Etoricoxib, which is chemically described as 5-chloro-6-methyl-3-[4-(methlysulfonyl)-2,3-bipyridine. Etoricoxib is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities. It is selective cyclo-oxygenase-2 (Cox-2) inhibitor. Its empirical formula is C18H15CIN2O2S and molecular weight is 358.84.
Clinical Pharmacology:
Pharmacodynamics:
Etoricoxib is an oral selective cyclo-oxygenase-2(cox-2) inhibitor within the clinical dose range. Across clinical pharmacology studies, etoricoxib produced dose-dependent inhibition of cox-2 with out inhibition of cox-1 at doses up to 150 mg daily. Etoricoxib did not inhibit gastric prostaglandin systhesis and had no effect on platelet function.
Cyclo –oxygenase is responsible for generation of prostaglandins. Two isoforms, cox-1 and cox-2, have been identified.cox-2 is the isoform of the enzyme that has been shown to be induced by pro-inflammatory stimuli and has been postulated to be primarily responsible for the synthesis of prostanoid mediators of pain inflammation, and fever. Cox-2 is also involved in ovulation, implantation and closure of the ductus arteriosus, regulation of renal function and central nervous system functions (fever induction,pain perception and cognitive function). It may also play a role in ulcer healing.
Pharmacokinetics: Absorption
Orally administered etoricoxib is well absorbed. The absolute bioavailability is approximately 100%. Following 120mg once – daily dosing to steady state, the peak plasma concentration was observed at approximately 1 hour (Tmax) after administration to fasted adults. The geometric mean area under the curve (AUC0-24hr) was 37.8hr/ml. the pharmacokinetics of etoricoxib are linear across the clinical dose range. Dosing with food had no effect on the extent of absorption was affected, resulting in a 36% decrease in Cmax and an increase in Tmax by 2 hours. These data are not considered clinically significant. In clinical trials, etoricoxib was administered without regard to food intake.
INDICATION:
It is indicated in the symptomatic relief of osteoarthritis (OA) rheumatoid arthritis (RA) acute gouty arthritis, acute pain associated with dental surgery and primary dysmenorrhoea. The decision to prescribe a selective cox-2 inhibitor should be based on an assessment of the individual patients overall risks.
CONTRAINDICATIONS:
. History of hypersensitivity to the active substance or to any of the excipients
. Active peptic ulceration or active gastro- intestinal (GI) bleeding.
. patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic type reactions after taking acetylsalicylic acid or NSAIDs including cox-2 inhibitors.
. pregnancy and lactation
. severe hepatic dysfunction
. Estimated renal creatinine clearance <30 ml/min
. children and adolescents under 16 years of age.
. Inflammatory bowl disease.
. Congestive heart failure
. patients with hypertension whose blood pressure has not been adequately controlled.
. Established ischaemic heart disease and/or cerebrovascular disease.
WARNINGS AND PRECAUTIONS:
Cardiovascular effects
This drug should bThe used with caution in patients suffering from coronary heart disease (CHD) cardiovascular disorder. Clinical trials suggest that the selective cox-2 inhibitor class of drugs may be associated with a risk of thrombotic events relative to placebo and some NSAIDs. As the cardiovascular risks of etoricoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patients need for symptomatic relief and response to therapy should be re-evaluated periodically especially in patients with osteoarthritis. Patients with significant risk factors for cardiovascular events or peripheral arterial disease should only be treated with etoricoxib after careful consideration. Cox-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of their lack of antiplatelet effect. Therefore antiplatelet therapies should not be discontinued.
Pregnancy and lactation: Pregnancy:
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. The potential for human risk in pregnancies are available for etoricoxib. 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 a woman becomes pregnant during treatment, etoricoxib should be discontinued.
Lactation:
It is not known whether etoricoxib is excreted in human milk.woman who use etoricoxib should not breast feed.
Adverse Reactions:
In clinical studies, the undersirable effects profile was similar in patients with OA or RA treated with etoricoxib for one year or longer. In a clinical study for acute gouty arthritis, patients were treated with Etoricoxib 120mg once daily for eight days. The adverse experience profile in this study was generally similar to that reported in the combined OA, RA and chronic low back pain studies.
Very rare: peptic ulcers including gastro- intestinal perforation and bleeding (mainly in the elderly)
Dosage and Administration
Etoricoxib is administered orally and may be taken with or without food. The onset of drug effect may be faster when etoricoxib is administered without food. This should be considered when rapid symptomatic relief is needed.
Paediatric use:
Etoricoxib is contraindicated in children and adolescents under 16 years of age.
Storage:
Store in a cool dry place, protected from light.
