Pyrazinamide

Trade Names:
Pyrazinamide
- Tablets 500 mg

Pharmacology

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Pyrazine analog of nicotinamide may be bacteriostatic or bactericidal against Mycobacterium tuberculosis .

Pharmacokinetics

Absorption

Rapid and almost complete from GI tract. T _max is 1 to 2 h (pyrazinamide) and 4 to 5 h (pyrazinoic acid). C _max is 19 to 39 mcg/mL (pyrazinamide) and 3 to 4.5 mcg/mL (pyrazinoic acid).

Distribution

Widely distributed to most fluids and tissues, including the liver, lungs, kidney, and bile. Excellent penetration into CSF (87% to 105%). Vd is 0.57 to 0.74 L/kg. Protein binding is 10% to 20% (pyrazinamide) and 31% (pyrazinoic acid). Distributes into breast milk.

Metabolism

Hepatic; hydrolyzed by microsomal deamidase to active metabolites pyrazinoic acid, then hydroxylated by xanthine oxidase to 5-hydroxypyrazinoic acid.

Elimination

Renal (3% as unchanged pyrazinamide, 33% pyrazinoic acid). The t _½ distribution is approximately 1.6 h. Elimination t _½ is approximately 9.5 h (pyrazinamide, normal renal function), approximately 26 h (pyrazinamide, chronic renal failure), approximately 12 h (pyrazinoic acid, normal renal function), and approximately 22 h (pyrazinoic acid, chronic renal failure).

Special Populations

The t _½ of pyrazinamide and metabolite is increased.

Indications and Usage

Initial treatment of active tuberculosis in adults and selected children when combined with other antituberculosis agents.

Contraindications

Severe hepatic damage; acute gout.

Dosage and Administration

PO 15 to 30 mg/kg every day (max, 2 g/day) or 50 to 70 mg/kg 2 times/week (max, 4 g/dose) or 50 to 70 mg/kg 3 times/wk (max, 3 g).

PO 15 to 30 mg/kg every day (max, 2 g/day) or 50 to 70 mg/kg 2 times/wk (max, 4 g) or 50 to 70 mg/kg 3 times/wk (max, 3 g).

General Advice

Administer without regard to meals. Administer with food if GI upset occurs.

Storage/Stability

Store at room temperature in tightly closed, light-resistant container.

Drug Interactions

None well documented.

Laboratory Test Interactions

May interfere with Acetest and Ketostix urine tests, producing pink-brown color.

Adverse Reactions

Dermatologic

Rash; acne; photosensitivity.

GI

Nausea; vomiting; anorexia.

Hepatic

Hepatotoxicity.

Metabolic

Gout; porphyria.

Miscellaneous

Arthralgia and myalgia; hypersensitivity reactions (eg, urticaria, pruritus); fever.

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established. Use only if therapy is essential.

Hepatic Function

Closely follow patients with preexisting liver disease or patients at increased risk (eg, alcohol abusers). It may be necessary to discontinue drug; do not resume therapy if signs of hepatocellular damage appear.

Diabetes mellitus

Management of diabetes mellitus may be more difficult.

Hyperuricemia

May inhibit renal excretion of urates, resulting in hyperuricemia.

Overdosage

Symptoms

Abnormal LFTs.

Patient Information

• Emphasize need to be compliant with regimen and not to miss any doses.
• Explain that long-term therapy (6 mo to 2 yr) will be necessary.
• Inform diabetic patients that drug may interfere with urine ketone values.
• Emphasize importance of follow-up examinations to monitor effectiveness of therapy and identify adverse reactions.
• Instruct patient to report the following symptoms to health care provider: fever; loss of appetite; malaise; nausea and vomiting; darkened urine, yellowish skin or eye discoloration; pain or swelling joints.
• Advise patient to avoid intake of alcoholic beverages and alcohol-containing products.

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