STARCOX Etoricoxib 120mg Film-Coated Tablet 1's

In clinical studies, administration of Etoricoxib at single doses up to 500 mg and multiple doses up to 150 mg/day for 21 days did not result in significant toxicity. There have been reports of acute overdosage with etoricoxib, although adverse experiences were not reported in the majority of cases. The most frequently observed adverse experiences were consistent with the safety profile for etoricoxib (e.g. gastrointestinal events, renovascular events).
In the event of overdosage, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.
Etoricoxib is not dialyzable by hemodialysis; it is not known whether etoricoxib is dialyzable by peritoneal dialysis.

 

 

Absolute contraindications: Not to be given to those patients who have history of: Stroke: Cerebrovascular Accident, CVA; Heart Attack: Myocardial Infarction, MI; Coronary Artery Bypass Graft: CABG; Uncontrolled Hypertension; Congestive Heart Failure (CHF), NYHA II - IV.

 

The use of etoricoxib, as with any drug substance known to inhibit COX-2, is not recommended in women attempting to conceive.
No clinical data on exposed pregnancies are available for etoricoxib. Studies in animals have shown reproductive toxicity. The potential for human risk in pregnancy is unknown. Etoricoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester. Etoricoxib is contraindicated in pregnancy. If woman becomes pregnant during treatment, etoricoxib must be discontinued.
Reproductive studies conducted in rats have demonstrated evidence of developmental abnormalities at doses up to 15 mg/kg/day (approximately 1.5 times the human dose [90 mg] based on systemic exposure).
At doses approximately 2 times the adult human exposure (90 mg) bases on systemic exposure, a low incidence of cardiovascular malformations and increase in post implantation loss were observed in etoricoxib-treated rabbits. No developmental effects were seen at systemic exposure of approximately equal to or less than daily human dosage (90 mg). However, animal reproduction studies are not always predictive of human response.
There are no adequate and well-controlled studies in pregnant women.
It is not known whether etoricoxib is excreted in human milk. Etoricoxib is excreted in the milk of lactating rats.
Women who use etoricoxib should not breast feed.

 

Store at temperatures not exceeding 30°C.

 

Pharmacology: Cyclooxygenase (COX) is an enzyme that is responsible for the formation of prostanoids. The three main groups of prostanoids - prostaglandins, prostacyclins, and thromboxanes - each involved in the inflammatory response. There are two, if not three, known types of cyclooxygenase (COX-1, COX-2, and COX-3).
COX-2 inhibitors are a class of drugs which selectively inhibit COX-2, an enzyme involved in the inflammation pathway, while sparing COX-1, thereby reducing gastrointestinal toxicity.
Etoricoxib is a selective COX-2 inhibitor. It selectively inhibits isoform 2 of cyclooxygenase enzyme (COX-2). This reduces the generation of prostaglandins (PGs) from arachidonic acid. Among the different functions exerted by PGs, their role in the inflammation cascade should be highlighted. COX-2 selective inhibitor (aka "COXIB") showed less marked activity on type 1 cyclooxygenase compared to traditional non-steroidal anti-inflammatory drugs (NSAID).
Pharmacokinetics: Absorption: Orally administered etoricoxib is well absorbed. The mean oral bioavailability is approximately 100%. Following 120 mg-once-daily dosing to steady state, the peak plasma concentration (geometric mean Cmax = 3.6 mcg/mL) was observed at approximately 1 hour (Tmax) after administration to fasted adults. The geometric mean AUC0-24 hrs was 37.8 mcg hr/mL. The pharmacokinetics of etoricoxib in 12 healthy subjects were similar (comparable AUC, Cmax within approximately 20%) when administered alone, with a magnesium/aluminum hydroxide antacid, or a calcium carbonate antacid (approximately 50 mEq acid-neutralizing capacity).
Distribution: Etoricoxib is approximately 92% bound to human plasma protein over the range of concentrations of 0.05 to 5 mcg/mL. The volume of distribution at steady state (Vdss) is approximately 120 L in humans.
Metabolism: Etoricoxib is extensively metabolized with <1% of a dose recovered in urine as the parent drug. The major route of metabolism to form the 6-hydroxymethyl derivative. These principal metabolites either demonstrate no measurable activity or are only weakly active as COX-2 inhibitors. None of these metabolites inhibit COX-1.
Elimination: Following administration of a single 25 mg radiolabeled intravenous dose of etoricoxib to healthy subjects, 70% of radioactivity was recovered in urine and 20% in feces, mostly as metabolites. Less than 2% was recovered as unchanged drug.
Elimination of etoricoxib occurs almost exclusively through metabolism followed by renal excretion. Steady state concentrations of etoricoxib are reached within seven days of once-daily administration of 120 mg, with an accumulation half-life of approximately 2, corresponding to an accumulation half-life of approximately 22 hours. The plasma clearance is estimated to be approximately 50 mL/min.