Dosing and uses of Uloric (febuxostat)
Adult dosage forms and strengths
tablet
- 40mg
- 80mg
Chronic Gout
40 mg/day PO initially; maintenance: 40-80 mg/day; increased if serum uric acid is >6 mg/mL after 2 weeks
Dosing Modifications
Renal impairment
- Mild to moderate (CrCl 30-89 mL/min): Dosage adjustment not necessary
- Severe (CrCl <30 mL/min): Data not available; use with caution
Hepatic impairment
- Mild to moderate (Child-Pugh class A or B): Dosage adjustment not necessary
- Severe (Child-Pugh class C): Data not available; use with caution
Pediatric dosage forms and strengths
Safety and efficacy not established
Uloric (febuxostat) adverse (side) effects
>1%
Arthralgia
Elevated liver function test (LFT) results
Liver function abnormalities
Nausea
Rash
Postmarketing Reports
Immunologic: Anaphylaxis, anaphylactic reaction
Musculoskeletal: Rhabdomyolysis
Hepatobiliary: Hepatic failure (some fatal), jaundice, serious cases of abnormal LFT results, liver disorders
Psychiatric: Psychotic behavior, including aggressive thoughts
Renal and urinary: Tubulointerstitial nephritis
Dermatologic: Generalized rash, Stevens-Johnson syndrome, hypersensitivity skin reactions
Warnings
Contraindications
Coadministration with azathioprine, mercaptopurine, or theophylline
Cautions
After initiation, gout flare frequently occurs; provide prophylaxis with nonsteroidal anti-inflammatory drug (NSAID) or colchicine upon initiation and for ≤6 months
Not indicated for asymptomatic hyperuricemia
Not tested for secondary hyperuricemia
Higher incidence of cardiovascular thromboembolic events than with allopurinol in clinical trials; monitor for symptoms of myocardial infarction and stroke
May increase liver enzyme activity; obtain LFTs at baseline, and do not initiate if alanine aminotransferase is 3 times upper limit of normal with total bilirubin >2 times upper limit of normaL
Postmarketing reports of fatal and nonfatal hepatic failure
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown whether drug is excreted into breast milk; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Uloric (febuxostat)
Mechanism of action
Xanthine oxidase inhibitor; inhibits conversion of hypoxanthine to xanthine to uric acid; at therapeutic dosages, decreases production of uric acid without disrupting synthesis of vital purines and pyrimidines
Absorption
Bioavailability: 49%
Peak plasma time: 1-1.5 hr
Distribution
Protein bound: 99.2%
Vd: 50 L
Metabolism
Metabolized by UGT1A1, UGT1A3, UGT1A9, and UGT2B7; oxidized by CYP1A2, CYP2C8, and CYP2C9; also metabolized by non-CYP450 enzymes
Elimination
Half-life: 5-8 hr
Excretion: Feces (45%; 12% unchanged), urine (49%; 3% unchanged)
