Schedule H

Oral, Intramuscular, Intravenous

Formulation Strength

Tablet 100 mg, 300 mg

Syrup 50 mg/5 mL

Injection 100 mg/mL (1 mL and 5 mL ampoules)

Fixed-Dose Combinations (FDCs) available under NTEP/NLEM:

• Isoniazid + Rifampicin (HR)

• Isoniazid + Rifampicin + Pyrazinamide (HRZ)

• Isoniazid + Rifampicin + Pyrazinamide + Ethambutol (HRZE)

• Paediatric dispersible FDCs (various weight-band formulations)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Pulmonary and Extrapulmonary Tuberculosis (Active Disease)

As part of multi-drug regimen under NTEP guidelines. Never use as monotherapy for active TB.

Parameter Recommendation

Starting dose 5 mg/kg orally once daily (usual adult dose: 300 mg)

Titration Not applicable (weight-band based fixed dosing)

Usual maintenance dose 5 mg/kg once daily (300 mg for adults ≥30 kg)

Maximum dose 300 mg/day

Weight-Band Dosing for Adults (NTEP Guidelines):

Body Weight Daily Isoniazid Dose

30–39 kg 225 mg once daily

40–54 kg 300 mg once daily

55–69 kg 300 mg once daily

≥70 kg 300 mg once daily

Duration per NTEP:

• New drug-susceptible TB: 6 months (2HRZE + 4HR)

• Previously treated: As per drug susceptibility testing

• TB meningitis/bone TB: 12 months (extended continuation phase)

Clinical Notes:

• Always use in combination as part of HRZE regimen

• Preferably use fixed-dose combinations (FDCs) to ensure adherence

• Administer on empty stomach for optimal absorption (1 hour before or 2 hours after meals)

• Always co-prescribe pyridoxine (vitamin B6) 10–25 mg/day in high-risk patients (HIV, diabetes, malnutrition, pregnancy, alcoholism)

1. Latent Tuberculosis Infection (LTBI) / TB Preventive Therapy (TPT)

Per NTEP and ICMR guidelines for preventive therapy.

Regimen Options:

Regimen Dose Duration Target Population

6H (Isoniazid monotherapy) 300 mg once daily 6 months PLHIV, close contacts, immunosuppressed

9H (Isoniazid monotherapy) 300 mg once daily 9 months Alternative duration per clinical judgment

3HP (Isoniazid + Rifapentine) INH 15 mg/kg (max 900 mg) + Rifapentine weekly 3 months (12 doses) PLHIV, contacts (if DOT possible)

3HR (Isoniazid + Rifampicin) INH 10 mg/kg (max 300 mg) + RIF daily 3 months Alternative short-course regimen

Parameter Recommendation (6H Regimen)

Starting dose 300 mg orally once daily

Titration Not applicable

Usual maintenance dose 300 mg once daily

Maximum dose 300 mg/day

Clinical Notes:

• Always rule out active TB before initiating preventive therapy (symptom screen, chest X-ray)

• Always co-prescribe pyridoxine 10–25 mg/day

• Priority populations: PLHIV, household contacts <5 years, immunosuppressed patients with positive TST/IGRA

• Monitor LFTs at baseline and during therapy

Secondary Indications – Adults (Off-label)

Not applicable — No established off-label indications outside TB-related use in India.

PAEDIATRIC DOSING (Specialist Only)

⚠️ Always use in combination therapy for active TB — monotherapy causes rapid resistance.

⚠️ Paediatric dispersible FDCs preferred under NTEP for accurate weight-band dosing.

Primary Indications (Approved/Standard Use in India)

1. Active Tuberculosis (Pulmonary and Extrapulmonary)

As part of HRZE multi-drug regimen per NTEP/IAP guidelines.

