isoniazide

Isoniazide, also known as isoniazid (INH), is a first-line antibiotic used to treat active tuberculosis and to prevent tuberculosis in people with latent infection. In active disease, it is given as part of a multi-drug regimen, typically with rifampin, pyrazinamide, and ethambutol during the initial intensive phase, followed by continued therapy with isoniazid and possibly other drugs for several months depending on the regimen and infection status. For latent infection, isoniazid alone or as part of a short-course regimen is used to reduce the risk of progression to active disease.

Mechanism of action: Isoniazid is a prodrug activated by the Mycobacterium tuberculosis catalase-peroxidase enzyme KatG. Once activated, it inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall, resulting in bactericidal effects against actively growing bacteria and sterilizing activity against dormant forms.

Pharmacokinetics: The drug is well absorbed orally and distributes widely, including into the central nervous system. It is primarily metabolized in the liver by acetylation via the NAT2 enzyme, producing slow and fast acetylator phenotypes that influence drug levels and toxicity. It is mainly excreted in the urine.

Adverse effects and safety: Hepatotoxicity is the major concern, with risk increasing with age, preexisting liver disease, or alcohol use. Peripheral neuropathy can occur due to pyridoxine (vitamin B6) deficiency; supplementation is commonly used to reduce this risk. Less frequent effects include rash, fever, hypersensitivity reactions, and rarely drug-induced lupus or seizures.

Interactions and monitoring: Co-administration with rifampin can raise the risk of liver injury. Alcohol use and other hepatotoxic drugs can exacerbate toxicity. Baseline and periodic liver function monitoring are recommended, especially in older patients or those with risk factors.