Indicated for chronic management of hyperuricemia in patients who: Responded inadequately to optimal allopurinol therapy. Febuxostat should not be used while breastfeeding. <>/ProcSet[/PDF/Text/ImageB/ImageC/ImageI]/Font<>>>/MediaBox[ 0 0 612 792]/Contents 101 0 R /Parent 2 0 R /Type/Page>> PDF Reference ID: 4139515 - Food and Drug Administration Carcinogenesis, mutagenesis, impairment of fertility. Sun & Moon. bha [Content_Types].xml ( MO0H*WfZGqhi=n!]kg4Y6[AD])@d*cI9wP FM 8a) %V You may find alternative ways to save with this medication. endobj 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). Fludarabine: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. This program is administered by Medical Security Card Company, LLC, Tucson, AZ. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. Following multiple oral 80 mg once daily doses or a single 120 mg dose with a high fat meal, there was a 49% and 38% decrease in Cmax and a 18% and 16% decrease in AUC, respectively. If patient has developed allergic/hypersensitivity reactions including Stevens-Johnson-Syndrome and acute anaphylactic reaction/shock, febuxostat must not be re-started in this patient at any time. Metabolized by conjugation by UGT 1A1, 1A3, 1A9, and 2B7; oxidation by CYP 1A2, 2C8, and 2C9; and metabolism by other enzymes. Since patients who have lost therapeutic response to pegloticase are at higher risk of developing anaphylaxis and infusion reactions, oral urate-lowering therapy should be discontinued prior to pegloticase initiation and withheld during the course of treatment. Advise patients to report unusual or persistent muscle pain and/or weakness as rhabdomyolysis has been reported during post-marketing use of febuxostat. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. febuxostat + pegloticase. PRODUCT MONOGRAPH PRODUCT MONOGRAPH PrMAR-FEBUXOSTAT Febuxostat Tablets 80 mg febuxostat (as febuxostat hemihydrate) Preparations Inhibiting Uric Acid Production Marcan Pharmaceuticals Inc., 77 Auriga Drive, Suite#4, Ottawa, ON, K2E 7Z7 Date of Preparation: March 2, 2018 Control # 207117 PrMAR-FEBUXOSTAT Febuxostat Tablets, 80 mg dN,>Madg xYo. Manufacturer states that febuxostat may be used with caution in patients with lesser elevations of ALT or bilirubin if an alternate probable cause of liver function test abnormalities determined. Flare prophylaxis with colchicine or an NSAID is recommended and may be beneficial for up to 6 months.Maximum Dosage Limits:-AdultsDoses of up to 120 mg/day PO have been used in clinical trials.-GeriatricDoses of up to 120 mg/day PO have been used in clinical trials.-AdolescentsSafety and efficacy have not been established.-ChildrenSafety and efficacy have not been established.-InfantsSafety and efficacy have not been established.Patients with Hepatic Impairment DosingNo dosage adjustment is needed in patients with mild to moderate hepatic impairment. Members are required to pay for all prescription purchases. The study was designed to exclude a prespecified risk margin of 1.3 for the hazard ratio of MACE. All-cause mortality was higher in the febuxostat group (243 deaths [7.8%]; 2.6 per 100 patient-years) than the allopurinol group (199 deaths [6.4%]; 2.2 per 100 patient-years) [HR: 1.22, 95% CI: 1.01, 1.47], due to a higher rate of CV deaths. Severe renal impairment: AUC is increased by 9698%. At least 65% of the patients had mild-moderate renal impairment (with creatinine clearance of 30-89 mL/min). Elevated hepatic enzymes were reported in 6.6% and 4.6% of patients who received febuxostat 40 mg and 80 mg daily, respectively. 