Information about Adenoxat
Composition:
Each F.C tablet contains 40 mg or 80 mg febuxostat.
CLINICAL PHARMACOLOGY
Mechanism of Action:
ADENOXAT, a xanthine oxidase inhibitor,achieves its therapeutic effect by decreasing serum uric acid. ADENOXAT is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.
Pharmacokinetics:
Absorption:
The absorption of radio labeled febuxostat following oral dose administration was estimated to be at least 49% (based on total radioactivity recovered in urine). Maximum plasma concentrations of febuxostat occurred between 1 and 1.5 hours’ post-dose. After multiple oral 40 mg and 80 mg once daily doses, C max is approximately 1.6 ± 0.6 mcg/mL (N=30), and 2.6 ± 1.7mcg/mL (N=227), respectively. Absolute bioavailability of the febuxostat tablet has not been studied.
Distribution:
The mean apparent steady state volume of distribution of febuxostat was approximately 50 L. The plasma protein binding of febuxostat is approximately 99.2% (primarily to albumin).
Metabolism:
Febuxostat is extensively metabolized by both conjugations via uridine diphosphate glucuronosyl transferase (UGT)enzymes including UGT1A1, UGT1A3, UGT1A9, and UGT2B7 and oxidation viacytochrome P450 (CYP) enzymes including CYP1A2, 2C8 and 2C9 and non-P450 enzymes. The relative contribution of each enzyme isoform in the metabolism offebuxostat is not clear. The oxidation of the isobutyl side chain leads to the formation of four pharmacologically active hydroxyl metabolites, all of which occur in plasma of humans at a much lower extent than febuxostat.
Elimination:
Febuxostat is eliminated by bothhepatic and renal pathways. Following an 80 mg oral dose of 14 C-labeled febuxostat, approximately 49% of the dose was recovered in the urine as unchanged febuxostat (3%). In addition to the urinary excretion, approximately 45% of the dose was recovered in the feces as the unchanged febuxostat (12%).
The apparent mean terminal elimination half-life (t 12/) of febuxostat was approximately 5 to 8 hours.
INDICATIONS AND USAGE:
ADENOXAT is a xanthine oxidase(XO) inhibitor indicated for the chronic management of hyperuricemia inpatients with gout.
ADENOXAT is not recommended for the treatment of asymptomatic hyperuricemia.
CONTRAINDICATIONS:
ADENOXAT is contraindicated in patients being treated with azathioprine or mercaptopurine.
WARNINGS AND PRECAUTIONS:
Gout Flare:
After initiation of ADENOXAT, 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 ADENOXAT is initiated, concurrent prophylactic treatment with an NSAID or colchicine is recommended.
Cardiovascular Events:
A higher rate of cardiovascular thromboembolic events was observed in patients treated with ADENOXAT than allopurinol in clinical trials. Monitor for signs and symptoms of myocardial infraction and strokes.
Hepatic Effects:
Post marketing reports of hepatic failure, sometimes fatal. If liver injury is detected, promptly interrupt ADENOXAT and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart ADENOXAT if liver in juryis confirmed and no alternate etiology can be found.
ADVERSE REACTIONS
Adverse reactions occurring in at least 1% of ADENOXAT-treated patients, and at least 0.5% greater than placebo, are liver function abnormalities, nausea, arthralgia, and rash.
DRUG INTERACTIONS
Feboxostat alters the metabolism of theophylline in humans. therefore, use with caution when both drugs co-administered.
Concomitant administration of ADENOXAT with, azathioprine or mercaptopurine could increase plasma concentrations of these drugs resulting in severe toxicity. Adenoxat is contraindicated inpatients being treated with azathioprine or mercaptopurine.
USE IN SPECIFIC POPULATIONS
Pregnancy:
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. ADENOXAT should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers:
Febuxostat is excreted in the milk of rats. It is not known whether this drug is excreted in human milk.
Because many drugs are excreted inhuman milk, caution should be exercised when ADENOXAT is administered to a nursing woman.
Pediatric Use:
Safety and effectiveness in pediatric patients under 18 years of age have not been established.
Geriatric Use:
No dose adjustment is necessary in elderly patients.
Renal Impairment:
No dose adjustment is necessary inpatients with mild or moderate renal impairment (Cl cr 30 to 89 mL/min). There are insufficient data in patients with severe renal impairment (Cl cr less than 30 mL/min); therefore, caution should be exercised in these patients.
Hepatic Impairment:
No dose adjustment is necessary inpatients with mild or moderate hepatic impairment. No studies have been conducted in patients with severe hepatic impairment; therefore, caution should be exercised in these patients.
Secondary Hyperuricemia:
No studies have been conducted inpatients with secondary hyperuricemia (including organ transplant recipients); ADENOXAT is not recommended for use in patients whom the rate of urateformation is greatly increased. The concentration of xanthine in urine could,in rare cases, rise sufficiently to allow deposition in the urinary tract.
Dosage and administration:
For treatment of hyperuricemia in patients with gout, ADENOXAT is recommended at 40 mg or 80 mg once daily. The recommended starting dose of ADENOXAT is 40 mg once daily. For patients who do not achieve a serum uric acid (sUA) less than 6 mg/dL after two weeks with 40mg, ADENOXAT 80 mg is recommended.
ADENOXAT can be taken without regard to foodor antacid use
OVER DOSAGE
ADENOXAT was studied in healthy subjects in doses up to 300 mg daily for seven days without evidence of dose-limiting toxicities. No overdose of ADENOXAT was reported in clinical studies.
Patients should be managed by symptomatic and supportive care when there is an overdose.
STORAGE:
Store at 25°C, away from light.
Keep all medicines out of the reach of children.
PACKAGING:
Pack of 10 or 20 F.C tablets for both strengths.