FEBSAN 40 Febuxostat 40mg Film-Coated Tablet 10's
RXDRUG-DR-XY43846
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Febuxosat is a XO inhibitor indicated for the chronic management of hyperuricaemia in patients with gout.
Dosage/Direction for Use
Recommended Dose: For the treatment of hyperuricaemia in patients with gout, Febuxostat tablets are recommended at a dosage of 40 mg or 80 mg or 120 mg once daily.
The recommended starting dose is 40 mg once daily. For patient who do not achieve a serum uric acid (sUA) less than 6 mg per dL after 2 weeks with 40 mg, Febuxostat tablets 80 mg is recommended.
Febuxostat tablets can be taken without regard to food or antacid use.
Uric Acid Level: Testing for the target sUA level <6 mg/dL may be performed as early as 2 weeks after initiating Febuxostat tablets therapy.
Gout Flares: Gout flares may occur after initiation of Febuxostat tablets due to changing sUA levels, resulting in mobilization of urate from tissue deposits. Flare prophylaxis with a nonsteroidal anti-inflammatory drug (NSAID) or colchicine is recommended upon initiation of therapy with Febuxostat tablets. Prophylactic therapy may be beneficial for up to 6 months.
If a gout flare occurs during Febuxostat tablets treatment, they need not be discontinued. The gout flare should be managed concurrently, as appropriate for the individual patient.
Febuxostat tablets are not recommended for the treatment of asymptomatic hyperuricaemia.
The recommended starting dose is 40 mg once daily. For patient who do not achieve a serum uric acid (sUA) less than 6 mg per dL after 2 weeks with 40 mg, Febuxostat tablets 80 mg is recommended.
Febuxostat tablets can be taken without regard to food or antacid use.
Uric Acid Level: Testing for the target sUA level <6 mg/dL may be performed as early as 2 weeks after initiating Febuxostat tablets therapy.
Gout Flares: Gout flares may occur after initiation of Febuxostat tablets due to changing sUA levels, resulting in mobilization of urate from tissue deposits. Flare prophylaxis with a nonsteroidal anti-inflammatory drug (NSAID) or colchicine is recommended upon initiation of therapy with Febuxostat tablets. Prophylactic therapy may be beneficial for up to 6 months.
If a gout flare occurs during Febuxostat tablets treatment, they need not be discontinued. The gout flare should be managed concurrently, as appropriate for the individual patient.
Febuxostat tablets are not recommended for the treatment of asymptomatic hyperuricaemia.
Overdosage
Febuxostat was studied in healthy subjects in doses up to 300 mg daily for 7 days without evidence of dose-limiting toxicities. No overdose of febuxostat was reported in clinical studies. In case of an overdose, patients should be managed by symptomatic and supportive care.
Administration
May be taken with or without food: May be taken w/o regard to antacid use.
Contraindications
Febuxostat tablets are contraindicated in patients being treated with azathioprine, mercaptopurine or theophylline.
Special Precautions
General: Patients should be advised of the potential benefits and risks of febuxostat.
Patients should be informed about the potential for gout flares, elevated liver enzymes and adverse cardiovascular events after initiation of Febuxostat tablets therapy.
Concomitant prophylaxis with a non steroidal anti-inflammatory drug (NSAID) or colchicine for gout flares should be considered.
Patients should be instructed to inform their healthcare professional if they develop a rash, chest pain, shortness of breath or neurologic symptoms suggesting stroke. Patients should be instructed to inform their healthcare professional of any other medications they are currently taking with Febuxostat Tablets, including over-the-counter medications.
Gout Flare: After initiation of febuxostat, an increase in gout flares is frequently observed. This increase is due to reduction in the sUA levels, resulting in mobilization of urate from tissue deposits.
In order to prevent gout flares when therapy with Febuxostat tablets is initiated, concurrent prophylactic treatment with an NSAID or colchicine is recommended.
Cardiovascular Events: In randomized controlled studies, there was a higher rate of cardiovascular thromboembolic events (cardiovascular deaths, non-fatal myocardial infarctions and non-fatal strokes) in patients treated with febuxostat [0.74/100 P-Y (95% CI 0.36-1.37)] than allopurinol [0.60/100 P-Y (95% CI 0.16-1.53)]. A causal relationship with febuxostat has not been established. Monitor for signs and symptoms of myocardial infarction (MI) and stroke.
Secondary Hyperuricaemia: No studies have been conducted in patients with secondary hyperuricaemia (including organ transplant recipients); Febuxostat tablets are not recommended for use in patients in whom the rate of urate formation is greatly increased (e.g.; malignant disease and its treatment, Lesch-Nyhan syndrome). The concentration of xanthine in urine could, in rare cases, rise sufficiently to allow deposition in the urinary tract.