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. Patients should exercise caution before driving, using machinery or participating in dangerous activities until they are reasonably certain that Febuxostat tablets do not adversely affect performance. Febuxostat tablets work sufficiently quickly to allow retesting of the serum uric acid after 2 weeks. It allows continued monitoring of the benefit/risk balance of the medicinal product. }rtTxtBEDg Initial dose: 40 mg PO qDay. risk of anaphylaxis (febuxostat uricosuric effects may interfere w/ laboratory test) topotecan. By blocking uric acid production, febuxostat decreases serum concentrations of uric acid. Mild or moderate renal impairment: AUC is increased by 718 or 4549%, respectively; not considered clinically important. Two hundred and forty mg febuxostat (2 times the recommended highest dose) was used as a safety evaluation dose. Other dermatologic and allergic reactions reported in less than 1% of patients include angioedema, alopecia, dermatitis, dermographism, ecchymosis, eczema, hair color changes, abnormal hair growth, hyperhidrosis, peeling skin, petechiae, photosensitivity, pruritus, purpura, skin discoloration/altered pigmentation, skin lesion, abnormal skin odor, and urticaria.Psychosis, reported as psychotic behavior including aggressive thoughts, has been reported during post-marketing use of febuxostat. Like other chronic gout treatments, the drug is not recommended in patients with asymptomatic hyperuricemia. The proportion of patients with serum urate levels of < 6.0 mg/dL (357 mol/L) at the final visit, was 45% for 40 mg febuxostat, 67% for febuxostat 80 mg and 42% for allopurinol 300/200 mg, respectively. Drug interaction studies of febuxostat with other cytotoxic chemotherapy have not been conducted. In this subgroup febuxostat achieved the primary efficacy endpoint (sUA < 6.0 mg/dL at the last 3 visits) in 41% (80 mg QD), 48% (120 mg QD), and 66% (240 mg QD) of patients compared to 9% in the allopurinol 300 mg/100 mg QD and 0 % in the placebo groups. <>>>/MediaBox[ 0 0 612 792]/Contents 107 0 R /Parent 2 0 R /Type/Page>> After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. No data is available regarding the safety of febuxostat during other cytotoxic therapy. Rare serious hypersensitivity reactions to febuxostat, some of which were associated to systemic symptoms, have occurred in the post-marketing experience. Somnolence, dizziness, paraesthesia and blurred vision have been reported with the use of Febuxostat. Melphalan Flufenamide: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. Febuxostat appears to be more selective for xanthine oxidase than allopurinol. This program does not make payments directly to pharmacies. ]%l6*^Jp/]wK,;|YKl PK ! (FDA), and USP defined impurities are classified into . Uloric (febuxostat) dosing, indications, interactions, adverse effects 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. Perform liver function tests (serum ALT, AST, alkaline phosphatase, and total bilirubin concentrations) prior to initiation of therapy and repeat promptly in patients with manifestations suggestive of liver damage (see Advice to Patients). The USP Pending Monograph process allows for development of monographs or monograph revisions for articles awaiting approval by FDA, and permits publication of these proposals in the Pharmacopeial Forum (PF) for notice and comment where required in accordance with USP's typical Request for Revision processes. It is 99.2% plasma protein bound and has a calculated apparent volume of distribution at steady state of approximately 0.7 L/kg. Febuxostat Uses, Side Effects & Warnings - Drugs.com Gout flare prophylaxis may be beneficial for up to 6 months. Importance of promptly reporting any symptoms suggestive of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice). Following an 80 mg oral dose of 14C- labeled febuxostat, approximately 49% of the dose was recovered in the urine as unchanged febuxostat (3%), the acyl glucuronide of the active substance (30%), its known oxidative metabolites and their conjugates (13%), and other unknown metabolites (3%). endobj These rates were similar to the rates reported on allopurinol (4.2%) (see section 4.4). Dizziness was reported in > 1% of febuxostat-treated patients during clinical trials, but not at a rate more than 0.5% greater than placebo. Increased systemic exposure in patients with severe renal impairment; dosage adjustment recommended. Lomustine, CCNU: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. Mild to moderate hepatic impairment: Peak concentrations and AUC are increased by 2030%; not considered clinically important. 