ISONIAZID (ISONICOTINIC ACID HYDRAZIDE)

(eye-soe-nye'a-zid)

INH, Isotamine

, Laniazid, Nydrazid, PMS Isoniazid

Classifications: antibioitic; antituberculosis agent;
Therapeutic: antibiotic; antituberculosis
Pregnancy Category: C

Availability

50 mg, 100 mg, 300 mg tablets; 50 mg/5 mL syrup; 100 mg/mL injection

Action

Hydrazide of isonicotinic acid with highly specific action against Mycobacterium tuberculosis. Postulated to act by interfering with biosynthesis of bacterial proteins, nucleic acid, and lipids.

Therapeutic Effect

Exerts bacteriostatic action against actively growing tubercle bacilli; may be bactericidal in higher concentrations.

Uses

Treatment of all forms of active tuberculosis caused by susceptible organisms and as preventive in high-risk persons (e.g., household members, persons with positive tuberculin skin test reactions). May be used alone or with other tuberculostatic agents.

Unlabeled Uses

Treatment of atypical mycobacterial infections; tuberculous meningitis; action tremor in multiple sclerosis.

Contraindications

History of isoniazid-associated hypersensitivity reactions, including hepatic injury; acute liver damage of any etiology; pregnancy (category C) unless risk is warranted.

Cautious Use

Chronic liver disease; HIV infection; hepatitis; severe renal dysfunction; history of convulsive disorders; chronic alcoholism; persons over 50 y.

Route & Dosage

Treatment of Active Tuberculosis
Adult: PO/IM 5 mg/kg (max: 300 mg/d)
Child: PO/IM 10–20 mg/kg (max: 300–500 mg/d)

Preventive Therapy
Adult: PO 300 mg/d
Child: PO 10 mg/kg up to 300 mg/d or 15 mg/kg 3 times/wk

Administration

Oral

Give on an empty stomach at least 1 h before or 2 h after meals. If GI irritation occurs, drug may be taken with meals.

Intramuscular

Note: Isoniazid solution for IM injection tends to crystallize at low temperatures; if this occurs, solution should be allowed to warm to room temperature to redissolve crystals before use.
Give deep into a large muscle and rotate injection sites; local transient pain may follow IM injections.
Store in tightly closed, light-resistant containers.

Adverse Effects (≥1%)

Body as a Whole: Drug-related fever, rheumatic and lupus erythematosus-like syndromes, irritation at injection site; hypersensitivity (fever, chills, skin eruption, vasculitis). CNS: Paresthesias, peripheral neuropathy, headache, unusual tiredness or weakness, tinnitus, dizziness, hallucinations. Special Senses: Blurred vision, visual disturbances, optic neuritis, atrophy. GI: Nausea, vomiting, epigastric distress, dry mouth, constipation; hepatotoxicity (elevated AST, ALT; bilirubinemia, jaundice, hepatitis). Hematologic: Agranulocytosis, hemolytic or aplastic anemia, thrombocytopenia, eosinophilia, methemoglobinemia. Metabolic: Decreased vitamin B₁₂ absorption, pyridoxine (vitamin B₆) deficiency, pellagra, gynecomastia, hyperglycemia, glycosuria, hyperkalemia, hypophosphatemia, hypocalcemia, acetonuria, metabolic acidosis, proteinuria. Other: Dyspnea, urinary retention (males).

Diagnostic Test Interference

Isoniazid may produce false-positive results using copper sulfate tests (e.g., Benedict's solution, Clinitest) but not with glucose oxidase methods (e.g., Clinistix, Dextrostix, TesTape).

Interactions

Drug: Cycloserine, ethionamide enhance CNS toxicity; may increase phenytoin levels, resulting in toxicity; aluminum-containing antacids decrease GI absorption; disulfiram may cause coordination difficulties or psychotic reactions; alcohol increases risk of hepatotoxicity. Food: Food decreases rate and extent of isoniazid absorption; should be taken 1 h before meals.

Pharmacokinetics

Absorption: Readily from GI tract; food may reduce rate and extent of absorption. Peak: 1–2 h. Distribution: Distributed to all body tissues and fluids including the CNS; crosses placenta. Metabolism: Inactivated by acetylation in liver. Elimination: 75–96% in urine in 24 h; excreted in breast milk. Half-Life: 1–4 h.

Nursing Implications

Assessment & Drug Effects

Monitor for therapeutic effectiveness: Evident within the first 2–3 wk of therapy. Over 90% of patients receiving optimal therapy have negative sputum by the sixth month.
Perform appropriate susceptibility tests before initiation of therapy and periodically thereafter to detect possible bacterial resistance.
Lab tests: Monitor hepatic function periodically. Isoniazid hepatitis (sometimes fatal) usually develops during the first 3–6 mo of treatment, but may occur at any time during therapy; much more frequent in patients 35 y or older, especially in those who ingest alcohol daily.
Monitor for visual disturbance. An eye examination may be warranted.
Note: Inactivation of the drug is genetically determined. Slow inactivation leads to high plasma drug levels and increased risk of toxicity.
Isoniazid-induced pyridoxine (vitamin B₆) depletion causes neurotoxic effects. B₆ supplementation (10–50 mg) usually accompanies isoniazid use.
Peripheral neuritis, the most common toxic effect, is usually preceded by paresthesias of feet and hands (numbness, tingling, burning). Patients particularly susceptible include alcoholics and patients with liver disease, malnourished patients, diabetics, slow inactivators, pregnant women, and older adults.
Monitor BP during period of dosage adjustment. Some experience orthostatic hypotension; therefore, caution against rapid positional changes.
Monitor diabetics for loss of glycemic control.
Check weight at least twice weekly under standard conditions.

Patient & Family Education

Note: Eating tyramine-containing foods (e.g., aged cheeses, smoked fish) may cause palpitation, flushing, and blood pressure elevation. Histamine-containing foods (e.g., skipjack, tuna, sauerkraut juice, yeast extracts) may cause exaggerated drug response (headache, hypotension, palpitation, sweating, itching, flushing, diarrhea).
Withhold medication and notify physician if S&S of hepatotoxicity develop (e.g., dark urine, jaundice, clay-colored stools).
Avoid or at least reduce alcohol intake while on isoniazid therapy because of increased risk of hepatotoxicity.
Withhold all drugs and notify physician of hypersensitivity reaction immediately; generally occurs within 3–7 wk after initiation of therapy.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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