isoniazid

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

Contraind./Precautions ⬆ ⬇

Contraindicated in:

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

Use Cautiously in:

History of liver damage or chronic alcohol ingestion;
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: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), rash, TOXIC EPIDERMAL NECROLYSIS

EENT: visual disturbances

Endo: gynecomastia

GI: HEPATOTOXICITY, nausea, vomiting

Hemat: blood dyscrasias

Neuro: peripheral neuropathy, 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.

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

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.

Availability ⬆ ⬇

(Generic available)

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

Assessment ⬆ ⬇

Mycobacterial studies and susceptibility tests should be performed prior to and periodically during therapy to detect possible resistance. About 50–65% of Caucasians, Blacks, South Indians, and Mexicans are slow acetylators at risk for toxicity, while 80–90% of Inuit, Japanese, and Chinese are rapid acetylators at risk for decreased levels and treatment failure.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

Lab Test Considerations:

Hepatic function should be evaluated prior to and monthly throughout therapy. Increased AST, ALT, and serum bilirubin may indicate drug-induced hepatitis. Black and Hispanic women, pregnant women, postpartal women, and patients >50 yr are at highest risk. Risk is lower in children; therefore, liver function tests are usually ordered less frequently for children. If AST, ALT, or serum bilirubin are >3–5 × upper limit of normal, temporarily discontinue isoniazid and consider restarting therapy.

Toxicity and Overdose:

If isoniazid overdose occurs, treatment with pyridoxine (vitamin B) is instituted.

Implementation ⬆ ⬇

PO: Administer on an empty stomach.
IM: Medication may cause discomfort at injection site. Massage site after administration and rotate injection sites.
- Solution may form crystals at low temperatures; crystals will redissolve upon warming to room temperature.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication as directed. Take missed doses as soon as possible unless almost time for next dose; do not double up on missed 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 professional promptly if signs and symptoms of hepatitis (yellow eyes and skin, nausea, vomiting, anorexia, dark urine, unusual tiredness, or weakness) or peripheral neuritis (numbness, tingling, paresthesia) occur. Pyridoxine may be used concurrently to prevent neuropathy. Any changes in visual acuity, eye pain, or blurred vision should also be reported immediately.
Caution patient to avoid the use of alcohol during this therapy, as this may increase the risk of hepatotoxicity. Avoid ingestion of Swiss or Cheshire cheeses, fish (tuna, skipjack, and sardines), and tyramine-containing foods (see Food Sources for Specific Nutrients); may result in redness or itching of the skin; hot feeling; rapid or pounding heartbeat; sweating; chills; cold, clammy feeling; headache; or light-headedness.
Rep: May be used as treatment for active TB during pregnancy. Begin preventative therapy after delivery. May increase the risk of isoniazid-associated peripheral neurotoxicity in the mother; pyridoxine supplementation is recommended in pregnant patients during therapy. May be used during breastfeeding, as the small concentrations in breast milk do not produce toxicity in the nursing newborn; breastfeeding should not be discouraged. Low levels of isoniazid in breast milk can not be relied upon for prophylaxis or therapy in nursing infants. Monitor breastfed infants for jaundice; discontinue breastfeeding or consider changing to a different maternal medication if jaundice develops. Pyridoxine supplementation is recommended for the mother and infant.
Emphasize the importance of regular follow-up physical and ophthalmologic exams to monitor progress and to check for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