Obtain liver function tests before initiating febuxostat. Pharmacokinetic values in geriatric adults similar to those in younger adults. <>stream xl/workbook.xmlKO0#Um&J0BNY"4W8vdN'r9j(Csc@F'g-2r_'?o3hvEnlZROn"Z QQY|OanMm@=[E Inhibition of XO by febuxostat may cause increased plasma concentrations of mercaptopurine, 6-MP, leading to serious toxicity. If a gout flare occurs during febuxostat treatment, it should not be discontinued. Uses Warnings Before taking Side effects Dosage Interactions What is febuxostat? After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. By declining you will be logged out of your account, FEBUXOSTAT (Generic for ULORIC) Monographs, We occasionally send emails with money-saving tips to people who request them. Consider the use of prophylactic low-dose aspirin therapy in patients with a history of cardiovascular (CV) disease. Febuxostat should be used with caution in these patients.Because of the increased risk of cardiovascular mortality, febuxostat 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. Patients should always consult their physician with any questions regarding a medical condition and to obtain medical advice and treatment. Asux2{k,15&opaEv! The relative contribution of each enzyme isoform in metabolism is not clear.-Route-Specific PharmacokineticsOral RouteApproximately 49% of an orally administered dose is absorbed with peak febuxostat plasma concentrations occurring between 1 to 1.5 hours post-dose. Febuxostat is in a class of medications called xanthine oxidase inhibitors. This information is for use by healthcare professionals, Rivopharm UK Ltd, 100 Bishopsgate, London, EC2N 4AG. APEX study: During the 8-week prophylaxis period, a greater proportion of subjects in the febuxostat 120 mg (36%) treatment group required treatment for gout flare compared to febuxostat 80 mg (28%), allopurinol 300 mg (23%) and placebo (20%). Dissolution Methods Database | FDA endobj Febuxostat is more sensitive toward acidic conditions than oxidation and very resistant toward alkaline, thermal and photolytic degradations. FACT Study: The Febuxostat Allopurinol Controlled Trial (FACT) Study was a Phase 3, randomized, double-blind, multicenter, 52-week study. Stage 6 Harmonization Official December 1, 2011 905 Uniformity of Dosage Units1 905 UNIFORMITY OF DOSAGE The test for Content Uniformity is required for all dosage forms not meeting the above conditions for the Weight Variation test. Folate analogs: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. An approximately 400-fold increase in the amount of 1-methylxanthine (a major metabolite of theophylline) excreted in the urine was also noted. Each tablet contains febuxostat hemihydrate equivalent to 80 mg of febuxostat. XcYT`(a>2e6)CVzcKR D40oe_N7tKaa*b]XC? endobj `'uW After single or multiple oral 80 and 120 mg once daily doses, Cmax is approximately 2.8-3.2 g/mL, and 5.0-5.3 g/mL, respectively. Patients with secondary hyperuricemia (i.e. Rare serious hypersensitivity reactions to febuxostat, some of which were associated to systemic symptoms, have occurred in the post-marketing experience. ?YA33--Z- }Y|ebG Patients with an overdose should be managed by symptomatic and supportive care. Fatal and non-fatal hepatic failure as well as increases in transaminase concentrations above the upper limit of normal (ULN), specifically AST and ALT, have been observed. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Product Monograph Page 6 of 46 Hepatic Function: Hepatic function should be assessed before starting treatment and periodically thereafter. > xl/_rels/workbook.xml.rels ( J0n""Ej}Lm2ef2k&WP%&w For patients with lesser elevations of serum ALT or bilirubin and with an alternate probable cause, treatment can be used with caution.Patients with Renal Impairment DosingCrCl 30 to 89 mL/minute: No dosage adjustment needed.CrCl 15 to 29 mL/minute: Do not exceed 40 mg PO once daily.CrCl less than 15 mL/minute: Febuxostat has not been studied in end-stage renal impairment patients who are on dialysis. In placebo- and alternative drug-controlled study, rash (unspecified) was reported in 0.5% of patients taking 40 mg/day, 1.6% of patients taking 80 mg/day, 1.6% of patients taking allopurinol 100-300 mg/day, and 0.7% of those on placebo. The ability of febuxostat to lower serum uric acid levels was prompt and persistent. (See Hepatic Impairment under Cautions. After single or multiple oral 80 and 120 mg once daily doses, Cmax is approximately 2.83.2 g/mL, and 5.05.3 g/mL, respectively. <>>>/MediaBox[ 0 0 612 792]/Contents 103 0 R /Parent 2 0 R /Type/Page>> endobj