Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis, it is often used together 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. It is usually taken by mouth, but may be used by injection into muscle.
Side effects and mechanism of action
Common side effects include increased blood levels of liver enzymes and numbness in the hands and feet. Serious side effects may include liver inflammation and acute liver failure. It is unclear if use during pregnancy is safe for the baby. Use during breastfeeding is likely safe. Pyridoxine may be given to reduce the risk of side effects. Isoniazid works in part by disrupting the formation of the bacteria's cell wall which results in cell death.
History, society, and culture
Isoniazid was first made in 1952. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies isoniazid as critically important for human medicine. Isoniazid is available as a generic medication.
Medical uses
Tuberculosis
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 when persons adhere to the prescribed treatment. However, in persons 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 (purified protein derivative) 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. 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.
Non-tuberculous mycobacteria
Isoniazid was widely used in the treatment of Mycobacterium avium complex as part of a regimen including rifampicin and ethambutol. Evidence suggests that 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 greatly decreasing. However, since rifampicin is broadly underdosed in M. avium complex treatment, this effect may be worth re-investigating.
Special populations
It is recommended that women with active tuberculosis who are pregnant or breastfeeding take isoniazid. Preventive therapy should be delayed until after giving birth. Nursing mothers excrete a relatively low and non-toxic concentration of INH in breast milk, and their babies are at low risk for side effects. 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, and may need a lower dose.
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.
