AdultPediatricDosage Forms & Strengths tablet 40mg 80mg Chronic Gout Indicated for chronic management of hyperuricemia in patients who: Responded inadequately to optimal allopurinol therapy Are intolerant to allopurinol Treatment with allopurinol not advisable Initial dose: 40 mg PO qDay May increase to 80 mg PO qDay after 2 wk if serum uric acid <6 mg/dL is not achieved Dosage Modifications Renal impairment Mild to moderate (CrCl 30-89 mL/min): No dosage adjustment necessary Severe (CrCl <30 mL/min): Not to exceed 40 mg/day 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 Prophylaxis for gout flares during treatment Upon initiation, recommend for flare prophylaxis with a nonsteroidal anti-inflammatory drug (NSAID) or colchicine Prophylactic therapy may be beneficial for up to 6 months If a gout flare occurs, managed gout flare concurrently; treatment does not need to be discontinued Dosing Considerations Limitation of use: Not recommended for the treatment of asymptomatic hyperuricemia Perform serum uric acid level as early as 2 weeks after initiating therapySafety and efficacy not establishedInteraction CheckerEnter a drug name and febuxostatNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (4)azathioprinefebuxostat increases levels of azathioprine by decreasing metabolism. Contraindicated.didanosinefebuxostat will increase the level or effect of didanosine by decreasing metabolism. Contraindicated.mercaptopurinefebuxostat increases levels of mercaptopurine by decreasing metabolism. Contraindicated. Potential for increased myelosuppression.theophyllinefebuxostat increases levels of theophylline by decreasing metabolism. Contraindicated.Serious - Use Alternative (0)Monitor Closely (3)apalutamideapalutamide will decrease the level or effect of febuxostat by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.dichlorphenamidedichlorphenamide and febuxostat both decrease serum potassium. Use Caution/Monitor.ethambutolethambutol decreases effects of febuxostat by Other (see comment). Use Caution/Monitor. Comment: Hyperuricemia reported with ethambutol and precipitation of gout reported; uric acid lowering agents may be require dosage adjustment.Minor (0)apalutamideMonitor Closely (1)apalutamide will decrease the level or effect of febuxostat by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.azathioprineContraindicated (1)febuxostat increases levels of azathioprine by decreasing metabolism. Contraindicated.dichlorphenamideMonitor Closely (1)dichlorphenamide and febuxostat both decrease serum potassium. Use Caution/Monitor.didanosineContraindicated (1)febuxostat will increase the level or effect of didanosine by decreasing metabolism. Contraindicated.ethambutolMonitor Closely (1)ethambutol decreases effects of febuxostat by Other (see comment). Use Caution/Monitor. Comment: Hyperuricemia reported with ethambutol and precipitation of gout reported; uric acid lowering agents may be require dosage adjustment.mercaptopurineContraindicated (1)febuxostat increases levels of mercaptopurine by decreasing metabolism. Contraindicated. Potential for increased myelosuppression.theophyllineContraindicated (1)febuxostat increases levels of theophylline by decreasing metabolism. Contraindicated. 1-10% Liver function abnormalities (4.6-6.6%) Rash (0.5-1.6%) Nausea (1.1-1.3%) Arthralgia (0.7-1.1%) >1% Blood and lymphatic system disorders: Anemia, idiopathic thrombocytopenic purpura, leukocytosis/leukopenia, neutropenia, pancytopenia, splenomegaly, thrombocytopenia Cardiac disorders: Angina pectoris, atrial fibrillation/flutter, cardiac murmur, ECG abnormal, palpitations, sinus bradycardia, tachycardia Ear and labyrinth disorders: Deafness, tinnitus, vertigo Eye disorders: Vision blurred Gastrointestinal disorders: Abdominal distention, abdominal pain, constipation, dry mouth, dyspepsia, flatulence, frequent stools, gastritis, gastroesophageal reflux disease, gastrointestinal discomfort, gingival pain, hematemesis, hyperchlorhydria, hematochezia, mouth ulceration, pancreatitis, peptic ulcer, vomiting General disorders and administration site conditions: Asthenia, chest pain/discomfort, edema, fatigue, feeling abnormal, gait disturbance, influenza-like symptoms, mass, pain, thirst Hepatobiliary disorders: Cholelithiasis/cholecystitis, hepatic steatosis, hepatitis, hepatomegaly Immune system disorder: Hypersensitivity Infections and infestations: Herpes zoster Procedural complications: Contusion Metabolism and nutrition disorders: Anorexia, appetite decreased/increased, dehydration, diabetes mellitus, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypokalemia, weight