 45 (dihydroergotamine mesylate injection) is currently difficult to find. The drug has been on the ASHP official drug shortage list since August 2024. The shortage began when Bausch Health discontinued the original brand in 2022, followed by Perrigo also discontinuing their generic formulation — leaving only Hikma and Provepharm as U.S. suppliers, both of which have experienced back-order periods.
Chain pharmacies are often the first to run out of stock due to centralized sourcing. Independent pharmacies, specialty pharmacies, and compounding pharmacies may have better access. Newer formulations — Trudhesa (nasal spray via specialty pharmacies) and Brekiya (SC autoinjector, FDA approved 2025) — have their own supply chains and may be more consistently available.
Use medfinder to find which pharmacies near you currently have D.H.E. 45 in stock. medfinder calls pharmacies on your behalf and texts you the results — saving you the time and frustration of calling pharmacies one by one during a shortage.
D.H.E. 45 (dihydroergotamine mesylate) is not a controlled substance, so any licensed prescriber can prescribe it within their scope of practice. There are no DEA scheduling restrictions on who may prescribe it or how it is transmitted. The following provider types commonly prescribe D.H.E. 45:
Neurologists — Primary prescribers for complex migraine and cluster headache; most familiar with DHE protocols.
Headache specialists — Neurologists with additional training in headache medicine (UCNS-certified); most experienced with DHE indications.
Emergency medicine physicians — Administer IV DHE in emergency settings for intractable migraine.
Primary care physicians (PCPs) and internists — May prescribe for established migraine patients, often after triptan failure.
Nurse practitioners (NPs) and physician assistants (PAs) — Can prescribe in most states under state practice laws; many headache specialty practices have NP/PA providers.
Telehealth prescribing is available for D.H.E. 45. Because it is not a controlled substance, there are no DEA-based telehealth restrictions. Migraine-focused telehealth platforms (Cove, Nurx Health) and general telehealth services (Teladoc, MDLive) may be able to evaluate and prescribe DHE for established migraine or cluster headache patients.
No. Dihydroergotamine mesylate is not a DEA-scheduled controlled substance. It is not classified under Schedule I, II, III, IV, or V. This means there are no special DEA-based prescribing restrictions — any licensed physician, nurse practitioner, or physician assistant can prescribe it within their scope of practice.
Because D.H.E. 45 is not a controlled substance, prescriptions can be called in by phone, sent electronically, or transmitted via fax without the restrictions that apply to Schedule II drugs. Refills can be authorized by the prescriber without a new in-person visit (per their clinical judgment). Telehealth prescribing is not restricted by DEA scheduling requirements for this drug.
Nausea and vomiting
Dizziness or lightheadedness
Paresthesia (tingling, numbness in fingers/toes)
Chest tightness or pressure
Abdominal cramping
Flushing or warmth
Rhinitis or nasal congestion (nasal spray forms)
Myocardial ischemia or infarction (heart attack)
Arterial vasospasm (coronary, cerebral, or peripheral)
Hypertensive crisis (severe blood pressure elevation)
Stroke and other cerebrovascular events
Peripheral ischemia / ergotism (cold or numb extremities, severe cramping) — with excessive use
Fibrosis (pleural, retroperitoneal, cardiac valvular) — with prolonged daily use
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Sumatriptan (Imitrex)
First-line triptan; available as oral, nasal spray, and SC injection; widely available generic; effective for both migraine and cluster headache
Zolmitriptan (Zomig)
Triptan available as oral tablet and nasal spray; good option for patients who prefer nasal delivery
Ubrogepant (Ubrelvy)
CGRP receptor antagonist; oral tablet; no vasoconstriction; can be used in patients with cardiovascular risk factors who cannot use ergotamines or triptans
Lasmiditan (Reyvow)
5-HT1F agonist (ditan); oral; no vasoconstriction; Schedule V controlled substance; impairs driving — caution needed
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Macrolide antibiotics (erythromycin, clarithromycin, troleandomycin)
majorContraindicated. Strong CYP3A4 inhibitors increase DHE levels, causing dangerous vasospasm. Boxed Warning.
HIV protease inhibitors (ritonavir, indinavir, nelfinavir)
majorContraindicated. Strong CYP3A4 inhibitors — same risk as macrolide antibiotics. Boxed Warning.
Azole antifungals (ketoconazole, itraconazole)
majorContraindicated. Strong CYP3A4 inhibitors — risk of severe peripheral and cerebral ischemia.
Triptans (sumatriptan, zolmitriptan, rizatriptan, etc.)
majorDo not use within 24 hours of each other. Additive vasoconstriction risk.
Peripheral vasoconstrictors (pseudoephedrine, phenylephrine)
majorSynergistic blood pressure elevation; avoid combination.
SSRIs/SNRIs (fluoxetine, paroxetine, sertraline, fluvoxamine)
moderateRare serotonin syndrome symptoms (weakness, hyperreflexia, incoordination) reported. Use with caution.
Beta-blockers (propranolol, metoprolol)
moderateMay enhance peripheral vasoconstriction risk. Requires careful monitoring.
Grapefruit juice
minorLess potent CYP3A4 inhibitor; may modestly increase DHE levels. Use with caution.
D.H.E. 45 (dihydroergotamine mesylate) remains one of the most effective acute treatments for migraine and cluster headache, particularly for patients who have failed triptans or who need a parenteral option. Despite the discontinuation of the original brand and an active ASHP shortage since 2024, generic formulations from Hikma and Provepharm continue to supply the market, and newer delivery forms (Trudhesa, Brekiya, Atzumi) provide additional options.
The key challenges for patients in 2026 are finding it in stock and managing cost. Chain pharmacies frequently run out; independent and specialty pharmacies are often a better bet. Discount programs like GoodRx can bring cash prices down to approximately $262. For those on brand formulations, manufacturer savings programs and carefully documented prior authorization submissions can reduce the cost burden significantly.
If you're struggling to find D.H.E. 45 in stock, medfinder can help. Provide your medication, dosage, and location, and medfinder calls pharmacies near you to find current stock — sending results directly to your phone by text.
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