Drug Interaction Report

Azithromycin and Sotalol: Interaction Details

A pharmacist-reviewed analysis of the Azithromycin and Sotalol interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

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

Sotalol

Betapace Betapace® Betapace® AF Sorine Sorine® Sotylize
+

Azithromycin

AzaSite Zithromax Zithromax® Zithromax® Single Dose Packets Zithromax® Tri-Paks® Zithromax® Z-Paks® Zmax®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Jul 11, 2026
Editorial policy · Data sources
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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
theoretical
Severity
Major

What happens

An increased risk of cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest)

Interaction Deep Dive

Use of macrolides, including azithromycin, has been associated with prolonged cardiac repolarization and QT interval. Rare reports of torsades de pointes during azithromycin therapy have occurred during postmarketing surveillance. Concomitant therapy with azithromycin and Class III antiarrhythmic agents may cause additive effects on QT prolongation and increased risk for serious cardiac events1. If concomitant use is clinically warranted, carefully assess potential risks and benefits before using azithromycin and Class III antiarrhythmic agents together 234.

Why it happens (mechanism)

Additive QT interval prolongation

Literature reports

2 reports — tap to read

a) One case report describes a female patient maintained on amiodarone 200 mg/day, furosemide 40 mg/day, enalapril 7.5 mg twice a day and aspirin 325 mg/day, who experienced a marked prolongation of the QT interval and increased QT dispersion on day 3 of azithromycin treatment for pneumonia. The patient's admission EKG showed a regular sinus rhythm with a heart rate of 60 beats/min, normal PR, QRST, and QTc (510 msec), and QT dispersion of 58 msec. Serum electrolytes were within normal limits. On day 3 of azithromycin therapy (500 mg on day one, followed by 250 mg/day) the patient was seen again for not feeling well and intermittent dizziness. Clinical examination was significant for improved lung symptoms and an electrocardiogram showing bradycardia (53 beats/min), increased QT interval (676 msec), QTc (660 msec), and QT dispersion (140 msec). Azithromycin was discontinued, and EKG values returned to baseline 4 days later. Prior to the azithromycin, the patient had tolerated the amiodarone without incident 5.

b) Cases of QTc prolongation and/or torsades de pointes have been reported with all class III antiarrhythmic agents, including acecainide 6, amiodarone 7, bretylium 8, ibutilide 9, dofetilide 10, sotalol 11, and tedisamil 12.

Common questions

Can I take Azithromycin and Sotalol together?

An increased risk of cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Azithromycin and Sotalol 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Azithromycin or Sotalol 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 (12)

  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: CORDARONE(R) oral tablets, amiodarone hcl oral tablets. Wyeth Pharmaceuticals Inc, Philadelphia, PA, 2008. DailyMed
  3. Product Information: BETAPACE AF(R) oral tablets, sotalol hcl oral tablets. Bayer Healthcare Pharmaceuticals,Inc, Wayne, NJ, 2007. DailyMed
  4. Product Information: TIKOSYN(R) oral capsules, dofetilide oral capsules. Pfizer,Inc, New York, NY, 2004. DailyMed
  5. Samarendra P, Kumari S, Evans S, et al: QT prolongation associated with azithromycin/amiodarone combination. PACE 2001; 24:1572-1574. PubMed
  6. Chow MJ, Piergies AA, Bowsher DJ, et al: Torsade de pointes induced by N-acetylprocainamide. J Am Coll Cardiol 1984; 4:621-624. DOI
  7. Faggiano P, Gardini A, D'Aloia A, et al: Torsade de pointes occurring early during oral amiodarone treatment. Int J Cardiol 1996; 55(2):205-208. DOI
  8. Gilman AG, Goodman LS, Rall TW, et alGilman AG, Goodman LS, Rall TW, et al (Eds): The Pharmacological Basis of Therapeutics, 7th. Macmillan Publishing Co, New York, NY, 1985.
  9. Rodriguez I, Kilborn MJ, Liu XK, et al: Drug-induced QT prolongation in women during the menstrual cycle. JAMA 2001; 285(10):1322-1326. PubMed
  10. Allen MJ, Oliver SD, Newgreen MW, et al: Pharmacodynamic effect of continuous vs intermittent dosing of dofetilide on QT interval. Br J Clin Pharmacol 2002; 53:59-65.
  11. Marill KA & Runge T: Meta-analysis of the risk of torsades de pointes in patients treated with intravenous racemic sotalol. Acad Emerg Med 2001; 8(2):117-124. DOI
  12. Bargheer K, Bode F, Klein HU, et al: Prolongation of monophasic action potential duration and the refractory period in the human heart by tedisamil, a new potassium-blocking agent. Eur Heart J 1994; 15:1409-1414. PubMed
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Sotalol

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All Sotalol interactions (124) Sotalol drug information
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Azithromycin

Keep reading about Azithromycin

All Azithromycin interactions (299) Azithromycin drug information
Also serious with: Pimozide Mesoridazine Levoketoconazole Colchicine
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Sotalol + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Indian Snakeroot Sida Cordifolia + 35 more
Azithromycin + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Oleander Sida Cordifolia + 84 more

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