非布司他的详细说明书

(feburic) instruction manual

Generic name: Febuxostat

Product name: uloric

Full names: febuxostat, febuxostat, feburic, febuxostat, uloric, zurig

Indications: For the treatment of chronic hyperuricemia (gout). 

Dosage: Start with febuxostat at 10 mg/day for 2 weeks, then increase to 20 mg/day for 4 weeks, then increase to 40 mg/day. Starting with a low dose and gradually increasing the dose can prevent acute gout attacks caused by initial changes in blood uric acid levels. Treat with febuxostat 40 mg/day for 6 months, and check the uric acid level regularly. Generally, it takes 6 months to clean up excess blood uric acid in the body. 

After 6 months of treatment: (1) If the blood uric acid level remains between 240 umol/l and 360 umol/l, maintain febuxostat 40 mg/day treatment. (2) If the blood uric acid level is higher than 360 umol/l, increase the dose of fexostatin by 60 mg/day, up to a maximum of 80 mg/day, and monitor blood uric acid, liver and kidney function regularly. (3) If the blood uric acid level is lower than 240 umol/l, the dose of febuxostat can be reduced to 20 mg/day and the treatment can be maintained for 6 months. 

Adverse reactions:

Major side effects: 1. Liver function damage (unknown frequency), because the increase in AST (GOT) and ALT (GPT) is accompanied by liver function damage, patients should have regular examinations and discontinue medication if they are found to be unwell. 2. Allergy (unknown frequency), systemic rash, skin rash, etc. Patients should be checked regularly and discontinue medication if any discomfort is found. 

Other side effects: 1. (Unknown frequency): Decreased number of platelets, anemia; 2. (Less than 1%): Decreased number of white blood cells; 3. (Less than 1%): Increased TSH; 4. (Unknown frequency) Headache, abnormal taste; 5. (Less than 1%) Numbness in hands and feet, dizziness; 6. Rapid heartbeat; 7. (Less than 1%) Abnormal electrocardiogram; 8 . (Less than 1%) Diarrhea, abdominal discomfort, nausea, and abdominal pain; 9. (1%-5%) Abnormal liver function test values [increased ALT (GPT), increased GOT (AST), γ- GTP, etc.) increase; 10. (unknown frequency) urticaria; 11. (less than 1%) rash, pruritus, erythema; 12. (less than 1%) joint pain; 13. (1%-5%) limb pain, limb discomfort, increased CK (CPK), muscle pain; 14 . (Unknown frequency) Decreased urine output; 15. (Less than 1%) Increased β2 microglobulin in urine, increased creatinine in blood, and increased blood urea; 16. (Unknown frequency) Edema; 17. (Less than 1%) Fatigue, thirst, increased blood triglycerides, and increased CRP. 

Contraindications: 1. Patients with past allergies to the essential ingredients; 2. Patients taking sulfhydryl-containing drugs or azathioprine tablets at the same time. 

Precautions: Due to the rapid decrease in serum uric acid concentration in the early stage of taking febuxostat, uric acid deposited in tissues can be mobilized, so symptoms similar to gout attacks may occur. In this case, nonsteroidal anti-inflammatory drugs or colchicine can be used for preventive administration. In addition, some patients need to be monitored for symptoms related to myocardial infarction and liver damage during febuxostat treatment.

  Storage: Store in a cool place.

Mechanism of action: Febuxostat can be rapidly and extensively absorbed by >80% after oral administration, with a tmax of approximately 1.0 to 1.8 hours. Febuxostat does not accumulate in the body after multiple oral doses of febuxostat administered daily. The effect of multiple doses of 80 mg of febuxostat on reducing serum uric acid concentration is not affected by food, so the clinical use of febuxostat does not require consideration of food factors. After oral administration of 10 mg to 300 mg of febuxostat, the apparent steady-state volume of distribution (Vss/F) is 29 to 75 L. The plasma protein binding rate of febuxostat is approximately 99.2% (mainly to albumin). Four hours after oral administration of febuxostat, the unchanged drug in plasma accounted for 84%-96% of the total radioactivity. The plasma half-life of febuxostat is 5 to 8 hours. Taking the drug once a day will reach steady-state plasma concentration within 1 week. Febuxostat is mainly eliminated from the blood by being metabolized by the liver into glucuronide conjugates, and a smaller amount is oxidized and metabolized by CYP450 in the liver. Glucuronide-conjugated febuxostat is excreted in the urine, and less than 4% of febuxostat is excreted unchanged in the urine after oral administration. 

Efficacy and safety:

A multicenter, double-blind, randomized phase II clinical study evaluated the safety and efficacy of febuxostat in gout. A total of 136 male and 17 female gout patients were randomly assigned to receive placebo or febuxostat (40, 80 or 120 mg/d). After 4 weeks, tests found that the serum uric acid concentration of patients in each dose group of febuxostat was significantly lower than before treatment, with an average decrease of 3 in each group from low to high doses. 7%, 44% and 59%, while patients in the placebo group only decreased by 2%; the vast majority of patients persisted in completing the trial. The incidence of adverse reactions in the febuxostat and placebo groups was similar, and most of these adverse reactions were mild and self-limiting, with common ones including diarrhea, pain, back pain, headache and joint pain.

A phase III clinical trial compared the efficacy of febuxostat (80 and 120 mg/d) and allopurinol (300 mg/d) in parallel. A 1-year study of 760 patients showed that compared with the allopurinol group, more patients in the febuxostat group achieved the main trial efficacy indicator - the sUA concentration was measured below 60 mg/L in the last 3 months (all subjects were gout patients, and the sUA concentration before the trial were all above 80 mg/L); after 52 weeks of treatment, the area of tophi was not significantly reduced (tophus is unique to gout) aggregates of urate crystals), but in the high-dose group in the early stages of the trial, this effect was more obvious; in each treatment group, patients with sUA concentrations reaching the target (<60 mg/L) were less likely to have gout attacks, and their tophi area was more significantly reduced; adverse reactions and their incidence rates were similar in each treatment group, including abnormal liver function, diarrhea, headache, joint-related signs and symptoms, and musculoskeletal/connective tissue symptoms.