decreased/increased Musculoskeletal and connective tissue disorders: Arthritis, joint stiffness, joint swelling, muscle spasms/twitching/tightness/weakness, musculoskeletal pain/stiffness, myalgia Nervous system disorders: Altered taste, balance disorder, cerebrovascular accident, Guillain-Barré syndrome, headache, hemiparesis, hypoesthesia, hyposmia, lacunar infarction, lethargy, mental impairment, migraine, paresthesia, somnolence, transient ischemic attack, tremor Psychiatric disorders: Agitation, anxiety, depression, insomnia, irritability, libido decreased, nervousness, panic attack, personality change Renal and urinary disorders: Hematuria, nephrolithiasis, pollakiuria, proteinuria, renal failure, renal insufficiency, urgency, incontinence Reproductive system and breast changes: Breast pain, erectile dysfunction, gynecomastia Respiratory, thoracic and mediastinal disorders: Bronchitis, cough, dyspnea, epistaxis, nasal dryness, paranasal sinus hypersecretion, pharyngeal edema, respiratory tract congestion, sneezing, throat irritation, upper respiratory tract infection Skin and subcutaneous tissue disorders: Alopecia, angio edema, dermatitis, dermographism, ecchymosis, eczema, hair color changes, hair growth abnormal, hyperhidrosis, peeling skin, petechiae, photosensitivity, pruritus, purpura, skin discoloration/altered pigmentation, skin lesion, skin odor abnormal, urticaria Vascular disorders: Flushing, hot flush, hypertension, hypotension Laboratory parameters: Activated partial thromboplastin time prolonged, creatine increased, bicarbonate decreased, sodium increased, EEG abnormal, glucose increased, cholesterol increased, triglycerides increased, amylase increased, potassium increased, TSH increased, platelet count decreased, hematocrit decreased, hemoglobin decreased, MCV increased, RBC decreased, creatinine increased, blood urea increased, BUN/creatinine ratio increased, creatine phosphokinase increased, alkaline phosphatase increased, LDH increased, PSA increased, urine output increased/decreased, lymphocyte count decreased, neutrophil count decreased, WBC increased/decreased, coagulation test abnormal, low density lipoprotein increased, prothrombin time prolonged, urinary casts, urine positive for white blood cells and protein 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, drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN) Blood and lymphatic system disorders: Agranulocytosis, eosinophilia Black Box Warnings Cardiovascular death Patients with established cardiovascular (CV) disease treated with febuxostat had a higher rate of CV death compared with those treated with allopurinol in a CV outcomes study Evaluate risks and benefits when prescribing febuxostat or continuing treatment Contraindications Coadministration with azathioprine or mercaptopurine Cautions After initiation, an increase in gout flares is frequently observed; increase is due to reduction in serum uric acid levels, resulting in mobilization of urate from tissue deposits Not tested for secondary hyperuricemia; not recommended in patients whose rate of urate formation is greatly increased (eg, malignant disease and its treatment, Lesch-Nyhan syndrome) Postmarketing reports of serious skin and hypersensitivity reactions reported; discontinue if serious skin reactions are suspected; caution in patients who reported previous similar skin reactions to allopurinol Serious skin and hypersensitivity reactions, including Stevens-Johnson Syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN) reported; discontinue therapy if serious skin reactions suspected; many patients reported previous similar skin reactions to allopurinol; administer therapy with close monitoring in these patients Cardiovascular death A cardiovascular (CV) outcome study (ClinicalTrials.gov identifier NCT01101035) in patients with a history of major CV disease, cerebrovascular disease, or diabetes mellitus with micro- and/or macrovascular disease showed that febuxostat had a significantly higher incidence of CV deaths compared with allopurinol Most common cause of adjudicated CV deaths in the febuxostat group was sudden cardiac death compared with the allopurinol group; similar results to allopurinol were observed for nonfatal MI, nonfatal stroke, and unstable angina with urgent coronary revascularization (see Black Box Warnings) Because of increased risk of CV death, drug should only be used in patients who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable Consider risks and benefits of therapy when deciding to prescribe or continue patients