Febuxostat

# Febuxostat ## Overview - **Classification**: Xanthine Oxidase Inhibitor (XOI) - **Mechanism**: Selectively inhibits xanthine oxidase, an enzyme essential for uric acid synthesis, thereby reducing serum uric acid levels. ## Primary Indications 1. **Chronic Management of Hyperuricemia in Patients with Gout**: Indicated for lowering serum uric acid (SUA) levels. 2. **Tumor Lysis Syndrome Prophylaxis**: Unlabeled use, typically when allopurinol is contraindicated or not tolerated. ## Adult Dosing ### Standard Dosing **Chronic Management of Hyperuricemia in Patients with Gout** - **Dose**: Initially **40 mg** - **Frequency**: Once daily - **Route**: Oral - **Duration**: Ongoing, target SUA < 6 mg/dL. * If SUA > 6 mg/dL after 2 weeks, increase to **80 mg** once daily. - **Maximum Dose**: **80 mg** once daily ### Dose Adjustments - **Renal Impairment**: - CrCl 30-89 mL/min: No dose adjustment needed. - CrCl < 30 mL/min: Limited data, use with caution. - **Hepatic Impairment**: - Mild to moderate (Child-Pugh Class A or B): No dose adjustment. - Severe (Child-Pugh Class C): Limited data, not recommended. - **Elderly Patients**: No specific dose adjustment required based on age alone. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Not recommended. - **Frequency**: Not applicable. - **Maximum**: Not applicable. - **Special Notes**: Safety and efficacy not established in pediatric patients. ### Infants (1-12 months) - **Dose**: Not recommended. - **Frequency**: Not applicable. - **Maximum**: Not applicable. - **Special Notes**: Safety and efficacy not established in pediatric patients. ### Children (1-12 years) - **Dose**: Not recommended. - **Frequency**: Not applicable. - **Maximum**: Not applicable. - **Special Notes**: Safety and efficacy not established in pediatric patients. ### Adolescents (13-18 years) - **Dose**: Not recommended. - **Maximum**: Not applicable. - **Special Notes**: Safety and efficacy not established in pediatric patients. ## Safety Information ### Contraindications - **Absolute**: Concomitant use with azathioprine or mercaptopurine (risk of severe toxicity). - **Absolute**: History of serious hypersensitivity to febuxostat. ### Common Adverse Effects - **Common (1-10%)**: Liver function abnormalities (elevated transaminases), nausea, arthralgia, rash. - **Serious but Rare**: Cardiovascular events (CV death, non-fatal MI, non-fatal stroke) - Boxed Warning due to higher rate compared to allopurinol in some studies. ### Key Drug Interactions - **Azathioprine/Mercaptopurine**: Febuxostat inhibits xanthine oxidase, significantly increasing plasma levels of these drugs. **Concomitant use is contraindicated.** - **Theophylline**: Febuxostat may increase theophylline levels. Monitor theophylline levels and adjust dose as needed. - **Pegloticase**: Concomitant use not recommended. ## Monitoring & Follow-up - **Before Treatment**: Baseline liver function tests (LFTs), serum uric acid (SUA), renal function (CrCl). - **During Treatment**: - **SUA**: Monitor every 2 weeks until target (< 6 mg/dL) is reached, then periodically. - **LFTs**: Periodically (e.g., at 2 and 4 months, then annually). Discontinue if AST/ALT > 3x ULN. - **Clinical Signs**: Monitor for gout flares, cardiovascular symptoms (e.g., chest pain, shortness of breath, numbness), and hypersensitivity reactions. ## Clinical Pearls - 💡 **Initial Gout Flare**: Febuxostat may precipitate acute gout flares during initiation. Prophylaxis with NSAIDs or colchicine is often recommended for 3-6 months. - 💡 **Goal SUA**: The target serum uric acid level for chronic gout management is typically **< 6 mg/dL**. - 💡 **Cardiovascular Risk**: Counsel patients on the potential increased risk of cardiovascular events, especially if they have pre-existing CV disease. Report new or worsening CV symptoms immediately. - 💡 **Administration**: Can be taken with or without food. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.