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Antituberculous Agents — MDR-TB Pregnancy: Avoid if possible — limited data; weigh against risks of untreated MDR-TB; consult specialist TB physician; animal data show no teratogenicity

Bedaquiline

Brand names: Sirturo

Adult dose

Dose: 400 mg once daily for 2 weeks, then 200 mg three times weekly for 22 weeks (total 24 weeks)
Route: Oral
Frequency: Daily for 2 weeks, then 3 times weekly
Max: 400 mg/day (initial phase)
Take with food (fatty meal increases absorption 2-fold). Take under directly observed therapy (DOT). Must be given with at least 2 other active TB drugs. Only prescribe if at least 2 background drugs are susceptible.

Paediatric dose

Dose: Seek specialist opinion N/A/kg
Route: Oral
Frequency: N/A
Max: N/A
Licensed from age 5 (weight 15 kg and above) in UK for MDR-TB; seek specialist paediatric infectious disease opinion at national MDR-TB centre

Dose adjustments

Renal

No dose adjustment for mild-moderate impairment; use with caution in severe renal impairment — limited data

Hepatic

No dose adjustment in mild-moderate impairment; avoid in severe hepatic impairment — hepatically metabolised by CYP3A4

Paediatric weight-based calculator

Licensed from age 5 (weight 15 kg and above) in UK for MDR-TB; seek specialist paediatric infectious disease opinion at national MDR-TB centre

Clinical pearls

  • Mechanism: first novel TB drug in 40 years — inhibits mycobacterial ATP synthase (F-type, subunit c); unique mechanism of action; effective against both replicating and dormant M. tuberculosis; no cross-resistance with other TB drugs
  • STREAM and OPTIC trials: bedaquiline-containing regimens significantly improve culture conversion and treatment success in MDR-TB vs older regimens; WHO now recommends bedaquiline as core drug in all MDR-TB regimens
  • QT MONITORING MANDATORY: baseline ECG before starting; repeat ECG at 2, 12, and 24 weeks; and whenever symptomatic; stop if QTc above 500 ms; avoid other QT-prolonging drugs; electrolyte replacement (K+, Mg2+) critical
  • WHO 2022: bedaquiline is recommended in 6-month BPaL (bedaquiline + pretomanid + linezolid) regimen for XDR-TB and treatment-intolerant/non-responsive MDR-TB — ZeNix trial data
  • MHRA: licensed for MDR-TB as part of appropriate combination therapy; prescribing must be supervised by specialist TB centres; all cases must be notified to PHE/UKHSA
  • Long half-life: bedaquiline has a biphasic terminal half-life of 5.5 months — drug remains in body for extended period after stopping; resistance risk if inadvertently monotherapy; drug interactions persist after stopping

Contraindications

  • QTc prolongation (baseline QTc above 500 ms)
  • Known hypersensitivity to bedaquiline
  • Concurrent use with other QT-prolonging MDR-TB drugs without baseline ECG monitoring

Side effects

  • QT prolongation (mean increase 15.7 ms — class effect; fatal arrhythmia risk with other QT-prolonging drugs)
  • Hepatotoxicity (raised aminotransferases)
  • Nausea
  • Arthralgia
  • Headache
  • Haemoptysis

Interactions

  • Strong CYP3A4 inhibitors (ketoconazole, lopinavir/ritonavir) — increase bedaquiline exposure significantly; avoid prolonged co-administration
  • Strong CYP3A4 inducers (rifampicin) — reduce bedaquiline AUC by 52%; AVOID concurrent rifampicin (contradicts MDR-TB regimen — use only in fully susceptible TB)
  • Other QT-prolonging drugs (delamanid, clofazimine, fluoroquinolones, chlorpromazine) — additive QTc prolongation; weekly ECG monitoring required

Monitoring

  • ECG (baseline, 2 weeks, 12 weeks, 24 weeks — QTc prolongation)
  • LFTs (baseline, monthly)
  • Sputum smear and culture monthly (treatment response and resistance surveillance)
  • Electrolytes (K+, Mg2+, Ca2+ — correct hypo before starting)
  • Drug susceptibility testing (DST) of M. tuberculosis isolate

Reference: BNFc; BNF 90; NICE NG33; WHO TB Guidelines 2022; STREAM trial; OPTIC trial; ZeNix trial NEJM 2022; MHRA SPC Sirturo. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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