Isoniazid

Antibiotic Class

Isonicotinic acid hydrazide

Antimicrobial Spectrum

Isoniazid is highly specific in that it is active only against mycobacteria. 

Mechanism of Action

Although the mechanism of action of isoniazid is not fully understood, it appears to act by inhibiting mycolic acid synthesis, which results in loss of acid fastness and disruption of the cell wall.  

Pharmacodynamics

Based on clinical data, the AUC/MIC appears to be the most predictive PD parameter.

Pharmacokinetics

Cmax: 3-5 mg/L for 300 mg dose, 9-15 mcg/ml for 900 mg dose; Tmax: 1-2 hours; Bioavailability: over 90%; Protein binding: 10%.

Adverse Effects

Hepatic: hepatotoxicity, jaundice, hepatitis

Neurotoxicity: Isoniazid causes pyridoxine (vitamin B6) deficiency, leading to peripheral or central neuropathies.

Musculo-skeletal: arthralgias, drug-induced lupus syndrome

Skin: Rash

Dosage

PO: 100 and 300 mg tablets

IM or IV: 300 mg for injection (IV can be given in 25 ml of normal saline over 5 minutes)

Typical daily dose of isoniazid is 300 mg.

Typical twice or 3 times weekly dose of isoniazid is 900 mg.

Disease state based dosing

Hepatic failures: No specific recommendations, however, half-life may be prolonged in patients with hepatic insufficiency

Renal failures: No adjustment necessary in most patients.

Contraindications/Warnings/Precautions

Hepatic impairment

Drug Interactions

Isoniazid can block the metabolism of phenytoin and carbamazepine, leading to increased concentrations and potential toxicity.

Pregnancy

Category A: No evidence of risk in humans. Note that in some case series, post-partum women may be at greater risk of hepatotoxicity.

Monitoring Requirements

Toxic: baseline liver function tests, bilirubin, serum creatinine, complete blood count and platelet count. Repeat liver function tests particularly in patients over 35 years of age.

Brand names/Manufacturer

Isoniazid (various, including Nydrazid, Sandoz)