Febuxostat

Febuxostat is a 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. …

• Recommended dosage is 40 mg or 80 mg once daily
• The recommended starting dosage is 40 mg once daily
• For patients who do not achieve a serum uric acid (sUA) less than 6 mg/dL after 2 weeks, the recommended dosage is 80 mg once daily
• Patients with severe renal impairment: Limit the dosage to 40 mg once daily
• Flare prophylaxis is recommended upon initiation of febuxostat tablets
• Can be administered without regard to food or antacid use
• Recommended Dosage The recommended febuxostat tablets dosage is 40 mg or 80 mg once daily
• The recommended starting dosage of febuxostat tablets is 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 ]
• Concurrent prophylactic treatment with a non-steroidal anti-inflammatory drug (NSAID) or colchicine is recommended [see Dosage and Administration and Warnings and Precautions ]
• Dosage Recommendations in Patients with Renal Impairment and Hepatic Impairment The recommended dosage of febuxostat tablets is 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 and Clinical Pharmacology ] . …

Febuxostat tablets 40 mg are Light yellow to yellow color, biconvex round shaped film-coated tablets debossed with “FEB” on one side and “40” on the other side. Febuxostat tablets 80 mg are Light yellow to yellow color, biconvex oval shaped film-coated tablets debossed with “FEB” on one side and “80” on the other side. Tablet: 40 mg, 80 mg. ( 3 )

• Safety and effectiveness of febuxostat
• In pediatric patients have not been established

No dose adjustment is necessary in elderly patients. Of the total number of patients in Studies 1, 2, and 3 (clinical studies of febuxostat in the treatment of gout) [see Clinical Studies (14.1) ], 16% were 65 and over, while 4% were 75 and over. Comparing patients in different age groups, no clinically significant differences in safety or effectiveness were observed but greater sensitivity of some older individuals cannot be ruled out. …

• Advise the patient to read the FDA-approved patient labeling ( Medication Guide )
• CV Death Inform patients that gout patients with established CV disease treated with febuxostat had a higher rate of CV death compared to those treated with allopurinol in a CV outcomes study
• Inform all patients of the higher rate of CV death with febuxostat compared to allopurinol
• Alert all patients (those with and without CV disease) for the development of signs and symptoms of CV events and to seek medical care promptly should they occur [see Warnings and Precautions ] . …

• Febuxostat tablets are contraindicated in patients being treated with azathioprine or mercaptopurine [see Drug Interactions ]
• Febuxostat tablets are contraindicated in patients being treated with azathioprine or mercaptopurine

Concomitant administration of febuxostat with XO substrate drugs, azathioprine or mercaptopurine could increase plasma concentrations of these drugs resulting in severe toxicity. ( 7 ) 7.1 Xanthine Oxidase Substrate Drugs Febuxostat is an XO inhibitor. Based on a drug interaction study in healthy patients, febuxostat altered the metabolism of theophylline (a substrate of XO) in humans [see Clinical Pharmacology (12.3) ]. Therefore, use with caution when coadministering febuxostat with theophylline. …

Gout Flares : An increase in gout flares is frequently observed after initiation of febuxostat. If a gout flare occurs during treatment, febuxostat need not be discontinued. Prophylactic therapy (i.e., non-steroidal anti-inflammatory drug or colchicine) upon initiation of treatment may be beneficial for up to six months. ( 2.4 , 5.2 ) Hepatic Effects : Cases of hepatic failure, some fatal, have been reported. If liver injury is detected, promptly interrupt febuxostat and treat cause, if possible, to resolution or stabilization. Permanently discontinue febuxostat if liver injury is confirmed, and no alternate etiology can be found. …

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) ] Adverse reactions in ≥ 1% of patients treated with febuxostat are liver function abnormalities, nausea, arthralgia, and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

8.1 Pregnancy Risk Summary Limited available data with febuxostat use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. No adverse developmental effects were observed in embryo-fetal development studies with oral administration of febuxostat to pregnant rats and rabbits during organogenesis at doses that produced maternal exposures up to 40 and 51 times, respectively, the exposure at the maximu …

Febuxostat was studied in healthy patients in doses up to 300 mg daily for seven days without evidence of dose-limiting toxicities. No overdose of febuxostat was reported in clinical studies. Patients should be managed by symptomatic and supportive care should there be an overdose.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.