PYRAZINAMIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Converted to pyrazinoic acid, which disrupts membrane potential and inhibits mycobacterial fatty acid synthase (FAS-1).
| Metabolism | Hepatic via xanthine oxidase and aldehyde oxidase; major metabolite is 5-hydroxypyrazinoic acid. |
| Excretion | Renal: approximately 70% (40% unchanged, 30% as metabolites); biliary/fecal: minimal (less than 10%) |
| Half-life | 9–10 hours in patients with normal renal function; prolonged to 15–20 hours in renal impairment; requires dose adjustment in renal failure |
| Protein binding | 10–20% bound primarily to albumin |
| Volume of Distribution | 0.6–0.8 L/kg; distributes well into tissues including lungs, liver, and CSF (inflamed meninges) |
| Bioavailability | Oral: >90% (rapidly and nearly completely absorbed) |
| Onset of Action | Oral: 2–3 weeks for bacteriostatic effect in tuberculosis; peak plasma concentrations reached 1–2 hours after oral administration |
| Duration of Action | 24 hours; clinical effect is continuous with daily dosing; requires consistent plasma levels above MIC for Mycobacterium tuberculosis |
15-30 mg/kg orally once daily (max 2 g/day) for initial phase of tuberculosis treatment.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-60 mL/min: 25-35 mg/kg 3 times weekly; GFR <30 mL/min or hemodialysis: 25-35 mg/kg 3 times weekly after dialysis. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). In mild to moderate impairment, use with caution and monitor liver function; no specific dose adjustment guidelines available. |
| Pediatric use | 30-40 mg/kg orally once daily (max 2 g/day) for initial phase of tuberculosis treatment. |
| Geriatric use | Use lower end of dosing range (15-20 mg/kg) due to age-related decline in renal function; monitor for hepatotoxicity and hyperuricemia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
May increase uric acid levels Can cause hepatotoxicity and hyperuricemia.
| Breastfeeding | Pyrazinamide is excreted into human milk in low concentrations (M/P ratio ~0.5). American Academy of Pediatrics considers it compatible with breastfeeding. Monitor infant for gastrointestinal disturbances, hepatotoxicity, and jaundice. |
| Teratogenic Risk | Pyrazinamide crosses the placenta. First trimester: limited human data; animal studies not suggestive of teratogenicity, but risk cannot be excluded. Second and third trimesters: no evidence of embryotoxicity or fetotoxicity; used in standard regimens for active tuberculosis. Avoid unless clearly needed in first trimester. |
■ FDA Black Box Warning
None.
| Common Effects | Hepatotoxicity |
| Serious Effects |
["Severe hepatic damage","Acute gout","Hypersensitivity to pyrazinamide"]
| Precautions | ["Hepatotoxicity (monitor LFTs)","Hyperuricemia (may precipitate gout)","Hypersensitivity reactions","Photosensitivity"] |
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| Fetal Monitoring | Monitor maternal liver function tests (AST, ALT, bilirubin) at baseline and periodically; serum uric acid. Fetal monitoring: standard prenatal care; assess for adverse effects of tuberculosis itself if untreated. |
| Fertility Effects | No known adverse effects on human fertility. Pyrazinamide is not reported to impair spermatogenesis or oogenesis. Tuberculosis disease itself may impair fertility due to systemic illness. |