PYRAZINAMIDE
(peer-a-zin'a-mide)
PZA, Tebrazid

Classifications: antiinfective; antituberculosis agent
Pregnancy Category: C

Availability

500 mg tablets

Actions

Pyrazinoic acid amide, analog of nicotinamide which is bacteriostatic against Mycobacterium tuberculosis. When employed alone, resistance may develop in 6–7 wk; therefore, administration with other effective agents is recommended. Appears to interfere with renal capacity to concentrate and excrete uric acid. Thus it may cause hyperuricemia.

Therapeutic Effects

Bacteriostatic against Mycobacterium tuberculosis. Not used as sole agent against TB infection.

Uses

Short-term therapy of advanced tuberculosis before surgery and to treat patients unresponsive to primary agents (e.g., isoniazid, streptomycin).

Contraindications

Severe liver damage, pregnancy (category C), and lactation.

Cautious Use

Presence or family history of gout or diabetes mellitus; impaired kidney function; history of peptic ulcer; acute intermittent porphyria.

Route & Dosage

Tuberculosis
Adult: PO 15–35 mg/kg/d in 3–4 divided doses (max: 2 g/d)
Child: PO 20–40 mg/kg/d divided q12–24h (max: 2 g/d)

Administration

Oral

Discontinue drug if hepatic reactions (jaundice, pruritus, icteric sclerae, yellow skin) or hyperuricemia with acute gout (severe pain in great toe and other joints) occur.
Store at 15°–30° C (59°–86° F) in tightly closed container.

Adverse Effects (1%)

Body as a Whole: Active gout, arthralgia, lymphadenopathy. Urogenital: Difficulty in urination. CNS: Headache. Skin: Urticaria. Hematologic: Hemolytic anemia, decreased plasma prothrombin. GI: Splenomegaly, fatal hemoptysis, aggravation of peptic ulcer, hepatotoxicity, abnormal liver function tests. Metabolic: Rise in serum uric acid.

Diagnostic Test Interference

Pyrazinamide may produce a temporary decrease in 17-ketosteroids and an increase in protein-bound iodine.

Interactions

Drug: Increase in liver toxicity (including fatal hepatoxicity in when treating latent TB) with rifampin.

Pharmacokinetics

Absorption: Readily absorbed from GI tract. Peak: 2 h. Distribution: Crosses blood–brain barrier. Metabolism: Metabolized in liver. Elimination: Excreted slowly in urine. Half-Life: 9–10 h.

Nursing Implications

Assessment & Drug Effect

Observe and supervise closely. Patients should receive at least one other effective antituberculosis agent concurrently.
Examine patients at regular intervals and question about possible signs of toxicity: Liver enlargement or tenderness, jaundice, fever, anorexia, malaise, impaired vascular integrity (ecchymoses, petechiae, abnormal bleeding).
Hepatic reactions appear to occur more frequently in patients receiving high doses.
Lab tests: Obtain liver function tests (especially AST, ALT, serum bilirubin) prior to and at 2–4 wk intervals during therapy. Blood uric acid determinations are advised before, during, and following therapy.

Patient & Family Education

Report to physician onset of difficulty in voiding. Keep fluid intake at 2000 mL/d if possible.
Monitor blood glucose (diabetics) for possible loss of glycemic control.
Do not breast feed while taking this drug without consulting physician.

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