Isoniazid

Indications

Isoniazid is used for: Tuberculosis

Adult Dose

Oral Active Tuberculosis Disease 5 mg/kg PO qDay, not to exceed 300 mg qDay 15 mg/kg PO up; not to exceed 900 mg 1-3 times/week Used in multi-drug regimen containing rifampin (or ribabutin or rifapentin), pyrazinamide, and ethambutol Latent Tuberculosis Infection Treatment of latent TB infection greatly reduces the risk that TB infection will progress to acitve disease >30 kg: 300 mg PO qDay x9 months

Child Dose

Active Tuberculosis Disease 10-15 mg/kg PO qDay; not to exceed 300 mg/day OR 20-30 mg/kg (up to 900 mg) 2 times/week Used in multi-drug regimen Latent Tuberculosis Infection Treatment of latent TB infection greatly reduces the risk that TB infection will progress to acitve disease 10-15 mg/kg PO qDay; not to exceed 300 mg/day

Renal Dose

Renal impairment: Severe: Dose reduction may be needed.

Administration

Should be taken on an empty stomach. Best taken on an empty stomach 1 hr before or 2 hr after meals. May be taken w/ meals to reduce GI discomfort.

Contra Indications

Acute liver disease or history of hepatic damage during INH therapy; hypersensitivity.

Precautions

Renal or hepatic impairment; convulsive disorders; history of psychosis; patients at risk of neuropathy or pyridoxine deficiency eg, diabetic, alcoholic, malnourished, uraemic, infected with HIV. Careful monitoring of hepatic function is necessary for black and hispanic women. Check hepatic function before and during treatment. Pregnancy and lactation. Lactation: distributed into milk but safe for nursing infants

Pregnancy-Lactation

Interactions

Inhibit the hepatic metabolism of antiepileptics (e.g. carbamazepine, ethosuximide, primidone, phenytoin), benzodiazepines (e.g. diazepam, triazolam), chlorzoxazone, theophylline, disulfiram, sometimes leading to increased toxicity. Increased metabolism of enflurane, resulting in potentially nephrotoxic levels of fluoride. Increased concentrations and enhanced effects or toxicity of clofazimine, cycloserine and warfarin. Reduced absorption w/ Al-containing antacids. Increased risk of peripheral neuropathy w/ zalcitabine and stavudine.

Adverse Effects

Side effects of Isoniazid : >10% Mild incr LFTs (10-20%),Peripheral neuropathy (dose-related incidence, 10-20% incidence with 10 mg/kg/d) Loss of appetite,Nausea,Vomiting,Stomach pain,Weakness 1-10% Dizziness,Slurred speech,Lethargy,Progressive liver damage (increases with age; 2.3% in pts > 50 yo),Hyperreflexia <1% Agranulocytosis,Anemia,Megaloblastic anemia,Thrombocytopenia,Systemic lupus erythematosus,Seizure Potentially Fatal: Hepatotoxicity.

Mechanism of Action

Isoniazid inhibits the synthesis of mycoloic acids in susceptible bacteria which results in loss of acid-fastness and disruption of bacterial cell wall. At therapeutic levels, it is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.