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Dihydroergotamine Mesylate

Pronunciation: DIE-high-droe-err-GOT-uh-meen MEH-sih-LATE
Class: Ergotamine derivative

Trade Names

D.H.E. 45
- Injection 1 mg/mL

- Spray, nasal 4 mg/mL. With 10 mg caffeine and 50 mg dextrose.


Constricts peripheral and cranial blood vessels, depresses central vasomotor centers, and reduces extracranial blood flow.

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93% protein bound. Vd approximately 800 L.


Four metabolites identified, with one being equivalent to dihydroergotamine in potency.


Major elimination route is via the bile in the feces. 6% to 7% excreted unchanged in the urine after IM injection. Renal Cl is 0.1 L/min. t ½ approximately 9 h.


15 to 30 min (IM).


3 to 4 h (IM).

Indications and Usage

Acute treatment of migraine headaches with or without aura; acute treatment of cluster headache episodes (injection).


Hypersensitivity to ergot alkaloids; hepatic or renal function impairment; severe pruritus; coronary artery disease; uncontrolled peripheral vascular disease; hypertension; sepsis; use during pregnancy, lactation or in women who may become pregnant; concurrent vasoconstrictor therapy. CYP3A4 inhibitors (eg, macrolide antibiotics [eg, erythromycin], protease inhibitors [eg, ritonavir]).

Dosage and Administration


Intranasal 1 spray (0.5 mg) in each nostril; administer an additional spray (0.5 mg) in each nostril 15 min later for a total dosage of 4 sprays (2 mg).

IM / IV / Subcutaneous Administer 1 mL (1 mg); repeat dose as needed at 1-h intervals to a total dose of 3 mL (3 mg) for IM or subcutaneous administration or 2 mL (2 mg) for IV administration in a 24-h period (max, 6 mL/wk).

General Advice

  • For IM administration, inject at first sign of headache. To determine minimal effective dose, adjust dose for several headaches and then use minimal effective dose at onset of subsequent attacks.
  • For rapid effect, administer IV. May be given undiluted; give 1 mg or fraction thereof over 1 min.
  • After drug is administered, have patient lie supine and relax for few minutes, preferably in quiet, darkened room.


Protect ampules from light and heat.

Drug Interactions

Beta-blockers, vasoconstrictors (eg, epinephrine)

Can increase peripheral ischemia, cyanosis, and numbness caused by ergot alkaloids.

CYP3A4 inhibitors (eg, macrolide antibiotics [eg, erythromycin], protease inhibitors [eg, ritonavir])

May increase the risk of life-threatening peripheral ischemia.

Nitrates (eg, nitroglycerin)

May oppose effects of nitrates.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Pulselessness; precordial distress or pain; transient tachycardia or bradycardia; raised arterial pressure; coronary vasoconstriction.


Nausea; vomiting; abdominal pain.


Numbness and tingling of fingers and toes; muscle pain in extremities; weakness in legs; localized edema; itching. Drug has oxytocic and spasmolytic properties.



Monitor for changes in vital signs, especially pulse and BP. Monitor for changes in mental status (eg, confusion, drowsiness). Monitor for effectiveness of headache relief with pain assessments every 15 min and for minimal effective dose. Check neurocirculatory status of extremities, especially distally (eg, pulse, warmth, color).


Category X .


Excreted in breast milk and may inhibit lactation. Drug can cause symptoms of ergotism in infant.


Safety and efficacy not established.

Dependence/Withdrawal syndrome

Dependence/withdrawal has occurred with other ergot alkaloids; therefore, recommended dosage should not be exceeded.



Nausea, vomiting, leg weakness, pain in limb muscles, numbness and tingling of toes, precordial pain, changes in heart rate and BP, localized edema, itching, peripheral ischemia, gangrene, confusion, depression, drowsiness, convulsions.

Patient Information

  • Caution patient that this medication must not be taken during pregnancy or when pregnancy is possible. Advise patient to use reliable form of birth control while taking this drug.
  • Teach patient to measure or rate drug effectiveness (eg, use analog or other validated rating scale).
  • Instruct patient to take drug at first sign of impending headache and not to exceed maximum dosage.
  • Advise patient to relax in supine position in quiet, darkened room after drug administration.
  • Tell patient to inform health care provider if diagnosed with any peripheral vascular disease.
  • Instruct patient to report the following symptoms to health care provider: pain, itching, weakness, tingling, edema, pallor, coolness, numbness (especially in distal extremities), chest discomfort, pain or any change in mental status (eg, drowsiness, light-headedness, syncope, seizures).
  • Advise patient to avoid intake of alcoholic beverages, smoking, and exposure to cold because these vasoconstrictors may further impair peripheral circulation and cause or aggravate migraine headache.

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