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Antituberculous Agents Pregnancy: Use with caution — benefits outweigh risks for active TB; isoniazid + rifampicin recommended throughout pregnancy; pyridoxine supplementation essential; neonatal pyridoxine at delivery

Isoniazid

Brand names: Rifinah (combination), Rimactazid (combination)

Adult dose

Dose: 300 mg once daily (treatment); 300 mg once daily (LTBI prophylaxis with rifampicin for 3 months)
Route: Oral
Frequency: Once daily
Max: 300 mg/day
Give on empty stomach for best absorption. Always co-prescribe pyridoxine 25–50 mg/day to prevent peripheral neuropathy. Part of RIPE regimen (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) for first 2 months.

Paediatric dose

Dose: 10 mg/kg once daily (max 300 mg) mg/kg
Route: Oral
Frequency: Once daily
Max: 300 mg/day
WHO recommends higher weight-band dosing in children due to pharmacokinetic variability; seek specialist paediatric infectious disease opinion

Dose adjustments

Renal

Use with caution in severe renal impairment — isoniazid and metabolites accumulate; monitor for toxicity; no dose reduction usually needed for mild-moderate impairment

Hepatic

Avoid in severe hepatic impairment — isoniazid is hepatotoxic; baseline LFTs mandatory; stop if ALT above 5× ULN

Paediatric weight-based calculator

WHO recommends higher weight-band dosing in children due to pharmacokinetic variability; seek specialist paediatric infectious disease opinion

Clinical pearls

  • PYRIDOXINE MANDATORY: peripheral neuropathy occurs in 10–20% without pyridoxine co-prescription — especially high risk in malnourished patients, diabetics, alcoholics, pregnancy, CKD, and HIV; prescribe 25–50 mg/day throughout TB treatment
  • HEPATOTOXICITY MONITORING: LFTs at baseline; at 2 weeks for high-risk patients (age above 35, alcohol use, liver disease); then monthly; stop if: (1) any symptoms of hepatitis (nausea, vomiting, jaundice, RUQ pain), or (2) ALT above 5× ULN asymptomatic, or above 3× ULN with symptoms
  • ACETYLATOR STATUS: isoniazid is metabolised by N-acetyltransferase 2 (NAT2) — slow acetylators (50% of European/African populations) have higher plasma levels → more neuropathy and hepatotoxicity risk; fast acetylators may have lower efficacy
  • MHRA / NICE TB Guidelines 2016: standard first-line TB treatment is RIPE for 2 months (initial phase), then RI for 4 months (continuation phase) — isoniazid throughout all 6 months; LTBI treatment: 3 months isoniazid + rifampicin OR 6 months isoniazid alone
  • Resistance: primary isoniazid resistance in UK is 6.8%; MDR-TB (resistant to isoniazid + rifampicin) requires specialist management with bedaquiline/delamanid-containing regimens — always send sputum for drug susceptibility testing
  • OVERDOSE ANTIDOTE: isoniazid overdose causes refractory seizures (depletes pyridoxal phosphate — GABA synthesis blocked); antidote is pyridoxine gram-for-gram IV equal to estimated isoniazid dose; if dose unknown, give 5 g IV pyridoxine

Contraindications

  • Acute liver disease or previous isoniazid-induced hepatitis
  • Known hypersensitivity to isoniazid
  • Acute porphyria

Side effects

  • Peripheral neuropathy (most common — dose-dependent; prevented by pyridoxine 25–50 mg/day)
  • Hepatotoxicity (2–3%; clinical hepatitis 0.1–0.15%; stop if symptoms or ALT above 5× ULN)
  • Hypersensitivity reactions (fever, rash, lymphadenopathy)
  • CNS effects (seizures in overdose — pyridoxine antidote)
  • Systemic lupus erythematosus (drug-induced DILE — isoniazid-induced ANA)

Interactions

  • Phenytoin (isoniazid inhibits CYP2C19 — increases phenytoin levels significantly; monitor and reduce phenytoin dose)
  • Carbamazepine (similar CYP inhibition — increase carbamazepine toxicity)
  • Antacids containing aluminium (reduce isoniazid absorption — separate by 1 hour)
  • Rifampicin (co-administration increases risk of hepatotoxicity — monitor LFTs monthly during first 2 months of RIPE)

Monitoring

  • LFTs (baseline, monthly or per risk stratification)
  • Neurological symptoms (peripheral neuropathy — despite pyridoxine)
  • Monthly sputum smear and culture (TB treatment response)
  • Drug susceptibility testing on initial positive culture (resistance profiling)
  • Weight and nutritional status

Reference: BNFc; BNF 90; NICE NG33 (TB 2016); WHO TB Guidelines 2022; PHE TB Framework; British Thoracic Society TB Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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