Coxicare

Each COXICARE 90 mg film coated tablet contains: Etoricoxib 90 mg.
Each COXICARE 120 mg film coated tablet contains: Etoricoxib 120 mg.
Etoricoxib (COXICARE) tablet contain etoricoxib which is described chemically as 5-chloro-6'-methyl-3-[4-(methylsulfonyl)phenyl]-2,3'-bipyridine. The empirical formula is C₁₈H₁₅ClN₂O₂S. The molecular weight is 358.84.
Etoricoxib is a white to off-white powder. Etoricoxib is freely soluble in methanol, tetrahydrofuran, dimethyl sulfoxide, methyl ethyl ketone, dimethyl formamide, and chloroform. Etoricoxib is soluble in isopropyl acetate, ethanol and toluene, sparingly soluble in 2-propanol, and practically insoluble in water.

Pharmacology: Mechanism of Action: Etoricoxib is a member of a new class of agents called Coxibs. Etoricoxib is a potent, orally active cyclooxygenase-2 (COX-2) specific inhibitor within, and significantly above, the clinical dose range. Two isoforms of cyclooxygenase have been identified: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). COX-1 is responsible for prostaglandin-mediated normal physiologic functions such as gastric cytoprotection and platelet aggregation. Inhibition of COX-1 by nonselective NSAIDs has been associated with gastric damage and inhibition of platelet aggregation. COX-2 has been shown to be primarily responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever. Selective inhibition of COX-2 by etoricoxib (within the clinical dose range) decreases these clinical signs and symptoms with decreased potential for GI toxicity and effects on platelet aggregation.
Across clinical pharmacology studies, Etoricoxib produced dose-dependent inhibition of COX-2 without inhibition of COX-1 at doses up to 150mg daily.
The influence on gastro protective COX-1 activity was also assessed in a clinical study where prostaglandin synthesis was measured in gastric biopsy samples from subjects administered either Etoricoxib 120mg daily, naproxen 500mg twice daily, or placebo. Etoricoxib did not inhibit gastric prostaglandin synthesis as compared to placebo. In contrast, naproxen inhibited gastric prostaglandin synthesis by approximately 80% compared with placebo. These data further support the COX-2 selectivity of Etoricoxib.
Pharmacokinetics: Absorption: Orally administered etoricoxib is well absorbed. The mean oral bioavailability is approximately 100%. Following 120mg once-daily dosing to steady state, the peak plasma concentration (geometric mean Cmax = 3.6mcg/mL) was observed at approximately 1hour (Tmax) after administration to fasted adults. The geometric mean AUC0-24hr was 37.8 mcg·hr/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 120mg. In clinical trials, etoricoxib was administered without regard to food.
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 50mEq acid-neutralising capacity).
Distribution: Etoricoxib is approximately 92% bound to human plasma protein over the range of concentrations of 0.05 to 5mcg/mL. The volume of distribution at steady state (Vdss) is approximately 120L in humans.
Etoricoxib crosses the placenta in rats and rabbits, and the blood-brain barrier in rats.
Metabolism: Etoricoxib is extensively metabolised with <1% of a dose recovered in urine as the parent drug. Five metabolites have been identified in humans. Metabolism in vitro involves conversion primarily to the 6'-hydroxymethyl derivative, mainly (ca. 60%) by CYP3A4, with less contribution by CYPs 1A2, 2C9, 2C19 and 2D6 (ca. 40% collectively). The 6'-hydroxymethyl derivative is further metabolised by oxidation to the principal metabolite, the 6'-carboxylic acid derivative of etoricoxib. These principal metabolites either demonstrate no measurable activity or are only weakly active as COX-2 inhibitors. None of these metabolites inhibit COX-1.
Excretion: Following administration of a single 25mg radiolabelled intravenous dose of etoricoxib to healthy subjects, 70% of radioactivity was recovered in urine and 20% in faeces, 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 120mg, 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 50mL/min.

Etoricoxib is indicated for: Symptomatic relief of rheumatoid arthritis, osteoarthritis (OA) and acute gouty arthritis.