116 patients were enrolled and received initially febuxostat 80 mg QD. [iTb/N(A3b{jxVb"giaWl_xb#b4Or0Qahe=P-{>;vCfBI"c&\O8q"KHT_ PK ! The recommended dose in patients with mild hepatic impairment is 80 mg. Limited information is available in patients with moderate hepatic impairment. endobj These changes were not considered statistically significant. As there has been no experience with febuxostat, its use in these populations is not recommended. Continuous treatment with febuxostat decreases frequency and intensity of gout flares. Talk to your pharmacist about the potential option(s) noted below. Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products and any concomitant illnesses (e.g., cardiovascular or cerebrovascular disease). Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. Febuxostat is a non-purine selective inhibitor of both the oxidized and reduced forms of xanthine oxidase. Centre, also called Centre-Val-de-Loire, rgion of France encompassing the central dpartements of Cher, Indre, Indre-et-Loire, Loir-et-Cher, Loiret, and Eure-et-Loir. 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. Febuxostat inhibits xanthine oxidase, the enzyme that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid. At therapeutic concentrations febuxostat does not inhibit other enzymes involved in purine or pyrimidine metabolism, namely, guanine deaminase, hypoxanthine guanine phosphoribosyltransferase, orotate phosphoribosyltransferase, orotidine monophosphate decarboxylase or purine nucleoside phosphorylase. Not known whether febuxostat distributes into human milk, affects human milk production, or affects breast-fed infant. PDF [Product Monograph Template - Standard] &$W4KH"xRdN9Aw(7ey/O Pending Monograph Program | USP-NF Patients with secondary hyperuricemia (i.e. Association between US Pharmacopeia (USP) monograph standards, generic Pharmacokinetic values in geriatric adults similar to those in younger adults. The Centre-Val de Loire is the fourth largest region, covering 39,151 km. Febuxostat initiation may increase frequency of acute gout attacks (gout flare). Febuxostat is an oral, non-purine selective xanthine oxidase inhibitor (XOI). Monitor theophylline concentrations. As with allopurinol, it is advisable for patients to maintain a urine output >= 2 L/day in an attempt to avoid the formation of xanthine calculi under the influence of xanthine oxidase inhibitor therapy and to help prevent renal precipitation of urates in patients receiving concurrent uricosuric agents. Febuxostat Monograph for Professionals - Drugs.com Between 46% and 55% of subjects received treatment for gout flares from Week 8 and Week 28. 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. Xanthine oxidase inhibition is dose dependent. <>>>/MediaBox[ 0 0 612 792]/Contents 116 0 R /Parent 2 0 R /Type/Page>> Monograph: Monograph Name Monograph: Monograph Type Monograph: ID Monograph: Assays Monograph: Impurities IVERMECTIN ORAL SOLUTION New OXYTETRACYCLINE . Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. WARNINGS AND PRECAUTIONS, Endocrine and Metabolism section. PDF HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include Febuxostat use in patients with secondary hyperuricemia has not been studied and use is not recommended. <>>>/MediaBox[ 0 0 612 792]/Contents 75 0 R /Parent 2 0 R /Type/Page>> WellRx will never sell your personal information. Following multiple oral doses of febuxostat, the Cmax and AUC were 24% and 12% higher in females than in males, respectively. Additional information can be found at: FAQs Pending Monograph Process. The gout flare should be managed concurrently as appropriate for the individual patient. is the primary source of official quality standards for medicines and their ingredients in Europe. Febuxostat contains sodium. Medicinal product allergy / hypersensitivity. 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). Intermediate density: 27.82% of the population. endstream Thioguanine, 6-TG: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Monitor theophylline concentrations. 2. Febuxostat: MedlinePlus Drug Information No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C). Azathioprine: (Contraindicated) The use of febuxostat with azathioprine is contraindicated. A solid oral composition comprising micronized febuxostat form-G and one or more pharmaceutically acceptable excipients. The day supply is based upon the average dispensing patterns for the specific drug and strength. 