Formulary
Isoniazid (INH): Uses, Dosing, Side Effects and Indian Brand Names
Isoniazid is the most important anti-TB drug with the highest early bactericidal activity, present throughout the entire 6-month DOTS regimen, requiring pyridoxine supplementation to prevent peripheral neuropathy.
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Isoniazid (INH): Uses, Dosing, Side Effects and Indian Brand Names
Isoniazid is the most important anti-TB drug with the highest early bactericidal activity, present throughout the entire 6-month DOTS regimen, requiring pyridoxine supplementation to prevent peripheral neuropathy.
NEET PG High-Yield: Highest early bactericidal activity. Prodrug activated by KatG (mutation = isoniazid resistance). NAT2 polymorphism: fast vs slow acetylators. Peripheral neuropathy prevented by pyridoxine. Hepatotoxicity potentiated by rifampicin and alcohol. Sideroblastic anaemia (B6-dependent). Drug-induced SLE (slow acetylators). Seizures in overdose: antidote is IV pyridoxine (gram-for-gram). Weak MAO inhibitor (tyramine interaction). Pellagra (niacin depletion).
Clinical overview
Isoniazid is the most important drug in tuberculosis treatment and the cornerstone of every anti-TB regimen. It has the highest early bactericidal activity (EBA) of any anti-TB drug, meaning it kills actively multiplying bacilli faster than any other agent in the first 2 days of treatment, rapidly reducing the infectious burden. India bears the world's largest TB burden, with approximately 2.8 million new cases annually (NTEP data), making isoniazid among the most consumed drugs in the country. Under NTEP (National Tuberculosis Elimination Programme, formerly RNTCP), the standard Category I regimen is 2HRZE/4HR -- isoniazid is present in both the intensive (2-month) and continuation (4-month) phases, the only drug used throughout the entire 6-month course. Isoniazid is metabolised by hepatic N-acetyltransferase 2 (NAT2), and the population is divided into fast and slow acetylators -- a polymorphism with major clinical implications. Slow acetylators (approximately 40-50% of Indians) have higher drug levels and increased risk of peripheral neuropathy and hepatotoxicity. Peripheral neuropathy is caused by isoniazid interfering with pyridoxine (vitamin B6) metabolism; prophylactic pyridoxine 10 mg/day is recommended for all patients on isoniazid, especially malnourished individuals, diabetics, HIV-positive patients, pregnant women, and alcoholics. Isoniazid latent TB infection (LTBI) treatment -- 6-9 months of isoniazid monotherapy -- is standard practice for close contacts and immunosuppressed individuals.
Pharmacological class
Isoniazid (INH) belongs to the First-Line Antitubercular Agents (Isonicotinic Acid Hydrazide) class. Prodrug activated by the mycobacterial catalase-peroxidase enzyme KatG. The activated form inhibits InhA (enoyl-ACP reductase), blocking synthesis of mycolic acids -- the unique long-chain fatty acids that form the mycobacterial cell wall. Isoniazid is bactericidal against actively growing M. tuberculosis (the most potent early bactericidal activity of any anti-TB drug) and bacteriostatic against resting bacilli.
Indian brand names and formulations
Available as: INH (Lupin), Isokin (Macleods), R-Cinex (Lupin, as FDC with rifampicin), Isoniazid IP (various generic).
Tablets: 100 mg, 300 mg. Syrup: 50 mg/5 mL. Injection: 100 mg/mL (10 mL vial, for IV/IM use). FDCs: with rifampicin (R-Cinex), with rifampicin + pyrazinamide (Akurit-3), with rifampicin + pyrazinamide + ethambutol (Akurit-4, NTEP kit).
Regulatory status
Isoniazid (INH) is classified under Schedule H in India under the Drugs and Cosmetics Act, 1940. Prescription-only. Supplied free under NTEP (National Tuberculosis Elimination Programme). Must not be dispensed as monotherapy for active TB.
Indications
- Active pulmonary and extrapulmonary tuberculosis (always in combination with other anti-TB drugs)
- Latent TB infection (LTBI) treatment and prophylaxis (6-9 months monotherapy or 3 months with rifapentine)
- TB chemoprophylaxis in close contacts, HIV-positive individuals, and immunosuppressed patients
Dosing
Active TB: 5 mg/kg/day (max 300 mg) daily. Intermittent therapy (NTEP thrice weekly): 10 mg/kg (max 600 mg). LTBI prophylaxis: 5 mg/kg/day (max 300 mg) for 6-9 months. Always co-prescribe pyridoxine 10-25 mg/day. Children: 10 mg/kg/day (max 300 mg).