Centre-Val de Loire: presentation and key figures - Ministre de la A numerical greater incidence of investigator-reported cardiovascular APTC events (defined endpoints from the Anti-Platelet Trialists' Collaboration (APTC) including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) was observed in the febuxostat total group compared to the allopurinol group in the APEX and FACT studies (1.3 vs. 0.3 events per 100 Patient Years (PYs)), but not in the CONFIRMS study (see section 5.1 for detailed characteristics of the studies). FOCUS Study (TMX-01-005) was a 5 years Phase 2, open-label, multicenter, safety extension study for patients who had completed the febuxostat 4 weeks of double blind dosing in study TMX-00-004. (See Cardiovascular Death under Cautions.). Use with caution in patients with history of dermatologic reactions to allopurinol. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. The method was validated as per the guidelines of the International Conference on Harmonization. Centre is bounded by the rgions of Normandy and le-de-France to the north, Bourgogne-Franche-Comt to the east, Auvergne-Rhne-Alpes to the southeast, Nouvelle-Aquitaine to the south, and Pays de la Loire to the west . <>/ProcSet[/PDF/Text/ImageB/ImageC/ImageI]/Font<>>>/MediaBox[ 0 0 612 792]/Contents 105 0 R /Parent 2 0 R /Type/Page>> %PDF-1.4 57 0 obj Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. Not recommended in patients whose rate of urate formation is greatly increased. By signing up I agree to WellRx's terms of use and privacy policy. <>>>/MediaBox[ 0 0 612 792]/Contents 74 0 R /Parent 2 0 R /Type/Page>> Less than 1% of patients who received febuxostat in doses ranging from 40-240 mg daily experienced arthritis; joint stiffness or swelling; muscle weakness, spasms, twitching, or tightness; musculoskeletal pain or stiffness; or myalgia. risk of anaphylaxis (febuxostat uricosuric effects may interfere w/ laboratory test) topotecan. <>>>/MediaBox[ 0 0 612 792]/Contents 100 0 R /Parent 2 0 R /Type/Page>> Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Absolute bioavailability of the febuxostat tablet formulation has not been studied. Increased systemic exposure in patients with severe renal impairment; dosage adjustment recommended. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. <>/ProcSet[/PDF/Text/ImageB/ImageC/ImageI]/Font<>>>/MediaBox[ 0 0 612 792]/Contents 111 0 R /Parent 2 0 R /Type/Page>> The mean total AUC of febuxostat increased by approximately 1.8-fold from 7.5 g.h/mL in the normal renal function group to 13.2 g.h/mL in the severe renal dysfunction group. Brand name: Uloric Febuxostat has minimal effects on other enzymes involved in purine and pyrimidine synthesis and metabolism. Increased TSH values (>5.5 IU/mL) were observed in patients on long-term treatment with febuxostat (5.5%) and patients with allopurinol (5.8%) in the long-term open label extension studies (see section 4.4). A solid oral composition comprising micronized febuxostat form-G and one or more pharmaceutically acceptable excipients. WARNING: CARDIOVASCULAR DEATH . Instruct patients to recognize the signs and symptoms of myocardial infarction and stroke, and to seek medical help immediately if they experience such symptoms. Fatal and nonfatal hepatic failure reported; causal relationship to drug cannot be excluded. In animals, reproduction studies up to 48 mg/kg/day showed no dose-dependent adverse effects on fertility (see section 5.3). w/Xyxp7.bNyYS=Sy^n0/'%v t$)1zmaPE:f;N@sa p}YQ`N i82n;GE:\ NH-&H % _!H3Ge]>=v;og=dJ[Td#:#S!"D> d2Rd+Nx8DPjAPGo~Xt. 240 mg febuxostat was used to evaluate the safety of febuxostat at twice the recommended highest dose. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. Febuxostat does not require a dosage adjustment in patients with mild to moderate renal impairment and appears less likely than allopurinol to cause serious hypersensitivity. Figure 1 Mean Serum Uric Acid Levels in Combined Pivotal Phase 3 Studies. endobj *By signing up I am agreeing to receive price drop alert emails. endobj 28 0 obj Serious dermatologic reactions (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms [DRESS]) and hypersensitivity reactions reported. 12.1 Mechanism of Action - Febuxostat, a xanthine oxidase inhibitor, achieves its therapeutic effect by decreasing serum uric acid. No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. <>>>/MediaBox[ 0 0 612 792]/Contents 82 0 R /Parent 2 0 R /Type/Page>> febuxostat + topotecan. In healthy subjects, maximum plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) of febuxostat increased in a dose proportional manner following single and multiple doses of 10 mg to 120 mg. For doses between 120 mg and 300 mg, a greater than dose proportional increase in AUC is observed for febuxostat. