Isoniazid

Pronunciation
( Isonicotinic Acid Hydrazide ; INH )

Pronunciation: eye-so-NYE-uh-zid
Class: Antituberculosis agent

Trade Names

Nydrazid
- Injection 100 mg/mL

Isoniazid
- Tablets 100 mg
- Tablets 300 mg
- Tablets 500 mg
- Syrup 50 mg/5 mL

Isotamine (Canada)

Pharmacology

Interferes with lipid and nucleic acid biosynthesis in actively growing tubercle bacilli.

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Pharmacokinetics

Absorption

T max is 1 to 2 h.

Distribution

Diffuses readily into cerebrospinal, pleural, and ascitic fluids, tissues, organs, saliva, sputum, feces, placental barrier, and in breast milk.

Metabolism

Primarily by acetylation and dehydrazination.

Elimination

50% to 70% excreted in the urine in 24 h.

Indications and Usage

Treatment of all forms of tuberculosis.

Unlabeled Uses

Improvement of severe tremor in multiple sclerosis.

Contraindications

Previous isoniazid-associated hepatic injury, drug fever, chills, or arthritis; acute liver disease.

Dosage and Administration

Tuberculosis
Adults

PO / IM 5 mg/kg/day as single daily dose (max, 300 mg/day) or 15 mg/kg 2 to 3 times/wk (max, 900 mg).

Infants and Children

PO / IM 10 to 20 mg/kg/day in single daily dose (max, 300 mg/day) or 20 to 40 mg/kg 2 or 3 times/week (max, 400 mg).

Drug Interactions

Aluminum salts

May reduce oral absorption of isoniazid; give isoniazid 1 to 3 h before aluminum salts.

Carbamazepine

May result in carbamazepine toxicity or isoniazid hepatotoxicity. Monitor carbamazepine concentrations and liver function.

Disulfiram

May result in increased incidence of CNS effects (eg, coordination difficulties, confusion, irritability, aggressiveness).

Enflurane

May result in high-output renal failure in rapid acetylators. Monitor renal function.

Hydantoins

May increase serum hydantoin levels.

Rifampin

May result in higher rate of hepatotoxicity.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Peripheral neuropathy; convulsions; toxic encephalopathy; optic neuritis and atrophy; memory impairment; toxic psychosis.

Dermatologic

Morbilliform, maculopapular, purpuric, or exfoliative skin eruptions.

GI

Nausea; vomiting; epigastric distress.

Hematologic

Agranulocytosis; hemolytic, sideroblastic, or aplastic anemia; thrombocytopenia; eosinophilia.

Hepatic

Hepatotoxicity, including elevated serum transaminase levels, bilirubinemia, bilirubinuria, jaundice, severe and sometimes fatal hepatitis.

Metabolic

Pyridoxine deficiency; pellagra; hyperglycemia; metabolic acidosis; hypocalcemia; hypophosphatemia.

Miscellaneous

Gynecomastia; rheumatic syndrome; systemic lupus erythematosus-like syndrome; local irritation at IM injection site.

Precautions

Warnings

Severe and sometimes fatal hepatitis may occur during and many mo after treatment. Risk is related to age and increased with daily alcohol consumption. If reinitiated, start in small and gradual doses. Not for use in patients with active liver disease. Careful monitoring and monthly interviews are recommended.


Pregnancy

Safety undetermined.

Lactation

Excreted in breast milk.

Hypersensitivity

Discontinue drug at first sign of hypersensitivity reaction. Restart only after symptoms have cleared.

Renal Function

Monitor patients with severe renal function impairment carefully.

Hepatic Function

Common prodromal symptoms of hepatotoxicity include anorexia, nausea, vomiting, fatigue, malaise, and weakness. Patients with acute hepatic disease should have preventive tuberculosis treatment deferred. Incidence of hepatic reaction increases in patients older than 50 yr of age.

Pyridoxine administration

Prophylactic coadministration of pyridoxine (6 to 50 mg/day) is recommended in malnourished patients and those predisposed to neuropathy (eg, alcoholics, diabetics).

Overdosage

Symptoms

Nausea, vomiting, dizziness, slurring of speech, blurring of vision, visual hallucinations, respiratory distress, CNS depression, stupor, coma, severe seizures.

Patient Information

  • Advise patient to minimize daily alcohol consumption while taking isoniazid because of the increased risk of hepatitis.
  • Instruct patient to report the following symptoms to health care provider: weakness; fatigue; loss of appetite; nausea and vomiting; yellowing of skin or eyes; darkening of urine; numbness or tingling in hands or feet.
  • Emphasize to patient that treatment will be lengthy and that patient must complete entire course of therapy. Relapse of tuberculosis is higher if chemotherapy is discontinued prematurely.
  • Advise patient to return for laboratory follow-up.
  • Caution patient not to perform activities that require mental alertness if adverse CNS symptoms occur.

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