LOPURIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOPURIN (LOPURIN).
LOPURIN is a brand name for allopurinol, a xanthine oxidase inhibitor. It reduces uric acid production by inhibiting the conversion of hypoxanthine to xanthine and xanthine to uric acid.
| Metabolism | Primarily hepatic via aldehyde oxidase to oxypurinol (alloxanthine), which is also active; minor metabolism by xanthine oxidase. |
| Excretion | Renal (primarily as unchanged drug and active metabolite oxypurinol): ~70% urinary excretion; remainder biliary/fecal. Dose adjustment required in renal impairment. |
| Half-life | Allopurinol: 1-2 hours; oxypurinol: 18-30 hours (renal function dependent). Accumulation in renal failure; half-life of oxypurinol may exceed 100 hours in ESRD. |
| Protein binding | Allopurinol: <1%; oxypurinol: ~20% (primarily to albumin). Negligible displacement interactions. |
| Volume of Distribution | Allopurinol: ~1.6 L/kg; oxypurinol: ~0.6 L/kg. Indicates extensive tissue distribution, including renal and hepatic tissues. |
| Bioavailability | Oral allopurinol: ~80% (mean); conversion to oxypurinol reduces systemic availability of parent drug. Food delays absorption but does not affect extent. |
| Onset of Action | Oral: Serum urate reduction begins within 24-48 hours; maximal effect in 1-2 weeks. No parenteral form. |
| Duration of Action | Effect persists for duration of therapy; after discontinuation, serum urate returns to baseline within 1-2 weeks. Oxypurinol activity extends half-life effect. |
| Molecular Weight | 284.24 |
200-600 mg orally once daily, typically starting at 300 mg/day and adjusting based on serum urate levels.
| Dosage form | TABLET |
| Renal impairment | For GFR 10-20 mL/min: 200 mg/day; GFR <10 mL/min: 100 mg/day or avoid use; consider alternative in severe impairment. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use or reduce by 75%. |
| Pediatric use | Children 6-10 years: 100 mg orally once daily; 11-16 years: 200-300 mg orally once daily; adjust based on serum urate. |
| Geriatric use | Start at lower end of dosing range (100-200 mg/day) due to age-related renal decline; monitor renal function and urate levels. |
| 1st trimester | Risk of fetal harm based on animal data; human data limited. Use only if benefit outweighs risk. |
| 2nd trimester | Avoid use during organogenesis unless no alternative. Monitor fetal growth. |
| 3rd trimester | May cause neonatal adverse effects; avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for LOPURIN (LOPURIN).
| Placental transfer | Crosses placenta; concentrations in fetal plasma ~50% of maternal. |
| Breastfeeding | Excreted into breast milk in low concentrations; monitor infant for hypoglycemia and hyperuricemia. |
| Lactation Rating | L3 (Moderately Safe) |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to allopurinol or any excipientsLactation (relative)Severe renal impairment (CrCl <10 mL/min)
| Precautions | Hypersensitivity syndrome (DRESS) may occur; discontinue at first sign of rash, Acute gout flares may occur upon initiation; prophylactic colchicine or NSAIDs recommended, Renal impairment requires dose adjustment; increase doses cautiously, Monitor liver function; hepatotoxicity reported, Bone marrow suppression (leukopenia, thrombocytopenia) may occur, Anticoagulant effect of warfarin may be enhanced |
| Food/Dietary | Avoid high-purine foods (organ meats, sardines, anchovies, shellfish, red meat). Limit alcohol intake, particularly beer and spirits. Maintain adequate hydration. No significant food-drug interactions reported. |
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| Teratogenic Risk | FDA Pregnancy Category D. First trimester: risk of congenital heart defects, cleft palate, and hypospadias based on animal studies and limited human data. Second and third trimesters: risk of fetal renal dysfunction, oligohydramnios, and neonatal renal impairment due to fetal renin-angiotensin system suppression. |
| Fetal Monitoring | Monitor fetal growth and amniotic fluid volume via ultrasound at least monthly after 20 weeks. Maternal blood pressure and renal function (serum creatinine, BUN) should be monitored regularly. Perform fetal echocardiography if first-trimester exposure occurred. |
| Fertility Effects | No adverse effects on fertility have been reported in animal studies. Human data are insufficient to determine a definitive impact. Theoretical risk of impaired spermatogenesis from long-term use has been suggested but not substantiated. |
| Clinical Pearls | Allopurinol is a xanthine oxidase inhibitor. Initiate at low dose (100 mg/day) and titrate to reduce risk of gout flares. Monitor for hypersensitivity reactions, especially in renal impairment. Doses must be adjusted for renal function (CrCl <60 mL/min). Do not use with azathioprine or 6-mercaptopurine without dose reduction of cytotoxic agents. Avoid restarting after severe hypersensitivity. |
| Patient Advice | Take after meals to reduce GI upset. · Drink plenty of fluids (2-3 liters/day) to prevent kidney stones. · Report any rash, itching, or swelling immediately as these may signal a serious allergic reaction. · Do not stop medication abruptly; gout flares may occur during early treatment. · Avoid alcohol, especially beer, as it can increase uric acid levels. · Keep regular appointments for blood tests to monitor uric acid and kidney function. |