Patients should be informed about the potential for gout flares, elevated liver enzymes and adverse cardiovascular events after initiation of Febuxostat tablets therapy.
Concomitant prophylaxis with a non steroidal anti-inflammatory drug (NSAID) or colchicine for gout flares should be considered.
Patients should be instructed to inform their healthcare professional if they develop a rash, chest pain, shortness of breath or neurologic symptoms suggesting stroke. Patients should be instructed to inform their healthcare professional of any other medications they are currently taking with Febuxostat Tablets, including over-the-counter medications.
Gout Flare: After initiation of febuxostat, an increase in gout flares is frequently observed. This increase is due to reduction in the sUA levels, resulting in mobilization of urate from tissue deposits.
In order to prevent gout flares when therapy with Febuxostat tablets is initiated, concurrent prophylactic treatment with an NSAID or colchicine is recommended.
Cardiovascular Events: In randomized controlled studies, there was a higher rate of cardiovascular thromboembolic events (cardiovascular deaths, non-fatal myocardial infarctions and non-fatal strokes) in patients treated with febuxostat [0.74/100 P-Y (95% CI 0.36-1.37)] than allopurinol [0.60/100 P-Y (95% CI 0.16-1.53)]. A causal relationship with febuxostat has not been established. Monitor for signs and symptoms of myocardial infarction (MI) and stroke.
Secondary Hyperuricaemia: No studies have been conducted in patients with secondary hyperuricaemia (including organ transplant recipients); Febuxostat tablets are not recommended for use in patients in whom the rate of urate formation is greatly increased (e.g.; malignant disease and its treatment, Lesch-Nyhan syndrome). The concentration of xanthine in urine could, in rare cases, rise sufficiently to allow deposition in the urinary tract.
Use In Pregnancy & Lactation
Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Febuxostat Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Lactation: Febuxostat is excreted in the milk of rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Febuxostat tablets are administered to a nursing mother.
Lactation: Febuxostat is excreted in the milk of rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Febuxostat tablets are administered to a nursing mother.
Adverse Reactions
Adverse events occurring most frequently and with a greater incidence than placebo have included liver function abnormalities, nausea, arthralgia, and rash. Other adverse reactions reported during febuxostat therapy included diarrhea, headache, musculoskeletal stiffness, constipation, gastroesophageal reflux, flushing, dizziness, and gout flares.
Drug Interactions
XO Substrate Drugs: Febuxostat is a XO inhibitor. Drug interaction studies of febuxostat with drugs that are metabolized by XO (e.g., theophylline, mercaptopurine, azathioprine) have not been conducted. Inhibition of XO by febuxostat may cause increased plasma concentrations of these drugs leading to toxicity. Febuxostat tablets are contraindicated in patients being treated with azathioprine, mercaptopurine or theophylline.
Cytotoxic Chemotherapy Drugs: Drug interaction studies of febuxostat with cytotoxic chemotherapy have not been conducted. No data are available regarding the safety of febuxostat during cytotoxic chemotherapy.
P450 Substrate Drugs: In vitro studies have shown that febuxostat does not inhibit P450 enzymes, CYP1A2, 2C9, 2C19, 2D6 or 3A4, and it also does not induce CYP1A2, 2B6, 2C9, 2C19 or 3A4 at clinically relevant concentrations. As such, pharmacokinetic interactions between febuxostat and drugs metabolized by these CYP enzymes are unlikely.
In vivo Drug Interaction Studies: Based on drug interaction studies in healthy subjects, febuxostat does not have clinically significant interactions with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin or desipramine. Therefore, Febuxostat tablets may be used concomitantly with these medications without any dose adjustments.
Effect of Other Drugs on Febuxostat: Febuxostat is metabolized by conjugation and oxidation via multiple metabolizing enzymes. The relative contribution of each enzyme isoform is not clear. Drug interactions between febuxostat and a drug that inhibits or induces one particular enzyme isoform is, in general, not expected.
Renal Impairment: No dose adjustment is necessary in patients with mild or moderate renal impairment (Clcr 30-89 mL/min). The recommended starting dose of Febuxostat tablets is 40 mg once daily. For patients who do not achieve a sUA <6 mg/dL after 2 weeks with 40 mg, Febuxostat tablets 80 mg is recommended.
There are insufficient data in patients with severe renal impairment (Clcr <30 mL/min); therefore, caution should be exercised in these patients.
Hepatic Impairment: No dose adjustment is necessary in patients with mild or moderate hepatic impairment (Child-Pugh Class A or B). No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C); therefore, caution should be exercised in these patients.