Weight-Band Dosing (NTEP Paediatric Guidelines):

Weight Band Isoniazid Dose (Once Daily)

4–7 kg 50 mg

8–11 kg 100 mg

12–15 kg 150 mg

16–24 kg 200 mg

25–29 kg 250 mg

≥30 kg 300 mg (adult dosing)

General Paediatric Dosing:

Parameter Recommendation

Starting dose 10 mg/kg orally once daily

Titration Not applicable

Usual maintenance dose 10 mg/kg once daily

Maximum dose 300 mg/day

Duration:

• Drug-susceptible pulmonary TB: 6 months (2HRZE + 4HR)

• TB meningitis/bone TB: 12 months

Clinical Notes:

• Use paediatric dispersible FDC tablets for children <25 kg

• Syrup formulation (50 mg/5 mL) available for precise dosing in infants

• Always co-prescribe pyridoxine in malnourished, HIV-positive, or exclusively breastfed children

• Administer all drugs together as single daily dose

1. Latent TB Infection (LTBI) / TB Preventive Therapy

Parameter Recommendation

Starting dose 10 mg/kg orally once daily

Titration Not applicable

Usual maintenance dose 10 mg/kg once daily

Maximum dose 300 mg/day

Duration: 6 months (6H regimen)

Eligibility per NTEP:

• Household contacts <5 years of pulmonary TB patients

• Children living with HIV

• Children on immunosuppressive therapy

Secondary Indications – Paediatrics (Off-label)

Not applicable.

Age Restrictions:

• Infants <12 weeks: Use only under specialist supervision (neonatologist/paediatric pulmonologist) in TB exposure scenarios

• Pyridoxine supplementation mandatory in all infants on isoniazid

Safety Monitoring in Paediatrics:

• Baseline LFTs in children with HIV, malnutrition, or hepatic disease

• Clinical monitoring for jaundice, hepatomegaly, vomiting

• Monitor for peripheral neuropathy symptoms

• Weight monitoring for dose adjustments

Note: Isoniazid and its metabolites are removed by haemodialysis — schedule dose post-dialysis to avoid subtherapeutic levels.

Drug-Induced Liver Injury (DILI) Management:

• If ALT >5× ULN (asymptomatic) or >3× ULN with symptoms: Stop isoniazid immediately

• Rechallenge only after LFTs normalise; reintroduce at 50% dose with close monitoring

• Consider modified regimens (e.g., streptomycin-based) in patients with severe hepatotoxicity

• Known hypersensitivity to isoniazid

• Active acute hepatitis or acute liver failure

• History of severe isoniazid-induced hepatotoxicity

• History of severe adverse CNS reactions (psychosis, seizures) attributed to prior isoniazid use

• Concurrent use with disulfiram (severe CNS toxicity risk)

• Pre-existing chronic liver disease or chronic hepatitis — increased hepatotoxicity risk

• Chronic alcoholism — additive hepatotoxic potential; higher neuropathy risk

• HIV infection — increased risk of peripheral neuropathy and hepatotoxicity

• Malnutrition or vitamin B6 deficiency — mandatory pyridoxine supplementation

• Diabetes mellitus — increased peripheral neuropathy risk

• Epilepsy or seizure disorder — may lower seizure threshold

• Slow acetylator phenotype (common in Indian population) — higher drug levels and toxicity risk

• Concurrent hepatotoxic drugs (rifampicin, pyrazinamide, methotrexate, antiretrovirals)

• Pregnancy — use with pyridoxine supplementation

• Age >35 years — increased hepatotoxicity risk; enhanced LFT monitoring required

Parameter Recommendation

Risk Category Generally considered safe; benefits outweigh risks for TB treatment/prevention

Overall Recommendation Safe and indicated for TB treatment throughout pregnancy

Preferred Alternatives No alternative needed; isoniazid is first-line agent for TB in pregnancy

When to use All trimesters; do not defer TB treatment due to pregnancy; TPT can be initiated during pregnancy in high-risk women (PLHIV)

