ALOPRIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALOPRIM (ALOPRIM).
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.
| Metabolism | Allopurinol is metabolized primarily by xanthine oxidase to its active metabolite, oxypurinol. Both allopurinol and oxypurinol are further metabolized to a lesser extent by aldehyde oxidase. |
| Excretion | Renal: ~70% (30% as allopurinol, 40% as oxypurinol); fecal: ~20%; biliary: minor (<5%) |
| Half-life | Allopurinol: 1-2 h; Oxypurinol: 18-30 h (prolonged in renal impairment, up to 7 days in severe CKD) |
| Protein binding | Allopurinol: <1%; Oxypurinol: ~20% (primarily to albumin) |
| Volume of Distribution | Allopurinol: 0.6-1.6 L/kg (suggests distribution in total body water); Oxypurinol: 0.6-1.0 L/kg |
| Bioavailability | Oral: 67-90% (allopurinol); rapidly converted to oxypurinol |
| Onset of Action | Oral: 24-48 h for serum urate reduction; peak effect at 1-3 weeks |
| Duration of Action | Allopurinol: 6-8 h; Oxypurinol: 24-48 h; clinical effect persists >72 h due to active metabolite |
300 mg orally once daily; may be increased to 600-800 mg/day in divided doses for severe gout.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-60 mL/min: start at 200 mg/day; GFR 10-29 mL/min: 100 mg/day; GFR <10 mL/min: 100 mg every other day or 50 mg/day. |
| Liver impairment | No specific adjustment recommended; use with caution in severe hepatic impairment. |
| Pediatric use | Children 10-20 mg/kg/day in 2-3 divided doses, maximum 400 mg/day. |
| Geriatric use | Initiate at lower doses (e.g., 100 mg/day) due to age-related renal decline; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALOPRIM (ALOPRIM).
| Breastfeeding | Allopurinol and its metabolite oxypurinol are excreted in breast milk; M/P ratio not established. No adverse effects reported in nursing infants. Use with caution, especially in infants with G6PD deficiency. |
| Teratogenic Risk | First trimester: No evidence of teratogenicity in humans; animal studies show no fetal harm. Second/third trimester: No known risks; allopurinol crosses placenta but no congenital anomalies reported. Postnatal: No adverse effects reported. |
| Fetal Monitoring |
■ FDA Black Box Warning
Allopurinol has been associated with hypersensitivity reactions including severe skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening. The risk is higher in patients with renal impairment and those receiving thiazide diuretics. Discontinue at first sign of rash or other signs of hypersensitivity.
| Serious Effects |
Absolute: Patients with a history of a severe hypersensitivity reaction to allopurinol. Relative: Renal impairment (dose adjustment needed), pregnancy (only if benefit outweighs risk), and lactation (use caution).
| Precautions | Risk of severe hypersensitivity reactions including SJS/TEN; increased risk in patients with renal impairment or concomitant thiazide use. Monitor for rash. Acute gout attacks may increase during early therapy; prophylaxis with colchicine or NSAIDs is recommended. Hepatic and renal function should be monitored. May cause drowsiness or dizziness. |
| Food/Dietary | Avoid high-purine foods (e.g., organ meats, anchovies, sardines, mussels, scallops, red meat, beer) as they may increase serum uric acid levels and reduce drug efficacy. Maintain adequate hydration to prevent urate nephropathy. Grapefruit juice has no known interaction. No significant interaction with caffeine. |
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| Monitor serum uric acid levels periodically. Assess renal function (serum creatinine, BUN) at baseline and during therapy. Clinical monitoring for hypersensitivity reactions (e.g., rash, eosinophilia). |
| Fertility Effects | No adverse effects on fertility reported in animal studies. Human data limited but no evidence of impaired fertility. |
| Clinical Pearls | Initiate therapy after acute gout flare has subsided; consider gradual dose titration to reduce flare risk; monitor for hypersensitivity reactions, especially in patients with renal impairment; use with caution in patients on thiazide diuretics or ACE inhibitors due to increased risk of hypersensitivity; assess renal function before starting and during therapy; adjust dose in renal impairment (CrCl <60 mL/min); avoid use with azathioprine or mercaptopurine unless dose reduction of these agents is implemented; educate patient to report rash, fever, or lymphadenopathy immediately. |
| Patient Advice | Take this medication exactly as prescribed, usually once daily. · Do not start or stop taking this medication during an acute gout attack; wait until the flare has resolved. · Drink plenty of fluids (at least 2 liters of water per day) unless otherwise directed by your doctor. · Avoid alcohol and foods high in purines (e.g., red meat, organ meats, shellfish) as they may increase uric acid levels. · Report any skin rash, itching, swelling, or difficulty breathing to your doctor immediately. · Inform your doctor of all medications you are taking, including over-the-counter drugs and supplements. · Do not take this medication with azathioprine, mercaptopurine, or theophylline unless specifically instructed by your doctor. · Store at room temperature away from moisture and heat. |