on therapy; consider use of prophylactic low-dose aspirin therapy in patients with history of CV disease; monitor patients for development of CV events; inform patients about symptoms of serious CV events and steps to take if they occur Hepatic effects Postmarketing reports of fatal and nonfatal hepatic failure; may increase liver enzyme activity Measure liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice; in this clinical context, if patient presents abnormal liver tests (ALT or AST greater than three times the upper limit of the reference range), interrupt treatment while investigating probable cause Permanently discontinue therapy if liver injury is confirmed, and no alternate etiology can be found Permanently discontinue therapy in patients who have serum ALT or AST >3x ULN the reference range with serum total bilirubin >2x ULN the reference range without alternative etiologies because they are at risk for severe drug-induced liver injury; for patients with lesser elevations of serum ALT or bilirubin and with an alternate probable cause, treatment can be used with close monitoring Drug interaction overview Xanthine oxidase substrates Febuxostat inhibits xanthine oxidase (XO) Based on a drug interaction study in healthy patients, febuxostat altered the metabolism of theophylline in humans; caution if coadministered Other drugs that are metabolized by XO (eg, mercaptopurine and azathioprine) have not been conducted; XO inhibition may increase plasma concentrations of these drugs leading to toxicity (see Contraindications) Pregnancy Limited available data in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes Animal data No adverse developmental effects observed in embryo-fetal development studies with oral administration of febuxostat to pregnant rats and rabbits during organogenesis at doses that produced maternal exposures up to 40 and 51 times, respectively, the exposure at the maximum recommended human dose (MRHD) No adverse developmental effects observed in a pre- and postnatal development study with administration of febuxostat to pregnant rats from organogenesis through lactation at an exposure ~11 times the MRHD Lactation There are no data on presence of febuxostat in human milk, effects on breastfed infant, or on milk production; drug is present in rat milk Consider the developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal conditionPregnancy 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. 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 Absorption: 49% Peak plasma concentration: ~1.6 mcg/mL (40-mg dose); 2.6 mcg/mL (80-mg dose) Peak plasma time: 1-1.5 hr Following multiple 80 mg qDay doses with a high fat meal, peak plasma concentration decreased by 49% and AUC decreased by 18% 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; 25% their conjugates; 7% other unknown metabolites), urine (49%; 3% unchanged) Oral Administration Take without regard to food or antacid use Storage Protect from light Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) BRAND FORM. UNIT PRICE PILL IMAGE Uloric oral- 40 mg tabletUloric oral- 80 mg tabletfebuxostat oral- 40 mg tabletfebuxostat oral- 40 mg tabletfebuxostat oral- 40 mg tabletfebuxostat oral- 80 mg tabletfebuxostat oral- 80 mg tabletfebuxostat oral- 80 mg tabletfebuxostat oral- 40 mg tabletfebuxostat oral- 40 mg tabletfebuxostat oral- 80 mg tabletfebuxostat oral- 40 mg tabletfebuxostat oral- 80 mg tabletfebuxostat oral- 80 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationfebuxostat oral FEBUXOSTAT - ORAL (feb-UX-oh-stat) COMMON BRAND NAME(S): Uloric WARNING: Febuxostat may rarely cause very serious side effects including heart attack, stroke, or possibly fatal heart-related problems. Before taking this medication, tell your doctor if you have heart disease, chest pain (angina), or have had a heart attack or stroke in the past since these conditions may increase your risk. Discuss the risks and benefits of this medication and treatment options with your doctor. Get medical help right away if you have any of these very serious side effects: chest/jaw/left arm pain, unusual sweating, shortness of breath, fast/irregular heartbeat, dizziness, fainting, weakness on one side of the body, sudden vision changes, confusion, trouble speaking, sudden severe headache. USES: Febuxostat is used to lower uric acid levels in people with gout. Febuxostat works by reducing the amount of uric acid made by the body. An increased uric acid level can cause gout.Because of the risk of very serious heart-related problems and stroke with febuxostat (see also Warning