isoniazid

Contraindicated in:

Hypersensitivity;
Acute liver disease;
History of hepatitis from previous use.

Use Cautiously in:

History of liver damage, chronic alcohol ingestion, or use of illicit injectable drugs
;
Black and Hispanic women, women in the postpartum period, or patients >50 yr (↑ risk of drug-induced hepatitis);
Severe renal impairment (dose ↓ may be necessary);
Malnourished patients, patients with diabetes, or chronic alcoholics (↑ risk of neuropathy).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: visual disturbances

Endo: gynecomastia

GI: HEPATOTOXICITY, nausea, vomiting

Hemat: blood dyscrasias

Neuro: peripheral neuropathy, cerebellar syndrome, psychosis, seizures

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Additive CNS toxicity with other antituberculars.
BCG vaccine may not be effective during isoniazid therapy.
Isoniazid may ↑ levels and risk of toxicity of phenytoin.
Aluminum-containing antacids may ↓ absorption.
Psychotic reactions and coordination difficulties may result with disulfiram.
Concurrent administration of pyridoxine may prevent neuropathy.
↑risk of hepatotoxicity with other hepatotoxic agents, including alcohol, acetaminophen, and rifampin
.
Isoniazid may ↓ levels and effectiveness of ketoconazole.
May ↑ carbamazepine levels and risk of hepatotoxicity.
May ↓ effectiveness of clopidogrel; avoid concurrent use.

Drug-Food:

Severe reactions may occur with ingestion of foods containing high concentrations of tyramine (see Food Sources for Specific Nutrients).

Availability ⬆ ⬇

(Generic available)

Tablets: 100 mg; 300 mg
Oral solution orange, raspberry flavor: 50 mg/5 mL
Solution for injection: 100 mg/mL

Route/Dosage ⬆ ⬇

PO IM (Adults ): 5 mg/kg/day (max dose = 300 mg once daily) or 15 mg/kg (max dose = 900 mg) 2–3 times weekly.
PO IM (Children <40 kg): Latent TB infection: 10–20 mg/kg/day (max dose = 300 mg once daily) or 20–40 mg/kg (max dose = 900 mg) 2 times weekly; Active TB infection: 10–15 mg/kg/day (max dose = 300 mg once daily) or 20–40 mg/kg (max dose = 900 mg) 2 times weekly.

Action ⬆ ⬇

Inhibits mycobacterial cell wall synthesis and interferes with metabolism.

Therapeutic effects:

Bacteriostatic or bactericidal action against susceptible mycobacteria.

Classifications ⬆ ⬇

Therapeutic Classification: antituberculars

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following PO/IM administration.

Distribution: Widely distributed; readily crosses the blood-brain barrier.

Metabolism/Excretion: 50% metabolized by the liver by N-acetyltransferase (rate of acetylation is genetically determined [slow acetylators have ↑ isoniazid levels and ↑ risk of toxicity; fast acetylators have ↓ isoniazid levels and ↑ risk for treatment failure]); 50% excreted unchanged by the kidneys.

Half-Life: 1–4 hr in patients with normal renal and hepatic function; 0.5–1.6 hr in fast acetylators; 2–5 hr in slow acetylators.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	1–2 hr	up to 24 hr
IM	rapid	1–2 hr	up to 24 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to take missed doses as soon as possible unless almost time for next dose; do not double doses. Emphasize the importance of continuing therapy even after symptoms have subsided. Therapy may be continued for 6 mo–2 yr.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Advise patient to notify health care provider immediately if signs and symptoms of hepatotoxicity (yellow eyes and skin, nausea, vomiting, abdominal tenderness, anorexia, dark urine, rash, fatigue, weakness, or fever >3 days) occur.
Advise patient to notify health care provider immediately if signs and symptoms of peripheral neuritis (numbness, tingling, paresthesia) or visual changes (pain, blurred vision, ↓ acuity) occur. Pyridoxine may be used concurrently to prevent neuropathy.
Caution patient to avoid the use of alcohol during therapy, as this may ↑ risk of hepatotoxicity. Avoid ingestion of Swiss or Cheshire cheeses, fish (tuna, skipjack, sardines), and tyramine-containing foods (see Food Sources for Specific Nutrients).
Rep: Caution pregnant patient that isoniazid may ↑ risk of peripheral neurotoxicity and pyridoxine supplementation is recommended. Advise patient to notify health care provider and discontinue breastfeeding if jaundice occurs in the breastfed infant. Pyridoxine supplementation is recommended for breastfed infants.
Emphasize the importance of regular follow-up including laboratory tests, and physical and ophthalmic exams.

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Indications ⬇

Contraind./Precautions ⬆ ⬇