Monitoring Maternal LFTs (baseline and every trimester); clinical symptoms of hepatitis; pyridoxine 25–50 mg/day mandatory

Special Considerations:

• Pyridoxine supplementation prevents neonatal seizures and maternal neuropathy

• Third-trimester hepatotoxicity risk may be slightly increased — enhanced vigilance required

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug Levels in Milk Low (approximately 20% of maternal plasma concentration reaches infant)

Preferred Alternatives None needed; continue isoniazid during breastfeeding

Infant Monitoring Observe for adequate weight gain, feeding patterns, jaundice; rare hepatotoxicity reported

Special Considerations:

• Pyridoxine supplementation recommended for both mother and exclusively breastfed infant

• Amount of drug in milk insufficient to provide therapeutic effect or prophylaxis in infant — treat infant separately if indicated

Parameter Recommendation

Starting Dose Standard adult dose (5 mg/kg/day, usually 300 mg)

Titration Not applicable; however, lower threshold for holding drug if LFT abnormalities

Special Risks Increased hepatotoxicity risk (age >35 years is independent risk factor); peripheral neuropathy; cognitive changes; polypharmacy interactions

Monitoring LFTs at baseline, 2 weeks, 4 weeks, then monthly; mandatory pyridoxine supplementation; clinical surveillance for confusion, neuropathy

Interacting Drug Mechanism/Effect Management

Phenytoin Isoniazid inhibits CYP2C19 → increased phenytoin levels → toxicity (ataxia, nystagmus, confusion) Monitor phenytoin levels; may need 25–50% dose reduction

Carbamazepine Isoniazid inhibits carbamazepine metabolism → increased levels → toxicity Monitor carbamazepine levels; clinical surveillance for toxicity

Disulfiram Additive CNS toxicity → psychosis, coordination difficulties Avoid combination; if essential, close neuropsychiatric monitoring

Rifampicin Additive hepatotoxicity; both are hepatotoxic first-line TB drugs Use together as standard practice but with enhanced LFT monitoring; stop both if significant hepatotoxicity

Paracetamol (chronic/high dose) Isoniazid induces CYP2E1 → increased toxic paracetamol metabolite → hepatotoxicity Limit paracetamol to <2 g/day during isoniazid therapy

Interacting Drug Effect Management

Theophylline Isoniazid may increase theophylline levels Monitor theophylline levels if used chronically

Warfarin Variable effect on metabolism; may increase INR Monitor INR closely; adjust warfarin dose as needed

Efavirenz/Nevirapine Additive hepatotoxicity; possible CYP interaction Monitor LFTs; can be used together with vigilance

Valproate May increase valproate levels Monitor valproate levels

Ketoconazole/Fluconazole Additive hepatotoxicity Monitor LFTs

Aluminium-containing antacids Reduced isoniazid absorption Separate administration by at least 1 hour

Prednisolone/Corticosteroids Isoniazid may reduce corticosteroid efficacy slightly May need minor dose adjustment in some cases

Alcohol Increased hepatotoxicity risk; accelerated isoniazid metabolism Advise avoidance or strict limitation of alcohol intake

• Peripheral neuropathy (dose-dependent; preventable with pyridoxine)

• Hepatotoxicity (elevated ALT/AST — usually transient and asymptomatic)

• Gastrointestinal: nausea, vomiting, epigastric discomfort, anorexia

• Cutaneous: rash, acneiform eruptions, pruritus

• CNS: irritability, insomnia, restlessness, headache

• Mild drug fever

Adverse Effect Clinical Significance

Fulminant hepatitis / Acute liver failure Potentially fatal; requires immediate discontinuation; hospitalisation for supportive care

Severe peripheral neuropathy May be irreversible if not detected early; stop isoniazid; high-dose pyridoxine

Stevens-Johnson Syndrome / TEN Rare; immediate discontinuation and dermatology consultation

