Schedule H1

Oral

• Tablets: 50 mg

• Dispersible tablets: 25 mg (paediatric formulation)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ Multidrug-Resistant Pulmonary Tuberculosis (MDR-TB) — Adults

As part of combination regimen under NTEP or expert-guided protocols

Parameter Dosing Details

Starting dose 100 mg twice daily with food for first 2 weeks

Titration Increase to 200 mg once daily from week 3 onwards

Usual maintenance dose 200 mg once daily

Maximum dose 200 mg once daily

Duration 24 weeks (may extend up to 48 weeks in individualized longer regimens)

Key Clinical Notes:

• Must be administered only as part of multi-drug MDR-TB regimen with at least 3–4 other effective second-line agents

• Monotherapy is contraindicated due to rapid resistance development

• Not used in BPaL-based shorter regimens; reserved for longer individualized MDR-TB regimens

• Always administer with food to enhance absorption

• ECG monitoring mandatory before and during treatment

▶ Multidrug-Resistant Pulmonary Tuberculosis (MDR-TB) — Adolescents (≥13 years and ≥35 kg)

Parameter Dosing Details

Starting dose 100 mg twice daily with food for first 2 weeks

Titration Increase to 200 mg once daily from week 3

Usual maintenance dose 200 mg once daily

Maximum dose 200 mg once daily

• Use adult tablet formulation

• ECG and LFT monitoring essential

Secondary Indications — Adults (Off-label, if any)

Not applicable.

No established off-label uses documented in Indian practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

▶ Multidrug-Resistant Tuberculosis (MDR-TB) — Children ≥6 years

Only under specialist supervision at designated NTEP centres or equivalent

Weight Band Formulation Starting Dose (Weeks 1–2) Maintenance Dose (Week 3 onwards)

20 kg to <35 kg 25 mg dispersible tablet 25 mg twice daily 50 mg once daily

≥35 kg 50 mg tablet 100 mg twice daily 200 mg once daily (adult dosing)

Key Clinical Notes:

• Minimum age: 6 years

• Children <6 years: Use only under exceptional circumstances at expert TB centres with close monitoring

• Dispersible tablets should be dissolved in water before administration

• Always part of combination regimen under NTEP/PMDT guidance

• Duration as per national guidelines for longer MDR-TB regimens

Mandatory Monitoring in Paediatrics:

• ECG (QTc interval) at baseline, weekly for first month, then monthly

• Serum electrolytes (potassium, magnesium)

• Liver function tests every 2–4 weeks

Secondary Indications — Paediatric Doses (Off-label, if any)

Not applicable.

• Known hypersensitivity to delamanid or any excipients

• Baseline QTc interval >500 ms

• Severe hepatic impairment (Child-Pugh C)

• Concurrent use with strong QT-prolonging drugs where alternatives exist

• Serum albumin <2.8 g/dL (relative contraindication due to increased QT risk)

• Pre-existing cardiac disease or history of arrhythmias

• Electrolyte abnormalities (hypokalaemia, hypomagnesaemia) — correct before initiation

• Moderate hepatic impairment — requires close LFT monitoring

• Concurrent use of other QT-prolonging agents (fluoroquinolones, azoles, bedaquiline)

• Hypoalbuminaemia — associated with increased QT prolongation risk

• Patients on CYP3A4 inhibitors or inducers

• Malnutrition — may affect drug levels and increase toxicity risk

Parameter Detail

Safety Limited human data; animal studies do not show clear teratogenicity

Use in pregnancy Only if potential benefit clearly outweighs risk; use under specialist supervision

Preferred alternatives Bedaquiline has more established use in pregnancy under expert protocols (per NTEP guidance)

Monitoring Maternal ECG monitoring; fetal growth assessment

Parameter Detail

Compatibility Not recommended — no human lactation data available

Milk levels Expected to be low based on pharmacokinetic properties

Preferred alternatives Consider bedaquiline if part of MDR-TB regimen (under specialist guidance)

Infant monitoring If breastfeeding unavoidable: monitor for GI disturbances, feeding tolerance, weight gain

• Starting dose: Standard adult dosing (100 mg twice daily for 2 weeks, then 200 mg once daily)

• Titration: No specific slower titration required, but close monitoring essential