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Increased TSH values (>5.5 IU/mL) were observed in patients on long-term treatment with febuxostat (5.5%) in the long term open label extension studies. Absorption . PDF Reference ID: 4139515 - Food and Drug Administration Four pharmacologically active hydroxyl metabolites have been identified, of which three occur in plasma of humans. Acute gout attacks (gout flare) may occur after initiation of febuxostat. Mild to moderate hepatic impairment: Peak concentrations and AUC are increased by 2030%; not considered clinically important. FEBUXOSTAT TABLETS FENOFIBRIC ACID FENOFIBRIC ACID TABLETS FENTANYL BUCCAL TABLETS FENTANYL CITRATE INJECTION FENTANYL LOZENGES FENTANYL NASAL SPRAY Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. jF*@A/)%Ty8TytK- >aRIL K$Fa$,1R. However, weight-corrected Cmax and AUC were similar between the genders. 116 patients were enrolled and received initially febuxostat 80 mg QD. 1 interaction. Since the long-term safety of exposure to 1-methylxanthine in humans is unknown, use with caution when coadministering febuxostat with aminophylline. Febuxostat should not be used during pregnancy. Discontinue febuxostat if serious skin reactions are suspected. endobj endobj PDF 211533 Uloric Apm malignant disease and its treatment, Lesch-Nyhan syndrome) the absolute concentration of xanthine in urine could, in rare cases, rise sufficiently to allow deposition in the urinary tract. Febuxostat has minimal effects on other enzymes involved in purine and pyrimidine synthesis and metabolism. DISCOUNT ONLY - NOT INSURANCE. Treat the cause, if possible, to resolution or stabilization. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat was similar to allopurinol for nonfatal MI, nonfatal stroke, and unstable angina with urgent coronary revascularization. Like other chronic gout treatments, the drug is not recommended in patients with asymptomatic hyperuricemia. After initiation, liver-function testing is recommended at 2 months, 4 months, and periodically thereafter; measure liver function immediately in patients who report symptoms suggestive of liver injury, including fatigue, anorexia, abdominal discomfort, dark urine, or jaundice. The mean serum uric acid levels over time for each treatment group from the two pivotal Phase 3 studies are shown in Figure 1. For the full list of excipients, see section 6.1. 51 0 obj Limit the use of febuxostat to patients who are not treated effectively by, are contraindicated to receive, or experience severe adverse effects due to allopurinol. Two thousand and two hundred sixty-nine (2269) patients were randomized: Febuxostat 40 mg QD (n=757), febuxostat 80 mg QD (n=756), or allopurinol 300/200 mg QD (n=756). LIMITS OF USE: Due to a risk of CV death, used in those with an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable. qXz'[{MxgI Hyvq(o_>}>E&$8_IIa_y pSIjWtfayWaaHx=h5\ The composition of claim 1, wherein said micronized febuxostat form-G has particle size distribution of; D90 less than 30, D 5 o less than 1-5 and D1 0 less than 1 . Febuxostat inhibits xanthine oxidase, the enzyme that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid. Gout patients with established cardiovascular (CV) disease treated with ULORIC had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study. Passing clouds. This medicinal product does not require any special storage conditions. <>>>/MediaBox[ 0 0 612 792]/Contents 114 0 R /Parent 2 0 R /Type/Page>> Time/General. Peak plasma concentrations of febuxostat are reached in 11.5 hours. Discounts are available exclusively through participating pharmacies. Plasma protein binding of the active metabolites ranges from about 82% to 91%. <>>>/MediaBox[ 0 0 612 792]/Contents 73 0 R /Parent 2 0 R /Type/Page>> Initial dose: 40 mg PO qDay. