Schedule H

Oral

Form Strength

Tablet 250 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

▶ Multidrug-Resistant Tuberculosis (MDR-TB) — Pulmonary and Extrapulmonary

Use only as part of combination regimen under NTEP protocols or specialist supervision

Parameter Details

Starting dose 250 mg once daily (patients <50 kg) OR 250 mg twice daily (patients ≥50 kg)

Titration Increase gradually over 1–2 weeks to target dose of 15–20 mg/kg/day as tolerated

Usual maintenance dose 500–750 mg/day in 2 divided doses

Maximum dose 1 g/day

Duration As per NTEP MDR-TB regimen (typically 18–20 months total treatment)

Key Clinical Notes:

• Classified as WHO Group C drug for MDR-TB treatment

• Must be combined with at least 3–4 other effective second-line drugs; never use as monotherapy

• Administer with food to minimize gastrointestinal intolerance

• Co-administer pyridoxine 50–100 mg/day to prevent peripheral neuropathy

• Gradual dose escalation improves tolerability significantly

• Interchangeable with ethionamide but NOT co-used in same regimen

Secondary Indications – Adults Only (Off-label):

Not routinely used off-label in India. NOT RECOMMENDED outside structured TB treatment programmes.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

▶ MDR-TB in Children (as per NTEP Paediatric MDR-TB Guidelines)

Weight Band Starting Dose Titration Usual Maintenance Dose Maximum Dose

5–9 kg 62.5 mg once daily Gradual increase as tolerated 15–20 mg/kg/day in 2 divided doses 125 mg/day

10–15 kg 125 mg once daily Gradual increase as tolerated 15–20 mg/kg/day in 2 divided doses 250 mg/day

16–23 kg 187.5 mg once daily Gradual increase as tolerated 15–20 mg/kg/day in 2 divided doses 375 mg/day

24–30 kg 250 mg once daily Gradual increase as tolerated 15–20 mg/kg/day in 2 divided doses 500 mg/day

31–45 kg 375 mg once daily Gradual increase as tolerated 15–20 mg/kg/day in 2 divided doses 750 mg/day

45 kg 500 mg once daily Gradual increase as tolerated 15–20 mg/kg/day in 2 divided doses 1 g/day

Key Clinical Notes:

• Use only under NTEP or TB specialist supervision in individualized regimens

• Administer with food to reduce GI intolerance

• Co-administer pyridoxine 1–2 mg/kg/day (maximum 50 mg/day) for neuroprotection

• Tablet may need to be split or crushed for younger children (formulation limitation)

Safety Monitoring:

• Baseline and periodic LFTs, thyroid function (TSH)

• Monitor for GI symptoms (nausea, vomiting), neuropsychiatric effects

• Weight monitoring at each visit

• Vision screening if treatment prolonged

Secondary Indications – Paediatrics (Off-label):

None documented in Indian guidelines. Not recommended outside NTEP-supervised MDR-TB programmes.

Age Restriction Statement:

May be used in children of all ages under specialist supervision for MDR-TB as per NTEP guidelines. Use in children <6 years requires careful specialist oversight due to formulation limitations, palatability issues, and monitoring challenges.

Note: Prothionamide is primarily metabolized hepatically; renal excretion is minimal.

• Known hypersensitivity to prothionamide or ethionamide

• Severe hepatic impairment or active hepatitis

• History of drug-induced hepatitis due to thioamides

• Acute psychosis or severe uncontrolled psychiatric illness

• Pre-existing liver disease — high hepatotoxicity risk; requires frequent LFT monitoring

• Diabetes mellitus — may worsen glycaemic control; monitor blood glucose closely

• Pre-existing hypothyroidism — may exacerbate; monitor TSH

• Chronic alcoholism — significantly increased hepatotoxicity risk; counsel abstinence

• History of depression or psychiatric illness — may worsen symptoms

• Co-administration with cycloserine — additive CNS toxicity risk

• Pregnancy — use only when no safer alternatives and benefit outweighs risk

• Use only within structured MDR-TB regimens under close monitoring; never as monotherapy

Parameter Recommendation

Risk category Not formally classified in India; teratogenic in animal studies; limited human data

Overall safety Use only if benefit clearly outweighs risk

Preferred alternatives Not applicable for MDR-TB (essential component); construct regimen to minimize fetal exposure if possible

When may be used In MDR-TB when resistance pattern requires; under specialist supervision; avoid in first trimester if possible

Monitoring Maternal LFTs, thyroid function; fetal growth surveillance; ensure pyridoxine supplementation

Parameter Recommendation

Excretion in milk Yes; levels expected to be low to moderate

Compatibility Compatible with breastfeeding under programmatic MDR-TB treatment (WHO/NTEP guidance)

Preferred alternatives Not applicable for MDR-TB (essential component of regimen)

Infant monitoring Feeding pattern, weight gain, GI symptoms (diarrhoea, vomiting), signs of hepatic dysfunction

Additional notes Mother should receive pyridoxine supplementation; continue breastfeeding while monitoring both mother and infant

Parameter Recommendation

Starting dose 250 mg once daily (lower end of range)

Titration Slower titration (increase every 5–7 days) due to increased risk of adverse effects

