LANIAZID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LANIAZID (LANIAZID).
Isoniazid inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall, by targeting the enoyl-acyl carrier protein reductase InhA after activation by the mycobacterial catalase-peroxidase KatG.
| Metabolism | Primarily hepatic via acetylation by N-acetyltransferase 2 (NAT2); also metabolized by CYP2E1. Slow acetylators are at higher risk for toxicity. |
| Excretion | Renal: 70-80% as unchanged drug and metabolites (acetylisoniazid, isonicotinic acid); fecal: negligible (approximately 7%) |
| Half-life | Fast acetylators: 0.5-1.5 hours; slow acetylators: 2-5 hours. Clinical context: Accumulation risk in slow acetylators with standard dosing, requiring monitoring for hepatotoxicity and peripheral neuropathy. |
| Protein binding | 0-10% (bound to albumin); minimal binding, no significant drug interactions via protein displacement. |
| Volume of Distribution | 0.57-0.79 L/kg; distributes into total body water and tissues including CSF, pleural fluid, and caseous granulomas. Higher Vd in meningitis (penetrates inflamed meninges). |
| Bioavailability | Oral: 100% (rapid and complete absorption); IM: similar to oral; IV: 100%. |
| Onset of Action | Oral: 1-2 hours (peak serum concentrations); IM: 30-60 minutes; IV: immediate. Antimycobacterial effect: bactericidal within 2-4 days of therapy initiation. |
| Duration of Action | Bactericidal levels maintained for 6-12 hours post-dose in fast acetylators, 18-24 hours in slow acetylators. Clinical: Short half-life necessitates daily dosing; intermittent dosing (e.g., twice weekly) possible with higher doses under supervision. |
5 mg/kg orally once daily, maximum 300 mg/day; or 300 mg intramuscularly once daily.
| Dosage form | SYRUP |
| Renal impairment | CrCl 10-50 mL/min: 50% of dose; CrCl <10 mL/min: 25% of dose. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 50% of dose; Child-Pugh C: contraindicated. |
| Pediatric use | 10-20 mg/kg orally once daily, maximum 300 mg/day. |
| Geriatric use | Use lower end of dosing range (5 mg/kg/day max 300 mg) due to increased risk of hepatotoxicity; monitor hepatic function frequently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LANIAZID (LANIAZID).
| Breastfeeding | Isoniazid is excreted into breast milk in small amounts. M/P ratio is approximately 1.0. The American Academy of Pediatrics considers it compatible with breastfeeding, but monitor the infant for signs of hepatotoxicity and peripheral neuropathy (e.g., jaundice, poor feeding). |
| Teratogenic Risk | LANIAZID (isoniazid) is not associated with major congenital malformations in humans. However, there is an increased risk of hepatotoxicity and peripheral neuropathy in the fetus if maternal liver dysfunction occurs. In the third trimester, use is generally considered safe, but monitoring for maternal hepatitis is essential. |
■ FDA Black Box Warning
Severe and sometimes fatal hepatitis associated with isoniazid therapy; the risk is age-related and increases with daily alcohol consumption.
| Serious Effects |
Acute liver disease, history of isoniazid-associated hepatotoxicity, severe adverse reactions to isoniazid.
| Precautions | Hepatotoxicity (monitor liver function tests), peripheral neuropathy (prevent with pyridoxine), hypersensitivity reactions, drug-induced lupus. |
| Food/Dietary | Avoid tyramine-rich foods (e.g., aged cheeses, cured meats, fermented foods) in high doses only; moderate intake is generally safe. Take isoniazid on an empty stomach; high-fat meals may delay absorption. Avoid alcohol completely during therapy and for at least 2 weeks after stopping. |
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| Fetal Monitoring | Monthly liver function tests (ALT, AST, bilirubin) during pregnancy. Monitor for symptoms of hepatitis (nausea, vomiting, abdominal pain, jaundice). Assess fetal growth and well-being with serial ultrasound if maternal complications arise. Monitor infant for jaundice and neurological symptoms postpartum. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility. |
| Clinical Pearls | Laniazid (isoniazid) is a first-line antituberculosis agent. Monitor for hepatotoxicity, especially in patients >35 years, alcohol users, and slow acetylators. Administer pyridoxine (vitamin B6) 25-50 mg/day to prevent peripheral neuropathy. Use with caution in patients with renal impairment; dose adjustment is required for severe renal failure. Drug interactions: increases phenytoin and carbamazepine levels; reduce doses accordingly. Avoid concurrent alcohol consumption due to increased hepatitis risk. |
| Patient Advice | Take on an empty stomach 1 hour before or 2 hours after meals to maximize absorption. · Avoid alcohol completely while taking this medication to prevent liver damage. · Report symptoms of hepatitis: persistent nausea, vomiting, dark urine, yellowing of eyes/skin, or abdominal pain. · Report numbness, tingling, or burning in hands/feet immediately; take vitamin B6 as prescribed. · Complete full course of therapy; do not skip doses even if feeling better. |