Yes

Antitubercular Agent

Treatment of susceptible tuberculosis infections and prophylactically to those individuals exposed to tuberculosis

C

Acute liver disease; hypersensitivity to isoniazid or any component; previous history of hepatic damage during isoniazid therapy

Use with caution in patients with renal impairment and chronic liver disease. Severe and sometimes fatal hepatitis may occur or develop even after many months of treatment; patients must report any prodromal symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea, or vomiting. Children with low milk and low meat intake should receive concomitant pyridoxine therapy. Periodic ophthalmic examinations are recommended even when usual symptoms do not occur; pyridoxine (10-50 mg/day) is recommended in individuals likely to develop peripheral neuropathies.

>10%:

Gastrointestinal: Loss of appetite, nausea, vomiting, stomach pain

Hepatic: Mild increased LFTs (10% to 20%)

Neuromuscular & skeletal: Weakness, peripheral neuropathy (dose-related incidence, 10% to 20% incidence with 10 mg/kg/day)

1% to 10%:

Central nervous system: Dizziness, slurred speech, lethargy

Hepatic: Progressive liver damage (increases with age; 2.3% in patients >50 years of age)

Neuromuscular & skeletal: Hyper-reflexia

<1%: Fever, seizures, mental depression, psychosis, rash, blood dyscrasias, arthralgia, blurred vision, loss of vision

Symptoms of overdose include nausea, vomiting, slurred speech, dizziness, blurred vision, hallucinations, stupor, coma, intractable seizures, onset of metabolic acidosis is 30 minutes to 3 hours. Because of the severe morbidity and high mortality rates with isoniazid overdose, patients who are asymptomatic after an overdose, should be monitored for 4-6 hours.

Pyridoxine has been shown to be effective in the treatment of intoxication, especially when seizures occur. Pyridoxine I.V. is administered on a milligram to milligram dose. If the amount of isoniazid ingested is unknown, 5 g of pyridoxine should be given over 3-5 minutes and may be followed by an additional 5 g in 30 minutes. Treatment is supportive; may require airway protection, ventilation; diazepam for seizures, sodium bicarbonate for acidosis; forced diuresis and hemodialysis can result in more rapid removal.

CYP2E1 enzyme substrate; CYP2E1 enzyme inducer; and CYP1A2, 2C, 2C9, 2C18, 2C19, and 3A3/4 enzyme inhibitor

Decreased effect/levels of isoniazid with aluminum salts

Increased toxicity/levels of oral anticoagulants, carbamazepine, cycloserine, meperidine, hydantoins, hepatically metabolized benzodiazepines with isoniazid; reaction with disulfiram occurs; enflurane with isoniazid may result in renal failure especially in rapid acetylators

Increased hepatic toxicity with alcohol or with rifampin and isoniazid

Protect oral dosage forms from light

Unknown, but may include the inhibition of myocolic acid synthesis resulting in disruption of the bacterial cell wall

Absorption: Rapid and complete; rate can be slowed when orally administered with food

Distribution: Crosses the placenta; appears in breast milk; distributes into all body tissues and fluids including the CSF

Protein binding: 10% to 15%

Metabolism: By the liver with decay rate determined genetically by acetylation phenotype

Half-life: Fast acetylators: 30-100 minutes; Slow acetylators: 2-5 hours; half-life may be prolonged in patients with impaired hepatic function or severe renal impairment

Time to peak serum concentration: Within 1-2 hours

Elimination: In urine (75% to 95%), feces, and saliva

Recommendations often change due to resistant strains and newly developed information; consult MMWR for current CDC recommendations: Oral (injectable is available for patients who are unable to either take or absorb oral therapy):

Infants and Children:

Prophylaxis: 10 mg/kg/day in 1-2 divided doses (maximum: 300 mg/day) 6 months in patients who do not have HIV infection and 12 months in patients who have HIV infection

Treatment:

Daily therapy: 10-20 mg/kg/day in 1-2 divided doses (maximum: 300 mg/day)

Directly observed therapy (DOT): Twice weekly therapy: 20-40 mg/kg (maximum: 900 mg/day); 3 times/week therapy: 20-40 mg/kg (maximum: 900 mg)

Adults:

Prophylaxis: 300 mg/day for 6 months in patients who do not have HIV infection and 12 months in patients who have HIV infection

Treatment:

Daily therapy: 5 mg/kg/day given daily (usual dose: 300 mg/day); 10 mg/kg/day in 1-2 divided doses in patients with disseminated disease

Directly observed therapy (DOT): Twice weekly therapy: 15 mg/kg (maximum: 900 mg); 3 times/week therapy: 15 mg/kg (maximum: 900 mg)

Note: Concomitant administration of 6-50 mg/day pyridoxine is recommended in malnourished patients or those prone to neuropathy (eg, alcoholics, diabetics)

Hemodialysis: Dialyzable (50% to 100%)

Administer dose postdialysis

Peritoneal dialysis effects: Dose for Cl_cr <10 mL/minute

Continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD): Dose for Cl_cr <10 mL/minute

Dosing adjustment in hepatic impairment: Dose should be reduced in severe hepatic disease

Should be administered 1 hour before or 2 hours after meals on an empty stomach; avoid foods with histamine or tyramine (cheese, broad beans, dry sausage, salami, nonfresh meat, liver pate, soy bean, liquid and powdered protein supplements, wine); increase dietary intake of folate, niacin, magnesium

Periodic liver function tests; monitoring for prodromal signs of hepatitis

Therapeutic: 1-7 mg/mL (SI: 7-51 mmol/L); Toxic: 20-710 mg/mL (SI: 146-5176 mmol/L)

False-positive urinary glucose with Clinitest®

May cause drowsiness or dizziness; may rarely cause depression or psychosis; reports of insomnia, restlessness, disorientation, hallucinations, delusions, obsessive-compulsive symptoms, and exacerbation of schizophrenia

Isoniazid may impair the metabolism of carbamazepine and oxidatively metabolized benzodiazepines; monitor for adverse effects

No information available to require special precautions

No effects or complications reported

Best if taken on an empty stomach (1 hour before or 2 hours after meals). Avoid missing any dose and do not discontinue without notifying prescriber. Avoid alcohol and tyramine-containing foods (eg, fish, preserved meats or sausages, tuna, sauerkraut, aged cheeses, broad beans, liver pate, wine, protein supplements, etc). Increase dietary intake of folate, niacin, magnesium. If diabetic, use serum testing (isoniazid may affect Clinitest® results). You may experience GI distress (taking dose with meals may help). Use caution to prevent injury. You will need to have frequent ophthalmic exams and periodic medical check-ups to evaluate drug effects. Report tingling or numbness in hands or feet, loss of sensation, unusual weakness, fatigue, nausea or vomiting, dark colored urine, change in urinary pattern, yellowing skin or eyes, or change in color of stool. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

The American Academy of Pediatrics recommends that pyridoxine supplementation (1-2 mg/kg/day) should be administered to malnourished patients, children or adolescents on meat or milk-deficient diets, breast feeding infants, and those predisposed to neuritis to prevent peripheral neuropathy; administration of isoniazid syrup has been associated with diarrhea

Injection: 100 mg/mL (10 mL)

Syrup (orange flavor): 50 mg/5 mL (473 mL)

Tablet: 50 mg, 100 mg, 300 mg

A 10 mg/mL oral suspension was stable for 21 days when refrigerated when compounded as follows:

Shake well before using and keep in refrigerator

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