Additional risks Increased susceptibility to hepatotoxicity, neuropsychiatric effects (confusion, depression), GI intolerance

Special considerations Monitor LFTs, mental status, thyroid function, and GI tolerance closely; ensure pyridoxine co-administration

Interacting Drug/Class Mechanism / Risk Recommendation

Cycloserine Additive CNS toxicity — confusion, psychosis, seizures Avoid combination if possible; if essential, use with close neuropsychiatric monitoring and pyridoxine

Isoniazid Additive hepatotoxicity and peripheral neuropathy Avoid concurrent use if possible (rarely co-administered in MDR-TB); monitor LFTs closely

Alcohol Additive hepatotoxicity; may precipitate psychotic reactions Avoid alcohol use during treatment

Rifampicin CYP enzyme induction may reduce prothionamide levels Avoid combination (usually not co-administered in MDR-TB regimens)

Interacting Drug/Class Mechanism / Risk Recommendation

Ethionamide Pharmacologically duplicative; no added benefit Do NOT co-use; choose one or the other

Fluoroquinolones (levofloxacin, moxifloxacin) No direct pharmacokinetic interaction; additive QT prolongation risk with moxifloxacin Monitor ECG if combining; prefer levofloxacin if QT concern

Antidiabetic agents (metformin, sulfonylureas, insulin) Prothionamide may impair glucose control Monitor blood glucose frequently; adjust antidiabetic therapy as needed

Clofazimine No direct interaction; monitor cumulative QT effect ECG monitoring if combining

Bedaquiline / Delamanid Part of MDR-TB regimens; monitor for overlapping toxicities (QT, hepatic) Use as per NTEP protocols with appropriate monitoring

Linezolid Cumulative peripheral neuropathy risk Monitor neuropathy symptoms; ensure pyridoxine supplementation

• Nausea and vomiting (dose-limiting in many patients)

• Anorexia

• Metallic taste

• Abdominal discomfort / epigastric pain

• Excessive salivation

• Drowsiness and dizziness

• Headache

• Elevated hepatic transaminases (mild, transient)

• Hypothyroidism (especially with prolonged use)

Adverse Effect Notes

Hepatotoxicity May be severe; requires immediate discontinuation if significant transaminase elevation (>5× ULN) or clinical hepatitis

Psychosis or severe depression Stop drug immediately if symptoms severe; psychiatric evaluation required

Peripheral neuropathy May be irreversible if not recognized early; ensure pyridoxine prophylaxis

Severe hypothyroidism May require thyroxine supplementation or drug discontinuation

Optic neuritis Rare; requires urgent ophthalmologic evaluation

Seizures Rare; more likely with concurrent cycloserine use

Gynaecomastia Reported with prolonged use

Stevens-Johnson syndrome Rare; requires immediate discontinuation and hospitalisation

Early treatment (weeks 1–4) LFTs every 2 weeks; TSH at week 2–4; blood glucose in diabetics; monitor GI tolerance; assess neuropsychiatric status

Maintenance (monthly) LFTs monthly; TSH every 2–3 months; weight; peripheral neuropathy screening; mental health review

Long-term Continue monthly LFT monitoring throughout treatment duration; periodic TSH; symptom screening (GI, neurological, psychiatric) as part of DOTS-Plus protocol

• PTH 250 (Macleods)

• Ma-PTH (Macleods)

• Prothionamide tablets (NTEP/Government supply — generic labels)

Note: Supplied free of cost under NTEP for eligible patients enrolled in MDR-TB treatment programmes.

NLEM Status: Not currently listed under NLEM 2022 price control

Government Supply: Available free under NTEP for patients on programmatic MDR-TB treatment

• Prothionamide and ethionamide are interchangeable thioamides with similar efficacy and toxicity profiles — choose one; NEVER co-use both

• GI intolerance is the most common reason for treatment interruption — administer with food and consider gradual dose escalation over 1–2 weeks

• Always co-administer pyridoxine (vitamin B6) to prevent peripheral neuropathy — 50–100 mg/day in adults, 1–2 mg/kg/day in children

• Monthly TSH monitoring is essential due to significant risk of drug-induced hypothyroidism — particularly when used with PAS

• Counsel patients explicitly to avoid alcohol throughout treatment — hepatotoxicity risk increases substantially

• Never use as monotherapy — always part of structured MDR-TB regimen under NTEP or specialist supervision

prothionamide; MDR-TB; tuberculosis; second-line antitubercular; thioamide; NTEP; hepatotoxic; hypothyroidism; GI-intolerance; pyridoxine; Schedule H

RxIndia v1.0 — 28 May 2025

• CDSCO approved formulations

• Indian Pharmacopoeia / National Formulary of India

• NTEP (National Tuberculosis Elimination Programme) Guidelines for Programmatic Management of Drug-Resistant TB (2021)

• RNTCP Technical and Operational Guidelines

• API Textbook of Medicine

• Harrison's Principles of Internal Medicine

• WHO Consolidated Guidelines on Drug-Resistant Tuberculosis Treatment (2020) — adapted for India (supportive reference)

• AIIMS MDR-TB Treatment Protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (pharmacology reference)