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Isoniazid
(INH, Isonicotinic acid hydrazide)
Isoniazid
INH
Isonicotinic acid hydrazide
Isoniazid
(eye-so-NYE-ah-zid)
Pregnancy Category: C Dom-Isoniazide Isotamine Laniazid Laniazid C.T. Nydrazid Injection PMS-Isoniazid (Rx)

Classification: Primary antitubercular agent

Action/Kinetics: The most effective tuberculostatic agent. Probably interferes with lipid and nucleic acid metabolism of growing bacteria, resulting in alteration of the bacterial wall. Is tuberculostatic. Readily absorbed after PO and parenteral (IM) administration and widely distributed in body tissues, including cerebrospinal, pleural, and ascitic fluids. Peak plasma concentration: PO, 1-2 hr. t1/2, fast acetylators: 0.5-6 hr; t1/2, slow acetylators: 2-5 hr. Liver and kidney impairment increase these values. Metabolized in liver and excreted primarily in urine.
The metabolism of isoniazid is genetically determined. Clients fall into two groups, depending on the rapidity with which they metabolize isoniazid. As a rule, 50% of whites and blacks inactivate the drug slowly, whereas the majority of American Indians, Eskimos, Japanese, and Chinese are rapid acetylators (inactivators).

1. Slow acetylators: These clients show earlier, favorable response but have more toxic reactions (e.g., neuropathies because of higher blood levels of drug).

2. Rapid acetylators: These clients have possible poor clinical response due to rapid inactivation, which is 5-6 times faster than slow acetylators. This group requires an increased daily dose of the drug. They are more likely to develop hepatitis.

Uses: Tuberculosis caused by human, bovine, and BCG strains of Mycobacterium tuberculosis. Not to be used as the sole tuberculostatic agent. Prophylaxis of tuberculosis. Investigational: To improve severe tremor in clients with multiple sclerosis.

Contraindications: Severe hypersensitivity to isoniazid or in clients with previous isoniazid-associated hepatic injury or side effects.

Special Concerns: Severe and sometimes fatal hepatitis may occur even after several months of therapy; incidence is age-related and current alcohol use increases the risk. Increased risk of fatal hepatitis in minority women, especially Blacks and Hispanics; also increased risk postpartum. Extreme caution should be exercised in clients with convulsive disorders, in whom the drug should be administered only when the client is adequately controlled by anticonvulsant medication. Also, use with caution for the treatment of renal tuberculosis and, in the lowest dose possible, in clients with impaired renal function and in alcoholics.

Side Effects: Neurologic: Peripheral neuropathy characterized by symmetrical numbness and tingling of extremities (dose-related). Rarely, toxic encephalopathy, optic neuritis, optic atrophy, seizures impaired memory, toxic psychosis. GI: N&V;, epigastric distress, xerostomia. Hypersensitivity: Fever, skin rashes and eruptions, vasculitis, lymphadenopathy. Hepatic: Liver dysfunction, jaundice, bilirubinemia, bilirubinuria, serious and sometimes fatal hepatitis (especially in clients over 50 years of age). Increases in serum AST and ALT. Hematologic: Agranulocytosis eosinophilia, thrombocytopenia, hemolytic, sideroblastic, or aplastic anemia. Metabolic/Endocrine: Metabolic acidosis, pyridoxine deficiency, pellagra, hyperglycemia, gynecomastia. Miscellaneous: Tinnitus, urinary retention, rheumatic syndrome, lupus-like syndrome, arthralgia.
NOTE: Pyridoxine, 10-50 mg/day, may be given concomitantly with isoniazid to decrease CNS side effects. Ophthalmologic and liver function tests are recommended periodically.

Laboratory Test Alterations: Altered liver function tests. False + or potassium, AST, ALT, urine glucose (Benedict's test, Clinitest).

Overdose Management: Symptoms: N&V;, dizziness, blurred vision, slurred speech, visual hallucinations within 30-180 min. Severe overdosage may cause respiratory distress, CNS depression (coma can occur), severe seizures, metabolic acidosis, acetonuria, hyperglycemia. Treatment: Maintain respiration and undertake gastric lavage (within first 2-3 hr providing seizures are not present). To control seizures, give diazepam or a short-acting IV barbiturate followed by pyridoxine (1 mg IV/1 mg isoniazid ingested). Sodium bicarbonate, IV, to correct metabolic acidosis. Forced osmotic diuresis; monitor fluid I&O.; For severe cases, consider hemodialysis or peritoneal dialysis.

Drug Interactions: Aluminum salts / Effect of isoniazid R/T GI tract absorption Anticoagulants, oral / Anticoagulant effect Atropine / Side effects of isoniazid Benzodiazepines / Effect of benzodiazepines that undergo oxidative metabolism (e.g., diazepam, triazolam) Carbamazepine / Risk of both carbamazepine and isoniazid toxicity Chlorzoxazone / Chlorzoxazone peak levels and plasma elimination t1/2 R/T liver metabolism Cycloserine / Risk of cycloserine CNS side effects Disulfiram / Risk of acute behavioral and coordination changes Enflurane / May high levels of hydrazine defluorination of enflurane Ethanol / Chance of isoniazid-induced hepatitis Halothane / Risk of hepatotoxicity and hepatic encephalopathy Hydantoins (phenytoin) / Hydantoins effect R/T liver breakdown Ketoconazole / Serum ketoconazole levels effect Meperidine / Risk of hypotension or CNS depression PAS / Effect of isoniazid by blood levels Rifampin / Additive liver toxicity

How Supplied: Syrup: 50 mg/5 mL; Tablet: 100 mg, 300 mg

Dosage
•Syrup, Tablets Active tuberculosis.
Adults: 5 mg/kg/day (up to 300 mg/day) as a single dose; children and infants: 10-20 mg/kg/day (up to 300 mg total) in a single dose.
Prophylaxis.
Adults: 300 mg/day in a single dose; children and infants: 10 mg/kg/day (up to 300 mg total) in a single dose.
•IM Active tuberculosis.
Adults: 5 mg/kg (up to 300 mg) once daily. Pediatric: 10-20 mg/kg (up to 300 mg) once daily.
Prophylaxis.
Adults/adolescents: 300 mg/day. Pediatric: 10 mg/kg/day.
NOTE: Pyridoxine, 6-50 mg/day, is recommended in the malnourished and those prone to neuropathy (e.g., alcoholics, diabetics).