Drug-resistant tuberculosis — RNTCP 2025

Red Flags

Bedaquiline + linezolid + clofazimine — QTc monitoring at baseline, week 2, then monthly; pause if QTcF >500 ms^[2]
Linezolid peripheral neuropathy or optic neuropathy — dose reduction or substitution; may persist after stopping^[2]
Pre-XDR TB (MDR + fluoroquinolone resistance) and XDR TB — specialist PMDT centre; complex individualised regimens^[2]
Hepatitis on DR-TB regimen — ALT >3× ULN with symptoms or >5× without — pause regimen; sequential reintroduction under specialist^[2]

First-line treatment

Interventions

Programmatic Management of Drug-Resistant TB (PMDT)^[2]
All DR-TB managed under PMDT centres with directly observed treatment, structured monitoring, and comorbidity management. Drugs procured free at point of care under NTEP
Active drug safety monitoring
Use the monitoring schedule for the selected regimen. For BPaLM after baseline assessment: clinical review monthly; CBC and ECG at days 15 and 30, then monthly through month 6; visual acuity and colour vision at weeks 9, 13 and 26; LFTs and chest X-ray at month 3 and treatment completion. Assess more often when clinically indicated. Thyroid monitoring is not routine for every regimen; without ethionamide, the shorter linezolid regimen does not require TSH monitoring. [2]

First-line drug therapy

Drug	Class	Adult	Paediatric	Notes
Bedaquiline + pretomanid + linezolid (BPaL), after specialist modification for severe fluoroquinolone intolerance	Specialist-modified 39-week MDR/RR-TB regimen [2]	For the specialist-modified BPaL course after grade 3–4 fluoroquinolone intolerance: bedaquiline 400 mg orally daily in weeks 1–2, then 200 mg three times weekly in weeks 3–39; pretomanid 200 mg orally daily and linezolid 600 mg orally daily through week 39. Linezolid toxicity requires N/DDR-TB specialist assessment under the full NTEP toxicity pathway, including dose modification, interruption or discontinuation as indicated. Do not apply an automatic dose reduction. Full eligibility, monitoring and interruption rules apply. [2]	The NTEP BPaLM pathway and its specialist modifications apply from age 14 years with the stated standard doses and full eligibility criteria; this source does not authorize this regimen below 14 years. [2]	Under NTEP November 2024 guidance, BPaLM is the first choice for eligible patients aged ≥14 years regardless of fluoroquinolone resistance. Grade 3–4 fluoroquinolone intolerance may require dropping moxifloxacin and completing BPaL with extension to 39 weeks after specialist assessment. This is not a blanket recommendation to start a 6-month BPaL regimen for every MDR/pre-XDR case. [2]
Bedaquiline + pretomanid + linezolid + moxifloxacin (BPaLM)	All-oral 6-month MDR-TB regimen with FQ	For eligible patients aged ≥14 years, NTEP BPaLM is normally 26 weeks: bedaquiline 400 mg orally daily in weeks 1–2, then 200 mg three times weekly in weeks 3–26; pretomanid 200 mg, linezolid 600 mg and moxifloxacin 400 mg orally daily. Give with food; apply the programme’s toxicity, interruption and extension rules. Severe fluoroquinolone intolerance or qualifying linezolid dose reduction may require a specialist-modified 39-week course. [2]	—	NTEP November 2024 guidance recommends BPaLM as first choice for eligible patients aged ≥14 years with MDR/RR-TB, irrespective of fluoroquinolone resistance or HIV status. Apply the full inclusion/exclusion criteria; moxifloxacin remains part of the regimen unless severe intolerance requires specialist modification. [2]
Conventional longer all-oral regimen	Individualised 18–20-month multidrug regimen [2]	Bedaquiline + linezolid + levofloxacin + cycloserine + clofazimine (variable per DST)	Per weight band	If BPaLM is unsuitable, assess eligibility for the 9–11-month shorter oral regimen. If neither shorter regimen can be used, the N/DDR-TB centre selects an individualised longer oral regimen, usually 18–20 months. Pregnancy or paediatric age alone does not mandate the longer regimen. [2]
Pyridoxine supplementation; clofazimine as a selected longer-regimen component	Vitamin supplementation / antitubercular regimen component [2]	For the NTEP longer oral regimen, use weight bands: pyridoxine 50 mg daily at 16–29 kg and 100 mg daily at ≥30 kg; clofazimine 50 mg daily at 16–29 kg, 100 mg at 30–70 kg, and 200 mg at >70 kg. Clofazimine is a regimen component selected by the specialist, not a routine add-on to BPaLM. [2]	Per weight	NTEP includes pyridoxine supplementation with BPaLM. Clofazimine is a selected drug in other programme regimens, including the longer oral regimen; it is not a routine adjunct to BPaLM. Use each regimen’s own dosing table and monitoring requirements. [2]

