pyrazinamide
PMS-Pyrazinamide ◆, Tebrazid ◆

Pharmacologic classification: synthetic pyrazine analogue of nicotinamide
Therapeutic classification: antituberculotic
Pregnancy risk category C


Available forms
Available by prescription only
Tablets: 500 mg

Indications and dosages
 Adjunctive treatment of tuberculosis (when primary and secondary antituberculotics can’t be used or have failed). Adults: 15 to 30 mg/kg P.O. daily, in one or more doses. Maximum dose is 3 g daily. Or a twice-weekly dose of 50 to 70 mg/kg (based on lean body weight) has been developed to promote patient compliance. Lower dosage is recommended in patients with decreased renal function.

Pharmacodynamics
Antibiotic action: Mechanism unknown. May be bactericidal or bacteriostatic depending on organism susceptibility and drug level at infection site. Active only against Mycobacterium tuberculosis. Considered adjunctive in tuberculosis therapy and is given with other drugs to prevent or delay development of resistance to pyrazinamide by M. tuberculosis.

Pharmacokinetics
Absorption: Well absorbed after oral administration.
Distribution: Distributed widely into body tissues and fluids, including lungs, liver, and CSF; 50% protein-bound. Not known if drug crosses the placental barrier.
Metabolism: Hydrolyzed in liver; some hydrolysis occurs in stomach.
Excretion: Excreted almost completely in urine by glomerular filtration. Not known if drug appears in breast milk. Elimination half-life in adults is 9 to 10 hours; prolonged half-life in renal and hepatic impairment.

Route Onset Peak Duration
P.O. Unknown 1-2 hr Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with severe hepatic disease or acute gout. Use cautiously in patients with diabetes mellitus, renal failure, or gout.

Interactions
Drug-lifestyle. Sun exposure: May cause photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: malaise, fever.
GI: anorexia, nausea, vomiting.
GU: dysuria, interstitial nephritis.
Hematologic: sideroblastic anemia, thrombocytopenia.
Hepatic: hepatitis.
Metabolic: hyperuricemia, gout.
Musculoskeletal: arthralgia, myalgia.
Skin: rash, urticaria, pruritus, photosensitivity.
Other: porphyria.

Effects on lab test results
• May increase uric acid and liver enzyme levels.
• May decrease hemoglobin and platelet count.

Overdose and treatment
No specific recommendations are available. Treatment is supportive. Within 4 hours of ingestion, empty stomach by induced emesis or gastric lavage. Follow with activated charcoal to decrease absorption.

Special considerations
• In patients with diabetes mellitus, pyrazinamide therapy may hinder stabilization of serum glucose levels.
• In many cases, drug elevates serum uric acid levels. Although usually asymptomatic, a uricosuric drug, such as probenecid or allopurinol, may be needed.
• Monitor liver function, especially enzyme and bilirubin levels, and renal function, especially serum uric acid levels, before therapy and thereafter at 2- to 4-week intervals.
• Patients with concomitant HIV infection may need a longer course of treatment.
• Pyrazinamide may interfere with urine ketone determinations.
• Drug temporarily decreases 17-ketosteroid levels and increases protein-bound iodine and urate levels.
Breast-feeding patients
• Drug appears in breast milk. Safety in breast-feeding women hasn’t been established. An alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Safe use in children hasn’t been definitely established.
Geriatric patients
• Because elderly patients commonly have diminished renal function, which decreases drug excretion, drug should be used cautiously.

Patient education
• Explain disease process and rationale for long-term therapy.
• Teach patient signs and symptoms of hypersensitivity and other adverse reactions, and emphasize need to report them; urge patient to report unusual reactions, especially signs of gout.
• Make sure patient understands how and when to take drugs; urge patient to complete entire prescribed regimen, to comply with instructions for around-the-clock dosage, and to keep follow-up appointments.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use