• Special considerations:

• Limited data in patients >65 years

• Increased susceptibility to QT prolongation — baseline and periodic ECG mandatory

• Assess renal and hepatic function before initiation

• Monitor for signs of cardiac arrhythmia

Interacting Drug Effect/Risk Recommendation

Rifampicin Significant reduction in delamanid exposure via CYP3A4 induction Avoid co-administration

Moxifloxacin, Levofloxacin Additive QT prolongation Avoid if possible; if unavoidable, intensive ECG monitoring

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) Increased delamanid levels, heightened QT risk Avoid or use with extreme caution; frequent ECG monitoring

Bedaquiline Additive QT prolongation (both drugs prolong QT) Use together only under expert supervision with cardiology input and weekly ECG monitoring

Haloperidol, other antipsychotics Additive QT prolongation Avoid combination where possible

Interacting Drug Effect/Risk Recommendation

Protease inhibitors (lopinavir/ritonavir) Increased QT risk; possible PK interaction Close ECG monitoring; consider alternatives

Macrolides (azithromycin, erythromycin, clarithromycin) QT prolongation risk Monitor ECG if co-administered

CYP3A4 inducers (carbamazepine, phenytoin, phenobarbital) Reduced delamanid efficacy Avoid if alternatives exist

Fluconazole Moderate QT prolongation risk ECG monitoring advised

Clofazimine Additive QT prolongation Monitor QTc closely

• Nausea

• Vomiting

• Dizziness

• Headache

• QT prolongation (dose-related, usually asymptomatic)

• Elevated transaminases

• Insomnia

• Tremor

• Paraesthesia

Adverse Effect Clinical Note

Torsades de Pointes / Ventricular arrhythmia Discontinue immediately if QTc >500 ms or symptomatic arrhythmia occurs

Severe hepatotoxicity Discontinue if ALT/AST >5× ULN or clinical signs of hepatic failure

Severe electrolyte disturbances Requires prompt correction; may precipitate arrhythmias

Hypersensitivity reactions Rare; discontinue if severe allergic reaction occurs

After initiation ECG weekly for first month, then monthly; LFTs every 2–4 weeks

During treatment Serum electrolytes monthly; more frequently if abnormal; clinical assessment for neuropathy

Long-term Periodic ECG and LFT monitoring throughout treatment duration; adherence counselling at each visit

• Deltyba (Otsuka — available mainly through global donation programs and NTEP)

• Delypro (Mylan/Viatris)

Primarily distributed through NTEP-designated DR-TB centres; limited private market availability

25 mg dispersible tablet Limited private availability; mainly through program supply

• Not included in NLEM 2022

• Supplied free of cost under National TB Elimination Programme (NTEP) through conditional access at designated MDR-TB treatment centres

• Private procurement limited and requires specialist prescription

1. QTc confirmation mandatory: Always document QTc <500 ms before starting delamanid; repeat ECG weekly for first month.

1. Never use as monotherapy: Delamanid must always be combined with at least 3–4 other effective anti-TB agents to prevent resistance.

1. Food enhances absorption: Administer with meals to optimise bioavailability.

1. Bedaquiline + Delamanid combination: If both are required, intensive ECG monitoring (weekly) with cardiology input is essential due to additive QT effects.

1. Not for BPaL regimens: Delamanid is reserved for longer, individualized MDR-TB regimens; it is not part of the 6-month BPaLM regimen.

1. Correct electrolytes first: Hypokalaemia and hypomagnesaemia must be corrected before initiation and monitored throughout therapy.

1. Adherence is critical: Early discontinuation promotes resistance; ensure DOT and regular counselling.

delamanid; MDR-TB; XDR-TB; tuberculosis; QT-prolongation; NTEP; antimycobacterial; second-line-TB; hepatotoxicity; cardiotoxicity

RxIndia v1.0 — 05 Jun 2025

• CDSCO approval data

• NTEP PMDT Guidelines India (2021, 2023)

• WHO Consolidated Guidelines for Drug-Resistant TB Treatment (2022)

• ICMR Guidance on Drug-Resistant TB Management

• AIIMS Pulmonary Medicine MDR-TB Protocols

• Indian Pharmacopoeia

• Goodman & Gilman's Pharmacological Basis of Therapeutics