Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis.
For active tuberculosis, it is often used with rifampicin, pyrazinamide, and either streptomycin or ethambutol.
For latent tuberculosis, it is often used alone.
It may also be used for atypical types of mycobacteria, such as M. avium, M. kansasii, and M. xenopi.
Trade names Hydra, Hyzyd, Isovit, others
Pregnancy category AU: A
Routes of administration: By mouth, intramuscular, intravenous
Protein binding-Very low (0–10%)
Metabolism liver; CYP450: 2C19, 3A4 inhibitor
Elimination half-life 0.5–1.6h (in fast acetylators), 2-5h (in slow acetylators)
Excretion urine is primarily, feces
Isoniazid is often used to treat latent and active tuberculosis infections.
In persons with isoniazid-sensitive Mycobacterium tuberculosis infection, drug regimens based on isoniazid are usually effective.
With isoniazid-resistant Mycobacterium tuberculosis infection, drug regimens based on isoniazid have a high rate of failure.
Isoniazid has been approved as prophylactic therapy for the following populations: People with HIV infection and a PPD reaction of at least 5 mm induration
Contacts of people with tuberculosis and who have a PPD reaction at least 5 mm induration
People whose PPD reactions convert from negative to positive in a two-year period – at least 10 mm induration for those up to 35 years of age, and at least 15 mm induration for those at least 35 years old.
People with pulmonary damage on their chest X-ray that is likely to be due to healed tuberculosis and also have a PPD reaction at least 5 mm induration Injection drug users whose HIV status is negative who have a PPD reaction at least 10 mm induration
People with a PPD of greater than or equal to 10 mm induration who are foreign-born from high prevalence geographical regions, low-income populations, and patients residing in long-term facilities.
Isoniazid can be used alone or in combination with Rifampin for treatment of latent tuberculosis: or as part of a four-drug regimen for treatment of active tuberculosis.
Isoniazid was widely used in the treatment of Mycobacterium avium complex as part of a regimen including rifampicin and ethambutol.
Isoniazid prevents mycolic acid synthesis in M. avium complex as in M. tuberculosis and although this is not bactericidal to M. avium complex, it greatly potentiates the effect of rifampicin.
The introduction of macrolides led to this use to be greatly decreased.
It is recommended that women with active tuberculosis who are pregnant or breastfeeding take isoniazid.
Nursing mothers excrete a relatively low and non-toxic concentration of INH in breast milk.
Both pregnant women and infants being breastfed by mothers taking INH should take vitamin B6 in its pyridoxine form to minimize the risk of peripheral nerve damage.
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.
People with liver dysfunction are at a higher risk for hepatitis caused by INH.
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.
Side effects
Up to 20% of people taking isoniazid experience peripheral neuropathy when taking daily doses of 6 mg/kg of body weight or higher.
Gastrointestinal reactions include nausea and vomiting.
Aplastic anemia, thrombocytopenia, and agranulocytosis due to lack of production of red blood cells, platelets, and white blood cells by the bone marrow respectively, has been reported.
Hypersensitivity reactions can present with a maculopapular rash and fever.
Gynecomastia may occur.
Asymptomatic elevation of serum liver enzyme concentrations occurs in 10% to 20% of people taking INH.
Such liver enzyme concentration elevations usually return to normal even when treatment is continued.
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.
Black and Hispanic women are at higher risk for isoniazid-induced hepatotoxicity.
Isoniazid-induced liver toxicity has been shown to occur in 50% of patients within the first 2 months of therapy.
Headache, poor concentration, weight gain, poor memory, insomnia, and depression have all been associated with isoniazid use.
Isoniazid is associated with pyridoxine (vitamin B6) deficiency due to its similar structure. Isoniazid is also associated with increased excretion of pyridoxine.
Pyridoxal phosphate is required for δ-aminolevulinic acid synthase, the enzyme responsible for the rate-limiting step in heme synthesis.
Isoniazid-induced pyridoxine deficiency causes insufficient heme formation in early red blood cells, leading to sideroblastic anemia.
Taking isoniazid and acetaminophen is at risk of acetaminophen toxicity.
Isoniazid decreases the metabolism of carbamazepine, slowing down its clearance from the body.
Isoniazid may decrease the serum levels of ketoconazole after long-term treatment.
Isoniazid may increase the amount of phenytoin and valproate in the body.
Isoniazid may increase the plasma levels of theophylline.
Isoniazid is a prodrug that inhibits the formation of the mycobacterial cell wall.
It must be activated by KatG, a bacterial catalase-peroxidase enzyme in Mycobacterium tuberculosis.
Isoniazid is a mild non-selective monoamine oxidase inhibitor possibly explaning its antidepressant action as well as its ability to cause mania.
This drug can reach therapeutic levels in serum, CSF, and within caseous granulomas.
Two forms of the enzyme are responsible for acetylation, so some patients metabolize the drug more quickly than others: “slow acetylators” and “fast acetylators”.
Widely used for the management of active and latent tuberculosis.
Since the 1960’s it has been the main agent for the treatment of latent tuberculosis with treatment over 6-9 months.
Associated with hematologic, neurologic, pulmonary and dermatologic side effects.
Hepatocellular changes with asymptomatic liver enzyme elevations and fulminant liver failure may occur.
From 2004-2008 17 serious adverse events were reported for long term treatment of tuberculosis infection-severe liver disease.
The risks associated with isoniazid preventive therapy during pregnancy is greater than those associated with the initiation of therapy during the postpartum period