43 0 obj This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. 55 0 obj Febuxostat is extensively metabolized by both conjugation via uridine diphosphate glucuronosyltransferase (UGT) enzymes, including UGT1A1, UGT1A3, UGT1A9, and UGT2B7, and . No relationship between the incidence of transaminase elevations and febuxostat dose was identified. Because of the increased risk of CV death, 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 allopurinol treatment is not advisable. 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. <>]/Type/Catalog/MarkInfo<>/Lang(en-CA)/Metadata 1929 0 R >> endobj 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. PDF 211533 Uloric Apm Mercaptopurine, 6-MP: (Contraindicated) The use of febuxostat with mercaptopurine is contraindicated. Eur.) 3 0 obj Gout flares during the last 4 weeks of the study (Weeks 49-52) were observed in 6-8% (febuxostat 80 mg, 120 mg) and 11% (allopurinol 300 mg) of subjects. No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out. The corresponding median AUC values of febuxostat at steady-state in patients with renal impairment were increased by 18%, 49%, and 96% after 40 mg dose, and 7%, 45% and 98% after 80 mg dose, respectively, compared to patients with normal renal function.PediatricsSafety and efficacy has not been established in patients under 18 years of age.GeriatricNo clinically significant differences were noted in the pharmacokinetics, pharmacodynamics, and safety of febuxostat based on age.Gender DifferencesNo clinically significant differences were noted in the pharmacokinetics, pharmacodynamics, and safety of febuxostat based on gender in adult populations.Ethnic DifferencesRace-based statistically significant differences in febuxostat efficacy were reported in a 5-year open-label trial, with 87% of Caucasian patients reaching target serum urate concentrations of < 6 mg/dL compared to 65% of non-Caucasian patients (p = 0.025). Physicians and patients should remain alert for adverse CV signs and symptoms. The Loire Valley (French: Val de Loire, pronounced [val d lwa]; Breton: Trao al Liger), spanning 280 kilometres (170 mi), is a valley located in the middle stretch of the Loire river in central France, in both the administrative regions Pays de la Loire and Centre-Val de Loire.The area of the Loire Valley comprises about 800 square kilometres (310 sq mi). 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. Febuxostat has minimal effects on other enzymes involved in purine and pyrimidine synthesis and metabolism. 91% and 93% of patients on initial treatment with febuxostat 80 mg and 120 mg, respectively, had sUA <6 mg/dL at Month 36). However, there was a significant increase in CV deaths in patients treated with febuxostat (1.5 per 100 patient-years) vs. patients treated with allopurinol (1.1 per 100 patient-years) [HR: 1.34, 95% CI: 1.03, 1.73]. Time Zone. Uses Warnings Before taking Side effects Dosage Interactions What is febuxostat? Product Monograph Page 6 of 46 Hepatic Function: Hepatic function should be assessed before starting treatment and periodically thereafter. topotecan. May increase to 80 mg PO once daily if the serum uric acid concentration is more than 6 mg/dL after 2 weeks of therapy. You may contact customer care anytime with questions or concerns, to cancel your registration, or to obtain further information. If a gout flare occurs during febuxostat treatment, it should not be discontinued. test and reference products generated using USP Apparatus I at 100 rpm and/or Apparatus II at 50 rpm in at least three dissolution media (pH 1.2, 4.5 and 6.8 buffer) should be submitted. AHFS DI Essentials. !6b=a.`Wf\mg44T+)?$h6~\V#f0wi `3N?FQ9:yB&b The elimination half-life is 5 to 8 hours. However, weight-corrected Cmax and AUC were similar between the genders. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi. endobj Three years data showed a decrease in the incidence of gout flares with less than 4% of patients requiring treatment for a flare (i.e. Are intolerant to allopurinol. Sign up or log in to your free WellRx account to gain access to this and other tools to help make managing your medications and wellness easier. endstream TEIH(_O2>x4O)u\s\1+e{@oxx"q This feature requires registration. [= After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. 