What it's for (Indications)
- Isoniazid is indicated for the treatment of active tuberculosis (TB) infections, always used in conjunction with other effective anti-tuberculous agents.
- It is also used alone for the preventive treatment of latent tuberculosis infection in individuals who may be infected with Mycobacterium tuberculosis (e.
- g.
- , positive TB skin test or interferon-gamma release assay).
Dosage Information
| Type | Guideline |
|---|---|
| Standard | Dosage should be individualized based on the patient's age, weight, and the specific regimen used (daily vs. intermittent). For adults, the usual oral dosage for treatment of tuberculosis is 5 mg/kg daily (up to a maximum of 300 mg per day in a single dose) or 15 mg/kg (up to 900 mg) two or three times per week, in conjunction with other effective anti-tuberculous agents. For preventive therapy, 300 mg daily for adults. Susceptibility testing should be performed on initially isolated organisms from all patients with newly diagnosed tuberculosis. Physicians should be familiar with current recommendations from expert bodies regarding treatment and preventive therapy of tuberculosis. |
Safety & Warnings
Common Side Effects
- The most frequent and significant adverse reactions involve the nervous system and the liver.
- * **Nervous System**: Peripheral neuropathy (common, dose-related, presenting as numbness, tingling, or paresthesias of the feet and hands) is a primary concern, especially in malnourished individuals, alcoholics, diabetics, and 'slow inactivators'.
- Other neurotoxic effects, though less common at conventional doses, include cerebellar syndrome (e.
- g.
- , gait/limb ataxia, dysmetria, nystagmus), optic neuritis and atrophy (potentially leading to blurred vision or loss of vision), convulsions, toxic encephalopathy, memory impairment, and toxic psychosis.
- * **Hepatic System**: Elevated serum transaminases (SGOT, SGPT), bilirubinemia, bilirubinuria, jaundice, and occasionally severe and potentially fatal hepatitis.
- Nausea, vomiting, and upset stomach can also occur.
- * **Other**: Fever, rash.
Serious Warnings
- Black Box Warning: Severe and sometimes fatal hepatitis associated with isoniazid therapy has been reported and may occur or develop even after many months of treatment. The risk of developing hepatitis is age-related, with higher rates observed in older individuals (e.g., approximately 12 per 1,000 for persons aged 35-49 years, and 23 per 1,000 for persons aged 50-64 years). Patients should be monitored for signs and symptoms of hepatic injury.
- * **Hepatotoxicity**: Severe and sometimes fatal hepatitis is a major risk, which can occur even after many months of treatment.
- The risk is age-related and increases with age.
- Liver function should be monitored.
- * **Peripheral Neuropathy**: Isoniazid can cause peripheral neuropathy, especially in individuals with predisposing conditions such as malnutrition, alcoholism, diabetes, or in 'slow inactivators' of isoniazid.
- Concomitant administration of pyridoxine (vitamin B6) is strongly recommended to prevent this, particularly in patients at higher risk.
- * **Ocular Toxicity**: Optic neuritis and atrophy can occur.
- Patients experiencing blurred vision, loss of vision, or eye pain should be immediately evaluated by an ophthalmologist.
- * **Alcohol Consumption**: Concurrent use of alcohol should be avoided due to an increased risk of hepatotoxicity and neuropathy.
- * **Pregnancy**: Preventive treatment with isoniazid can be safely undertaken during pregnancy when combined with pyridoxine (vitamin B6).
- * **Lactation**: Isoniazid is excreted into breast milk.
- Its use should be avoided in lactating females due to potential risks to the infant.
- * **Drug Resistance**: Monotherapy with isoniazid for active tuberculosis is strongly discouraged as it leads to rapid development of drug resistance.
- Susceptibility testing should be performed.
How it Works (Mechanism of Action)
Isoniazid acts by inhibiting the synthesis of mycolic acids, which are essential components of the bacterial cell wall. At therapeutic concentrations, it is bactericidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Resistance to isoniazid develops rapidly when used as monotherapy, typically due to mutations in genes such as katG, inhA, kasA, and ahpC. Susceptibility testing is crucial for guiding therapy.