FEBUXOSTAT TAB
Clinical Criteria Summary
Exclusion Criteria
- Hypersensitivity or history of intolerance to febuxostat (or inactive tablet ingredients)
- Asymptomatic hyperuricemia
- Concomitant administration of drugs that are metabolized by xanthine oxidase (e.g., theophylline, mercaptopurine, azathioprine)
Inclusion Criteria
- Patient is a candidate for chronic treatment of gout (hyperuricemic with recurrent gouty attacks ≥ 2 acute attacks/year or other manifestations of chronic gout including tophaceous disease, erosive gouty arthritis, or uric acid urolithiasis)
- Documentation of lack of adequate response, contraindication, or inability to tolerate appropriately dose-maximized trials of allopurinol and/or probenecid
- For patients with known cardiovascular disease: encourage use of low-dose aspirin (if no contraindications exist) and discontinue NSAIDs if possible or use at the lowest dose for the shortest possible duration
Dosage and Administration
- Initial recommended starting dose: 40 mg daily
- Dose of 80 mg daily recommended if serum urate < 6 mg/dL is not achieved after 2 weeks of treatment at the lower dose
- Doses >80 mg daily are not approved for use in the United States
- Severe renal impairment (CrCl 10-29 mL/min): dose should be limited to 40 mg daily
- Mild to moderate hepatic impairment (Child-Pugh Class A or B): no dose adjustment needed; caution advised for severe hepatic disease due to lacking evidence
- May be administered without regard to food or antacid use
- Prophylaxis against acute gout flare (with colchicine or NSAIDs) is recommended during the first 6 months of urate lowering therapy
Monitoring
- Baseline liver function testing upon initiation and periodically thereafter in patients with symptoms suggestive of liver toxicity (fatigue, anorexia, right upper abdominal discomfort, darkened urine, or jaundice)
- If liver injury is confirmed: withhold febuxostat and investigate cause; do not restart if no other etiology is found
- Serum uric acid target of < 6 mg/dL for effective gout management; a target of < 5 mg/dL may be recommended for selected patients with more severe disease until urate crystals and symptoms resolve
- Monitor for signs and symptoms of myocardial infarction and stroke due to observed higher rate of cardiovascular thromboembolic events in clinical development
- Discontinue febuxostat if serious skin reactions are suspected (e.g., Stevens-Johnson syndrome, DRESS, toxic epidermal necrolysis)
Renewal Criteria
- Patient is tolerating febuxostat and adherent to therapy
- Patient has achieved a clinically significant reduction in serum urate within 6 months of initiation (reached serum urate < 6 mg/dL to reduce frequency of acute gout flares and/or favorably alter other manifestations of chronic gout)
Issues for Consideration & Provider Recommendations
- CARES trial demonstrated higher rates of cardiovascular death and all-cause mortality with febuxostat compared to allopurinol, with heterogeneity observed regarding NSAID use or lack of daily low-dose aspirin
- Engage in shared decision-making with the patient regarding CARES trial findings to determine the best course of therapy
- Options include: reevaluating treatment to replace febuxostat with allopurinol (with appropriate dose titration) OR continuing febuxostat while emphasizing low-dose aspirin use in patients with known/high-risk cardiovascular disease, discontinuing NSAIDs if possible, and considering a Rheumatology referral to assess ongoing necessity
- Caution is advised for patients without known cardiovascular disease due to unknown risk profile compared to allopurinol