Allopurinol

# Allopurinol ## Overview - **Classification**: Xanthine Oxidase Inhibitor (XOI) - **Mechanism**: Blocks xanthine oxidase, an enzyme required for uric acid production, thereby lowering serum uric acid levels. ## Primary Indications 1. **Chronic Gout** - Management of hyperuricemia to prevent gout flares and tophi formation. 2. **Tumor Lysis Syndrome (TLS) Prophylaxis** - Prevention of hyperuricemia and urate nephropathy associated with chemotherapy. 3. **Recurrent Calcium Oxalate Kidney Stones** - In patients with hyperuricosuria. ## Adult Dosing ### Standard Dosing **Chronic Gout / Hyperuricemia** - **Dose**: Start **50-100 mg** - **Frequency**: Once daily (QD) - **Route**: Oral - **Titration**: Increase by **50-100 mg** every **2-5 weeks** until target serum uric acid (<6 mg/dL) is achieved. - **Maximum Dose**: **800 mg/day** **Tumor Lysis Syndrome Prophylaxis** - **Dose**: **600-800 mg** - **Frequency**: Divided doses (e.g., TID or QID) - **Route**: Oral or IV - **Duration**: Start **1-3 days prior** to chemotherapy. - **Maximum Dose**: **800 mg/day** ### Dose Adjustments - **Renal Impairment**: Dose reduction required. - CrCl 30-60 mL/min: Max **200 mg/day** - CrCl 10-30 mL/min: Max **100 mg/day** - CrCl <10 mL/min: Max **50 mg/day** or **100 mg every few days** - Hemodialysis: Administer after dialysis. - **Hepatic Impairment**: Use with caution. Consider lower starting doses and monitor LFTs. - **Elderly Patients**: Start with lower doses (e.g., **50 mg QD**) due to potential reduced renal function. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: **10 mg/kg/day** - **Frequency**: Divided every **8 hours (TID)** - **Maximum**: **400 mg/day** - **Special Notes**: Use for severe hyperuricemia only, e.g., in tumor lysis syndrome. Close monitoring of renal function essential. ### Infants (1-12 months) - **Dose**: **10-20 mg/kg/day** - **Frequency**: Divided every **8 hours (TID)** - **Maximum**: **400 mg/day** ### Children (1-12 years) - **Tumor Lysis Syndrome Prophylaxis**: - **Dose**: **10-20 mg/kg/day** - **Frequency**: Divided every **8-12 hours (TID-BID)** - **Maximum**: **800 mg/day** (usually **400-600 mg/day** for high-risk TLS) - **Chronic Gout/Hyperuricemia**: - **Dose**: **10 mg/kg/day** - **Frequency**: Divided every **8-12 hours (TID-BID)** - **Maximum**: **400 mg/day** ### Adolescents (13-18 years) - **Dose**: Generally follow adult dosing. - **Chronic Gout**: Start **100 mg QD**, titrate to **300 mg QD**. - **TLS Prophylaxis**: **600-800 mg/day** divided doses. - **Maximum**: **800 mg/day** ## Safety Information ### Contraindications - **Absolute**: Previous severe hypersensitivity reaction (e.g., SJS, TEN, DRESS) to allopurinol. - **Relative**: Asymptomatic hyperuricemia (unless high risk of complications), acute gout attack (do not initiate during attack). ### Common Adverse Effects - **Very Common (>10%)**: Skin rash (often mild), nausea, diarrhea. - **Common (1-10%)**: Vomiting, abdominal pain, increased LFTs. - **Serious but Rare**: - **Severe Cutaneous Adverse Reactions (SCARs)**: Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Higher risk in HLA-B\*5801 positive patients. - Bone marrow suppression (leukopenia, thrombocytopenia). - Hepatotoxicity, renal failure. ### Key Drug Interactions - **Azathioprine/Mercaptopurine**: Allopurinol inhibits metabolism. **Reduce azathioprine/mercaptopurine dose by 75%** to prevent severe myelosuppression. - **Warfarin**: May increase anticoagulant effect. Monitor INR closely. - **Ampicillin/Amoxicillin**: Increased risk of skin rash. Avoid co-administration if possible. - **Thiazide Diuretics**: Increased risk of hypersensitivity reactions, especially with renal impairment. - **Cyclosporine**: May increase cyclosporine levels. Monitor cyclosporine levels. ## Monitoring & Follow-up - **Before Treatment**: - Baseline serum uric acid. - Renal function (BUN, Cr, eGFR/CrCl). - Liver function tests (ALT, AST). - Complete Blood Count (CBC). - Consider HLA-B\*5801 testing in high-risk populations (e.g., Han Chinese, Korean, Thai ancestry). - **During Treatment**: - Serum uric acid: Every **2-5 weeks** during titration, then every **6-12 months** once stable. - Renal and Liver function: Periodically, especially in first few months or with dose changes. - CBC: Periodically, especially in first few months. - **Clinical Signs**: - Monitor for new rash, fever, malaise (signs of SCARs). Instruct patients to stop drug immediately and seek medical attention. - Signs of gout flares (may occur initially). ## Clinical Pearls - 💡 **Start low, go slow**: Titrate dose gradually to minimize hypersensitivity reactions. - 💡 **Hydration**: Encourage adequate fluid intake to prevent kidney stone formation. - 💡 **Acute Gout**: Do NOT initiate allopurinol during an acute gout flare. Continue if already on treatment. - 💡 **Prophylaxis**: Consider prophylactic colchicine or NSAIDs for the first **3-6 months** to prevent allopurinol-induced gout flares. - 💡 **Administration**: Take with food or after meals to reduce GI upset. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.