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Pyrazinamide

Pronunciation: PIR-a-ZIN-a-mide
Class: Antituberculosis agent

Trade Names

Pyrazinamide
- Tablets 500 mg

Tebrazid (Canada)

Pharmacology

Pyrazine analog of nicotinamide may be bacteriostatic or bactericidal (concentration dependent) against Mycobacterium tuberculosis .

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Pharmacokinetics

Absorption

Rapid and almost complete from GI tract. T max is within 2 h (pyrazinamide) and plasma concentrations range from 30 to 50 mcg/mL.

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 approximately 10%. Distributes into breast milk.

Metabolism

Hepatic; hydrolyzed by microsomal deamidase to the major active metabolite pyrazinoic acid, which is then hydroxylated by xanthine oxidase to 5-hydroxypyrazinoic acid.

Elimination

Renal (3% as unchanged pyrazinamide, 33% pyrazinoic acid). 70% of orally adminsitered dose is excreted in the urine. The t ½ distribution is approximately 1.6 h. Elimination t ½ is approximately 9.5 h (pyrazinamide, healthy renal function), approximately 26 h (pyrazinamide, chronic renal failure), approximately 12 h (pyrazinoic acid, healthy renal function), and approximately 22 h (pyrazinoic acid, chronic renal failure).

Special Populations

Renal Function Impairment

The t ½ of pyrazinamide and metabolite is increased.

Hepatic Function Impairment

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. After treatment failure with other primary drugs in any form of active tuberculosis.

Contraindications

Severe hepatic damage; acute gout.

Dosage and Administration

Adults

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

Children

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

General Advice

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

Storage/Stability

Store at room temperature (59° to 86°F) 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

Acne; photosensitivity.

GI

Anorexia; nausea; vomiting.

Genitourinary

Dysuria; interstitial nephritis.

Hematologic-Lymphatic

Increased serum iron; sideroblastic anemia with erythroid hyperplasia; thrombocytopenia; vacuolation of erythrocytes.

Hepatic

Hepatotoxicity.

Metabolic-Nutritional

Porphyria.

Musculoskeletal

Mild arthralgia, myalgia.

Miscellaneous

Fever; hypersensitivity reactions, including pruritus, rash, urticaria.

Precautions

Monitor

Measure baseline serum uric acid and liver function prior to the onset of therapy and periodically during treatment.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Use only if therapy is essential. Appears to be well tolerated in children.

Elderly

Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

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; use with caution.

Hyperuricemia

May inhibit renal excretion of urates, resulting in hyperuricemia.

Overdosage

Symptoms

Abnormal LFTs.

Patient Information

  • Emphasize need to be compliant with regimen and that doses should not be missed.
  • 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.

Copyright © 2009 Wolters Kluwer Health.

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