Drug Interaction Report

Azithromycin and Dihydroergotamine: Interaction Details

AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Azithromycin

AzaSite Zithromax Zithromax® Zithromax® Single Dose Packets Zithromax® Tri-Paks® Zithromax® Z-Paks® Zmax®
+

Dihydroergotamine

Brekiya Migranal Trudhesa
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jul 11, 2026
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 299 documented Azithromycin interactions, 264 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
probable
Severity
Major

What happens

An increased risk of acute ergot toxicity (ergotism)

Interaction Deep Dive

Carefully monitor patients receiving azithromycin (a weak CYP3A4 inhibitor) and dihydroergotamine until further data are developed regarding coadministration1. Coadministration of dihydroergotamine and strong CYP3A4 inhibitors, including certain macrolide antibiotics (eg, clarithromycin, erythromycin and troleandomycin), is contraindicated due to the potential for acute ergot toxicity (ergotism) characterized by vasospasm and ischemia of the extremities. While serious adverse events have not been reported with less potent CYP3A4 inhibitors, there is a potential risk for serious toxicity when these drugs are used concomitantly 2.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of dihydroergotamine

Common questions

Can I take Azithromycin and Dihydroergotamine together?

An increased risk of acute ergot toxicity (ergotism) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Azithromycin and Dihydroergotamine interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Azithromycin or Dihydroergotamine need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (2)

  1. Product Information: ZMAX(R) oral extended-release suspension, azithromycin oral extended-release suspension. Pfizer Inc (per FDA), New York, NY, 2021. DailyMed
  2. Product Information: Migranal(R) nasal spray, dihydroergotamine mesylate nasal spray. Valeant Pharmaceuticals North America LLC (per DailyMed), Bridgewater, NJ, 2017. DailyMed
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Beyond drug–drug

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.