INH
Clinical safety rating
cautionComprehensive clinical and safety monograph for INH (INH).
Comprehensive clinical and safety monograph for INH (INH).
First-line treatment and prophylaxis of tuberculosis (TB) caused by Mycobacterium tuberculosis
INH inhibits InhA, an enoyl-acyl carrier protein reductase involved in mycolic acid synthesis, essential for the mycobacterial cell wall. It also disrupts NAD and NADH metabolism via the KatG-activated isonicotinoyl-NAD adduct.
| Metabolism | Primarily hepatic via N-acetyltransferase 2 (NAT2); also metabolized by cytochrome P450 (CYP2E1) to hepatotoxic metabolites. |
| Excretion | Renal: 75-95% as unchanged drug and metabolites (including acetylisoniazid, isonicotinic acid). Biliary/fecal: minor (<5%). |
| Half-life | Fast acetylators: 0.5-1.5 hours; slow acetylators: 2-4 hours. Clinically, slow acetylators have higher risk of peripheral neuropathy and hepatotoxicity. |
| Protein binding | 0-10% (low binding; primarily albumin). |
| Volume of Distribution | 0.6-0.8 L/kg (distributes into total body water, including cerebrospinal fluid and tuberculous cavities). |
| Bioavailability | Oral: ~90%. Intramuscular: ~100%. |
| Onset of Action | Oral: 1-2 hours (peak plasma concentration). Intramuscular: 1-2 hours. |
| Duration of Action | 12-24 hours (bacteriostatic for first 24-48 hours, then bactericidal). For tuberculosis treatment, daily dosing is used due to need for sustained exposure. |
| Molecular Weight | 137.14 |
300 mg orally once daily (or 15 mg/kg orally once daily, up to 300 mg total) for active tuberculosis; for latent tuberculosis, 300 mg orally once daily or 900 mg orally twice weekly under directly observed therapy.
| Dosage form | TABLET |
| Renal impairment | In patients with GFR < 30 mL/min, reduce dose to 200 mg daily or 300 mg three times weekly. For GFR 30-50 mL/min, no adjustment necessary. For GFR < 10 mL/min, consider 150 mg daily or 300 mg twice weekly. |
| Liver impairment | In Child-Pugh class A, no adjustment. In Child-Pugh class B, reduce dose to 200 mg daily. In Child-Pugh class C, use 150 mg daily or avoid if severe hepatic impairment. |
| Pediatric use | 10-15 mg/kg orally once daily (max 300 mg) for active tuberculosis; for latent tuberculosis, 10-15 mg/kg orally once daily (max 300 mg) or 20-40 mg/kg orally twice weekly (max 900 mg per dose). |
| Geriatric use | No specific dose adjustment required, but monitor for hepatotoxicity and peripheral neuropathy, especially in patients with comorbidities or polypharmacy. |
| 1st trimester | Safe; no evidence of teratogenicity in humans; avoid if possible due to theoretical risk of hepatotoxicity. |
| 2nd trimester | Safe; used for treatment of active TB; monitor liver function. |
| 3rd trimester | Safe; used for treatment of active TB; monitor liver function. |
Clinical note
Comprehensive clinical and safety monograph for INH (INH).
| Placental transfer | Isoniazid crosses the placenta; fetal serum concentrations approximate maternal levels. |
| Breastfeeding | Isoniazid is excreted into breast milk in small amounts; concentrations are insufficient to cause adverse effects in the infant; monitor infant for signs of hepatotoxicity or peripheral neuropathy. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | INH (isoniazid) is not known to be a major teratogen. In first trimester, risk of malformations is not significantly increased. In second and third trimesters, there is a potential for hepatotoxicity and peripheral neuropathy, and possibly increased risk of neonatal hemorrhage due to vitamin K deficiency. |
| Fetal Monitoring | Monitor maternal liver function tests monthly during pregnancy. Assess for signs of peripheral neuropathy, hepatotoxicity, and hypersensitivity. In the fetus, consider ultrasound for growth and well-being, and monitor for neonatal effects such as neurotoxicity or hepatotoxicity after delivery. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies have not shown impaired fertility at clinically relevant doses. |
■ FDA Black Box Warning
Severe and sometimes fatal hepatitis (especially in patients >35 years, daily alcohol users, and those with pre-existing liver disease); monitor hepatic function closely.
| Serious Effects |
Acute liver diseaseHistory of severe adverse reaction to isoniazid
| Precautions | Hepatotoxicity (monitor LFTs, discontinue if signs of hepatitis), Peripheral neuropathy (pyridoxine prophylaxis recommended), CNS effects (seizures, psychosis; avoid in active CNS disease), Lupus-like syndrome, Drug interactions (e.g., carbamazepine, phenytoin) |
| Food/Dietary | Foods high in tyramine (e.g., aged cheese, cured meats, soy products) may rarely cause hypertensive crisis in patients also taking MAOIs, though interaction is less significant with INH alone. High-fat meals may delay absorption, so avoid fatty foods near dosing time. No specific dietary restrictions beyond taking on empty stomach. |
| Clinical Pearls | Administer on an empty stomach (1 hour before or 2 hours after meals) to maximize absorption. Monitor liver function tests (ALT, AST) at baseline and monthly during therapy. Pyridoxine (vitamin B6) 25-50 mg/day should be co-administered to prevent peripheral neuropathy. Hepatotoxicity risk increases with age, alcohol use, and concurrent use of other hepatotoxic drugs. Slow acetylators are more prone to toxicity. Patients with liver disease require careful monitoring and dose adjustment. |
| Patient Advice | Take on an empty stomach with a full glass of water. · Do not drink alcohol while taking this medication due to increased risk of liver damage. · Report immediately any signs of liver problems: dark urine, yellowing of skin or eyes, persistent nausea, or abdominal pain. · Take vitamin B6 as prescribed to prevent numbness or tingling in hands and feet. · Complete full course of therapy even if you feel better to prevent resistance. · Avoid antacids within 1 hour of taking this medication as they may reduce absorption. |
Loading safety data…