FAXOFER 40 Tablet

Indication:

FAXOFER 40 is a xanthine oxidase (XO) inhibitor indicated for the chronic management of hyperuricemia in patients with gout.

FAXOFER 40 is not recommended for the treatment of asymptomatic hyperuricemia.

Dosage:

For treatment of hyperuricemia in patients with gout, FAXOFER 40 is recommended at 40mg or 80mg once daily.

The recommended starting dose of FAXOFER 40 is 40mg once daily. For patients who do not archieve a serum uric acid (sUA) less than 6mg per dL after 2 weeks with 40mg, Febuxostat 80mg is recommended.

FAXOFER 40 can be taken without regard to food or antacid use.

Special Populations: No dose adjustment is necessary when administering Febuxostat in patients with mild to moderate renal impairment.

The recommended starting dose of Febuxostat is 40mg once daily. For patients who do not achieve a sUA less than 6mg per dL after 2 weeks with 40mg , Febuxostat 80mg is recommended. No dose adjustment is necessary in patients with mild to moderate hepatic impairment

Uric acid level: Testing for the target serum uric acid level of less than 6 mg per dL may be performed as early as 2 weeks after initiating Febuxostat therapy.

Gout Flares: Gout flares may occur after initiation of Febuxostat due to changing serum uric acid level resulting in mobilization of urate from tissue deposits. Flare prophylaxis with a non-steroidal anti-inflammation drug (NSAIDs) or colchicine is recommended upon initiation of Febuxostat. Prophylactic therapy may be beneficial for up to six months

If a gout flare occurs during Febuxostat treatment, Febuxostat need not be discontinued. The gout flare should be managed concurrently, as appropriate for the individual patient.

Febuxostat is contraindicated in patients being treated with azathioprine, mercaptopurine or theophylline.

Hypersensitivity to the active substance or to any of the excipients

Clinical trials experience:

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 2757 subjects with hyperuricemia and gout were treated with Febuxostat 40mg or 80 mg daily in clinical studies. For Febuxostat 40mg, 559 patients were treated for ≥ 6 months. For Febuxostat 80mg, 1377 subjects were treatment for ≥ 6 months, 674 patients were treatment for ≥ 1 year and 515 patients were treated for ≥ 2 years.

Most common advere reactions:

- liver function abnormalities

- nausea

- arthralgia

- rash

Less common adverse reactions:

- blood and lymphatic system disorders: anemia, idiopathic thrombocytopenic purpura, leukocytosis/leukopenia, neutropenia, pancytopenia, splenomegaly, thrombocytopenia.

- Cardiac disorders: angina pectoris, atrial fibrilation/flutter, cardiac murmur, ECG abnormal, palpitation, sinus bradycardia, tachycardia.

- Ear and labyrinth disorders: deafness, tinnitus, vertigo.

- Eye disorders: vision blurred.

- Gastrointestinal disorders: abdominal distention, abdominal pain, constipation, dry mouth, dyspepsia, flatulence, frequent stools, gastritis, gastroesophageal reflux disease, gastrointestinal discomfort, gingival pain, haematemesis, hyperchlorhydria, hematochezia, mouth ulceration, pancreatitis, peptic ulcer, vomiting.

- general disorders and administration site conditions

- Hepatobiliary disorder

- Immune system disorder

- infections and infestations: herpes zoster

- Procedural complications: confusion

- Metabolism and nutrition disorders

- nervous system disorders

- Psychiatric disorders:

- Renal and urinary disorders

- Respiratory, thoracic and mediastinal disorders

- Skin and subcutaneous tissue disorders

- Vascular disorders

Xanthine Oxidase Substate Drugs: Febuxostat is an XO inhibitor. Drug interaction studies of Febuxostat with drugs that are metabolized by XO (e.g., theophylline, mercaptopurine, azathioprine) have not beenconducted. Inhibition of XO Febuxostat may cause increased plasma concentrations of these drugs leading to toxicity. Febuxostat is contraindicated in patients being treated with azathioprine, mercaptopurine, or theophylline.

Cytotoxic Chemotherapy Drugs: Drug interaction studies of Febuxostat with cytotoxic chemotherapy have not been conducted. No data are available regarding the safety of Febuxostat does not have clinically significant interactions with colchicine, naproxen, indomethacin, hydrochlorothiazide, warfarin or desipramine. Therefore, Febuxostat may be used concomitantly with these medicantions.

In vivo drug interaction studies: Based on drug interaction studies in healthy subjects, Febuxostat does not have clinically significant interactions with colchicine, neproxen, indomethacin, hydrochlorothiazine, warfarin or desipramine. Therefore, Febuxostat may be used concomitantly with these medications.

Prenancy: data on a very limited number of exposed pregnancies have not indicated any adverse effects of febuxostat on pregnancy or on the health of the foetus/new born child. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development or parturition. The potential risk for human is unknown. Febuxostat should not be used during pregnancy.

Breastfeeding: it is unknown whether febuxostat is excreted in human breast milk. Animal studies have shown excretion of this active substance in breast milk and an impaired development of sucking pups. A risk to a sucking infant cannot be excluded. Febuxostat should not be used while breastfeeding .

Fertility: in animals, reproduction studies up to 48 mg/kg/day showed no dose-dependent adverse effects on fertility. The effect of Febuxostat on human fertility is unknown.

Uric acid is the end product of purine metabolism in humans and is generated in the cascade of hypoxanthine xanthine uric acid. Both steps in the above transformations are catalyzed by xanthine oxidase (XO). Febuxostat is a 2-arylthlazole derivative that achieves its therapeutic effect of decreasing serum uric acid by selectively inhibiting XO. Febuxostat is a potent, non-purine selective inhibit of XO (NP-SIXO) with an in vitro inhibition Ki value less than one nanomolar. Febuxostat has been shown to potently inhibit both the oxidized and reduced forms of XO. At therapeutic concentrations febuxostat does not inhit other enzymes invovled in purine or pyrimidine metabolism, namely, guanine, deaminase, hypoxanthine guanine phosporibosyltransferase, orotate phosphoribosyltransferase, orotidine monophosphate decarboxylase or purine nucleoside phosphorylase.