Atzumi Side Effects: What to Expect and When to Call Your Doctor

Atzumi (dihydroergotamine nasal powder) is an effective acute migraine treatment, but like all prescription medications, it comes with a side effect profile you should understand before starting. This guide covers what to expect — from the common, mild reactions to the serious warnings that warrant immediate medical attention.

BOXED WARNING: Risk With CYP3A4 Inhibitors

Atzumi carries a Boxed Warning — the FDA's most serious safety notice. The warning addresses the risk of serious and life-threatening peripheral ischemia when Atzumi is taken with strong CYP3A4 inhibitors. These are certain medications that block a liver enzyme (CYP3A4) that breaks down dihydroergotamine. When DHE cannot be metabolized normally, its blood levels rise to dangerous concentrations, causing vasospasm that can lead to:

Cerebral ischemia (reduced blood flow to the brain — stroke risk)

Ischemia of the extremities (reduced blood flow to arms and legs)

Strong CYP3A4 inhibitors that are CONTRAINDICATED with Atzumi include:

Macrolide antibiotics (clarithromycin, erythromycin — but NOT azithromycin)

HIV protease inhibitors (ritonavir, indinavir, nelfinavir, saquinavir)

Antifungals (ketoconazole, itraconazole — check with your doctor)

Always tell your doctor and pharmacist about ALL medications you take before starting Atzumi.

Common Side Effects of Atzumi

The following side effects occurred in more than 1% of patients in Atzumi clinical trials:

Rhinitis (nasal irritation/runny nose): The most frequently reported local side effect from intranasal administration. Typically mild and transient.

Nausea: A known side effect of DHE medications. Usually mild; using Atzumi as soon as a migraine begins (rather than waiting until severe) may help reduce nausea.

Altered sense of taste: Patients may notice a temporary change in how things taste after using Atzumi. Usually resolves quickly.

Application site reactions: Nasal burning, irritation, or discomfort at the site of administration.

Dizziness: Can occur, particularly when standing up quickly. Avoid driving immediately after taking Atzumi until you know how it affects you.

Vomiting, somnolence (sleepiness), pharyngitis (sore throat), and diarrhea were also reported in more than 1% of patients.

Serious Side Effects: When to Call 911 or Your Doctor Immediately

While serious side effects from Atzumi are rare, they can be severe. Seek emergency care immediately if you experience:

Chest pain, pressure, or tightening: Could indicate myocardial ischemia or infarction.

Sudden numbness, weakness, or coldness in arms or legs: May indicate peripheral ischemia.

Sudden severe headache, vision changes, confusion, or facial drooping: Possible cerebrovascular event (stroke).

Severe wheezing or difficulty breathing after use: Bronchospasm — particularly in patients with asthma or COPD. Stop Atzumi and seek emergency care.

Significant rise in blood pressure, severe headache, blurred vision: Hypertensive crisis risk — Atzumi can elevate blood pressure.

Medication Overuse Headache: A Risk With Frequent Use

Using Atzumi (or any acute migraine drug) too frequently can paradoxically worsen headache frequency — a condition called medication overuse headache (MOH). The safety of Atzumi beyond 4 doses in 7 days or 12 doses in 30 days has not been established. Do not use Atzumi more than recommended, and discuss your overall migraine treatment frequency with your doctor.

Atzumi in Pregnancy and Breastfeeding

Atzumi should not be used during pregnancy. Dihydroergotamine can decrease uterine blood flow and increase uterine muscle contractility, increasing the risk of preterm labor. Atzumi should also not be used during breastfeeding — a related compound (ergotamine) passes into breast milk and can cause adverse effects in infants, and DHE may suppress milk production. If you are pregnant or breastfeeding, talk to your doctor about safe migraine alternatives.

Bottom Line

Most patients tolerate Atzumi well — in the ASCEND trial, only 4.4% of patients discontinued due to side effects. The common side effects (rhinitis, nausea, taste changes) are manageable, and the serious side effects are rare. The key risk management step is ensuring you are not taking CYP3A4 inhibitors simultaneously. For a full list of drug interactions, see our guide on Atzumi drug interactions.