isoniazid

Action

Inhibits cell-wall biosynthesis by interfering with lipid and nucleic acid DNA synthesis in tubercle bacilli cells

Availability

Injection: 100 mg/ml

Syrup: 50 mg/5 ml

Tablets: 100 mg, 300 mg

Indications and dosages

➣ Active tuberculosis (TB)

Adults: 5 mg/kg P.O. or I.M. (maximum of 300 mg/day) daily as a single dose, or 15 mg/kg (maximum of 900 mg/day) two to three times weekly; given with other agents

Children: 10 to 15 mg/kg P.O. or I.M. (maximum of 300 mg/day) daily as a single dose, or 20 to 40 mg/kg (maximum of 900 mg/day) two to three times weekly

➣ To prevent TB in patients exposed to active disease

Adults: 300 mg P.O. daily as a single dose for 6 to 12 months

Children and infants: 10 mg/kg P.O. daily as a single dose for up to 12 months

Off-label uses

• Mycobacterium kansasii infection

Contraindications

• Hypersensitivity to drug

• Acute hepatic disease or previous hepatitis caused by isoniazid therapy

Precautions

Use cautiously in:

• severe renal impairment, diabetes, diabetic retinopathy, ocular defects, chronic alcoholism, hepatic damage

• Black or Hispanic women

• pregnant or breastfeeding patients

• children ages 13 and younger.

Administration

• Give on empty stomach 1 hour before or 2 hours after meals. If GI upset occurs, administer with food.

• Administer parenterally only if patient can't receive oral form.

• Use cautiously in diabetic or alcoholic patients and those at risk for neuropathy.

Adverse reactions

CNS: peripheral neuropathy, dizziness, memory impairment, slurred speech, psychosis, toxic encephalopathy, seizures

EENT: visual disturbances

GI: nausea, vomiting

GU: gynecomastia

Hematologic: eosinophilia, methemoglobinemia, hemolytic anemia, aplastic anemia, agranulocytosis, thrombocytopenia

Hepatic: hepatitis

Metabolic: pyridoxine deficiency, hyperglycemia, metabolic acidosis

Respiratory: dyspnea

Other: fever, pellagra, lupuslike syndrome, injection site irritation, hypersensitivity reaction

Interactions

Drug-drug. Aluminum-containing antacids: decreased isoniazid absorption

Bacille Calmette-Guérin vaccine: ineffective vaccination

Carbamazepine: increased carbamazepine blood level

Disulfiram: psychotic reactions, incoordination

Hepatotoxic drugs: increased risk of hepatotoxicity

Ketoconazole: decreased ketoconazole blood level and efficacy

Other antituberculars: additive CNS toxicity

Phenytoin: inhibition of phenytoin metabolism

Drug-diagnostic tests. Albumin: increased level

Drug-food. Foods containing tyramine: hypertensive crisis, other severe reactions

Drug-behaviors. Alcohol use: increased risk of hepatitis

Patient monitoring

• Assess hepatic enzyme levels.

• Watch for adverse reactions, such as peripheral neuropathy.

Patient teaching

• Advise patient to take once daily on empty stomach, 1 hour before or 2 hours after meals. If GI upset occurs, tell him to take with small amount of food.

• Caution patient to avoid foods containing tyramine (such as cheese, fish, salami, red wine, and yeast extracts), because drug-food interaction may cause chills, diaphoresis, and palpitations.

• Teach patient with peripheral neuropathy to take care to prevent burns and other injuries.

• Instruct patient to report anorexia, nausea, vomiting, jaundice, dark urine, and numbness or tingling of hands or feet.

• Tell patient he'll need periodic medical and eye examinations and blood tests to gauge drug effects.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and behaviors mentioned above.