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# Drug Information Request: Isoniazid ## Overview Isoniazid (INH) is a first-line antitubercular agent that works by inhibiting the synthesis of mycolic acids, essential components of the *Mycobacterium tuberculosis* cell wall. ## Primary Indications * Treatment of active tuberculosis (TB). * Prophylaxis (prevention) of latent TB infection. ## Adult Dosing * **Treatment of active TB:** 5 mg/kg once daily orally or IM, maximum 300 mg/day. For intermittent regimens (e.g., 2-3 times weekly), doses may be higher (e.g., 15 mg/kg, max 900 mg). Specific dosing depends on the TB regimen, which varies by duration and drug combinations. * **Prophylaxis of latent TB:** 300 mg once daily orally for 6 to 9 months. Alternatively, 900 mg twice weekly orally for 9 months (DOT). ## Pediatric Dosing * **Treatment of active TB:** 10 mg/kg once daily orally or IM, maximum 300 mg/day. * **Prophylaxis of latent TB:** 10 mg/kg once daily orally for at least 9 months, maximum 300 mg/day. ## Dose Adjustments * **Renal Impairment:** No dose adjustment needed for mild to moderate renal impairment. For severe impairment (CrCl <10 mL/min), consider halving the dose. * **Hepatic Impairment:** Use with caution. Monitor liver function closely. Discontinue if signs of hepatitis develop. ## Contraindications * Severe active liver disease. * History of hypersensitivity to isoniazid. ## Adverse Effects * **Hepatotoxicity:** Most serious adverse effect. Risk increases with age, alcohol use, and higher doses. Symptoms include jaundice, dark urine, fatigue, and abdominal pain. * **Peripheral Neuropathy:** Most common adverse effect. Characterized by numbness, tingling, and burning in the extremities. Risk increases with dose, duration, pregnancy, malnutrition, and certain genetic factors (slow acetylators). Co-administration with pyridoxine (vitamin B6) can prevent or treat this. * **Central Nervous System (CNS) effects:** Dizziness, headache, insomnia, psychosis, seizures. * **Gastrointestinal upset:** Nausea, vomiting, constipation. * **Hematologic abnormalities:** Anemia, thrombocytopenia. * **Hypersensitivity reactions:** Rash, fever, arthralgia. ## Key Drug Interactions * **Antacids (aluminum-containing):** May decrease isoniazid absorption. Separate administration by at least 1 hour. * **Anticonvulsants (e.g., phenytoin, carbamazepine):** Isoniazid can inhibit the metabolism of these drugs, increasing their levels and risk of toxicity. Monitor anticonvulsant levels and consider dose adjustments. * **Benzodiazepines:** Isoniazid may inhibit the metabolism of certain benzodiazepines (e.g., diazepam, alprazolam), increasing their levels. * **Corticosteroids:** May increase isoniazid metabolism, potentially reducing its efficacy. * **Disulfiram:** Concurrent use can lead to CNS effects (e.g., ataxia, confusion). Avoid co-administration. * **Ketoconazole and other azole antifungals:** Isoniazid can decrease the absorption and effectiveness of ketoconazole. * **Probenecid:** May increase isoniazid levels. * **Rifampin:** Concurrent use increases the risk of hepatotoxicity compared to either drug alone. Monitor liver function closely. * **Theophylline:** Isoniazid can inhibit theophylline metabolism, increasing its levels. Monitor theophylline levels. * **Warfarin:** Isoniazid can inhibit warfarin metabolism, increasing its anticoagulant effect. Monitor INR closely and adjust warfarin dose as needed. * **Alcohol:** Concurrent use significantly increases the risk of hepatotoxicity. Patients should avoid alcohol. ## Monitoring * **Baseline and periodic liver function tests (ALT, AST):** Especially important in patients with risk factors for liver disease, concurrent use of other hepatotoxic drugs, or during the first few months of therapy. Monitoring frequency depends on guidelines and patient risk. * **Signs and symptoms of peripheral neuropathy:** Educate patients to report numbness, tingling, or burning. * **Signs and symptoms of hepatotoxicity:** Educate patients to report jaundice, dark urine, fatigue, abdominal pain. * **Pyridoxine (Vitamin B6) levels:** Consider in patients at high risk for deficiency or neuropathy. ## Clinical Pearls * Pyridoxine (vitamin B6) is often co-administered (e.g., 10-50 mg daily) to prevent peripheral neuropathy, especially in at-risk populations (e.g., slow acetylators, pregnant women, diabetics, alcoholics, malnourished individuals). * Patients should be advised to avoid alcohol while taking isoniazid. * Isoniazid is available as a fixed-dose combination with rifampin, rifapentine, pyrazinamide, and ethambutol for easier regimen management. * Isoniazid can be a slow or rapid acetylator, which affects its half-life and potential for toxicity. Genetic testing can determine acetylator status, but clinical management is usually based on standard dosing and monitoring. *** *Disclaimer: This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for comprehensive details and to ensure patient safety and appropriate treatment.*