Isoniazid
Synonym :
INH
Mechanism :
Isoniazid inhibits the synthesis of mycologic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bactericidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. lsoniazid resistant Mycobacterium tuberculosis bacilli develop rapidly when lsoniazid monotherapy is administered.
Indication :
- Prophylaxis and treatment of tuberculosis
Contraindications :
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.
Dosing :
10 mg/kg/day PO for the entire course of treatment. Max: 300 mg/day.
Adverse Effect :
Common: Peripheral neuropathy.
Uncommon: Memory impairment, optic neuritis and atrophy, toxic encephalopathy, convulsions, and toxic psychosis. Elevated serum transaminase (SGOT SGPT), jaundice, hyperbilirubinemia, nausea, vomiting, epigastric distress, thrombocytopenia, agranulocytosis, sideroblastic, hemolytic, or aplastic anemia, and eosinophilia, systemic Lupus Erythematosus, fever, lymphadenopathy, skin eruptions, vasculitis, pyridoxine deficiency, metabolic acidosis, hyperglycemia, pellagra, and gynecomastia.
Interaction :
Food: Isoniazid should not be administered with food. Studies have shown that the bioavailability of isoniazid is reduced significantly when administered with food.
Carbamazepine: Isoniazid is known to slow the metabolism of carbamazepine and increase serum levels Carbamazepine levels.
Ketoconazole: Potential interaction of Ketoconazole and Isoniazid may exist.
Phenytoin: Isoniazid may increase serum levels of phenytoin.
Theophylline: A recent study has shown that concomitant administration of isoniazid and theophylline may cause elevated plasma levels of theophylline, and in some instances a slight decrease in the elimination of isoniazid.
Valproate: A recent case study has shown a possible increase in the plasma level of valproate when co administered with isoniazid.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | 200–300 mg daily |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Dialysed. Dose as in GFR<10 mL/ min |
| HD | Dialysed. Dose as in GFR<10 mL/ min |
| HDF/High flux | Dialysed. Dose as in GFR<10 mL/ min |
| CAV/VVHD | Probably dialysed. Dose as in normal renal function |
Hepatic Dose :
Contraindicated in patients with acute liver disease or previous isoniazid-associated hepatic injury.
For ALT or AST >3 times the ULN: Discontinue or temporarily withhold treatment. Therapy should be restarted in gradually increasing doses and should be stopped immediately if there is any indication of recurrent hepatic involvement.