ALLOPURINOL
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid, thereby reducing serum and urinary uric acid concentrations. It also inhibits de novo purine synthesis through feedback inhibition.
| Metabolism | Allopurinol is metabolized primarily by aldehyde oxidase to its active metabolite oxypurinol (alloxanthine), which also inhibits xanthine oxidase. Oxypurinol is further metabolized and eliminated renally. |
| Excretion | Renal: ~76% as unchanged drug and metabolites; oxypurinol (active metabolite) is primarily excreted renally. Biliary/fecal: minor, <5%. |
| Half-life | Allopurinol: 1–2 hours; oxypurinol: 18–30 hours (prolonged in renal impairment). |
| Protein binding | Allopurinol: <1%; oxypurinol: ~50% (mainly to albumin). |
| Volume of Distribution | Allopurinol: ~1.6 L/kg; distributes into total body water. |
| Bioavailability | Oral: ~79–90% for allopurinol; oxypurinol is formed rapidly via first-pass metabolism. |
| Onset of Action | Oral: serum urate reduction begins within 24–48 hours; maximal effect may take 1–3 weeks. |
| Duration of Action | Inhibits xanthine oxidase for up to 24 hours after a single dose; clinical effect on urate lasts throughout dosing interval. |
100-600 mg orally once daily; initial 100 mg/day with weekly increases of 100 mg/day; maximum 800 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR >50: no adjustment; GFR 10-50: 200 mg/day; GFR <10: 100 mg/day or dosing interval every 48-72 hours. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh C); consider dose reduction. |
| Pediatric use | Children <6 years: 150 mg/day; 6-10 years: 300 mg/day; 11-16 years: 300-600 mg/day; initial dose 10 mg/kg/day divided in 2-3 doses, max 300 mg/day. |
| Geriatric use | Start at lowest dose (100 mg/day) and titrate slowly; monitor renal function and adjust per GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Increases concentrations of azathioprine and mercaptopurine may increase risk of rash with ampicillin and amoxicillin Severe skin reactions like Stevens-Johnson syndrome can occur discontinue at first sign of rash.
| Breastfeeding | Excreted in breast milk; M/P ratio ~0.9. Relative infant dose ~1-2% of maternal weight-adjusted dose. Considered compatible with breastfeeding; monitor infant for rash or diarrhea. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: limited human data, no clear teratogenic signal; animal studies show fetal anomalies at high doses. Second/third trimester: potential for neonatal complications (e.g., hypersensitivity, rash) if used near term; avoid if possible. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Dryness in mouth Constipation Lightheadedness Drowsiness |
| Serious Effects |
["Hypersensitivity to allopurinol or any component of the formulation.","Idiopathic hemochromatosis (relative contraindication due to potential for increased iron storage).","Concurrent use with didanosine (increased risk of pancreatitis and peripheral neuropathy)."]
| Precautions | ["Hypersensitivity reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis) occur more frequently in patients with renal impairment or thiazide diuretic use.","Discontinue at first sign of rash or other signs of hypersensitivity.","Increased risk of bone marrow suppression in patients with renal impairment.","Hepatotoxicity (monitor liver function tests).","Acute gout flare may occur during initiation; prophylaxis with colchicine or NSAIDs recommended.","Dose adjustment required in renal impairment.","Azathioprine or 6-mercaptopurine dose reduction required due to inhibited metabolism."] |
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| Fetal Monitoring | Monitor maternal serum uric acid levels periodically; assess renal and hepatic function. Fetal monitoring: standard prenatal care; no specific fetal tests required. |
| Fertility Effects | No known adverse effects on human fertility; animal studies show no impairment. Limited data; theoretical risk of gonadal suppression is low. |
| Food/Dietary | Avoid high-purine foods such as organ meats (liver, kidney), anchovies, sardines, mussels, and scallops; limit red meat and shellfish; avoid excessive alcohol, especially beer and spirits; maintain adequate fluid intake. |
| Clinical Pearls | Start at low dose (100 mg/day) and titrate every 2-4 weeks to reduce risk of gout flare; check renal function before dosing and adjust accordingly; allopurinol hypersensitivity syndrome (AHS) is rare but life-threatening, discontinue immediately if rash or signs of hypersensitivity occur; avoid use with azathioprine or 6-mercaptopurine unless dose of these agents is reduced by 60-80%; monitor liver function tests periodically. |
| Patient Advice | Take exactly as prescribed, usually once daily with food. · Do not stop or change dose without consulting your doctor. · Report any rash, hives, itching, or swelling of face/lips immediately. · Drink plenty of fluids (8-10 glasses per day) to prevent kidney stones. · Avoid alcohol, especially beer, as it may increase uric acid levels. · It may take weeks or months to prevent gout attacks; do not skip doses. · During initial therapy, gout attacks may still occur; continue treatment as directed. · Store at room temperature away from moisture and heat. |