INH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INH (INH).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INH (INH).
| Breastfeeding | INH is excreted into breast milk in low concentrations (M/P ratio approximately 1.6). Breastfeeding is generally considered safe, but monitor infant for signs of peripheral neuropathy or liver toxicity. The American Academy of Pediatrics considers INH compatible with breastfeeding. |
| 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. |
■ 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 disease","History of INH-induced hepatotoxicity","Previous severe adverse reaction (e.g., drug fever, arthritis)"]
| 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)"] |
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| 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. |