Isoniazid

Isoniazid oral solution is recommended for all forms of tuberculosis in which organisms are susceptible. However, active tuberculosis must be treated with multiple concomitant anti-tuberculosis medications to prevent the emergence of drug resistance. Single-drug treatment of active tuberculosis with isoniazid or any other medication is inadequate therapy. Isoniazid oral solution is recommended as preventive therapy for the following groups, regardless of age. (Note: the criterion for a positive reaction to a skin test (in millimeters of induration) for each group is given in parentheses): Persons with human immunodeficiency virus (HIV) infection (greater than or equal to 5 mm) and persons with risk factors for HIV infection whose HIV infection status is unknown but who are suspected of having HIV infection.

Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bactericidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Resistance Resistance to isoniazid occurs because of mutations in the katG, inhA, kasA and ahpC genes. Resistance in M. tuberculosis develops rapidly when isoniazid monotherapy is administered. Susceptibility Testing For specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for isoniazid oral solution, please see: www.fda.gov/STIC.

NOTE For preventive therapy of tuberculous infection and treatment of tuberculosis, it is recommended that physicians be familiar with the following publications: the recommendations of the Advisory Council for the Elimination of Tuberculosis, published in the MMWR: vol 42, RR-4, 1993 and. Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children, American Journal of Respiratory and Critical Care Medicine: vol 149, 1359-1374, 1994. For Treatment of Tuberculosis Isoniazid is used in conjunction with other effective anti-tuberculous agents. Drug susceptibility testing should be performed on the organisms initially isolated from all patients with newly diagnosed tuberculosis. If the bacilli becomes resistant, therapy must be changed to agents to which the bacilli are susceptible.

Isoniazid is contraindicated in patients who develop severe hypersensitivity reactions, including drug-induced hepatitis, previous isoniazid-associated hepatic injury, severe adverse reactions to isoniazid such as drug fever, chills, arthritis, and acute liver disease of any etiology.

WARNING Severe and sometimes fatal hepatitis associated with isoniazid therapy has been reported and may occur or may develop even after many months of treatment. The risk of developing hepatitis is age related. See the boxed warning.

The most frequent reactions are those affecting the nervous system and the liver. Nervous System Reactions Peripheral neuropathy is the most common toxic effect. It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (e.g., alcoholics and diabetics) and is usually preceded by paresthesias of the feet and hands. The incidence is higher in "slow inactivators". Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment and toxic psychosis. Hepatic Reactions See boxed warning. Elevated serum transaminase (SGOT, SGPT), bilirubinemia, bilirubinuria, jaundice and occasionally severe and sometimes fatal hepatitis. The common prodromal symptoms of hepatitis are anorexia, nausea, vomiting, fatigue, malaise and weakness.

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° to 30°C (59° to 86°F).