非布司他的中文说明书

Chinese instruction manual

Name and properties: Febuxostat/Febuxostat; 40mg, 80mg tablets.

Description: Zurig (febuxostat) is a non-purine selective inhibitor of xanthine oxidase. Its chemical name is 2-[3-cyano-4-(2-isobutoxy-phenyl)-4-methylthiazole-5-carboxylic acid. Molecular formula: C16H16N2O3S.

Qualitative and Quantitative Ingredients: Zurig (febuxostat) tablets are for oral administration.

1. Zurig (Febuxostat) tablets 40mg, each film-coated tablet contains: Febuxostat 40mg

2. Zurig (Febuxostat) tablets 80 mg. Each film-coated tablet contains: Febuxostat 80 mg.

clinical pharmacology

Mechanism of action

Febuxostat is a potent non-purine selective inhibitor of xanthine oxidase (XO). It achieves the therapeutic effect of reducing serum uric acid by selectively inhibiting xanthine oxidase. Uric acid is the end product of purine metabolism and is produced in the cascade reaction of hypoxanthine → xanthine → uric acid. Each step of the conversion is catalyzed by xanthine oxidase. Febuxostat has been shown to effectively inhibit both the oxidized and reduced forms of xanthine oxidase. Febuxostat at therapeutic concentrations does not inhibit other enzymes involved in purine or pyrimidine metabolism, namely guanine deaminase, hypoxanthine guanine phosphoribosyltransferase, orotate phosphoribosyltransferase, orotate monophosphate decarboxylase, or purine nucleoside phosphorylase.

Pharmacokinetics

absorb

Febuxostat is rapidly and extensively absorbed after oral administration, with a peak time of approximately 1.0-1.5 hours and 84% absorption. There is no accumulation of febuxostat when therapeutic doses are applied every 24 hours. After one or more oral doses of 80 mg and 120 mg daily, peak concentrations are approximately 2.8-3.2 μg/mL and 5.0-5.3 μg/mL, respectively. If administered with a high-fat meal, the peak concentration was reduced by 49% and 38%, and the area under the curve was reduced by 18% and 16%, respectively, at a dose of 80 mg per day or once per day at a dose of 120 mg. However, no clinically significant change in the percentage reduction in serum uric acid concentration was observed.

Febuxostat is eliminated by hepatic and renal pathways, and the average apparent half-life of febuxostat is approximately 5-8 hours. Special Populations Renal Impairment Compared with patients with normal renal function, the peak concentration of febuxostat did not change after multiple doses of 80 mg of febuxostat in patients with mild, moderate or severe renal insufficiency. No dose adjustment is required in patients with mild or moderate renal impairment.

Hepatic Impairment Compared with patients with normal liver function, the peak concentration and area under the curve of febuxostat and its metabolites changed significantly in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment after multiple doses of 80 mg of febuxostat.

Treatment indications

Zurig (febuxostat) is indicated for the long-term treatment of hyperuricemia in patients with gout.

Usage and dosage

For the treatment of chronic hyperuricemia in patients with gout, Zurig (febuxostat) 40mg or 80mg is recommended, once a day. The recommended starting dose of Zurig (Febuxostat) is 40 mg once daily. For patients who fail to achieve serum uric acid levels below 6 mg/dL (360 μmol/L) after two weeks of 40 mg, Zurig (Febuxostat) 80 mg is recommended. There are no food or antacids to consider when taking Zurig (febuxostat).

Special groups

Renal Impairment: No dose adjustment is required when taking febuxostat in patients with mild to moderate renal impairment.

Adverse reactions:

Common: headache, diarrhea, nausea, rash, abnormal liver function.

Uncommon: increased blood amylase, decreased platelet count, increased blood creatinine, decreased hemoglobin, increased blood urea, increased lactate dehydrogenase (LDH), increased triglycerides, dizziness, abnormal sensation, drowsiness, taste changes, abdominal pain, gastroesophageal reflux disease, vomiting, dry mouth, indigestion, Constipation, frequent bowel movements, flatulence, gastrointestinal discomfort, kidney stones, hematuria, frequent urination, dermatitis, urticaria, itching, joint pain, arthritis, myalgia, muscle spasm, musculoskeletal pain, weight gain, increased appetite, high blood pressure, flushing, hot flashes, fatigue, edema, flu-like syndrome, decreased libido.

Rare:

Palpitations, renal insufficiency, weakness, thirst, nervousness, insomnia.

Contraindications

Febuxostat is contraindicated in the following patients:

-Hypersensitivity to the active substance or any excipients

- Are being treated with azathioprine, mercaptopurine or theophylline

-Asymptomatic hyperuricemia

pregnancy

Febuxostat should not be used during pregnancy.

wet nurse

Febuxostat should not be used during breastfeeding.

Things to note

-Febuxostat is not recommended for patients with ischemic heart disease or congestive heart failure.

-An increase in gout attacks is common after starting febuxostat. This increase is due to a decrease in serum uric acid levels, resulting in mobilization of urate deposited in tissues. To prevent gout attacks when starting febuxostat, concomitant prophylactic treatment with a nonsteroidal anti-inflammatory drug or colchicine is recommended.

- As with other urate-lowering drugs, in patients with extremely increased urate formation rates (e.g. malignant diseases and their treatment, Lesch-Nyhan syndrome), in rare cases the absolute concentration of xanthines in the urine can increase to the point where deposition in the urinary tract occurs. Since there is no experience with the use of febuxostat, its use in these populations is not recommended.

- Laboratory evaluation of liver function is recommended, for example, every 2-4 months after starting febuxostat and periodically thereafter.

drug interactions

-Naproxen and other glucuronidation inhibitors:

Febuxostat metabolism is dependent on glucuronosyltransferase. Drugs that inhibit glucuronidation, such as NSAIDs and probenecid, may theoretically affect the elimination of febuxostat. In healthy subjects, concurrent use of febuxostat and naproxen 250 mg twice daily was associated with increased febuxostat exposure. Febuxostat can be used concurrently with naproxen, and no dose adjustment of febuxostat or naproxen is required.

-Glucuronidation inducers:

Potent inducers of glucuronosyltransferase may result in increased metabolism and reduced efficacy of febuxostat. Therefore, it is recommended to monitor serum uric acid 1 to 2 weeks after starting administration of a potent inducer of glucuronidation. Conversely, discontinuation of treatment with an inducer may result in increased plasma levels of febuxostat.

overdose

Patients with overdose should receive symptomatic and supportive treatment.

storage

Store at 25℃ (15-30℃), away from sunlight and moisture.