Rivex 80

Yellow, oblong, biconvex film coated tablet with engraved 80 on one side and plain on the other.

Pharmacology: Pharmacodynamics: Selectively inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid thereby decreasing uric acid. At therapeutic concentration does not inhibit other enzymes involved in purine and pyrimidine synthesis.
Pharmacokinetics: Absorption: The oral bioavailability is approximately 75% to 85%.
C_max decrease by 49% and AUC decrease by 19% when taken with food. However. no clinically significant effect over time.
Distribution: Febuxostat is highly bound, 98% to 99% to plasma proteins, primarily albumin.
Volume of distribution is 41 to 50 L.
Metabolism: Febuxostat is extensively metabolized by conjugation via uridine diphosphate glucuronosyltransferases (UGTs) 1A1, 1A8, and 1A9 and oxidation via cytochrome P450 (CYP) 1A1, 1A2, 2C8, and 2C9 as well as non-P450 enzymes.
Excretion: Renal Excretion: Approximately 49% of the dose was excreted in the urine as unchanged Febuxostat (3%), the acyl glucuronide metabolite (30%), other known oxidative metabolites and conjugates (13%), and unknown metabolites (3%).
Feces: Approximately 45% of the dose was excreted in the feces as unchanged Febuxostat (12%), the acyl glucuronide metabolite (1%), other known oxidative metabolites and conjugates (25%), and unknown metabolites (7%).
Elimination Half-life: Febuxostat elimination half-life is 5 to 8 hours.

Febuxostat is indicated for: The treatment of chronic hyperuricemia in conditions where urate deposition has already occurred (including a history, or presence of tophus and/or gouty arthritis); The prevention and treatment of hyperuricaemia in adult patients receiving chemotherapy for haematologic malignancies at intermediate to high risk of tumor lysis syndrome (TLS).

Gout: Initially 80 mg once daily without regard to food. If serum uric acid is greater than 6 mg/dL (357 μmol/L) after 2-4 weeks of initial dose, the dose of 120 mg once daily may be considered. Febuxostat works sufficiently quickly to allow retesting of the serum uric acid after 2 weeks. The therapeutic target is to decrease and maintain serum uric acid below 6 mg/dL (357 μmol/L). Gout flare prophylaxis of at least 6 months is recommended.
Tumor lysis syndrome (TLS): The recommended oral dose of Febuxostat is 120 mg once daily without regard to food, should be started 2 days before start of cytotoxic therapy and continued for 7-9 days, according to chemotherapy duration.
Geriatric: No dosage adjustment necessary.
Pediatric: The safety and the efficacy of febuxostat in children aged below the age of 18 years have not been established. No data are available.
Renal Impairment: No dosage adjustments are considered necessary in patients with mild or moderate renal impairment, but the efficacy and safety have not been evaluated in those with severe renal impairment (creatinine clearance of less than 30 mL/min).
Hepatic Impairment: The recommended oral dose of Febuxostat in patients with mild hepatic impairment is 80 mg daily. Limited information is available in patients with moderate impairment. Efficacy and safety of Febuxostat has not been studied in those with severe (Child-Pugh class C) hepatic impairment.
Administration: Administer with or without meals.

There were no reports of human overdose. Treatment is symptomatic and supportive.

Hypersensitivity to Febuxostat or any component of the formulation.
Concurrent use with azathioprine or mercaptopurine.

Cardiovascular: Treatment with Febuxostat in patients with ischemic heart disease or congestive heart disease is not recommended. Cardiovascular thromboembolic events (cardiovascular deaths, non-fatal myocardial infarctions, and non-fatal strokes) have been reported. Gout patients with established cardiovascular disease had a higher rate of cardiovascular death when treated with Febuxostat compared to patients treated with allopurinol in a cardiovascular outcomes study. 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 when treatment with allopurinol is not advisable. Consider risks and benefits when prescribing or continuing Febuxostat therapy. Consider prophylactic low-dose aspirin in patients with a history of cardiovascular disease. Monitor patients for signs and symptoms of cardiovascular events.
Dermatologic: Serious skin and hypersensitivity reactions, including Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis, have been reported. Discontinue use if suspected. Use with caution in patients with previous similar skin reactions to allopurinol.
Endocrine and Metabolic: Use is not recommended with conditions which greatly increase urate formation rate (eg, malignant disease and treatment, Lesch-Nyhan syndrome).
Hepatic: Postmarketing cases of hepatic failure (both fatal and nonfatal) have been reported (causal relationship has not been established). Liver function tests should be evaluated at baseline and periodically thereafter. Evaluate liver function tests promptly in patients experiencing signs and symptoms of hepatic injury (eg, fatigue, liver function tests (eg, ALT >3 x ULN). Permanently discontinue use if no other explanation for the abnormalities is elucidated and in patients who develop ALT >3 x ULT and serum total bilirubin >2 x ULN. All other patients may be cautiously restarted on Febuxostat. Use with caution in patients with severe hepatic impairment (Child-Pugh class C); has not been studied.
Musculoskeletal: Increase in gout flares may occur after initiating treatment. Prophylactic treatment is recommended. Administer concurrently with an NSAID or colchicine (up to 6 months) to prevent gout flare.

Pregnancy: There are insufficient human data regarding the use of Febuxostat in pregnant women to determine the risk of adverse fetal outcomes. In animal studies, there was no evidence of teratogenicity when rats and rabbits were given oral Febuxostat, however, there was an increase in neonatal mortality and reduction in neonatal body weight gain when pregnant rats were given oral Febuxostat. Following oral administration, Febuxostat crossed the placenta in pregnant rats and was detected in fetal tissues. Febuxostat should not be used during pregnancy.
Lactation: There are no data regarding the presence of Febuxostat in human milk, and the effects, if any, on a breastfeeding infant or milk production are unknown. Febuxostat is excreted in rat milk up to approximately 7 times that of the plasma concentration. Febuxostat should not be used while breastfeeding.

Common: Dermatologic: Rash (0.5% to 1.6%).
Gastrointestinal: Diarrhea (Greater than 1%), Nausea (1.1% to 1.3%).
Musculoskeletal: Arthralgia (0.1% to 1.1%).
Serious: Cardiovascular: Cardiovascular death, Myocardial infarction.
Dermatologic: Drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, Toxic epidermal necrolysis.
Hepatic: Abnormal liver function (4.6% to 6.6%), ALT/SGPT level raised (3%), Aspartate aminotransferase serum level raised (2%).
Musculoskeletal: Acute gout, Myositis, Rhabdomyolysis.
Neurologic: Cerebrovascular accident.

Concomitant use of azathioprine or mercaptopurine and Febuxostat is contraindicated due to the risk of azathioprine or mercaptopurine toxicity. Similarly, caution is advised when Febuxostat is given with theophylline. Concomitant use of Febuxostat and theophylline may cause elevated levels of 1-methylxanthine, one of the major metabolites of theophylline. Although no dose adjustment is warranted for theophylline when used concomitantly with Febuxostat, caution should be used since the safety of long-term exposure to 1-methylxanthine has not been determined.

Store below 30°C.

Hyperuricemia & Gout Preparations

M04AA03 - febuxostat ; Belongs to the class of preparations inhibiting uric acid production. Used in the treatment of gout.

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