Last reviewed 2026-04-20 · How we verify

Isoniazid (ISONIAZID)

Isoniazid works by inhibiting the enzyme myeloperoxidase, which is essential for the survival of Mycobacterium tuberculosis.

Isoniazid is a small molecule antimycobacterial drug originally developed by Sandoz and currently owned by Epic Pharma LLC. It targets myeloperoxidase and has been FDA-approved since 1952 for the treatment of acute, inactive, and pulmonary tuberculosis. Isoniazid is off-patent and has 26 generic manufacturers. It has a short half-life of 1.0 hours and high bioavailability of 80%. Key safety considerations include the risk of hepatotoxicity and peripheral neuropathy.

At a glance

Mechanism of action

Mechanism of Action: Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Isoniazid resistant Mycobacterium tuberculosis bacilli develop rapidly when isoniazid monotherapy is administered.

Approved indications

• Acute tuberculosis
• Inactive tuberculosis
• Pulmonary tuberculosis

Boxed warnings

• 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. Approximate case rates by age are: less than 1 per 1,000 for persons under 20 years of age, 3 per 1,000 for persons in the 20 to 34 year age group, 12 per 1,000 for persons in the 35 to 49 year age group, 23 per 1,000 for persons in the 50 to 64 year age group and 8 per 1,000 for persons over 65 years of age. The risk of hepatitis is increased with daily consumption of alcohol. Precise data to provide a fatality rate for isoniazid-related hepatitis is not available; however, in a U.S. Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis. Therefore, patients given isoniazid should be carefully monitored and interviewed at monthly intervals. For persons 35 and older, in addition to monthly symptom reviews, hepatic enzymes (specifically, AST and ALT [formerly SGOT and SGPT, respectively]) should be measured prior to starting isoniazid therapy and periodically throughout treatment. Isoniazid-associated hepatitis usually occurs during the first three months of treatment. Usually, enzyme levels return to normal despite continuance of drug, but in some cases progressive liver dysfunction occurs. Other factors associated with an increased risk of hepatitis include daily use of alcohol, chronic liver disease and injection drug use. A recent report suggests an increased risk of fatal hepatitis associated with isoniazid among women, particularly black and Hispanic women. The risk may also be increased during the post partum period. More careful monitoring should be considered in these groups, possibly including more frequent laboratory monitoring. If abnormalities of liver function exceed three to five times the upper limit of normal, discontinuation of isoniazid should be strongly considered. Liver function tests are not a substitute for a clinical evaluation at monthly intervals or for the prompt assessment of signs or symptoms of adverse reactions occurring between regularly scheduled evaluations. Patients should be instructed to immediately report signs or symptoms consistent with liver damage or other adverse effects. These include any of the following: unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever of greater than 3 days duration and/or abdominal tenderness, especially right upper quadrant discomfort. If these symptoms appear or if signs suggestive of hepatic damage are detected, isoniazid should be discontinued promptly, since continued use of the drug in these cases has been reported to cause a more severe form of liver damage. Patients with tuberculosis who have hepatitis attributed to isoniazid should be given appropriate treatment with alternative drugs. If isoniazid must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement. Preventive treatment should be deferred in persons with acute hepatic diseases.

Common side effects

• Mild hepatic dysfunction
• Progressive liver damage
• Mild serum transaminase elevation
• Elevated serum transaminase (SGOT; SGPT)
• Bilirubinemia
• Bilirubinuria
• Jaundice
• Anorexia
• Nausea
• Vomiting
• Fatigue
• Malaise

Drug interactions

• ethotoin
• levodopa
• phenytoin
• warfarin

Key clinical trials

• Bedaquiline Roll-out Evidence in Contacts and People Living With HIV to Prevent TB (PHASE2,PHASE3)
• Safety and Tolerability of Metformin in People With Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) (PHASE2)
• Shortened Regimen for Drug-susceptible TB in Children (PHASE3)
• An Adaptive Multi-arm Trial to Improve Clinical Outcomes Among Children Recovering From Complicated SAM (PHASE3)
• Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis (PHASE2)
• Isoniazid-Related Hepatotoxicity in Clinical Practice: Incidence and Predictors
• AIPH-TB: AI-Optimised Pyrazinamide-Hydroxychloroquine vs Standard RIPE for Drug-Sensitive Pulmonary Tuberculosis - A Phase II RCT (PHASE2)
• Phase 2a Trial of Alpibectir Plus Ethionamide for Tuberculosis Meningitis (PHASE2)

Primary sources

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