[4] After F. Raschig developed a method to synthesize hydrazine, Hans Meyer and his doctoral student at the German University in Prague Josef Mally studied hydrazides of pyridinecarboxylic acids.

In the 1940s French physicians discovered that nicotinamide had some activity against tubercle bacilli in vitro and in infected guinea pigs.

[7][8] At the same time, German chemists led by G. Domagk investigating sulfo drugs at Bayer developed thioacetazone.

[8][9] It's believed that Soviet physicians A. Kachugin [ru] and Bella Keyfman also discovered this activity in 1949 but neither published their findings in a peer-reviewed article nor applied for an inventor's certificate.

[13][14] Three pharmaceutical companies unsuccessfully attempted to patent the drug at the same time,[15] the most prominent one being Roche in January 1951,[16] which launched its version, Rimifon, in 1952.

However, in persons with isoniazid-resistant Mycobacterium tuberculosis infection, drug regimens based on isoniazid have a high rate of failure.

[27] The drug regimen typically requires daily or weekly oral administration for a period of three to nine months, often under Directly Observed Therapy (DOT) supervision.

[27] Isoniazid was widely used in the treatment of Mycobacterium avium complex as part of a regimen including rifampicin and ethambutol.

[32] Vitamin B6 is used to prevent isoniazid-induced B6 deficiency and neuropathy in people with a risk factor, such as pregnancy, lactation, HIV infection, alcoholism, diabetes, kidney failure, or malnutrition.

[31] Levels of liver enzymes in the bloodstream should be frequently checked in daily alcohol drinkers, pregnant women, IV drug users, people over 35, and those who have chronic liver disease, severe kidney dysfunction, peripheral neuropathy, or HIV infection since they are more likely to develop hepatitis from INH.

[36] Isoniazid has a boxed warning for severe and sometimes fatal hepatitis, which is age-dependent at a rate of 0.3% in people 21 to 35 years old and over 2% in those over age 50.

Pyridoxal phosphate (a derivative of pyridoxine) is required for δ-aminolevulinic acid synthase, the enzyme responsible for the rate-limiting step in heme synthesis.

Therefore, isoniazid-induced pyridoxine deficiency causes insufficient heme formation in early red blood cells, leading to sideroblastic anemia.

[33] Isoniazid was found to significantly elevate the in vivo concentration of GABA and homocarnosine in a single subject via magnetic resonance spectroscopy.

Isoniazid is thought to induce a liver enzyme which causes a larger amount of acetaminophen to be metabolized to a toxic form.

[53] KatG catalyzes the formation of the isonicotinic acyl radical, which spontaneously couples with NADH to form the nicotinoyl-NAD adduct.

This complex binds tightly to the enoyl-acyl carrier protein reductase InhA, thereby blocking the natural enoyl-AcpM substrate and the action of fatty acid synthase.

A range of radicals are produced by KatG activation of isoniazid, including nitric oxide,[54] which has also been shown to be important in the action of another antimycobacterial prodrug pretomanid.

[62] Isonicotinic acid hydrazide is also used in chromatography to differentiate between various degrees of conjugation in organic compounds barring the ketone functional group.