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. DailyMed - FEBUXOSTAT tablet, film coated . Cladribine: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. Gout flares during the last 4 weeks of the study (Weeks 24-28) were observed in 15% (febuxostat 80, 120 mg), 14% (allopurinol 300 mg) and 20% (placebo) of subjects. Gout flares may occur during initiation of treatment due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits (see section 4.8 and 5.1). Consider the risks and benefits of Febuxostat Tablets when deciding to prescribe or continue patients on . Febuxostat is a potent, non-purine selective inhibitor of XO (NP-SIXO) with an in vitro inhibition Ki value less than one nanomolar. Table 1: Adverse reactions in combined phase 3, long-term extension studies and post-marketing experience, Pancytopenia, thrombocytopenia, agranulocytosis*, Anaphylactic reaction*, drug hypersensitivity*, Blood thyroid stimulating hormone increased, Diabetes mellitus, hyperlipidemia, decrease appetite, weight increase, Weight decrease, increase appetite, anorexia, Dizziness, paraesthesia, hemiparesis, somnolence, altered taste, hypoaesthesia, hyposmia, Atrial fibrillation, palpitations, ECG abnormal, Dyspnoea, bronchitis, upper respiratory tract infection, cough, Abdominal pain, abdominal distension, gastro-oesophageal reflux disease, vomiting, dry mouth, dyspepsia, constipation, frequent stools, flatulence, gastrointestinal discomfort, Rash (including various types of rash reported with lower frequencies, see below), Dermatitis, urticaria, pruritus, skin discolouration, skin lesion, petechiae, rash macular, rash maculopapular, rash papular, Toxic epidermal necrolysis*, Stevens-Johnson Syndrome*, angioedema*, drug reaction with eosinophilia and systemic symptoms*, generalized rash (serious)*, erythema, exfoliative rash, rash follicular, rash vesicular, rash pustular, rash pruritic*, rash erythematous, rash morbillifom, alopecia, hyperhidrosis, Musculoskeletal and connective tissue disorders, Arthralgia, arthritis, myalgia, musculoskeletal pain, muscle weakness, muscle spasm, muscle tightness, bursitis, Rhabdomyolysis*, joint stiffness, musculoskeletal stiffness, Renal failure, nephrolithiasis, haematuria, pollakiuria, proteinuria, Tubulointerstitial nephritis*, micturition urgency, General disorders and administration site conditions, Blood amylase increase, platelet count decrease, WBC decrease, lymphocyte count decrease, blood creatine increase, blood creatinine increase, haemoglobin decrease, blood urea increase, blood triglycerides increase, blood cholesterol increase, haematocritic decrease, blood lactate dehydrogenase increased, blood potassium increase, Blood glucose increase, activated partial thromboplastin time prolonged, red blood cell count decrease, blood alkaline phosphatase increase, blood creatine phosphokinase increase*, * Adverse reactions coming from post-marketing experience. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. 12 0 obj No dose adjustment is required in the elderly (see section 5.2). In male rats, a statistically significant increase in urinary bladder tumours (transitional cell papilloma and carcinoma) was found only in association with xanthine calculi in the high dose group, at approximately 11 times human exposure. Febuxostat inhibits uric acid formation but does not affect xanthine and hypoxanthine formation. Febuxostat inhibits xanthine oxidase, the enzyme that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid. As there has been no experience in organ transplant recipients, the use of febuxostat in such patients is not recommended (see section 5.1). No statistically significant differences were found and no causal relationship with febuxostat was established. Patients who have serum ALT more than 3 times the upper limit of normal (ULN) with serum total bilirubin more than 2 times the ULN without alternative etiologies are at risk for severe drug-induced liver injury. <>>>/MediaBox[ 0 0 612 792]/Contents 113 0 R /Parent 2 0 R /Type/Page>> Effects reported in < 1% of patients include bronchitis, cough, dyspnea, epistaxis, nasal dryness, paranasal sinus hypersecretion, pharyngeal edema, respiratory tract or nasal congestion, sneezing, throat irritation, and upper respiratory tract infection.Blurred vision, deafness, tinnitus, and vertigo were noted in < 1% of febuxostat recipients treated with doses ranging from 40 to 240 mg during phase 2 and 3 clinical trials. There was no significant increase in any other tumour type in either male or female mice or rats. Metabolized by UGT enzymes, including UGT 1A1, 1A3, 1A9, and 2B7; CYP isoenzymes, including CYP 1A2, 2C8, and 2C9; and non-CYP enzymes. Consider gout flare prophylaxis with an NSAIA or colchicine; start these agents when febuxostat therapy is initiated. AHFS DI Essentials. <>>>/MediaBox[ 0 0 612 792]/Contents 116 0 R /Parent 2 0 R /Type/Page>> If you are interested in working with USP to develop or revise a monograph through the pending monograph process, please contact pendingrevisions@usp.org. PVC/PVDC Aluminium blister of 14 tablets. Importance of informing patients that higher cardiovascular mortality reported with