ZYLOPRIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYLOPRIM (ZYLOPRIM).
Allopurinol is a xanthine oxidase inhibitor that reduces the production of uric acid by inhibiting the conversion of hypoxanthine to xanthine and xanthine to uric acid.
| Metabolism | Allopurinol is metabolized primarily by aldehyde oxidase to its active metabolite, oxypurinol; both are excreted renally. |
| Excretion | Renal: allopurinol ~10% unchanged, oxypurinol ~70% unchanged; total renal elimination ~76% (allopurinol + oxypurinol); fecal/biliary: minor (~12-20% as allopurinol, ~3-5% as oxypurinol). |
| Half-life | Allopurinol: 1-2 hours; oxypurinol: 18-30 hours (prolonged to 48-72 hours in renal impairment). Clinical context: oxypurinol half-life determines dosing interval; dose adjustment required for CrCl < 20 mL/min. |
| Protein binding | Allopurinol: <1% bound; oxypurinol: ~17-20% bound (primarily to albumin). |
| Volume of Distribution | Allopurinol: ~1.6 L/kg; oxypurinol: ~0.4-0.6 L/kg. Clinical meaning: allopurinol distributes widely into total body water, while oxypurinol has a smaller Vd consistent with limited tissue distribution. |
| Bioavailability | Oral: allopurinol 67-90% (mean ~80%); oxypurinol formed via first-pass metabolism has an effective systemic exposure. |
| Onset of Action | Oral: serum urate reduction begins within 24-48 hours; maximum effect at 1-2 weeks. |
| Duration of Action | Duration of urate-lowering effect: 24 hours (dose-dependent). Clinical note: sustained effect over time with chronic dosing due to oxypurinol accumulation; effect persists for 1-2 days after discontinuation. |
| Molecular Weight | 136.11 |
| Brand Substitutes | Moxikind-CV 625 Tablet, Moxiforce-CV 625 Tablet, Fightox 625 Tablet, Advent 625 Tablet, Keemox CV 500mg/125mg Tablet |
100-300 mg orally once daily, maximum 800 mg/day.
| Dosage form | TABLET |
| Renal impairment | CrCl >60 mL/min: no adjustment; CrCl 30-60 mL/min: 200 mg daily; CrCl 10-30 mL/min: 100 mg daily; CrCl <10 mL/min: 100 mg every 2-3 days or 50 mg daily. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment. |
| Pediatric use | 6-10 years: 150 mg/day; 11-16 years: 300 mg/day; <6 years: 50 mg/day; all given orally once daily. |
| Geriatric use | Start at lower dose (100 mg daily) due to reduced renal function; titrate to achieve serum urate target. |
| 1st trimester | Allopurinol is not recommended in first trimester unless essential; limited human data show possible association with congenital anomalies, but risk is low. Use only if benefit outweighs risk. |
| 2nd trimester | May be used if clearly needed; no evidence of specific fetal harm. Monitor for maternal hypersensitivity reactions. |
| 3rd trimester | May be used if clearly needed; no evidence of adverse fetal effects. Risk of neonatal hypersensitivity if mother develops rash. |
Clinical note
Comprehensive clinical and safety monograph for ZYLOPRIM (ZYLOPRIM).
| Placental transfer | Allopurinol and oxypurinol cross the placenta. Cord blood concentrations approximate maternal levels. Oxypurinol has a longer half-life in the fetus. |
| Breastfeeding | Allopurinol and its active metabolite oxypurinol are excreted into breast milk in low concentrations. Milk-to-plasma ratio approximately 0.9 for oxypurinol. No adverse effects reported in infants. Consider monitoring for rash or gastrointestinal disturbance in the infant. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to allopurinol or any component of the formulationConcurrent use with didanosine (increased risk of didanosine toxicity)
| Precautions | Allopurinol hypersensitivity syndrome (AHS) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN); increased risk in patients with HLA-B*5801 allele; renal impairment requires dose adjustment; use with caution in patients with liver dysfunction; may cause drowsiness or dizziness; discontinue at first sign of rash or other signs of hypersensitivity. |
| Food/Dietary | High-purine foods (e.g., organ meats, anchovies, sardines, mussels, beer) should be avoided as they increase uric acid levels. No significant food-drug interactions besides alcohol. |
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| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Allopurinol (Zyloprim) is a xanthine oxidase inhibitor. First trimester: Limited human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Second and third trimesters: No known increased risk; use only if clearly needed. Overall FDA pregnancy category C. |
| Fetal Monitoring | Monitor renal function, liver function, and complete blood count periodically in the mother. No specific fetal monitoring required; standard prenatal care. Observe for signs of maternal hypersensitivity reactions (e.g., rash, eosinophilia). |
| Fertility Effects | Allopurinol has not been associated with adverse effects on fertility in humans. Animal studies show no impairment of fertility at clinically relevant doses. |
| Clinical Pearls | Monitor serum uric acid levels monthly until goal is achieved; titrate every 2-4 weeks. Avoid use in acute gout flares; start after inflammation subsides. Check renal function and adjust dose accordingly (CrCl <30 mL/min: max 200 mg/day). Consider HLA-B*5801 screening in Han Chinese, Thai, or Korean patients to prevent severe hypersensitivity. Allopurinol hypersensitivity syndrome is rare but life-threatening; discontinue at first sign of rash. Concomitant azathioprine or 6-mercaptopurine requires dose reduction to 25-33% of original. |
| Patient Advice | Take exactly as prescribed; do not miss doses. · Drink at least 8 glasses of water daily to prevent kidney stones. · Report rash, itching, or swelling immediately; may indicate severe allergic reaction. · Avoid alcohol, especially beer and liquor, which can increase uric acid. · Use with caution if you have kidney disease; your dose may need adjustment. · Do not start or stop other medications like diuretics without consulting your doctor. · This drug prevents gout attacks, so continue even if you feel well. |