Azithromycin and Rifabutin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rifabutin
Azithromycin
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.
What happens
An increased risk of rifabutin toxicity (rash, GI disturbances, hematologic abnormalities)
Interaction Deep Dive
In a controlled study of healthy volunteers, concurrent use of azithromycin in addition to rifabutin was associated with an increased risk of neutropenia1. Similar findings have been observed with another macrolide antibiotic, clarithromycin. It has been suggested that clarithromycin may increase the serum and tissue concentrations of rifabutin possibly to the point of toxicity 34. Coadministration of azithromycin and rifabutin does not significantly alter the pharmacokinetics of either drug 5.
Why it happens (mechanism)
Inhibition of rifabutin metabolism
Literature reports
2 reports — tap to read
a) In a controlled study of 30 healthy volunteers, the pharmacokinetic interactions between rifabutin and azithromycin or clarithromycin were studied. Six people withdrew from the study due to adverse events, including neutropenia, fever, and myalgia. The 14-day study was terminated on day 10 due to these adverse effects. Neutropenia was seen in patients taking rifabutin, rifabutin plus clarithromycin, and rifabutin plus azithromycin. However, those who were taking rifabutin in addition to either clarithromycin or azithromycin experienced the most severe adverse events. The first volunteer to develop neutropenia was taking rifabutin 300 mg daily in addition to clarithromycin 500 mg twice daily. The patient was admitted to the hospital with an absolute neutrophil count of 0.8 x 10(9) on day 9 of the study and bone marrow aspirates taken on day 10 revealed hypoplastic bone marrow consistent with drug injury. A total of three volunteers were admitted to the hospital for neutropenia, and five patients were treated with granulocyte colony stimulating factor (G-CSF). Patients who received clarithromycin and rifabutin together also experienced an average 43% decrease in platelet counts. Volunteers who received clarithromycin in addition to rifabutin had increased levels of rifabutin, but this was not seen with azithromycin and rifabutin 1.
b) Coadministration of rifabutin and azithromycin did not significantly alter the pharmacokinetics of either drug. Azithromycin was administered in a dose of 250 mg daily for ten days, following a dose of 500 mg on the first day. Mean concentrations of azithromycin one day after the last dose were 53 ng/mL when coadministered with rifabutin 300 mg daily, and 49 ng/mL when coadministered with placebo. Mean concentrations five days after the last azithromycin dose were 23 ng/mL and 21 ng/mL in the two groups. The administration of rifabutin 300 mg daily for ten days produced mean concentrations of rifabutin one-half day after the last dose of 60 ng/mL when coadministered with azithromycin 250 mg daily and 71 ng/mL when coadministered with placebo. Mean azithromycin concentrations five days after the last dose were 8.1 ng/mL and 8.2 ng/mL in the two groups 2.
Common questions
Can I take Azithromycin and Rifabutin together?
An increased risk of rifabutin toxicity (rash, GI disturbances, hematologic abnormalities) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Azithromycin and Rifabutin interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Azithromycin or Rifabutin 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 anything you'd monitor while I'm on both?
References (5)
- Apseloff G, Foulds G, Laboy-Goral L, et al: Severe neutropenia caused by recommended prophylactic doses of rifabutin (letter). Lancet 1996; 348:685. PubMed
- Product Information: Zithromax(R), azithromycin. Pfizer Labs, New York, NY, 1997. DailyMed
- Shafran S, Deschenes J, Miller M, et al: Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and ethambutol. N Engl J Med 1994; 330:438-439. DOI
- Tseng AL & Walmsley SL: Rifabutin-associated uveitis. Ann Pharmacother 1995; 29:1149-1155. PubMed
- Product Information: Zithromax(R), azithromycin. Pfizer Labs, New York, NY, 1997. DailyMed
Keep reading about Rifabutin
Keep reading about Azithromycin
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist