ULORIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ULORIC (ULORIC).
ULORIC (febuxostat) is a xanthine oxidase inhibitor that reduces serum uric acid levels by inhibiting the enzyme xanthine oxidase, which catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid.
| Metabolism | Primarily metabolized by UGT1A1, UGT1A3, UGT1A9, and CYP2C8; minor metabolism by CYP1A2, CYP2C9, and CYP2D6. Approximately 22% excreted unchanged in urine. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 40-45% of the dose. Biliary/fecal excretion eliminates about 50-55% of the dose, primarily as oxidative metabolites. |
| Half-life | Terminal elimination half-life is approximately 5-8 hours. This short half-life supports once-daily dosing for maintenance of therapeutic urate-lowering effect. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is about 50 L (approximately 0.7 L/kg). This suggests distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability is approximately 85% (range 60-100%). Tablets are well absorbed, with food having no significant effect on overall absorption. |
| Onset of Action | Oral: Serum uric acid reduction begins within 2-4 hours after a single dose. Maximal effect on serum urate is seen by 2 weeks of daily dosing. |
| Duration of Action | After a single oral dose, urate-lowering effect persists for 24-36 hours. With once-daily dosing, steady-state is achieved in 7-14 days, providing continuous urate lowering throughout the dosing interval. |
| Molecular Weight | 316.37 |
| Action Class | Xanthine oxidase Inhibitors-gout |
| Brand Substitutes | Piloric 100mg Tablet, Ryloric 100mg Tablet, Zyrik 100 Tablet, Zyle 100 Tablet, Zyloric Tablet |
40 mg orally once daily; may increase to 80 mg once daily if serum uric acid not at target after 2 weeks.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR 30-89 mL/min). Not recommended for use in patients with severe renal impairment (GFR <30 mL/min) or end-stage renal disease on dialysis due to lack of efficacy data. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh Class A or B). Not recommended in severe hepatic impairment (Child-Pugh Class C) due to lack of data. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no FDA-approved dosing. |
| Geriatric use | No specific dose adjustment required; clinical studies included patients aged 65 and older with no overall differences in safety or efficacy observed. |
| 1st trimester | Insufficient human data; animal studies show no teratogenicity at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | Insufficient human data; avoid use unless benefit outweighs risk. |
| 3rd trimester | Insufficient human data; avoid use due to potential risk of gout flares and lack of safety data. |
Clinical note
Comprehensive clinical and safety monograph for ULORIC (ULORIC).
| Placental transfer | Expected to cross placenta due to molecular weight <500 Da; no specific human studies. |
| Breastfeeding | Unknown excretion into human milk; due to potential risk of adverse effects in infant, consider discontinuing breastfeeding or drug, taking into account importance of drug to mother. |
| Lactation Rating |
■ FDA Black Box Warning
Increased risk of cardiovascular death compared to allopurinol in patients with gout and cardiovascular disease. Febuxostat should be used only in patients who have not responded adequately to allopurinol or have contraindications to allopurinol.
| Serious Effects |
Concomitant use with azathioprineConcomitant use with mercaptopurineConcomitant use with theophylline
| Precautions | Cardiovascular events: Increased risk of cardiovascular death, especially in patients with pre-existing cardiovascular disease., Gout flare: May increase frequency of gout flares during initiation; prophylaxis with NSAIDs or colchicine recommended., Liver enzyme elevations: Monitor liver function tests; discontinue if persistent elevation or signs of liver injury., Thyroid disorders: Can increase TSH levels; monitor thyroid function., Renal impairment: Dose adjustment not required; limited data in severe renal impairment., Drug interactions: Use with caution with azathioprine, mercaptopurine, or theophylline; increase risk of toxicity. |
| Food/Dietary | No specific food interactions; however, high-purine foods (e.g., organ meats, anchovies, sardines, scallops, game meats, beer) may counteract efficacy by raising uric acid. Grapefruit juice has no known interaction with febuxostat. Avoid excessive alcohol, especially beer and spirits, as they increase urate levels. |
Loading safety data…
| L3 (Moderately Safe) or 'Avoid' |
| Teratogenic Risk | Pregnancy Category C: In animal studies, febuxostat caused fetal toxicity (reduced fetal weights, increased incidence of fetal malformations) at doses equivalent to 2-4 times the human exposure. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if potential benefit justifies potential risk to fetus. First trimester: limited data; second and third trimesters: theoretical risk of uric acid reduction impacting fetal growth due to role of uric acid in fetal development. |
| Fetal Monitoring | Monitor serum uric acid levels periodically. Assess renal function (serum creatinine, BUN) and liver function tests (AST, ALT) at baseline and periodically during therapy. Monitor for signs of hypersensitivity reactions, cardiovascular events, and gout flares. In pregnant patients, consider fetal ultrasound if exposure occurs. |
| Fertility Effects | Animal studies: no impairment of fertility observed in male and female rats at exposures up to 5 times human exposure. No human data available regarding effects on fertility. |
| Clinical Pearls | ULORIC (febuxostat) is a non-purine xanthine oxidase inhibitor indicated for chronic management of hyperuricemia in gout. Avoid use in patients with ischemic heart disease or heart failure due to increased cardiovascular events in the CARES trial. Do not use in asymptomatic hyperuricemia. Titrate from 40 mg to 80 mg if serum urate target not reached. SCr monitoring is not required, but caution with severe renal impairment (CrCl <30 mL/min) – no data. Avoid concomitant with azathioprine, 6-mercaptopurine, or theophylline due to XO inhibition. Coadministration with NSAIDs or colchicine is safe for flare prophylaxis. Check liver enzymes periodically as ALT elevations >3x ULN occurred in 2%. |
| Patient Advice | Take ULORIC once daily with or without food. Do not crush or chew tablets. · You may experience a gout flare when starting ULORIC; you will be prescribed medication (e.g., colchicine, NSAID) to prevent flares for at least 6 months. · Seek immediate medical attention if you develop chest pain, shortness of breath, rapid heartbeat, or sudden numbness/weakness – these may indicate a cardiovascular event. · Avoid drinking large amounts of alcohol or consuming high-purine foods (e.g., red meat, shellfish) as they can increase uric acid levels. · Tell your doctor if you have a history of heart disease, heart failure, stroke, or liver problems. · Report persistent nausea, right upper abdominal pain, dark urine, or yellowing of eyes/skin – signs of liver injury. |