Isoniazid (INH) is one of the most successful tuberculosis medications in the market today. In particular,
isoniazid is used as a prophylaxis medication to avoid resurgence of illness in those who have underlying
Mycobacterium tuberculosis (MTB) infection. The mode of action of isoniazid is complicated and
incorporates a number of distinct aspects in which various biomolecular routes are impacted, including
mycolic acid production. Catalase-peroxidase (KatG) activates the prodrug isoniazid and enzymes
such as β-ketoacyl ACP synthase (KasA) and enoyl acyl carrier protein (ACP) reductase target the
active isoniazid products. Various genes in diverse biochemical networks and pathways are involved
in the physiological mechanisms of isoniazid resistance. Isoniazid resistance is the most common of
all clinical drug-resistant isolates, with incidence in some areas of up to 20 to 30%. In this review
article, several existing components that may influence to the complexities of isoniazid function including
mechanism of action, resistance mechanisms in MTB, along with their history, different synthetic
procedures, uses, dosage forms, side effects, adverse drug reactions, physico-chemical characteristics,
ADME properties, contraindications as well as future perspectives are discussed. Studies of
pharmacokinetics have found that the cause of the drug mediated hepatotoxicity is possible by
metabolism of isoniazid. Because of inter-individual heterogeneity of polymorphism that affect isoniazid
metabolism rates, customized medicines may be required in various populations to prevent
hepatotoxicity. The isoniazid multidrug combination treatment which would proved to be effective
tuberculosis treatment in future. Further exploration is needed for better comprehension of pathogenesis
mechanism of Mycobacterium tuberculosis (MTB) and drug resistance studies are required for building
up better therapeutics and diagnostic against tuberculosis.