Seizures Risk increased in B6 deficiency or overdose; pyridoxine is antidote

Drug-induced lupus Rare; ANA positivity; discontinue if clinical lupus develops

Psychosis / Encephalopathy Rare; dose-dependent; more common in slow acetylators

Optic neuritis Rare; visual disturbances require immediate ophthalmology evaluation

Pellagra Rare; due to niacin depletion; supplementation may be needed

High-risk patients (first 2–4 weeks) LFTs at 2 weeks and 4 weeks; clinical assessment for hepatitis symptoms

Monthly during intensive phase Clinical symptom check (jaundice, anorexia, nausea, dark urine); LFTs if symptomatic or high-risk

Continuation phase Monthly clinical assessment; LFTs every 1–2 months if on concurrent hepatotoxic drugs

Long-term/TPT LFTs at baseline, 1 month, 3 months, then as needed; symptom-based monitoring

High-Risk Groups Requiring Enhanced Monitoring:

• Age >35 years

• Chronic alcoholism

• HIV infection

• Pre-existing liver disease

• Concurrent hepatotoxic drugs

• Pregnancy

• Malnutrition

Clinical Symptoms to Monitor:

• Prodromal hepatitis: anorexia, nausea, fatigue, malaise, dark urine

• Peripheral neuropathy: numbness, tingling, burning in extremities

• CNS effects: confusion, behavioural changes, seizures

Single-Agent Formulations:

• ISONEX® (Lupin)

• ISOKIN® (Cadila)

• ISONIAZID® (Various generics)

• I-NIZ® (Macleods)

Combinations with Pyridoxine:

• ISOVIT® (Isoniazid + Pyridoxine)

Fixed-Dose Combinations (NTEP-Compliant):

• AKURIT® (HRZE) — Lupin

• FORECOX® (HRZE) — Macleods

• Paediatric dispersible FDCs available through NTEP

Note: Government supply (NTEP) provides FDCs free of cost at designated TB centres.

Regulatory Notes:

• Included in NLEM 2022 (essential medicine for TB)

• Under NPPA price control

• Free supply under NTEP at government facilities and DOTS centres

1. Pyridoxine is non-negotiable in high-risk patients: Always co-prescribe vitamin B6 (10–25 mg/day) for HIV-positive, diabetic, malnourished, pregnant, alcoholic, or elderly patients to prevent peripheral neuropathy.

1. Never monotherapy for active TB: Isoniazid monotherapy is reserved only for latent TB infection; for active disease, always use in combination per NTEP regimens.

1. Acetylator status matters: Slow acetylators (common in Indian population) have higher drug levels and increased risk of toxicity — be vigilant for adverse effects even at standard doses.

1. Hepatotoxicity is age-dependent: Risk increases significantly after age 35; enhanced LFT monitoring is mandatory in older adults and those with additional risk factors.

1. Symptom-based education is crucial: Counsel all patients to report immediately: loss of appetite, nausea, vomiting, dark urine, jaundice, or unusual fatigue — these may indicate hepatotoxicity before LFT abnormalities.

1. Phenytoin interaction is clinically significant: If patient requires both drugs, monitor phenytoin levels and watch for toxicity signs (ataxia, nystagmus); dose reduction usually needed.

isoniazid; tuberculosis; antitubercular; NTEP; latent TB; TPT; hepatotoxicity; peripheral neuropathy; pyridoxine; slow acetylator; NLEM India; pregnancy-compatible

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Product Information

• Indian Pharmacopoeia 2018

• National TB Elimination Programme (NTEP) — Technical and Operational Guidelines (2021)

• ICMR Guidelines on LTBI Management

• API Textbook of Medicine (Tuberculosis Chapter)

• IAP Guidelines on Paediatric Tuberculosis

• AIIMS TB Management Protocols

• WHO Consolidated Guidelines on Tuberculosis (India-adapted version)

• MoHFW — Central TB Division Guidelines