5~y`E^H52[ %)O|3C-*1zrht?>.vyPTRzj)P;ocA* D "ay[rYP,q-L~.w*]PxPiy)[5:KkU)`rq0)Wq;0-0IIoxoF~.I'qPO'U>qQm9p~Z" RL'59D\1g*QP#TnVI0h!CB}oSr"jg?M|;^FgSc 1 2 endobj 49 0 obj Discount percentages represent savings provided off of pharmacies retail prices for consumers who do not have a discount program and pay cash. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and caliculi. 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. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development or parturition (see section 5.3). % 1 interaction. The USP Pending Monograph process allows for development of monographs or monograph revisions for articles awaiting approval by FDA, and permits publication of these proposals in the Pharmacopeial Forum (PF) for notice and comment where required in accordance with USPs typical Request for Revision processes. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. (See Cardiovascular Death under Cautions.). Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. Severe hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) were associated with fever, haematological, renal or hepatic involvement in some cases. Other adverse GI, metabolic, or nutritional effects that occurred in less than 1% of patients taking febuxostat in clinical trials include abdominal pain or distension, xerostomia, flatulence, diarrhea, gastritis, gastroesophageal reflux disease, gastrointestinal discomfort, gingival pain, hyperchlohydria, hematochezia, oral ulceration, pancreatitis, peptic ulcer, constipation, dyspepsia, hematemesis, weight gain or weight loss, anorexia, appetite stimulation, dehydration, diabetes mellitus, hypercholesterolemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hyperamylasemia, hypokalemia, hyperkalemia, hypernatremia, bicarbonate decreases, and TSH increases.Fatal and non-fatal hepatic failure has been reported in patients taking febuxostat. Treatment with febuxostat in patients with ischaemic heart disease or congestive heart failure is not recommended. Febuxostat use has not been studied in these populations.Limited available data with the use of febuxostat in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes resulting from fetal exposure during pregnancy. Alkylating agents: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. endobj DISCOUNT ONLY - NOT INSURANCE. Risk for severe drug-related liver injury if no alternate etiology is found and ALT is >3 times the ULN with total bilirubin concentrations >2 times the ULN; do not restart febuxostat in these patients. One thousand and seventy-two (1072) patients were randomized: placebo (n=134), febuxostat 80 mg QD (n=267), febuxostat 120 mg QD (n=269), febuxostat 240 mg QD (n=134) or allopurinol (300 mg QD [n=258] for patients with a baseline serum creatinine 1.5 mg/dL or 100 mg QD [n=10] for patients with a baseline serum creatinine >1.5 mg/dL and 2.0 mg/dL). VA class: MS400 Febuxostat is eliminated by both hepatic and renal pathways. TEVA-FEBUXOSTAT Page 1 of 32 PRODUCT MONOGRAPH PrTEVA-FEBUXOSTAT Febuxostat Tablets 80 mg febuxostat (as febuxostat hemihydrate) Preparations Inhibiting Uric Acid Production Teva Canada Limited 30 Novopharm Court Toronto, Ontario Canada, M1B 2K9 Date of Revision: January 27, 2020 Submission Control No: 234067 However, no clinically significant change in the percent decrease in serum uric acid concentration was observed where tested (80 mg multiple dose). }Dg"$4FY.2#59Y]bd@%s"0tB)[ PK ! Unlike allopurinol, febuxostat has not been studied in patients with secondary hyperuricemia. An approximately 400-fold increase in the amount of 1-methylxanthine (a major metabolite of theophylline) excreted in the urine was also noted. In the CARES study, incidence of major cardiovascular events (e.g., nonfatal MI, unstable angina requiring urgent coronary revascularization, nonfatal stroke) was similar in febuxostat- and allopurinol-treated patients.
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