Cytotoxic Chemotherapy Drugs: Drug interaction studies of febuxostat with cytotoxic chemotherapy have not been conducted. No data are available regarding the safety of febuxostat during cytotoxic chemotherapy.
P450 Substrate Drugs: In vitro studies have shown that febuxostat does not inhibit P450 enzymes, CYP1A2, 2C9, 2C19, 2D6 or 3A4, and it also does not induce CYP1A2, 2B6, 2C9, 2C19 or 3A4 at clinically relevant concentrations. As such, pharmacokinetic interactions between febuxostat and drugs metabolized by these CYP enzymes are unlikely.
In vivo Drug Interaction Studies: Based on drug interaction studies in healthy subjects, febuxostat does not have clinically significant interactions with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin or desipramine. Therefore, Febuxostat tablets may be used concomitantly with these medications without any dose adjustments.
Effect of Other Drugs on Febuxostat: Febuxostat is metabolized by conjugation and oxidation via multiple metabolizing enzymes. The relative contribution of each enzyme isoform is not clear. Drug interactions between febuxostat and a drug that inhibits or induces one particular enzyme isoform is, in general, not expected.
Renal Impairment: No dose adjustment is necessary in patients with mild or moderate renal impairment (Clcr 30-89 mL/min). The recommended starting dose of Febuxostat tablets is 40 mg once daily. For patients who do not achieve a sUA <6 mg/dL after 2 weeks with 40 mg, Febuxostat tablets 80 mg is recommended.
There are insufficient data in patients with severe renal impairment (Clcr <30 mL/min); therefore, caution should be exercised in these patients.
Hepatic Impairment: No dose adjustment is necessary in patients with mild or moderate hepatic impairment (Child-Pugh Class A or B). No studies have been conducted in patients with severe hepatic impairment (Child-Pugh Class C); therefore, caution should be exercised in these patients.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
Action
Pharmacology: Febuxostat, a xanthine oxidase (XO) inhibitor, achieves its therapeutic effect by decreasing serum uric acid (sUA). Febuxostat is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.
Pharmacokinetics: In healthy subjects, the maximum plasma concentrations (Cmax) and AUC of febuxostat increased in a dose proportional manner following single and multiple doses of 10 mg to 120 mg. There is no accumulation when the therapeutic doses are administered every 24 hours. Febuxostat has an apparent mean terminal elimination half-life (t½) of approximately 5 to 8 hours. Febuxostat pharmacokinetic parameters for patients with hyperuricaemia and gout estimated by population pharmacokinetic analyses were similar to those estimated in healthy subjects.
Absorption: The absorption of radiolabeled febuxostat following oral dose administration was estimated to be at least 49% (based on total radioactivity recovered in the urine).
Maximum plasma concentrations of febuxostat occurred between 1 to 1.5 hours postdose.
After multiple oral 40 mg and 80 mg once daily doses, the Cmax is approximately 1.6 ± 0.6 mcg/mL (N=30), and 2.6 ± 1.7 mcg/mL (N=227), respectively. Absolute bioavailability of the febuxostat tablet has not been studied.
Following multiple 80 mg once daily doses with a high fat meal, there was a 49% decrease in the Cmax and 18% decrease in the AUC, respectively. However, no clinically significant change in the percent decrease in the sUA concentration was observed (58% fed versus 51% fasting). Thus, febuxostat may be taken without regard to food.
Concomitant ingestion of an antacid containing magnesium hydroxide and aluminium hydroxide with an 80 mg single dose of febuxostat has been shown to delay absorption of febuxostat (approximately 1 hours) and to cause a 31% decrease in Cmax and a 15% decrease in the AUC∞. As the AUC rather than the Cmax was related to the drug effect, the change observed in the AUC was not considered clinically significant. Therefore, febuxostat may be taken without regard to antacid use.
Distribution: The mean apparent steady-state volume of distribution (Vss/F) of febuxostat was approximately 50 L (CV ~40%). The plasma protein binding of febuxostat is approximately 99.2%, (primarily to albumin), and is constant over the concentration range achieved with 40 mg and 80 mg doses.
Metabolism: Febuxostat is extensively metabolized by both conjugation via uridine diphosphate glucuronosyltransferase (UGT) enzymes, including UGT1A1, UGT1A3, UGT1A9 and UGT2B7, and oxidation via cytochrome P450 (CYP) enzymes, including CYP1A2, 2C8 and 2C9 and non-P450 enzymes. The relative contribution of each enzyme isoform in the metabolism of febuxostat is not clear. The oxidation of the isobutyl side chain leads to the formation of four pharmacologically active hydroxy metabolites, all of which occur in the plasma of humans at a much lower extent than febuxostat.
