1. Clinical & Scientific Overview
Bedaquiline Fumarate (TIP-MED-000540, Reference Code [R-21]) is classified under
Antitubercular Reserve Medicines (NTEP Group A) as a Diarylquinoline Mycobacterial ATP Synthase Inhibitor.
Within the Indian regulatory and compendial framework, it is governed under Schedule H1 Conditional Access (NTEP DR-TB Programme).
Sirturo (Janssen / Johnson & Johnson), Bedaquiline NTEP Supply (Lupin / Macleods)
Uncoated Tablet: 100 mg; Dispersible Tablet: 20 mg
Statutory Restriction, High-Alert & Dispensing Safeguards
Indian Regulatory & Statutory Control Basis: Schedule H1 Conditional Access (NTEP DR-TB Programme)
High-Alert Clinical Risk, Dependence & Narrow Therapeutic Index Warnings: Boxed Warning: QTc prolongation (via active M2 metabolite with a 5.5-month terminal tissue half-life) and hepatotoxicity; metabolised by CYP3A4 (avoid rifampicin/efavirenz which slash bedaquiline levels by 50–80%, and monitor ECG when combined with clofazimine, moxifloxacin, or delamanid).
Mandatory Dispensing Register & Institutional Custody Protocol: Loading: 400 mg once daily with food for 2 weeks, followed by 200 mg three times per week (at least 48 hours apart) for 22 weeks under NTEP supervision; perform ECG at baseline, week 2, and monthly.
3. Mechanism of Action & Pharmacodynamics
Specifically inhibits the proton pump (subunit c, encoded by atpE) of Mycobacterium tuberculosis ATP synthase, depleting bacterial ATP in both replicating and dormant bacilli.
4. Therapeutic Indications & Evidence-Supported Uses
- Multidrug-resistant (MDR-TB), pre-XDR, and XDR tuberculosis as part of BPaLM / BPaL or longer all-oral NTEP regimens
5. Educational Dosage Context, Formulations & Administration
Educational Dosing & Regimen Summary: Specialist-Supervised Educational Reference Summary: Dosing of Bedaquiline must be individualised by a qualified specialist according to clinical indication, organ function, and institutional protocol (Uncoated Tablet: 100 mg; Dispersible Tablet: 20 mg).
Administration & Meal Timing: Routes: Oral (must be taken with food to double bioavailability). Loading: 400 mg once daily with food for 2 weeks, followed by 200 mg three times per week (at least 48 hours apart) for 22 weeks under NTEP supervision; perform ECG at baseline, week 2, and monthly.
6. Pharmacokinetics, Metabolism & Renal/Hepatic Adjustment
Exhibits diarylquinoline mycobacterial atp synthase inhibitor pharmacokinetic disposition; verify baseline renal and hepatic clearance and check for active or prolonged-half-life metabolites before repeat dosing.
Hepatic Phase I (CYP450) and/or Phase II conjugation or specific non-renal clearance as detailed in clinical warnings.
Verify eGFR / CrCl before initiation; see specific metabolite and renal clearance notes above.
Assess baseline Child-Pugh status and hepatic transaminases prior to therapy.
7. Contraindications, Precautions & High-Risk Warnings
- Known severe hypersensitivity to Bedaquiline or formulation excipients
- Unsupervised outpatient self-administration or dispensing without mandatory statutory prescription verification
- Specific clinical contraindications detailed under High-Alert Warnings & Statutory Restrictions
Key Clinical Precautions: Boxed Warning: QTc prolongation (via active M2 metabolite with a 5.5-month terminal tissue half-life) and hepatotoxicity; metabolised by CYP3A4 (avoid rifampicin/efavirenz which slash bedaquiline levels by 50–80%, and monitor ECG when combined with clofazimine, moxifloxacin, or delamanid).
8. Adverse Effects Profile
- Boxed Warning: QTc prolongation (via active M2 metabolite with a 5.5-month terminal tissue half-life) and hepatotoxicity; metabolised by CYP3A4 (avoid rifampicin/efavirenz which slash bedaquiline levels by 50–80%, and monitor ECG when combined with clofazimine, moxifloxacin, or delamanid).
- Dose-dependent target-organ pharmacodynamic effects requiring clinical observation
- Boxed Warning: QTc prolongation (via active M2 metabolite with a 5.5-month terminal tissue half-life) and hepatotoxicity; metabolised by CYP3A4 (avoid rifampicin/efavirenz which slash bedaquiline levels by 50–80%, and monitor ECG when combined with clofazimine, moxifloxacin, or delamanid).
- High-alert toxicity, dependence/diversion risk, or severe organ-specific adverse events if administered outside protocol
9. Major Drug–Drug, Drug–Food & Drug–Herb Interactions
- Boxed Warning: QTc prolongation (via active M2 metabolite with a 5.5-month terminal tissue half-life) and hepatotoxicity; metabolised by CYP3A4 (avoid rifampicin/efavirenz which slash bedaquiline levels by 50–80%, and monitor ECG when combined with clofazimine, moxifloxacin, or delamanid).
- Review all concomitant CNS depressants, QTc-prolonging agents, nephrotoxins, or CYP450 modulators prior to dispensing.
10. Clinical Monitoring, Patient Counselling & Storage
Clinical & Laboratory Monitoring: Loading: 400 mg once daily with food for 2 weeks, followed by 200 mg three times per week (at least 48 hours apart) for 22 weeks under NTEP supervision; perform ECG at baseline, week 2, and monthly.
Pharmacist Patient Counselling Points:
- Loading: 400 mg once daily with food for 2 weeks, followed by 200 mg three times per week (at least 48 hours apart) for 22 weeks under NTEP supervision; perform ECG at baseline, week 2, and monthly.
- Must be used strictly under direct medical supervision; never share prescription medicines or alter the prescribed dose.
Storage, Stability & Dispensing Safeguards: Loading: 400 mg once daily with food for 2 weeks, followed by 200 mg three times per week (at least 48 hours apart) for 22 weeks under NTEP supervision; perform ECG at baseline, week 2, and monthly.
11. Visual Pharmacology & Mechanism Diagram (svg-v339-01-adme-12-step-journey)
12. Authoritative References, Regulatory Sources & Editorial Disclaimer
Primary Compendial & Guideline Reference: Drugs and Cosmetics Act, 1940 & Rules, 1945 (Schedule H / H1 / X); NDPS Act, 1985 & Essential Narcotic Drugs (END) Notification; Indian Pharmacopoeia (IP) & National Formulary of India (NFI).
Official Verification Portals: CDSCO — Drugs & Cosmetics Act and Rules (Schedules H, H1, X) • Department of Revenue — Narcotic Drugs and Psychotropic Substances (NDPS) Act • Indian Pharmacopoeia Commission (IPC) — National Formulary of India
Last Medically & Pharmaceutically Reviewed: 2026-11-10 • Verification Status: VERIFIED_EDUCATIONAL_CONTENT
Educational & Clinical Disclaimer: This reference profile is published solely for pharmacy education, academic study, and professional clinical reference. It does not substitute for patient-specific clinical judgement, qualified specialist oncology/medical supervision, or official CDSCO/IP prescribing information. Never self-medicate with prescription, Schedule H/H1/X, NDPS, or oncology medicines.