Presentation and Status in Health Basket
Film Coated Tablets
28 X 80 mg
The recommended oral dose of febuxostat is 80 mg once daily without regard to food. If serum uric acid is > 6 mg/dL (357 μmol/L) after 2-4 weeks, febuxostat 120 mg once daily may be considered. This drug 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.
Older people: No dose adjustment is required in the elderly.
Renal impairment: The efficacy and safety have not been fully evaluated in patients with severe renal impairment (creatinine clearance <30 mL/min). No dose adjustment is necessary in patients with mild or moderate renal impairment.
Hepatic impairment: The efficacy and safety of febuxostat has not been studied in patients with severe hepatic impairment (Child Pugh Class C).The recommended dose in patients with mild hepatic impairment is 80 mg. Limited information is available in patients with moderate hepatic impairment.
Treatment of chronic hyperuricaemia in conditions where urate deposition has already occurred (including a history, or presence of, tophus and/or gouty arthritis).
Hypersensitivity to the active substance or to any of the excipients.
Cardio-vascular disorders: Treatment with febuxostat in patients with ischaemic heart disease or congestive heart failure is not recommended.
Medicinal product allergy / hypersensitivity: Rare reports of serious allergic/hypersensitivity reactions, including life-threatening Stevens – Johnson syndrome, Toxic epidermal necrolysis and acute anaphylactic reaction/shock, have been collected in the post-marketing experience. In most cases, these reactions occurred during the first month of therapy with febuxostat. Some, but not all of these patients reported renal impairment and/or previous hypersensitivity to allopurinol. Severe hypersensitivity reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) were associated with fever, haematological, renal or hepatic involvement in some cases. Patients should be advised of the signs and symptoms and monitored closely for symptoms of allergic/hypersensitivity reactions. Febuxostat treatment should be immediately stopped if serious allergic/hypersensitivity reactions, including Stevens – Johnson syndrome, occur since early withdrawal is associated with a better prognosis. 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.
Acute gouty attacks (gout flare): Febuxostat treatment should not be started until an acute attack of gout has completely subsided. Gout flares may occur during initiation of treatment due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. At treatment initiation with febuxostat flare prophylaxis for at least 6 months with an NSAID or colchicine is recommended. If a gout flare occurs during febuxostat treatment, it should not be discontinued. The gout flare should be managed concurrently as appropriate for the individual patient. Continuous treatment with febuxostat decreases frequency and intensity of gout flares.
Xanthine deposition: In patients in whom the rate of urate formation is greatly increased (e.g. 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. As there has been no experience with febuxostat, its use in these populations is not recommended.
Mercaptopurine/azathioprine: Febuxostat use is not recommended in patients concomitantly treated with mercaptopurine/azathioprine. Where the combination cannot be avoided patients should be closely monitored. A reduction of dosage of mercaptopurine or azathioprine is recommended in order to avoid possible haematological effects.
Organ transplant recipients: As there has been no experience in organ transplant recipients, the use of febuxostat in such patients is not recommended.
Theophylline: Co-administration of febuxostat 80 mg and theophylline 400mg single dose in healthy subjects showed absence of any pharmacokinetic interaction .Febuxostat 80 mg can be used in patients concomitantly treated with theophylline without risk of increasing theophylline plasma levels.
Liver disorders: During the combined phase 3 clinical studies, mild liver function test abnormalities were observed in patients treated with febuxostat (5.0%). Liver function test is recommended prior to the initiation of therapy with febuxostat and periodically thereafter based on clinical judgment.
Thyroid disorders: Increased TSH values (>5.5 μIU/mL) were observed in patients on long-term treatment with febuxostat (5.5%) in the long term open label extension studies. Caution is required when febuxostat is used in patients with alteration of thyroid.
Lactose: Febuxostat tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: Somnolence, dizziness, paraesthesia and blurred vision have been reported with the use of Febuxostat. Patients should exercise caution before driving, using machinery or participating in dangerous activities until they are reasonably certain that febuxostat does not adversely affect performance.
For full details see prescribing information.
Gout flares, liver function abnormalities, diarrhea, nausea, headache, rash and edema.
For full details see prescribing information.
Mercaptopurine/azathioprine: On the basis of the mechanism of action of febuxostat on XO inhibition concomitant use is not recommended. Inhibition of XO by febuxostat may cause increased plasma concentrations of these drugs leading to toxicity. Drug interaction studies of febuxostat with drugs that are metabolized by XO have not been performed. Drug interaction studies of febuxostat with cytotoxic chemotherapy have not been conducted. No data is available regarding the safety of febuxostat during cytotoxic therapy.
Rosiglitazone/CYP2C8 substrates: Febuxostat was shown to be a weak inhibitor of CYP2C8 in vitro. In a study in healthy subjects, coadministration of 120 mg febuxostat QD with a single 4 mg oral dose of rosiglitazone had no effect on the pharmacokinetics of rosiglitazone and its metabolite N-desmethyl rosiglitazone, indicating that febuxostat is not a CYP2C8 enzyme inhibitor in vivo. Thus, co-administration of febuxostat with rosiglitazone or other CYP2C8 substrates is not expected to require any dose adjustment for those compounds.
Pregnancy and Lactation
Pregnancy: Data on a very limited number of exposed pregnancies have not indicated any adverse effects of febuxostat on pregnancy or on the health of the foetus/new born child.
Lactation: It is unknown whether febuxostat is excreted in human breast milk.
Patients with an overdose should be managed by symptomatic and supportive care.