D.H.E. 45 Side Effects: What to Expect and When to Call Your Doctor

D.H.E. 45 (dihydroergotamine mesylate) is an effective medication for acute migraine and cluster headaches, but it comes with a meaningful side effect profile that every patient should understand before starting treatment. Some side effects are common and manageable; others are serious and require immediate medical attention. This guide covers both — so you know what to watch for and when to act.

Always review side effects with your prescriber and read the full medication guide provided by your pharmacist. This article is for informational purposes only and does not replace medical advice.

Common Side Effects of D.H.E. 45

These side effects occur in a meaningful percentage of patients and are generally considered tolerable at recommended doses:

Nausea and vomiting — Among the most common side effects. Nausea can be significant. Pretreatment with an antiemetic (such as metoclopramide or prochlorperazine) is commonly recommended, especially with IV administration.

Dizziness — Lightheadedness or dizziness may occur, particularly after IV administration. Sit or lie down after use.

Paresthesia — Tingling or numbness, often in the fingers or toes. Mild paresthesia is common and usually resolves after the medication wears off.

Chest tightness or pressure — Can occur and may be mild, but must be evaluated promptly as it can also indicate a serious cardiac reaction (see below).

Abdominal cramps — May occur, especially at higher doses.

Flushing — Warmth or redness of the skin.

Nasal discomfort (nasal spray forms) — Rhinitis, nasal congestion, or unpleasant taste are common with intranasal administration.

Serious Side Effects — Call Your Doctor or 911 Immediately

The following are rare but serious side effects that require immediate medical attention. Although the incidence is extremely low given how many patients use DHE, they are real and must be taken seriously:

Myocardial ischemia or infarction (heart attack) — Serious adverse cardiac events, including acute myocardial infarction and life-threatening cardiac rhythm disturbances, have been reported. Symptoms: crushing chest pain, pressure, shortness of breath, left arm or jaw pain.

Vasospasm (arterial) — Spasm of coronary, cerebral, or peripheral arteries. Symptoms may include sudden severe chest pain, leg pain or cramps, or cold/numb extremities.

Hypertensive crisis — Significant elevations in blood pressure have been reported. Symptoms: severe headache, vision changes, pounding in chest.

Stroke and cerebrovascular events — Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have been reported. Symptoms: sudden numbness or weakness on one side, confusion, speech difficulty, severe sudden headache.

Peripheral ischemia (ergotism) — With excessive or prolonged use, severe ischemia of the extremities can occur. Symptoms: cold fingers or toes, severe cramping, skin turning blue or white.

Fibrosis (with prolonged daily use) — Prolonged daily use of injectable DHE has been associated with pleural and retroperitoneal fibrosis. Rare cases of cardiac valvular fibrosis have also been reported. This is why DHE is not approved for chronic daily use.

Pregnancy and Breastfeeding Warning

D.H.E. 45 is contraindicated in pregnancy (Pregnancy Category X). Dihydroergotamine possesses oxytocic properties (it can stimulate uterine contractions) and may cause fetal harm. Do not use this medication if you are pregnant or may become pregnant. It is also contraindicated in breastfeeding women due to potential serious adverse effects in nursing infants.

What Are the Boxed Warnings for D.H.E. 45?

The FDA prescribing information for D.H.E. 45 includes a Boxed Warning regarding the risk of serious and/or life-threatening peripheral ischemia when dihydroergotamine is coadministered with potent CYP3A4 inhibitors (such as macrolide antibiotics like erythromycin and clarithromycin, and HIV protease inhibitors like ritonavir and indinavir). This combination is contraindicated.

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Tips for Minimizing Side Effects

Take an antiemetic 30 minutes before DHE if nausea is a significant problem.

Use the lowest effective dose and never exceed the maximum (3 mg/day IM/SC, 2 mg/day IV, 6 mg/week total).

Do not use DHE chronically or daily — it is approved only for acute (episodic) use.

Tell your doctor and pharmacist all medications you take — especially antibiotics, antifungals, and HIV medications — before starting DHE.

For a complete list of drug interactions, see our article on D.H.E. 45 drug interactions. For a full overview of the drug, see what is D.H.E. 45.