In the urine and the faeces, acyl glucuronide metabolites of febuxostat (~35% of the dose), and oxidative metabolites, 67M-1 (~10% of the dose), 67M-2 (~11% of the dose), and 67M-4, a secondary metabolite from 67M-1 (~14% of the dose) appeared to be the major metabolites of febuxostat in vivo.
Elimination: Febuxostat is eliminated by both the hepatic and renal pathways. 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 drug (30%), its known oxidative metabolites and their conjugates (13%), and other unknown metabolites (3%). In addition to the urinary excretion, approximately 45% of the dose was recovered in the faeces as unchanged febuxostat (12%), the acyl glucuronide of the drug (1%), its known oxidative metabolites and their conjugates (25%), and other unknown metabolites (7%.)
The apparent mean terminal elimination t½ of febuxostat was approximately 5 to 8 hours.
Pharmacokinetics: In healthy subjects, the maximum plasma concentrations (Cmax) and AUC of febuxostat increased in a dose proportional manner following single and multiple doses of 10 mg to 120 mg. There is no accumulation when the therapeutic doses are administered every 24 hours. Febuxostat has an apparent mean terminal elimination half-life (t½) of approximately 5 to 8 hours. Febuxostat pharmacokinetic parameters for patients with hyperuricaemia and gout estimated by population pharmacokinetic analyses were similar to those estimated in healthy subjects.
Absorption: The absorption of radiolabeled febuxostat following oral dose administration was estimated to be at least 49% (based on total radioactivity recovered in the urine).
Maximum plasma concentrations of febuxostat occurred between 1 to 1.5 hours postdose.
After multiple oral 40 mg and 80 mg once daily doses, the Cmax is approximately 1.6 ± 0.6 mcg/mL (N=30), and 2.6 ± 1.7 mcg/mL (N=227), respectively. Absolute bioavailability of the febuxostat tablet has not been studied.
Following multiple 80 mg once daily doses with a high fat meal, there was a 49% decrease in the Cmax and 18% decrease in the AUC, respectively. However, no clinically significant change in the percent decrease in the sUA concentration was observed (58% fed versus 51% fasting). Thus, febuxostat may be taken without regard to food.
Concomitant ingestion of an antacid containing magnesium hydroxide and aluminium hydroxide with an 80 mg single dose of febuxostat has been shown to delay absorption of febuxostat (approximately 1 hours) and to cause a 31% decrease in Cmax and a 15% decrease in the AUC∞. As the AUC rather than the Cmax was related to the drug effect, the change observed in the AUC was not considered clinically significant. Therefore, febuxostat may be taken without regard to antacid use.
Distribution: The mean apparent steady-state volume of distribution (Vss/F) of febuxostat was approximately 50 L (CV ~40%). The plasma protein binding of febuxostat is approximately 99.2%, (primarily to albumin), and is constant over the concentration range achieved with 40 mg and 80 mg doses.
Metabolism: Febuxostat is extensively metabolized by both conjugation via uridine diphosphate glucuronosyltransferase (UGT) enzymes, including UGT1A1, UGT1A3, UGT1A9 and UGT2B7, and oxidation via cytochrome P450 (CYP) enzymes, including CYP1A2, 2C8 and 2C9 and non-P450 enzymes. The relative contribution of each enzyme isoform in the metabolism of febuxostat is not clear. The oxidation of the isobutyl side chain leads to the formation of four pharmacologically active hydroxy metabolites, all of which occur in the plasma of humans at a much lower extent than febuxostat.
In the urine and the faeces, acyl glucuronide metabolites of febuxostat (~35% of the dose), and oxidative metabolites, 67M-1 (~10% of the dose), 67M-2 (~11% of the dose), and 67M-4, a secondary metabolite from 67M-1 (~14% of the dose) appeared to be the major metabolites of febuxostat in vivo.
Elimination: Febuxostat is eliminated by both the hepatic and renal pathways. 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 drug (30%), its known oxidative metabolites and their conjugates (13%), and other unknown metabolites (3%). In addition to the urinary excretion, approximately 45% of the dose was recovered in the faeces as unchanged febuxostat (12%), the acyl glucuronide of the drug (1%), its known oxidative metabolites and their conjugates (25%), and other unknown metabolites (7%.)
The apparent mean terminal elimination t½ of febuxostat was approximately 5 to 8 hours.
MedsGo Class
Hyperuricemia & Gout Preparations
Features
Brand
FEBSAN 40
Full Details
Dosage Strength
40 mg
Drug Ingredients
- Febuxostat
Drug Packaging
Film-Coated Tablet 10's
Generic Name
Febuxostat
Dosage Form
Film-Coated Tablet
Registration Number
DR-XY43846
Drug Classification
Prescription Drug (RX)
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