Introduction
Uloric (febuxostat) is a xanthine oxidase inhibitor indicated for the chronic management of hyperuricemia in patients with gout. It represents a significant advancement in gout management as the first new medication in this class in over 40 years, offering an alternative treatment option for patients who cannot tolerate or have inadequate response to allopurinol.
Mechanism of Action
Febuxostat selectively inhibits xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid. Unlike allopurinol, febuxostat is a non-purine analog inhibitor that binds tightly to the molybdenum-pterin center of xanthine oxidase, effectively reducing serum uric acid concentrations by decreasing the production of uric acid without affecting other enzymes in purine or pyrimidine metabolism.
Indications
Uloric is FDA-approved for:
- Chronic management of hyperuricemia in patients with gout
- Not recommended for asymptomatic hyperuricemia
Dosage and Administration
Initial dose: 40 mg orally once daily Dose adjustment: May increase to 80 mg once daily if serum uric acid is >6 mg/dL after 2 weeks Administration: Can be taken with or without food Special populations:- Renal impairment: No dose adjustment necessary
- Hepatic impairment: Use with caution in severe impairment
- Geriatric patients: No dose adjustment required
- Pediatric: Safety and efficacy not established
Pharmacokinetics
Absorption: Well absorbed orally (≥84%), median Tmax 1-1.5 hours Distribution: Volume of distribution ~50 L, protein binding ~99.2% Metabolism: Extensive hepatic metabolism via conjugation with glucuronic acid and oxidation via CYP isoenzymes Elimination: Half-life ~5-8 hours, primarily excreted in feces (49%) and urine (45%) Steady state: Achieved within 5 daysContraindications
- Concomitant use with azathioprine, mercaptopurine, or theophylline
- History of hypersensitivity reaction to febuxostat
Warnings and Precautions
Cardiovascular events: Increased risk of cardiovascular death and all-cause mortality observed in clinical trials Gout flare: Initial therapy may increase acute gout flares; concurrent prophylactic anti-inflammatory therapy recommended for first 6 months Hepatic effects: Transaminase elevations reported; monitor liver function tests periodically Renal effects: Monitor renal function in patients with pre-existing renal impairment Hypersensitivity reactions: Rare but serious reactions including Stevens-Johnson syndrome reportedDrug Interactions
Major interactions:- Azathioprine/mercaptopurine: Contraindicated due to increased toxicity risk
- Theophylline: Contraindicated due to increased theophylline concentrations
- NSAIDs: Potential additive effects on renal function
- Diuretics: May affect uric acid levels
- Warfarin: Minimal effect on INR; monitor coagulation parameters
Adverse Effects
Common (≥1%):- Liver function abnormalities (4-6%)
- Nausea (1.5%)
- Arthralgia (1.5%)
- Rash (1.5%)
- Cardiovascular events (including MI, stroke)
- Hepatotoxicity
- Severe skin reactions
- Thrombocytopenia
Monitoring Parameters
Baseline:- Serum uric acid levels
- Liver function tests (ALT, AST)
- Renal function (BUN, creatinine)
- Complete blood count
- Cardiovascular risk assessment
- Serum uric acid (every 2-5 weeks until target achieved, then periodically)
- Liver function tests (periodically)
- Monitor for signs of cardiovascular events
- Assess for gout flares
- Renal function in patients with pre-existing impairment
Patient Education
- Take medication as prescribed, with or without food
- Continue treatment even during gout flares unless directed otherwise
- Report any signs of liver problems (yellowing skin/eyes, dark urine, abdominal pain)
- Be aware of potential cardiovascular symptoms (chest pain, shortness of breath, sudden numbness/weakness)
- Understand that gout flares may initially increase when starting therapy
- Maintain adequate hydration
- Follow dietary recommendations for gout management
- Do not take with azathioprine, mercaptopurine, or theophylline
- Inform all healthcare providers about Uloric use
References
1. FDA Prescribing Information: Uloric (febuxostat) tablets 2. Becker MA, Schumacher HR, Espinoza LR, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther. 2010;12(2):R63. 3. White WB, Saag KG, Becker MA, et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. N Engl J Med. 2018;378(13):1200-1210. 4. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-1446. 5. Schumacher HR, Becker MA, Lloyd E, et al. Febuxostat in the treatment of gout: 5-yr findings of the FOCUS efficacy and safety study. Rheumatology (Oxford). 2009;48(2):188-194.
Note: This monograph is for educational purposes only. Healthcare providers should consult current prescribing information and clinical guidelines when making treatment decisions.