febuxostat compared with allopurinol therapy in patients with gout and established cardiovascular disease. A monograph is a written document that reflects the quality attributes of medicines approved by the U.S. Food and Drug Administration (US FDA). <>>>/MediaBox[ 0 0 612 792]/Contents 92 0 R /Parent 2 0 R /Type/Page>> }Dg"$4FY.2#59Y]bd@%s"0tB)[ PK ! Lomustine, CCNU: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. PK ! Continue febuxostat therapy during gout flare, adding either an NSAID or colchicine acutely. Febuxostat is eliminated by both hepatic and renal pathways. Reserve febuxostat use for patients with an inadequate response to maximum recommended dosages of allopurinol or in whom allopurinol is not tolerated or is not recommended; evaluate risks and benefits of initiating or continuing febuxostat therapy. The recommended dose in patients with mild hepatic impairment is 80 mg. Limited information is available in patients with moderate hepatic impairment. Alkylating agents: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. Drug class: Antigout Agents Drug interaction studies of febuxostat with drugs (except theophylline) that are metabolized by XO have not been performed in humans. Adverse events included anemia, idiopathic thrombocytopenic purpura, leukocytosis, leukopenia, lymphopenia, neutropenia, pancytopenia, splenomegaly, and thrombocytopenia. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. In addition to the urinary excretion, approximately 45% of the dose was recovered in the feces, 12% as unchanged febuxostat, 1% as the acyl glucuronide, 25% as known oxidative metabolites and their conjugates, and 7% as other unknown metabolites. Ph. 1 0 obj Among patients with gout and mild, moderate or severe renal impairment, the mean oral clearance of febuxostat was decreased by 14%, 34%, and 48%, respectively, compared to patients with normal renal function. Distribution of population by communal density: Dense: 19.85% of the population. PVC/PCTFE Aluminium blister of 14 tablets. You will be redirected to your program in 5 seconds. Medical Security Card Company, LLC All Rights Reserved. Monograph: Monograph Number Monograph: Monograph Name LIAISON COMMITTEE Monograph: MIA Priority Monograph: ID Monograph: Assays Monograph: Impurities FIDAXOMICIN . Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. endobj WellRx will never sell your personal information. Administration with food decreases the rate and extent of absorption of febuxostat; not considered clinically important. DISCLAIMER: This drug information content is provided for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Steady-state serum uric acid concentration may be reached within 7 days of therapy initiation. Treatment guidelines recommend combination therapy with a uricosuric (e.g., lesinurad) plus a xanthine oxidase inhibitor (XOI) when treatment goals are not met with an XOI alone. endstream Note: 509 patients received allopurinol 300 mg QD; 10 patients with serum creatinine >1.5 and < 2.0 mg/dL were dosed with 100 mg QD. Theophylline, Aminophylline: (Moderate) Use caution if febuxostat and aminophylline are used concurrently. Consider prophylactic low-dose aspirin therapy in patients with a history of cardiovascular disease. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. (Moderate) Use caution if febuxostat and theophylline are used concurrently. I understand I can opt out at any time, by clicking the 'unsubscribe' button found in the price drop alert emails I receive. Febuxostat is a medication used to manage and treat hyperuricemia and gout. endobj Clinical Guidance - Drug Monographs - Pharmacy Benefits Management Services During these acute attacks, continue febuxostat and manage the gout flare as appropriate. &$W4KH"xRdN9Aw(7ey/O Stevens-Johnson-Syndrome and Toxic epidermal necrolysis are characterised by progressive skin rashes associated with blisters or mucosal lesions and eye irritation. Uloric (febuxostat) dosing, indications, interactions, adverse effects Febuxostat is extensively metabolized by both conjugation via uridine diphosphate glucuronosyltransferase (UGT) enzymes, including UGT1A1, UGT1A3, UGT1A9, and UGT2B7, and oxidation via cytochrome P450 enzymes, including CYP1A2, CYP2C8, and CYP2C9 and non-P450 enzymes. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. 43 0 obj In a postmarketing outcome study in patients with coexisting gout and cardiovascular disease, cardiovascular mortality was higher in those receiving febuxostat compared with those receiving allopurinol. endobj
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