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ANTIINFECTIVES FOR SYSTEMIC USE › ANTIMYCOBACTERIALS › DRUGS FOR TREATMENT OF TUBERCULOSIS › Hydrazides
isoniazid, combinations
J04AC51
Forms & Strengths
- Fixed-dose combination tablets containing isoniazid and rifampin
- Fixed-dose combination tablets containing isoniazid, rifampin, and pyrazinamide
Adult Dosing
- Active tuberculosis: Dosing is determined by specific fixed-dose combination product and patient weight, typically administered daily or 2-3 times weekly under direct observation (DOT)
Pediatric Dosing
- Safety and efficacy of fixed-dose combination products depend on the specific formulation and weight-band dosing; individual component adjustment is often preferred in pediatrics
Indications
- Treatment of active tuberculosis caused by susceptible strains of Mycobacterium tuberculosis
Mechanism of Action
- Isoniazid inhibits mycolic acid synthesis disrupting the bacterial cell wall; rifampin inhibits bacterial RNA synthesis by binding to DNA-dependent RNA polymerase; pyrazinamide lowers intrabacterial pH and disrupts membrane potential
Contraindications
- Previous hypersensitivity to isoniazid, rifamycins, pyrazinamide, or any component of the formulation
- Acute liver disease
- History of drug-induced hepatic injury from isoniazid or rifampin
Adverse Reactions
- Hepatotoxicity including elevated transaminases and severe, sometimes fatal hepatitis
- Peripheral neuropathy (associated with isoniazid, mitigated by pyridoxine)
- Gastrointestinal upset including nausea, vomiting, and abdominal pain
- Red-orange discoloration of body fluids (due to rifampin)
- Hyperuricemia and arthralgia (due to pyrazinamide)
Drug Interactions
- Rifampin is a potent inducer of CYP450 enzymes (e.g., CYP3A4) and P-glycoprotein, significantly decreasing serum concentrations of co-administered drugs like antiretrovirals, anticoagulants, and oral contraceptives
- Isoniazid is an inhibitor of CYP2C19 and CYP3A4, potentially increasing concentrations of substrates such as phenytoin and carbamazepine
- Concurrent use with other hepatotoxic medications increases the risk of severe liver injury
Curated Content: Needs Vetting Before Put to Clinical Use