Isoniazid Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology	Isoniazid (INH), a synthetic hydrazine derivative of isonicotinic acid, inhibits mycolic acid synthesis in mycobacterial cell walls, exerting tuberculostatic or tuberculocidal effects depending on concentration and bacterial growth rate. It is specific to mycobacteria, including Mycobacterium tuberculosis. Resistance is rare in preventive therapy but develops rapidly if used alone for active tuberculosis. Primary resistance is increasing in high-risk settings (e.g., HIV-prevalent areas, hospitals, prisons).
Administration and Adult Dosage	- PO for latent tuberculosis infection: 5 mg/kg/day (usually 300 mg) as a single dose, max 300 mg/day, for 6–9 months; or 15 mg/kg/dose (max 900 mg) twice weekly by directly observed therapy (DOT) for 6–9 months - PO for active tuberculosis: • Initial phase (8 weeks): 5 mg/kg/day (max 300 mg) with rifampin 600 mg/day, pyrazinamide 15–30 mg/kg/day • Continuation phase (16 weeks): INH and rifampin as above • Alternative (DOT): Daily INH (5 mg/kg, max 300 mg), rifampin (600 mg), ethambutol (15–25 mg/kg), pyrazinamide (15–30 mg/kg) for 2 weeks, then twice weekly INH (15 mg/kg, max 900 mg), rifampin (600 mg), ethambutol (50 mg/kg, max 2.5 g), pyrazinamide (50–70 mg/kg, max 4 g) for 6 weeks, followed by INH and rifampin twice weekly for 16 weeks • Three-times-weekly (DOT): INH (15 mg/kg, max 900 mg), rifampin (600 mg), pyrazinamide (50–70 mg/kg, max 4 g), ethambutol (25–30 mg/kg, max 2.5 g) for 6 months • Without pyrazinamide: INH (5 mg/kg, max 300 mg) and rifampin (600 mg/day) for 9 months - IM or IV (rare): Same as oral dosage
Special Populations - Pediatric Dosage	- PO for latent tuberculosis infection: 10–20 mg/kg/day (max 300 mg) as a single dose for 6–9 months; or 20–40 mg/kg/dose (max 900 mg) twice weekly by DOT for 6–9 months - PO for active tuberculosis: • Initial phase (8 weeks): 10–20 mg/kg/day (max 300 mg) with rifampin 10–20 mg/kg (max 600 mg), pyrazinamide 15–30 mg/kg (max 2 g) • Continuation phase (16 weeks): INH and rifampin as above • Alternative (DOT): Daily INH (10–20 mg/kg, max 300 mg), rifampin (10–20 mg/kg, max 600 mg), ethambutol (15–25 mg/kg), pyrazinamide (15–30 mg/kg) for 2 weeks, then twice weekly INH (20–40 mg/kg, max 900 mg), rifampin (10–20 mg/kg, max 600 mg), ethambutol (50 mg/kg, max 2.5 g), pyrazinamide (50–70 mg/kg, max 4 g) for 6 weeks, followed by INH and rifampin twice weekly for 16 weeks • Three-times-weekly (DOT): Pyrazinamide 50–70 mg/kg (max 3 g), with INH, rifampin, ethambutol as above for 6 months • Without pyrazinamide: INH (10–20 mg/kg, max 300 mg) and rifampin (10–20 mg/kg, max 600 mg) for 9 months - IM or IV (rare): Same as oral dosage
Special Populations - Geriatric Dosage	Same as adult dosage; monitor closely for hepatotoxicity.
