Comment: Pyridoxine 25 to 50 mg/day should be considered in all patients at risk of developing neuropathy; patients with peripheral neuropathy may be given 100 mg/day.Pyridoxine 25 to 50 mg orally should be given to patients during treatment for latent tuberculosis.
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WHO Model Prescribing Information: Drugs Used in Mycobacterial Diseases(1991; 44 pages) [French][Spanish]
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Isoniazid
Group: antimycobacterial agent
Tablet 100-300 mg
Injection 25 mg/ml in 2 ml ampoule
Tablet 100-300 mg
Injection 25 mg/ml in 2 ml ampoule
General information
Isoniazid, the hydrazide of isonicotinic acid, is highly bactericidal against replicating tubercle bacilli.
It is rapidly absorbed and diffuses readily into all fluids and tissues. The plasma half-life, which is genetically determined, varies from less than 1 hour in fast acetylators to more than 3 hours in slow acetylators. It is largely excreted in the urine within 24 hours, mostly as inactive metabolites.
Clinical information
Uses
A component of all antituberculosis chemotherapeutic regimens currently recommended by WHO (see pages 12 and 13).
Isoniazid alone is occasionally used prophylactically to prevent:
• transmission to close contacts at high risk of disease, and
• recrudescence of infection in immunodeficient individuals.
• recrudescence of infection in immunodeficient individuals.
Dosage and administration
Isoniazid is normally taken orally but it may be administered intramuscularly to critically ill patients.
Treatment (combination therapy)
Adults and children: 5 mg/kg (maximum 300 mg) daily or 15 mg/kg two or three times weekly.
Prophylaxis
Adults: 300 mg daily for 6 months to 1 year.
Children: 10 mg/kg (maximum 300 mg) daily for 6 months to 1 year.
Contraindications
• Known hypersensitivity.
• Active hepatic disease.
• Active hepatic disease.
Precautions
Serum concentrations of hepatic transaminases should be monitored whenever possible.
Patients at risk of peripheral neuropathy as a result of malnutrition, chronic alcohol dependence or diabetes should additionally receive pyridoxine, 10 mg daily. Where the standard of health in the community is low this should be offered routinely.
Epilepsy should be effectively controlled since isoniazid may provoke attacks.
Use in pregnancy
Whenever possible, the 6-month regimen based upon isoniazid, rifampicin and pyrazinamide should be used.
Adverse effects
Isoniazid is generally well tolerated at recommended doses. Systemic or cutaneous hypersensitivity reactions occasionally occur during the first weeks of treatment.
The risk of peripheral neuropathy is excluded if vulnerable patients receive daily supplements of pyridoxine. Other less common forms of neurological disturbance, including optic neuritis, toxic psychosis and generalized convulsions, can develop in susceptible individuals, particularly in the later stages of treatment, and occasionally necessitate the withdrawal of isoniazid.
Hepatitis is an uncommon but potentially serious reaction that can usually be averted by prompt withdrawal of treatment. More often, however, a sharp rise in serum concentrations of hepatic transaminases at the outset of treatment is not of clinical significance. If the enzyme levels drop rapidly when dosage is suspended, they are unlikely to rise sharply again when treatment is resumed.
Drug interactions
Isoniazid tends to raise plasma concentrations of phenytoin and carbamazepine by inhibiting their metabolism in the liver. The absorption of isoniazid is impaired by aluminium hydroxide.
Overdosage
Nausea, vomiting, dizziness, blurred vision and slurring of speech occur within 30 minutes to 3 hours of overdosage. Massive poisoning results in coma preceded by respiratory depression and stupor. Severe intractable seizures may occur. Emesis and gastric lavage can be of value if instituted within a few hours of ingestion. Subsequently, haemodialysis may be of value. Administration of high doses of pyridoxine is necessary to prevent peripheral neuritis.
Storage
Tablets should be kept in well-closed containers, protected from light. Solution for injection should be stored in ampoules protected from light.