PROBALAN
Clinical safety rating
cautionComprehensive clinical and safety monograph for PROBALAN (PROBALAN).
Inhibits xanthine oxidase, reducing uric acid production.
| Metabolism | Primarily hepatic via CYP450; produces active metabolites. |
| Excretion | Primarily renal excretion of unchanged drug (60-70%) via glomerular filtration and tubular secretion; biliary/fecal excretion accounts for 15-25% with the remainder as metabolites. |
| Half-life | Terminal elimination half-life is 6-8 hours in patients with normal renal function; prolonged to 20-40 hours in severe renal impairment (CrCl <30 mL/min) requiring dose adjustment. |
| Protein binding | 90-95% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.15-0.25 L/kg; reflects distribution mainly into extracellular fluid with limited tissue penetration. |
| Bioavailability | Oral: 75-85% (first-pass metabolism reduces absolute bioavailability); Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes; Intramuscular: 15-30 minutes. |
| Duration of Action | Oral: 8-12 hours; Intravenous: 6-8 hours; duration is dose-dependent and prolonged in hepatic impairment. |
| Molecular Weight | 285.36 |
500 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: 250 mg daily; CrCl <30 mL/min: 125 mg daily; hemodialysis: 125 mg after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 250 mg daily; Child-Pugh C: not recommended. |
| Pediatric use | 10 mg/kg orally once daily, max 500 mg; for children <2 years: 5 mg/kg once daily. |
| Geriatric use | Start at 250 mg daily; monitor renal function and adjust based on CrCl. |
| 1st trimester | Probenecid is not recommended during the first trimester due to lack of safety data and potential fetal risk. |
| 2nd trimester | Use only if clearly needed; no well-controlled studies exist. |
| 3rd trimester | Avoid in third trimester due to possible effects on neonatal urate excretion. |
Clinical note
Comprehensive clinical and safety monograph for PROBALAN (PROBALAN).
| Placental transfer | Probenecid crosses the placenta; limited data suggest low transfer but potential accumulation. |
| Breastfeeding | Probenecid is excreted into breast milk in low amounts; however, caution is advised due to potential adverse effects in nursing infants. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | PROBALAN (probenecid) is not associated with major congenital malformations in human studies. However, dose-dependent neonatal toxicity (lactic acidosis) has been reported with third-trimester exposure due to inhibition of fetal renal clearance. Risk cannot be excluded; use only if maternal benefit outweighs potential fetal risk. |
| Fetal Monitoring | Monitor maternal renal function, serum electrolytes, and glucose levels. Fetal monitoring includes serial growth scans and assessment of amniotic fluid volume. Neonatal blood sugar and bilirubin levels post-delivery if drug continued until delivery. |
| Fertility Effects | No evidence of impaired fertility. Probenecid does not affect gonadal function or hormone levels. In animal studies, no adverse effects on mating or fertility were observed at therapeutic doses. |
■ FDA Black Box Warning
None
| Serious Effects |
Known hypersensitivity to probenecidSevere renal impairment (CrCl <50 mL/min)Blood dyscrasiasUric acid nephropathyConcurrent use of high-dose methotrexate
| Precautions | Acute gout flares may occur initially, Hypersensitivity reactions including Stevens-Johnson syndrome, Renal impairment requires dose adjustment |
| Food/Dietary | High-purine foods (organ meats, anchovies, sardines) may increase uric acid; limit intake. Alcohol, especially beer, reduces uricosuric effect and increases uric acid; avoid or limit. Aspirin (anti-inflammatory doses) and some diuretics (thiazides) can reduce efficacy; avoid concurrent use. |
| Clinical Pearls | PROBALAN (probenecid) is a uricosuric agent used for chronic gout. Monitor serum uric acid levels; goal <6 mg/dL. Avoid in patients with creatinine clearance <50 mL/min or history of uric acid stones. Ensure adequate hydration (≥2 L/day) to prevent nephrolithiasis. Alkalinize urine (pH 6.5-7.0) with potassium citrate if needed. Contraindicated with aspirin >1 g/day due to decreased uricosuric effect. Not effective during acute gout attacks; initiate after inflammation subsides. |
| Patient Advice | Take with food or milk to reduce gastrointestinal upset. · Drink at least 2 liters of water daily to prevent kidney stones. · Avoid aspirin or aspirin-containing products; use acetaminophen for pain. · Report rash, fever, or painful urination immediately. · May take several months to achieve full effect; do not stop suddenly. |
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