Drug Interaction Report

Rifabutin and Atovaquone: Interaction Details

A pharmacist-reviewed analysis of the Rifabutin and Atovaquone 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

Rifabutin

Mycobutin
+

Atovaquone

Mepron Mepron®
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 65 documented Rifabutin interactions, 57 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

Reduced atovaquone exposure

Interaction Deep Dive

Concomitant use of atovaquone and rifabutin may result in reduced plasma concentration of atovaquone. During drug interaction studies, coadministration of atovaquone and rifabutin resulted in decreased atovaquone AUC. Therefore, coadministration of atovaquone and rifabutin is not recommended21.

Why it happens (mechanism)

Unknown

Literature reports

2 reports — tap to read

a) During drug interaction studies, coadministration of atovaquone 750 mg every 12 hours and rifAMPin 600 mg every 24 hours resulted in a 52% decrease in atovaquone steady state concentration (+/- 13%) and a 37% increase in rifAMPin steady state concentrations (+/- 42%). In a similar study in healthy volunteers, coadministration of atovaquone 750 mg twice daily and rifabutin 300 mg once daily resulted in a 35% decrease in atovaquone concentrations and a 19% decrease in rifabutin concentrations at steady state 2.

b) During drug interaction studies, concomitant use with rifAMPin and rifabutin resulted in a 50% and 34% decrease in atovaquone 1.

Common questions

Can I take Rifabutin and Atovaquone together?

Reduced atovaquone exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Rifabutin and Atovaquone 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 Rifabutin or Atovaquone 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: MALARONE(R) oral tablets, pediatric tablets, atovaquone proguanil HCl oral tablets, pediatric tablets. GlaxoSmithKline (per FDA), Research Triangle Park, NC, 2013. DailyMed
  2. Product Information: MEPRON(R) oral suspension, atovaquone oral suspension. GlaxoSmithKline (per Manufacturer), Research Triangle Park, NC, 2015. DailyMed
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Rifabutin

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All Rifabutin interactions (65)
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Atovaquone

Keep reading about Atovaquone

All Atovaquone interactions (19) Atovaquone drug information
Also serious with: Azathioprine Bupropion Clomipramine Efavirenz
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:

Rifabutin + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato Alkanna Alpine Ragwort + 172 more
Atovaquone + Activated Charcoal Coffee Charcoal European Mandrake Glucomannan Guar Gum Gum Arabic Slippery Elm Tragacanth + 9 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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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.