Bedaquiline + pretomanid + linezolid (BPaL), after specialist modification for severe fluoroquinolone intolerance

Specialist-modified 39-week MDR/RR-TB regimen [2]

Adult: For the specialist-modified BPaL course after grade 3–4 fluoroquinolone intolerance: bedaquiline 400 mg orally daily in weeks 1–2, then 200 mg three times weekly in weeks 3–39; pretomanid 200 mg orally daily and linezolid 600 mg orally daily through week 39. Linezolid toxicity requires N/DDR-TB specialist assessment under the full NTEP toxicity pathway, including dose modification, interruption or discontinuation as indicated. Do not apply an automatic dose reduction. Full eligibility, monitoring and interruption rules apply. [2]
Paediatric: The NTEP BPaLM pathway and its specialist modifications apply from age 14 years with the stated standard doses and full eligibility criteria; this source does not authorize this regimen below 14 years. [2]

Under NTEP November 2024 guidance, BPaLM is the first choice for eligible patients aged ≥14 years regardless of fluoroquinolone resistance. Grade 3–4 fluoroquinolone intolerance may require dropping moxifloxacin and completing BPaL with extension to 39 weeks after specialist assessment. This is not a blanket recommendation to start a 6-month BPaL regimen for every MDR/pre-XDR case. [2]

Bedaquiline + pretomanid + linezolid + moxifloxacin (BPaLM)

All-oral 6-month MDR-TB regimen with FQ

Adult: For eligible patients aged ≥14 years, NTEP BPaLM is normally 26 weeks: bedaquiline 400 mg orally daily in weeks 1–2, then 200 mg three times weekly in weeks 3–26; pretomanid 200 mg, linezolid 600 mg and moxifloxacin 400 mg orally daily. Give with food; apply the programme’s toxicity, interruption and extension rules. Severe fluoroquinolone intolerance or qualifying linezolid dose reduction may require a specialist-modified 39-week course. [2]
Paediatric: —

NTEP November 2024 guidance recommends BPaLM as first choice for eligible patients aged ≥14 years with MDR/RR-TB, irrespective of fluoroquinolone resistance or HIV status. Apply the full inclusion/exclusion criteria; moxifloxacin remains part of the regimen unless severe intolerance requires specialist modification. [2]

Conventional longer all-oral regimen

Individualised 18–20-month multidrug regimen [2]

Adult: Bedaquiline + linezolid + levofloxacin + cycloserine + clofazimine (variable per DST)
Paediatric: Per weight band

If BPaLM is unsuitable, assess eligibility for the 9–11-month shorter oral regimen. If neither shorter regimen can be used, the N/DDR-TB centre selects an individualised longer oral regimen, usually 18–20 months. Pregnancy or paediatric age alone does not mandate the longer regimen. [2]

Pyridoxine supplementation; clofazimine as a selected longer-regimen component

Vitamin supplementation / antitubercular regimen component [2]

Adult: For the NTEP longer oral regimen, use weight bands: pyridoxine 50 mg daily at 16–29 kg and 100 mg daily at ≥30 kg; clofazimine 50 mg daily at 16–29 kg, 100 mg at 30–70 kg, and 200 mg at >70 kg. Clofazimine is a regimen component selected by the specialist, not a routine add-on to BPaLM. [2]
Paediatric: Per weight

NTEP includes pyridoxine supplementation with BPaLM. Clofazimine is a selected drug in other programme regimens, including the longer oral regimen; it is not a routine adjunct to BPaLM. Use each regimen’s own dosing table and monitoring requirements. [2]

Safety-net

Take all DR-TB drugs daily under DOT — interruption causes resistance amplification and treatment failure^[2]
Watch for jaundice, dizziness, vision changes, numb hands/feet, palpitations, severe vomiting — same-day medical review^[2]
Avoid alcohol throughout treatment; tell other clinicians about your DR-TB therapy — many drug interactions^[2]

Referral criteria

Rifampicin-resistant TB on XpertPMDT centre — initiate BPaL/BPaLM after extended DST^[2]
Pre-XDR or XDR TBSpecialist PMDT centre with extended-DST capability^[2]
Severe ATT-related adverse event (hepatitis, optic neuropathy, prolonged QTc)Hospital admission; sequential reintroduction or regimen modification^[2]

Clinical summary

Management of MDR/pre-XDR/XDR TB with all-oral shorter regimens (BPaL/BPaLM); programmatic treatment under PMDT.

References

1.NTEP Guidelines on Programmatic Management of Drug-Resistant TB (2024); WHO Consolidated Guidelines on TB: Drug-Resistant TB Treatment (2024 update) (2024)
2.NTEP Guidelines on Programmatic Management of Drug-Resistant TB; WHO Consolidated Guidelines on TB: Drug-Resistant TB Treatment, 2024 Update. NTEP / WHO (2024)
3.National Guidelines for Management of Drug Resistant TB, November 2024 (official upload March 2025). Official national programme guidance (2024)