Other Conditions	- Renal impairment (slow acetylators): Consider 150–200 mg/day - HIV infection: Same regimens, but extend to 9 months total and ≥6 months post-culture conversion - Hepatic impairment: Use with caution; monitor liver function closely
Dosage Forms	- Tablet: 50, 100, 300 mg - Syrup: 10 mg/mL - Capsule (Rifamate): INH 150 mg + rifampin 300 mg - Tablet (Rifater): INH 50 mg + rifampin 120 mg + pyrazinamide 300 mg - Injection: 100 mg/mL
Patient Instructions	- Take on an empty stomach or with food if GI upset occurs - Report burning, tingling, numbness in extremities, unusual malaise, fever, dark urine, or yellowing of skin/eyes - Avoid alcohol to reduce hepatotoxicity risk - Take pyridoxine if prescribed to prevent neuropathy
Missed Doses	- Take missed dose as soon as remembered; if near next dose, take only that dose, leaving ≥12 hr between doses; do not double dose
Pharmacokinetics - Serum Levels	- Adequate absorption: Peak 3–5 mg/L (22–36 µmol/L) 2 hr post-dose
Pharmacokinetics - Fate	- Absorption: Rapid, nearly complete; peak 1–5 mg/L (7–36 µmol/L) 1 hr post 5 mg/kg dose - Distribution: Vd = 0.67 ± 0.15 L/kg; penetrates CSF (normal or inflamed) - Clearance: 0.22 ± 0.07 L/hr/kg (slow acetylators), 0.44 ± 0.12 L/hr/kg (rapid acetylators) - Metabolism: Hepatic acetylation to inactive metabolites; rate depends on acetylator phenotype - Excretion: Primarily urinary as metabolites
Pharmacokinetics - t¹⁄₂	- Rapid acetylators: 1.1 ± 0.1 hr - Slow acetylators: 2.1 ± 1.1 hr - Renal impairment: ~4 hr - Liver disease: ~6.7 hr
Adverse Reactions & Side Effects	Frequent: - Subclinical hepatitis (10–20%): Asymptomatic AST/ALT elevation, often resolves without discontinuation Occasional: - Peripheral neuropathy (pyridoxine-responsive): More common in alcoholics, diabetics, renal failure, malnourished, slow acetylators, doses >5 mg/kg/day Rare: - Clinical hepatitis: Age-related (2–3% in 50–65 yr); rare <20 yr; higher risk with alcohol or pre-existing liver disease - Severe hepatotoxicity: Massive liver atrophy, potentially fatal (first 6 months, often with alcoholism/liver disease) Overdose (6–10 g): - Severe CNS toxicity (coma, seizures), hypotension, acidosis, death
Contraindications	- Acute or chronic liver disease - Previous INH-associated hepatitis
Precautions & Warnings	- Use cautiously in pregnancy, lactation - High risk of hepatotoxicity in daily alcohol users, elderly, slow acetylators; monitor closely - Monitor for neuropathy in predisposed patients - Overdose risk: Requires urgent medical intervention
Drug Interactions	- Inhibits metabolism of carbamazepine, phenytoin (especially in slow acetylators), increasing toxicity risk - Disulfiram: May cause mental changes due to altered adrenergic neurotransmitter metabolism; avoid coadministration - Aluminum-containing antacids: Reduce INH absorption; separate by ≥2 hr - Rifampin: Increases INH metabolism to hepatotoxic metabolites
Parameters to Monitor	- Monthly questioning for hepatitis prodromes (fever, malaise) and neuropathy (burning, tingling, numbness) - Baseline and monthly AST, ALT in high-risk groups (>35 yr, daily alcohol users, liver dysfunction history); not predictive of clinical hepatitis - Clinical response to TB infection - Monitor phenytoin/carbamazepine levels if coadministered
Class and Drug Brand Name	- Class: Antimycobacterial Agents - Brand Name: Various
Notes	- Latent TB prophylaxis indications: Positive PPD (5 TU) in household contacts, recent converters, inactive TB, inadequately treated TB, high-risk immigrants, HIV-infected, or those with conditions increasing TB risk (e.g., silicosis, diabetes, immunosuppression) - Age >35 yr: Restrict prophylaxis due to hepatotoxicity risk (controversial) - Neuropathy prevention: Pyridoxine 50 mg/day for high doses (≥10 mg/kg/day) or at-risk patients (diabetics, HIV-infected, alcoholics) - Overdose treatment: Pyridoxine IV (dose equal to INH ingested) - Add ethambutol/streptomycin to initial TB regimen if resistance risk exists (e.g., >4% community INH resistance, prior TB treatment, high-prevalence country origin, drug-resistant case exposure)

References

Hand of Clinical Drug Data