Atenurix Special Precautions

Cardio-vascular disorders: Treatment with Febuxostat in patients with pre-existing major cardiovascular diseases (e.g. myocardial infarction, stroke or unstable angina) should be avoided, unless no other therapy options are appropriate. 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. The incidence of investigator-reported cardiovascular APTC events in the combined Phase 3 studies (APEX, FACT and CONFIRMS studies) was 0.7 vs. 0.6 events per 100 PYs. In the long-term extension studies the incidences of investigator-reported APTC events were 1.2 and 0.6 events per 100 PYs for Febuxostat and allopurinol, respectively. No statistically significant differences were found and no causal relationship with Febuxostat was established. Identified risk factors among these patients were a medical history of atherosclerotic disease and/or myocardial infarction, or of congestive heart failure.
In the post registrational CARES trial the rate of MACE events was similar in Febuxostat versus allopurinol treated patients (HR 1.03; 95% Cl 0.87-1.23), but a higher rate of cardiovascular deaths was observed (4.3% vs. 3.2% of patients; HR 1.34; (95% Cl 1.03-1.73).
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, hematological, 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 patients with Lesch-Nyhan Syndrome is not recommended.
Mercaptopurine/azathioprine: Febuxostat use is not recommended in patients concomitantly treated with mercaptopurine/azathioprine as inhibition of xanthine oxidase by Febuxostat may cause increased plasma concentrations of mercaptopurine/azathioprine that could result in severe toxicity.
No interaction studies have been performed in humans.
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 400 mg 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. No data is available for Febuxostat 120 mg.
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 function.
Lactose: Febuxostat Tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Sodium: This medicinal product contains less than 1 mmol sodium (23mg) per tablet, that is to say essentially 'sodium-free'.
Effects on Ability to Drive and Use Machines: Somnolence, dizziness, paresthesia 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 Tablets does not adversely affect performance.