isoniazid

Isoniazid, also known as INH, is a first-line antibiotic used to treat active tuberculosis and to prevent tuberculosis in individuals who are infected but asymptomatic. It is almost always given as part of a multidrug regimen.

Mechanism of action: Isoniazid is a prodrug activated by the mycobacterial enzyme KatG. The activated form forms a complex with NAD+, inhibiting the enoyl-ACP reductase InhA and thereby blocking synthesis of mycobacterial mycolic acids necessary for the cell wall.

Pharmacokinetics: It is well absorbed orally and distributes to most body tissues, including the central nervous system. It is metabolized in the liver by N-acetyltransferase 2, producing rapid and slow acetylator phenotypes, and is excreted in urine.

Dosing and regimens: For latent TB infection, typical regimens are 5 mg/kg daily (maximum 300 mg) for six to nine months. For active TB, isoniazid is used with other drugs (such as rifampin, pyrazinamide, and ethambutol) in an initial intensive phase followed by a continuation phase with isoniazid and rifampin.

Adverse effects: The most serious is hepatotoxicity, which can progress to hepatitis. Peripheral neuropathy is common, especially in slow acetylators or malnourished individuals; vitamin B6 supplementation is recommended in at-risk groups to prevent this. Other effects include rash and rarely drug-induced lupus-like syndrome.

Safety and interactions: Isoniazid is contraindicated in active liver disease. It can interact with alcohol, rifampin, and certain anticonvulsants (e.g., phenytoin), and may require liver function monitoring during therapy. Pregnant individuals may receive isoniazid with appropriate monitoring.

Resistance: Bacterial resistance to isoniazid commonly involves mutations in katG or the inhA promoter region. Because it is used in combination therapy, monotherapy is avoided to reduce resistance.