Diarylquinoline (2nd-line antituberculosis agent; QT prolongation)
Bedaquiline is an antibiotic used to treat resistant (multidrug-resistant) tuberculosis, always in combination with other medicines. It is taken orally with food. As a specialist medicine, it is used under the supervision of teams experienced in tuberculosis treatment.
Also known as: Sirturo
Clarithromycin prolongs the QT interval and inhibits CYP3A4, raising Bedaquiline levels — increased arrhythmia risk.
Bedaquiline is metabolised by CYP3A4 and clarithromycin inhibits this enzyme, potentially raising its concentrations substantially; both drugs prolong the QT interval, with an additive torsades de pointes risk. In multidrug-resistant tuberculosis regimens containing bedaquiline, avoid macrolides; if a macrolide is needed, prefer azithromycin (less interaction) and monitor the ECG and electrolytes.
Bedaquiline + clarithromycin: clarithromycin raises bedaquiline levels (CYP3A4 inhibition) and both prolong the QT. Avoid the combination.
Bedaquiline metabolism inhibition and additive QT prolongation.
ECG (QTc) and electrolytes.
Palpitations, syncope.
Avoid when possible; ECG and surveillance.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Rifampin substantially lowers Bedaquiline levels (about 50%) — risk of failure and resistance in multidrug-resistant TB.
Bedaquiline is metabolised by CYP3A4 and rifampicin, a potent inducer, can reduce its concentrations by more than 50%, compromising multidrug-resistant tuberculosis treatment. The bedaquiline label advises against combination with potent CYP3A4 inducers. The coadministration should be avoided; if needed, consider alternative regimens and monitor the clinical and microbiological response.
Bedaquiline + rifampicin: rifampicin markedly reduces bedaquiline levels (CYP3A4 induction), with risk of therapeutic failure. Avoid the combination.
CYP3A4 induction, the main Bedaquiline metabolic pathway.
Microbiological response (culture and smear).
Persistent positivity, emerging resistance.
Avoid coadministration; if unavoidable, consider therapeutic drug monitoring.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e ; approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b
Additive QT prolongation between Bedaquiline and Ciprofloxacin.
Bedaquiline, used in multidrug-resistant tuberculosis, prolongs the QT interval in a dose-dependent manner, and ciprofloxacin adds the same fluoroquinolone class effect. The combination increases the risk of torsade de pointes, especially in patients with risk factors (long QT, hypokalaemia, renal impairment, other QT-prolonging drugs). The bedaquiline label advises against co-administration with QT-prolonging drugs. In practice, prefer an antibiotic without QT effect when possible; if ciprofloxacin is unavoidable, monitor the ECG at start and during treatment and correct electrolytes.
Bedaquiline + ciprofloxacin: additive risk of QT prolongation. Avoid; if unavoidable, monitor the ECG.
Additive effect on cardiac repolarisation.
ECG (QTc).
Palpitations, syncope.
Caution; ECG if risk factors.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14c3bc33-201d-492e-9aee-a4d84c813a3d
Bedaquiline prolongs the QT interval; combining with Amiodarone raises the risk of ventricular arrhythmias.
Bedaquiline prolongs the QT interval (hERG blockade) and amiodarone prolongs it too; the effect is additive and the risk of torsades de pointes increases, especially with hypokalaemia, hypomagnesaemia or heart disease. Amiodarone also inhibits CYP3A4, the pathway by which bedaquiline is metabolised, potentially raising its levels and worsening QT prolongation. Avoid the combination in multidrug-resistant tuberculosis whenever an alternative exists; if unavoidable, monitor the ECG (ideally weekly) and electrolytes.
Bedaquiline + amiodarone: additive QT prolongation with risk of torsades de pointes. Avoid the combination; if unavoidable, monitor the ECG weekly.
Additive cardiac repolarisation prolongation.
ECG (QTc), potassium and magnesium.
Syncope, palpitations.
Avoid; if unavoidable, periodic ECG and electrolyte control.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Alcohol adds hepatotoxicity to that of bedaquiline, increasing the risk of liver injury.
Avoid alcohol during treatment.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e
Taking bedaquiline with food increases its absorption and reduces plasma level variability.
Take with food, preferably at the same daily meal.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e
Bedaquiline is hepatotoxic and should be used with caution in patients with liver disease, with transaminase monitoring.
Monitor transaminases; stop with significant elevations or hepatitis symptoms.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e
Bedaquiline prolongs the QT interval and the arrhythmia risk increases in patients with QT prolongation or with QT-prolonging drugs.
Avoid in known QT prolongation; monitor ECG and electrolytes.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e
Human data are very limited; bedaquiline is not recommended in pregnancy unless the benefit clearly outweighs the risk.
Avoid in pregnancy; consider only in multidrug-resistant tuberculosis without an alternative.
Excreted into breast milk; avoid while breastfeeding (insufficient data).
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Bedaquiline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1534c9ae-4948-4cf4-9f66-222a99db6d0e
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Diarylquinoline antimycobacterial with a specific and novel mechanism of action: inhibits the mycobacterial ATP synthase (c subunit), blocking the energy (ATP) production of the mycobacterium. Active against Mycobacterium tuberculosis, including multidrug-resistant strains, with specificity for mycobacteria.
Bedaquiline binds to the c subunit of the mycobacterial ATP synthase (F0F1), preventing ATP synthesis — the mycobacterium loses its main energy source and dies. This target differs from those of the classical antituberculosis classes, explaining activity against resistant strains.
A high-fat meal (22 grams of fat, 558 total kcal) increased Cmax and AUC by 2-fold — the medicine should be taken with food to enhance oral bioavailability. Tmax is around 5 hours after a single oral dose.
Bedaquiline is metabolised mainly by CYP3A4 to the N-monodesmethyl metabolite (M2), with a relative M2 exposure of 23–31%. Excretion is predominantly faecal; renal excretion of unchanged drug is ≤0.001% of the dose.
The terminal half-life is very long: approximately 5.5 months, for both bedaquiline and the M2 metabolite. Plasma protein binding is >99.9% and the apparent volume of distribution is ~117 L.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
