DOW-ISONIAZID
Clinical safety rating: safe
Inhibits CYP450 enzymes increasing levels of many drugs (eg phenytoin) Can cause severe hepatotoxicity and peripheral neuropathy.
Inhibits mycolic acid synthesis in Mycobacterium tuberculosis by targeting InhA, a NADH-dependent enoyl-acyl carrier protein reductase, leading to bacterial cell wall disruption.
| Metabolism | Primarily metabolized by N-acetyltransferase 2 (NAT2) in the liver, with acetylation as the major pathway. Minor routes include hydrolysis to isonicotinic acid. Metabolites are excreted renally. |
| Excretion | Renal: 75–95% (isoniazid and metabolites, primarily acetylisoniazid and isonicotinic acid); fecal <10%; biliary excretion minimal. |
| Half-life | Fast acetylators: 0.5–2 hours (mean 1.1 h); slow acetylators: 2–5 hours (mean 3 h). Clinical context: Determines dosing interval; slow acetylators at higher risk of peripheral neuropathy. |
| Protein binding | 0–10% (minimal binding to serum albumin). |
| Volume of Distribution | 0.6–0.7 L/kg (distributes into total body water, including CSF, pleural fluid, and caseous granulomas). |
| Bioavailability | Oral: 90% (fasting); 50–90% when taken with food (reduced absorption). |
| Onset of Action | Oral: 30–60 minutes (peak plasma levels); intramuscular: similar to oral; intravenous: immediate. Antimycobacterial effect begins within 24–48 hours. |
| Duration of Action | Due to short half-life, bacteriostatic effect persists 12–24 hours; clinical recommendation: daily dosing for active TB, but intermittent regimens (3×/week) possible with higher doses. |
300 mg orally once daily, or 5 mg/kg (max 300 mg) daily; alternatively, 15 mg/kg (max 900 mg) orally twice weekly directly observed therapy.
| Dosage form | TABLET |
| Renal impairment | No adjustment for GFR >30 mL/min. For GFR 10-30 mL/min, reduce dose by 50% (e.g., 150 mg daily or 450 mg twice weekly). For GFR <10 mL/min, give 150 mg daily or 300 mg twice weekly. For hemodialysis, dose after dialysis. |
| Liver impairment | Child-Pugh A: monitor closely; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use, consider alternative. |
| Pediatric use | 10-15 mg/kg/day (max 300 mg/day) orally once daily; for intermittent therapy, 20-30 mg/kg (max 900 mg) twice weekly. |
| Geriatric use | Initiate at 200 mg daily, titrate to 300 mg daily as tolerated; monitor hepatic function closely and reduce dose in patients with impaired hepatic or renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inhibits CYP450 enzymes increasing levels of many drugs (eg phenytoin) Can cause severe hepatotoxicity and peripheral neuropathy.
| FDA category | Human |
| Breastfeeding | Isoniazid is excreted into breast milk. The milk-to-plasma (M/P) ratio is approximately 0.5–1.0. In nursing infants, the dose received is low (less than 10% of the therapeutic dose). However, due to potential for hepatotoxicity and peripheral neuropathy, monitor breastfed infants for jaundice, poor feeding, and signs of neuropathy. Benefit of treatment for maternal tuberculosis usually outweighs risk. |
| Teratogenic Risk |
■ FDA Black Box Warning
Severe and sometimes fatal hepatitis has been reported during isoniazid therapy. The risk of hepatitis is increased in patients over 35 years old, daily alcohol users, and those with chronic liver disease. Obtain baseline liver function tests and monitor monthly. Discontinue if signs of hepatic injury occur.
| Common Effects | Hepatotoxicity |
| Serious Effects |
Known hypersensitivity to isoniazid, acute liver disease, history of severe adverse reactions such as drug-induced hepatitis, and concurrent use with hepatotoxic agents.
| Precautions | Hepatotoxicity (monitor LFTs), peripheral neuropathy (pyridoxine supplementation recommended, especially in malnourished, diabetic, or alcoholic patients), hypersensitivity reactions, drug interactions (e.g., increased phenytoin levels, CYP2E1 induction), and optic neuritis. |
| Food/Dietary |
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| Isoniazid crosses the placenta. In humans, isoniazid is not a major human teratogen. First trimester exposure does not significantly increase the risk of major congenital malformations. However, potential for hepatotoxicity exists in both mother and fetus, especially in the third trimester. Perinatal use may be associated with an increased risk of maternal hepatitis. |
| Fetal Monitoring | Monitor maternal liver function tests (AST, ALT, bilirubin) monthly during pregnancy and up to 3 months postpartum. Monitor for signs of maternal hepatitis (nausea, vomiting, fatigue, jaundice). Assess fetal growth and well-being with serial ultrasound if maternal liver dysfunction occurs. Evaluate infant for hyperbilirubinemia and signs of hepatic impairment after delivery. |
| Fertility Effects | Isoniazid has no known direct effects on fertility in humans. Animal studies have not shown impaired fertility. However, underlying tuberculosis infection may affect general health and fertility; treatment improves overall health and may indirectly improve fertility. |
| Avoid tyramine-rich foods such as aged cheeses, cured meats, pickled fish, sauerkraut, soy sauce, fava beans, and tap beer, as isoniazid can inhibit monoamine oxidase and precipitate hypertensive crisis. Foods high in histamine (e.g., tuna, mackerel) may also cause reactions. Take with pyridoxine to offset B6 depletion. |
| Clinical Pearls | Monitor liver function tests (ALT, AST) at baseline and monthly; risk of hepatotoxicity increases with age and alcohol use. Peripheral neuropathy prophylaxis with pyridoxine (vitamin B6) 25-50 mg/day is recommended, especially in malnourished, diabetic, or HIV-positive patients. Administer on an empty stomach (1 hour before or 2 hours after meals) to maximize absorption. Watch for drug interactions with phenytoin (increases phenytoin levels) and disulfiram (CNS toxicity). |
| Patient Advice | Take isoniazid on an empty stomach, at least 1 hour before or 2 hours after meals. · Avoid alcohol completely during treatment and for at least 1 month after stopping. · Report any signs of liver problems: dark urine, yellowing of skin/eyes, unexplained fatigue, nausea/vomiting, or abdominal pain. · Take vitamin B6 (pyridoxine) as prescribed to prevent numbness or tingling in hands and feet. · Complete the full course of therapy even if you feel better; do not skip doses. · Do not take any other medications, including over-the-counter drugs, without consulting your doctor. · If you miss a dose, take it as soon as you remember unless it is almost time for the next dose; do not double the dose. |