bedaquiline

Brand: Sirturo

⚠ BBW Prototype Drug

Drug Class: diarylquinoline antimycobacterial

Drug Family: antibiotic

Subclass: ATP synthase inhibitor (first-in-class for TB)

Organ Systems: infectious-disease

Mechanism of Action

Specifically inhibits mycobacterial ATP synthase by binding the c subunit of ATP synthase, blocking ATP production; bactericidal with selectivity for M. tuberculosis; first new TB drug class in 40 years.

mycobacterial ATP synthase (atpE subunit)

Indications

multidrug-resistant tuberculosis (MDR-TB) as part of combination therapy

Contraindications

QTc >500 ms
concurrent use of strong CYP3A4 inducers that would reduce bedaquiline levels

Adverse Effects

Common

nausea
arthralgia
headache

Serious

QTc prolongation (requires ECG monitoring throughout therapy)
hepatotoxicity
increased mortality signal in clinical trials (clinical significance uncertain)

Pharmacokinetics (ADME)

Absorption	increased with food (~2-fold with high-fat meal); administer with food
Distribution	highly lipophilic; large Vd; slow redistribution from deep compartment
Metabolism	hepatic CYP3A4 (primary)
Excretion	primarily fecal
Half-life	5.5 months (terminal half-life due to deep tissue distribution)
Onset	1–5 hours
Peak	5 hours
Duration	24 weeks treatment course
Protein Binding	>99%
Vd	very large

Drug Interactions

Drug / Agent	Mechanism	Severity
CYP3A4 inducers (rifamycins)	reduce bedaquiline levels by ~50%; avoid concurrent rifampin/rifabutin	major
QTc-prolonging drugs	additive QTc prolongation; obtain ECG at baseline and during therapy	major
CYP3A4 inhibitors	increase bedaquiline exposure and QTc risk	moderate

Nursing Considerations

Administer with food to ensure adequate absorption; obtain ECG at baseline, and at 2, 12, and 24 weeks of treatment.
Monitor serum potassium, calcium, and magnesium before starting; electrolyte abnormalities increase QTc risk.
Monitor LFTs monthly; instruct patient to report jaundice, fatigue, or right upper quadrant pain.
Bedaquiline is used only for MDR-TB as part of a multi-drug regimen under the supervision of a TB specialist.

Clinical Pearls

Bedaquiline's novel mechanism (ATP synthase inhibition) provides no cross-resistance with any existing TB drug class, making it a critical addition to MDR-TB and XDR-TB treatment regimens.
Its extremely long terminal half-life (~5.5 months) means drug persists in the body for months after a 24-week course ends; monitoring for QTc prolongation should continue even after discontinuation.

Safety Profile

Pregnancy use-with-caution

Lactation avoid

Renal Adjustment Not required

Hepatic Adjustment Required

TDM Not required

Guideline Update pending

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Diarylquinoline Antimycobacterial Multidrug-resistant Tuberculosis (MDR-TB) As Part Of Combination Therapy

← Back to Medications