Home Drug Guide Pyrazinamide

Drug Guide

Generic Name

Pyrazinamide

Brand Names PZA

Classification

Therapeutic: Antitubercular agent

Pharmacological: Prodrug, Pyrazinamide acts as a bactericidal agent against Mycobacterium tuberculosis

FDA Approved Indications

Treatment of tuberculosis, in combination with other antitubercular agents

Mechanism of Action

Pyrazinamide is converted to pyrazinoic acid, which disrupts mycobacterial cell membrane metabolism and transport functions, resulting in bacterial death.

Dosage and Administration

Adult: 15-30 mg/kg/day, usually given as part of a 4-drug regimen for the initial 2 months, then continued with other drugs.

Pediatric: Same as adults, based on weight; typically 25-30 mg/kg/day.

Geriatric: Adjust based on renal and hepatic function; monitor for toxicity.

Renal Impairment: Use cautiously; dosage adjustment may be necessary.

Hepatic Impairment: Use with caution; monitor liver function closely.

Pharmacokinetics

Absorption: Well absorbed from gastrointestinal tract.

Distribution: Widely distributed; crosses the placenta, small amounts in breast milk.

Metabolism: Metabolized in the liver to pyrazinoic acid.

Excretion: Excreted primarily via the kidneys.

Half Life: Approximately 9-10 hours.

Contraindications

Hypersensitivity to pyrazinamide or other first-line anti-TB drugs.

Precautions

Monitor liver function; use cautiously in patients with hepatic disease.
Risk of hepatotoxicity and hyperuricemia, which may precipitate gout.

Adverse Reactions - Common

Hepatotoxicity (Common)
Hyperuricemia (Common)
Gastrointestinal disturbances (nausea, vomiting) (Common)

Adverse Reactions - Serious

Hepatitis (Serious, requires immediate discontinuation)
Gout or gouty arthritis (Serious, especially in predisposed individuals)
Myalgia, arthralgia (Serious)

Drug-Drug Interactions

Rifampin, Isoniazid, Ethambutol, Streptomycin

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Assessment: Monitor liver function tests, uric acid levels, and signs of hepatitis.

Diagnoses:

Risk for hepatotoxicity
Risk for gout or hyperuricemia

Implementation: Administer with food to reduce gastrointestinal upset. Monitor for adverse effects.

Evaluation: Assess for signs of hepatotoxicity and gout. Ensure therapy efficacy.

Patient/Family Teaching

Take medication exactly as prescribed.
Report symptoms of hepatitis (jaundice, dark urine), gout (joint pain, swelling), or gastrointestinal upset.
Avoid alcohol and hepatotoxic substances.
Maintain regular follow-up for blood tests.

Special Considerations

Black Box Warnings:

Hepatotoxicity, including severe hepatic injury and hepatitis, can occur.

Genetic Factors: Consider genetic predisposition to drug-induced liver injury.

Lab Test Interference: May elevate liver enzymes and uric acid levels.

Overdose Management

Signs/Symptoms: Hepatic failure, hyperuricemia, nausea, vomiting, abdominal pain.

Treatment: Supportive care; activated charcoal if ingestion is recent; monitor for hepatic and renal function; managing symptoms accordingly.

Storage and Handling

Storage: Store at room temperature, protected from moisture and light.

Stability: Stable under recommended conditions.