Drug Detail

Isoniazid

Last Updated June 10, 2016

Trade Names

Drug Classification

Antimycobacterial

Formulations

  • Isoniazid: 100 mg, 300 mg tablets, 50 mg elixir (50 mg isoniazid, 12.5 mg citric acid monohydrate, 60 mg sodium citrate, 0.05 mL concentrated anise water, 0.05 mL tartrazine compound solution, 1 mL glycerol, 2 mL double-strength chloroform water, water to 5 mL);
  • Rifampicin/isoniazid: 150/75 mg tablets, 300/150 mg tablets, 60/60 mg tablets;
  • Rifampicin/isoniazid/pyrazinamide/ethambutol: 150/75/400/275 mg tablets

Indications and Pharmacology

Indication: treatment of primary tuberculosis and nontuberculous mycobacteria in combination with other antituberculosis drugs; prophylaxis of tuberculosis.

Mechanism of action: inhibits mycolic acid synthesis to disrupt formation of the mycobacterial cell wall, causing cell death.

Pharmacokinetics: well absorbed on empty stomach and widely distributed throughout body; half-life 1-6 hours. Hepatic metabolism, mostly by acetylation.

Dosage

Adult Dose: 4-6 mg/kg/day in single dose or fixed-dose combination regimen.

Prophylactic use: 4-6 mg/kg/day, maximum 300 mg/day.

Should be taken on empty stomach.

Use in Renal or Hepatic Insufficiency: 

  • Severe renal or hepatic impairment: no dose adjustment but patients should be carefully monitored for adverse effects.
  • Contraindicated in patients with severe acute hepatitis.

Use in Pregnancy and Breastfeeding: Pregnancy Category C, widely used. Excreted in breast milk at levels possibly higher than maternal plasma; monitor infant for adverse effects.

Use in Children: 7-15 mg/kg/day in single dose or fixed-dose combination regimen, maximum 300 mg/day.

For tuberculosis meningitis and miliary tuberculosis: 15-20 mg/kg/day.

Prophylactic use: 10 mg/kg/day, maximum 300 mg/day.

Warnings

Contraindicated in patients with severe hypersensitivity to isoniazid (fever, chills, arthritis) and patients with severe acute hepatitis.

Severe and sometimes fatal hepatitis reported with isoniazid; risk increased with alcohol use. Caution should be used in those at increased risk of drug-induced hepatitis. Regular hepatic function monitoring recommended.

Caution should be used in patients with epilepsy, porphyria, peripheral neuropathy.

Patients with severe hepatic or renal impairment should be closely monitored for adverse effects and worsening biochemical abnormalities.

Patients should be warned that excessive alcohol intake may increase risk of hepatotoxicity.

Drug–Drug Interactions

Isoniazid inhibits some microsomal CYP450 enzymes.

Increased levels of concomitant medication: antiepileptic agents (eg, carbamazepine, phenytoin, valproate), warfarin, theophylline.

Increased risk of hepatotoxicity: rifampicin (although use in combination is recommended), alcohol, paracetamol, acetaminophen.

Cycloserine: Increase toxicity (central nervous system effects).

Alcohol and corticosteroids: increased isoniazid metabolism.

Disulfiram: increased risk of disulfiram-induced psychosis.

Antacids containing aluminum hydroxide: reduced isoniazid absorption; avoid within 2 hours of isoniazid administration.

Considerations for Special Populations

Geriatric: Increased hepatitis risk.

Severe renal or hepatic impairment: no dose adjustment but patients should be carefully monitored for adverse effects.

Contraindicated in patients with severe acute hepatitis.

Pyridoxine (vitamin B6) supplementation recommended for all adult patients initiating TB treatment; 50-75 mg/day or higher doses for reversal of established neuropathy, then reduce to 25 mg/day.

Adverse Effects

Hepatotoxicity (hepatitis incidence < 2% but may be fatal), neurotoxicity (peripheral neuropathy, seizures, psychosis, ataxia, optic neuritis), haematologic effects (sideroblastic anaemia, haemolytic anaemia, thrombocytopenia, neutropenia, aplastic anaemia), production of antinuclear antibodies (small incidence of drug-induced lupus erythematosus), skin rash (pellagra-type dermatitis, acneiform eruptions), gastrointestinal disturbances, occasionally renal involvement.