Contraindications
- Active hepatic disease or isoniazid-associated hepatitis
- History of severe hypersensitivity to isoniazid
- Acute liver failure
Adverse effects
- Peripheral neuropathy (dose-dependent, prevented by pyridoxine; due to interference with vitamin B6 metabolism)
- Hepatotoxicity (ranges from asymptomatic transaminase elevation to fatal hepatitis; risk increases with age, alcohol, and concomitant rifampicin)
- Drug-induced lupus (positive ANA, arthralgia -- more common in slow acetylators)
- Sideroblastic anaemia (pyridoxine-responsive -- isoniazid inhibits delta-aminolevulinic acid synthase)
- Seizures (in overdose -- treat with high-dose IV pyridoxine as specific antidote)
- Pellagra-like syndrome (niacin deficiency -- isoniazid diverts tryptophan metabolism)
Drug interactions
- Rifampicin: additive hepatotoxicity -- monitor LFTs, especially in first 2 months
- Phenytoin: isoniazid inhibits CYP2C19/CYP2C9, increasing phenytoin levels (risk of toxicity in slow acetylators)
- Carbamazepine: increased levels due to CYP3A4 inhibition
- Tyramine-containing foods (aged cheese, red wine): isoniazid has weak MAO inhibitor activity; may cause hypertensive crisis (rare in practice at therapeutic doses)
- Paracetamol: isoniazid induces CYP2E1, increasing toxic metabolite formation; limit paracetamol use
- Aluminium-containing antacids: reduce isoniazid absorption
Pregnancy and lactation
Safe in pregnancy. Category C, but the risk of untreated TB to the mother and foetus far outweighs the drug risk. Always co-prescribe pyridoxine 25-50 mg/day in pregnancy (higher dose than usual).
Exam-style clinical scenario
A 35-year-old man on DOTS therapy for 6 weeks develops numbness and tingling in both feet in a glove-and-stocking distribution. Which drug is responsible and what is the treatment? Isoniazid-induced peripheral neuropathy due to pyridoxine (vitamin B6) deficiency. Treatment: therapeutic dose pyridoxine 50-200 mg/day. Prevention: pyridoxine 10-25 mg/day from the start.
Cost in India
Rs 5-15 for a strip of 10 tablets (300 mg). Supplied free under NTEP. FDC (HRZE kit): distributed free through DOTS centres.
Clinical governance
Author: MedNext Editorial Team. Clinical reviewer: Awaiting clinical review. Jurisdiction: India (Drugs and Cosmetics Act, 1940). Sources: CIMS India, Indian Pharmacopoeia. Publication state: Awaiting clinical review. Correction: Report errors at support@mednext.academy.
Frequently Asked Questions
What is the significance of fast and slow acetylators?
NAT2 (N-acetyltransferase 2) determines the rate of isoniazid acetylation. Slow acetylators (40-50% of Indians, higher in some populations) have higher isoniazid levels and increased risk of peripheral neuropathy, hepatotoxicity, and drug-induced SLE. Fast acetylators have lower drug levels and may theoretically have reduced efficacy, though clinical cure rates are similar with standard dosing. Slow acetylator status is autosomal recessive.
Why is pyridoxine essential with isoniazid?
Isoniazid structurally resembles pyridoxine and competitively inhibits pyridoxal phosphate-dependent enzymes. It also directly binds to pyridoxal phosphate, forming an inactive hydrazone that is renally excreted. The resulting functional B6 deficiency causes peripheral neuropathy (the most common ADR), sideroblastic anaemia (delta-ALA synthase is B6-dependent), and pellagra (tryptophan-to-niacin conversion requires B6). Prophylactic pyridoxine 10-25 mg/day prevents these effects.
How does isoniazid resistance develop?
The most common mechanism is mutation in the katG gene (especially S315T), which reduces catalase-peroxidase activity and prevents isoniazid activation. The second mechanism is mutations in the inhA promoter region, which increase InhA expression and overcome the drug's inhibitory effect (these mutations also confer low-level cross-resistance to ethionamide). KatG mutations account for ~50-95% of INH resistance and are associated with high-level resistance, while inhA mutations cause low-level resistance.
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