CORICIB Film-coated tablet Ref.[50490] Active ingredients: Etoricoxib

Absorption

Orally administered etoricoxib is absorbed with a mean oral bioavailability of approximately 100%. Following 120 mg once-daily dosing to steady state, the peak plasma concentration (geometric mean C_max=3,6 µg/mL) was observed at approximately 1 hour (T~max~) after administration to fasted adults. The geometric mean AUC~0-24h~ was 37,8 µg/h/mL. The pharmacokinetics of etoricoxib are linear across the clinical dose range. A standard meal had no clinically meaningful effect on the extent or rate of absorption of a dose of etoricoxib 120 mg. In reported clinical trials, etoricoxib was administered without regard to food.

The pharmacokinetics of etoricoxib in 12 healthy subjects (40 to 65 years of age) were similar (comparable AUC, C_max within approximately 20%) when administered alone or with a magnesium/aluminium hydroxide antacid or a calcium carbonate antacid (approximately 50 mEq acid-neutralising capacity).

Distribution

In humans, etoricoxib is approximately 92% bound to plasma protein over the range of concentrations of 0,05 µg/mL to 5 µg/mL. The volume of distribution at steady state (Vdss) is approximately 120 litre. Etoricoxib crosses the placenta and the blood-brain barrier.

Metabolism

Etoricoxib is extensively metabolised in the liver with <1% of a dose recovered in urine as the parent drug. The major route of metabolism to form the 6'-hydroxymethyl derivative is catalysed by cytochrome P450 (CYP) enzymes.

Five metabolites have been identified in man. The principal metabolite is the 6'-carboxylic acid derivative of etoricoxib formed by further oxidation of the 6'-hydroxymethyl derivative. These principal metabolites either demonstrate no measurable activity or are only weakly active as COX-2 inhibitors.

Elimination

Following administration of a single 25 mg radio-labelled intravenous dose of etoricoxib to healthy subjects, 70% of radioactivity was recovered in urine and 20% in faeces, mostly as metabolites. Plasma and urine were collected for 7 days and stool collected for 10 days postdose. 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 7 days of once-daily administration of 120 mg, with an accumulation ratio of approximately 2, corresponding to an accumulation half-life of approximately 22 hours. The plasma clearance is estimated to be approximately 50 mL/min.

Elderly

Pharmacokinetics in the elderly (65 years of age and older) with normal renal function are similar to those in the young. In reported clinical studies, a higher incidence of adverse experiences was seen in older patients compared to younger patients (see section 4.2).

Hepatic Insufficiency

Patients with mild hepatic insufficiency (Child-Pugh score 5 to 6) administered etoricoxib 60 mg once daily (for 21 days), had an approximately 16% higher mean AUC as compared to healthy subjects given the same regimen. Patients with moderate hepatic insufficiency (ChildPugh score 7 to 9) administered etoricoxib 60 mg every other day (for 21 days), had similar mean AUC to the healthy subjects given etoricoxib 60 mg once daily. There are no available clinical or pharmacokinetic data in patients with severe hepatic insufficiency (Child-Pugh score >9) [see section 4.2 & 4.3]

Renal Insufficiency

The pharmacokinetics of a single dose of etoricoxib 120 mg in patients with moderate (creatinine clearance 30 to 50 mL/min) to severe (creatinine clearance of <30 mL/min) renal insufficiency, and patients with end-stage renal disease on haemodialysis, were not significantly different from those in healthy subjects. Haemodialysis contributed negligibly to elimination (dialysis clearance approximately 50 mL/min).

Paediatric Population

The pharmacokinetics of etoricoxib in paediatric patients (<12 years of age) has not been studied. In a pharmacokinetic study (N=16) reported in adolescents (aged 12 to 17) the pharmacokinetics in adolescents weighing 40 kg to 60 kg given etoricoxib 60 mg once daily and in adolescents >60 kg given etoricoxib 90 mg once daily, were similar to the pharmacokinetics in adults given etoricoxib 90 mg once daily. Safety and efficacy of etoricoxib in paediatric and adolescent patients have not been established (see section 4.3).