FEBUXOSTAT — febuxostat tablet, film coated
MSN LABORATORIES PRIVATE LIMITED
Gout patients with established cardiovascular (CV) disease treated with febuxostat had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study [ see Warnings and Precautions (5.1)].
Consider the risks and benefits of febuxostat when deciding to prescribe or continue patients on febuxostat. 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 treatment with allopurinol is not advisable [see Indications and Usage (1)].
Febuxostat tablets are xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in adult patients with gout who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to allopurinol, or for whom treatment with allopurinol is not advisable.
Limitations of Use:
Febuxostat tablets are not recommended for the treatment of asymptomatic hyperuricemia.
The recommended febuxostat tablets dosage is 40 mg or 80 mg once daily.
The recommended starting dosage of febuxostat tablets are 40 mg once daily. For patients who do not achieve a serum uric acid (sUA) less than 6 mg/dL after two weeks, the recommended febuxostat tablets dosage is 80 mg once daily.
Febuxostat tablets can be taken without regard to food or antacid use [see Clinical Pharmacology (12.3)].
The recommended dosage of febuxostat tablets are limited to 40 mg once daily in patients with severe renal impairment. No dose modification is necessary when administering febuxostat tablets in patients with mild or moderate renal impairment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
No dosage modification is necessary in patients with mild to moderate hepatic impairment [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Testing for the target serum uric acid level of less than 6 mg/dL may be performed as early as two weeks after initiating febuxostat tablets therapy.
Gout flares may occur after initiation of febuxostat tablets due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits. Flare prophylaxis with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended upon initiation of febuxostat tablets. Prophylactic therapy may be beneficial for up to six months [see Clinical Studies (14.1)].
If a gout flare occurs during febuxostat tablets treatment, febuxostat tablets need not be discontinued. The gout flare should be managed concurrently, as appropriate for the individual patient [see Warnings and Precautions ( 5.2)] .
- 40 mg tablets are green colored, round shaped, biconvex, film coated tablets debossed with “40” on one side and “F” on other side.
- 80 mg tablets are yellow colored, capsule shaped, biconvex film coated tablets debossed with “80” on one side and plain surface on other side.
Febuxostat is contraindicated in patients being treated with azathioprine or mercaptopurine [see Drug Interactions (7)].
In a cardiovascular (CV) outcome study, gout patients with established CV disease treated with febuxostat had a higher rate of CV death compared to those treated with allopurinol. Sudden cardiac death was the most common cause of adjudicated CV deaths, 2.7% in the febuxostat group (83 of 3,098) as compared to 1.8% in the allopurinol group (56 of 3,092). Febuxostat was similar to allopurinol for nonfatal myocardial infarction (MI), nonfatal stroke and unstable angina with urgent coronary revascularization [see Clinical Studies (14.2)].
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 treatment with allopurinol is not advisable [see Indications and Usage (1)].
Consider the risks and benefits of febuxostat when deciding to prescribe or continue patients on febuxostat. Consider use of prophylactic low-dose aspirin therapy in patients with a history of CV disease. Monitor patients for the development of CV events. Inform patients about the symptoms of serious CV events and the steps to take if they occur.
After initiation of febuxostat, an increase in gout flares is frequently observed. This increase is due to reduction in serum uric acid levels, resulting in mobilization of urate from tissue deposits.
In order to prevent gout flares when febuxostat is initiated, concurrent prophylactic treatment with an NSAID or colchicine is recommended [ see Dosage and Administration (2.4)].
Cases of fatal and nonfatal hepatic failure in patients taking febuxostat have been reported. During randomized controlled studies, transaminase elevations greater than three times the upper limit of normal (ULN) were observed (AST: 2%, 2%, and ALT: 3%, 2% in febuxostat and allopurinol-treated patients, respectively). No dose-effect relationship for these transaminase elevations was noted [see Clinical Pharmacology (12.3)].
Obtain a liver test panel (serum alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, and total bilirubin) as a baseline before initiating febuxostat.
Measure liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice. In this clinical context, if the patient presents abnormal liver tests (ALT or AST greater than three times the upper limit of the reference range), interrupt febuxostat treatment while investigating the probable cause. Permanently discontinue febuxostat if liver injury is confirmed, and no alternate etiology can be found.
Permanently discontinue febuxostat in patients who have serum ALT or AST greater than three times the reference range with serum total bilirubin greater than two times the reference range without alternative etiologies because they are at risk for severe drug-induced liver injury. For patients with lesser elevations of serum ALT or bilirubin and with an alternate probable cause, treatment with febuxostat can be used with close monitoring.
Serious skin and hypersensitivity reactions, including Stevens-Johnson Syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN) have been reported postmarketing in patients taking febuxostat. Discontinue febuxostat if serious skin reactions are suspected [ see Patient Counseling Information (17)]. Many of these patients had reported previous similar skin reactions to allopurinol. Febuxostat should be used with close monitoring in these patients.
The following serious adverse reactions are described elsewhere in the prescribing information:
- Cardiovascular Death [ see Warnings and Precautions (5.1)]
- Hepatic Effects [ see Warnings and Precautions (5.3)]
- Serious Skin Reactions [ see Warnings and Precautions (5.4)]
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.