Antituberculosis agent (ansamycin; weaker inducer than rifampin)
Rifabutin is an antibiotic used to prevent and treat mycobacterial infections, including prevention of Mycobacterium avium complex infection in people with advanced HIV. Like rifampicin, it speeds up the elimination of many other medicines.
Also known as: Mycobutin
Two-way interaction: Clarithromycin raises Rifabutin levels (risk of uveitis and neutropenia) and Rifabutin lowers Clarithromycin levels.
The interaction is bidirectional: rifabutin induces CYP3A4 and lowers clarithromycin concentrations (compromising efficacy), while clarithromycin inhibits CYP3A4 and raises rifabutin levels, increasing the risk of uveitis, neutropenia and arthralgia. In mycobacterial regimens (e.g. Mycobacterium avium complex) with both drugs, reduce the rifabutin dose (often by half), monitor the blood count, ocular symptoms and the clinical response.
Rifabutin + clarithromycin: rifabutin lowers clarithromycin levels and clarithromycin raises rifabutin levels (risk of uveitis, neutropenia). Monitor both.
CYP3A4 inhibition by clarithromycin plus induction by rifabutin.
Ophthalmic review (eye pain and redness) and blood count.
Eye pain, redness, blurred vision (uveitis); fever, neutropenia.
Reduce the rifabutin dose (e.g. 150 mg/day or intermittent) and watch for toxicity.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Rifabutin lowers Atorvastatin levels — reduced lipid-lowering effect.
Rifabutin, like rifampicin, is an enzyme inducer (CYP3A4 and transporters) that accelerates atorvastatin metabolism, potentially lowering its concentrations and compromising lipid control during antimycobacterial treatment (e.g., prophylaxis in HIV). The effect is less marked than with rifampicin, but monitoring the lipid profile is recommended and, if needed, adjusting the statin dose (or considering a statin less dependent on CYP3A4, such as pravastatin).
Atorvastatin + rifabutin: rifabutin induces enzymes and can lower statin levels, reducing the lipid-lowering effect. Monitor lipids.
CYP3A4 induction (weaker than rifampin, but significant).
Lipid profile.
High LDL.
Monitor lipids and adjust the dose.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707 ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86841382-4229-4e03-958e-3ac22639efd4
Rifabutin lowers Amiodarone levels — risk of arrhythmia recurrence.
Rifabutin induces CYP3A4 and lowers amiodarone plasma concentrations (and its active metabolite), potentially compromising arrhythmia control. The interaction develops over days to weeks and persists after rifabutin discontinuation (long amiodarone half-life). Monitor the rhythm and clinical response, consider adjusting the amiodarone dose and monitor the ECG during and after rifabutin treatment.
Rifabutin + amiodarone: rifabutin induces CYP3A4 and lowers amiodarone levels, potentially reducing antiarrhythmic efficacy. Monitor the clinical effect.
CYP3A4 induction.
ECG and rhythm.
Palpitations, syncope.
Monitor rhythm; consider an alternative.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707 ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Alcohol adds hepatotoxicity to that of rifabutin, increasing the risk of liver injury.
Avoid alcohol during treatment.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707
Food decreases the rate and extent of rifabutin absorption; taking it on an empty stomach maximises plasma levels.
Take rifabutin on an empty stomach, 1 hour before or 2 hours after meals.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707
Rifabutin causes neutropenia and leucopenia; the risk increases in patients with prior low counts or in combination with myelosuppressive drugs.
Monitor the blood count; stop if severe neutropenia occurs.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707
Rifabutin is hepatotoxic and should be used with caution in patients with liver disease, with transaminase monitoring.
Monitor transaminases; adjust or stop if liver injury occurs.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707
Human data are limited; rifabutin should be used in pregnancy only if the benefit justifies the risk.
Use only if the benefit justifies the risk; not the first-line agent in pregnancy.
Excreted into breast milk; compatible with breastfeeding under supervision.
Rifabutin induces CYP3A4 and reduces the efficacy of hormonal contraceptives — use an additional (barrier) method.
DailyMed/FDA (NIH/NLM) — approved Rifabutin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2026b67-4755-4236-96b6-a6b5e7399707
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Bactericidal rifamycin antibiotic (rifamycin-S derivative) that inhibits bacterial DNA-dependent RNA polymerase, blocking transcription. Active against atypical mycobacteria (Mycobacterium avium complex), M. tuberculosis and various Gram-positives and Gram-negatives. Weaker enzyme inducer than rifampicin.
Rifabutin binds to the beta subunit of bacterial DNA-dependent RNA polymerase, preventing the initiation of RNA transcription. Resistance results from polymerase mutations; rifabutin retains activity against some rifampicin-resistant strains.
After a single oral 300 mg dose, rifabutin is readily absorbed, with mean peak plasma levels of 375 ng/mL in ~3.3 hours; absolute bioavailability is ~20% (at least 53% of the dose is absorbed). High-fat meals slow absorption without reducing the extent. Plasma protein binding is ~85%.
Rifabutin is extensively metabolised in the liver to five metabolites; the predominant ones are 25-O-desacetyl (with activity equal to the parent drug, contributing up to 10% of antimicrobial activity) and 31-hydroxy. Metabolism is inducible (autoinduction and CYP3A induction).
Rifabutin is slowly eliminated from plasma, with a mean terminal half-life of ~45 hours (range 16–69 hours), presumably because of distribution-limited elimination. ~53% of the oral dose is excreted in the urine (mainly as metabolites) and ~30% in the faeces.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