In osteoarthritis, etoricoxib is given orally in a usual dose of 30 mg once daily, increased to 60 mg once daily if necessary. The recommended dose in rheumatoid arthritis is 90 mg once daily; higher doses of 120 mg once daily are used in gouty arthritis although such doses should only be used for the acute symptomatic period and for a maximum of 8 days.
Administration in hepatic impairment: The maximum oral dose of etoricoxib in patients with mild hepatic impairment (Child-Pugh score of 5 to 6), regardless of indication, is 60 mg once daily; those with moderate impairment (Child-Pugh 7 to 9) should be given a maximum of 60 mg every other day or 30 mg once daily. Etoricoxib should not be given to patients with severe hepatic impairment (Child-Pugh 10 or more).
Musculoskeletal and joint disorders: The selective cyclo-oxygenase-2 (COX-2) inhibitor etoricoxib is used in the treatment of the musculoskeletal disorders osteoarthritis and rheumatoid arthritis. It is recommended that the use of selective COX-2 inhibitors is limited to those patients considered to be at high risk of developing serious gastrointestinal problems if given a non-selective NSAID.

There have been reports of acute overdosage with etoricoxib, although adverse events were not reported in the majority of cases. The most frequently observed adverse events were consistent with the safety profile for etoricoxib (e.g. gastrointestinal events, renovascular events).
In the event of overdose, it is reasonable to employ the usual supportive measures, e.g., employ clinical monitoring, and institute supportive therapy, if required.
Etoricoxib is not dialysable by haemodialysis; it is not known whether etoricoxib is dialysable by peritoneal dialysis.

Etoricoxib is contraindicated in patients with: Hypersensitivity to any component of this product. A history of asthma, urticaria, or other allergic reactions after taking aspirin or other NSAIDs.
Congestive heart failure (NYHA II-IV).
Patients with hypertension whose blood pressure is persistently elevated above 140/90mmHg and has not been adequately controlled.
Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease (including patients who have recently undergone coronary artery bypass graft surgery or angioplasty).
Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10, see footnote as follows) active peptic ulceration or gastrointestinal (GI) bleeding.
Estimated creatinine clearance < 30mL/min.
Etoricoxib should not be used as adjunctive therapy with other NSAIDs due to the absence of any evidence demonstrating synergistic benefits and the potential for additive adverse reactions.
[The Child-Pugh score employs five clinical measures of liver disease - bilirubin, serum albumin, INR, ascites and hepatic encephalopathy. Each measure is scored 1-3, with 3 indicating most severe derangement. The individual scores are tallied to derive the Child-Pugh score.]

Cardiovascular effects: Clinical trials suggest that the selective COX-2 inhibitor class of drugs may be associated with a risk of thrombotic events (especially MI and stroke), relative to placebo and some NSAIDs. Long term safety data beyond one year are not currently available for etoricoxib compared to placebo or NSAIDs other than diclofenac. In the MEDAL Program, there was no significant difference between etoricoxib and diclofenac in the rate of cardiovascular thrombotic events over a mean treatment duration of 18 months.
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 patient's need for symptomatic relief and response to therapy should be re-evaluated periodically. A combined analysis of controlled clinical trials in which patients were treated with etoricoxib ≥30mg daily for 4 weeks or longer was conducted to compare the incidence rate of serious thrombotic cardiovascular events among patients taking etoricoxib, placebo, naproxen or non-naproxen NSAIDs. This analysis was not powered to provide a precise estimate of the relative risk of CV events in patients taking etoricoxib versus the other treatments. The analysis showed a statistically significant increase in relative risk with etoricoxib vs. naproxen 1000mg with respect to the Anti-Platelet Trialists' Collaboration (APTC) combined endpoint (ie. cardiovascular, haemorrhagic and unknown death, non-fatal myocardial ischaemia, and non-fatal stroke) [RR 2.72 (95% CI 1.18, 6.27)]. This analysis did not demonstrate any statistically significant increase in the rate of serious thrombotic cardiovascular events in patients taking etoricoxib over those taking non-naproxen NSAIDs. Etoricoxib should be used with caution for patients with significant risk factors for cardiovascular events (including those with diabetes, hypertension, hypercholesterolaemia, a first degree relative with ischaemic heart disease, cardiac failure or who are smokers).
Aspirin substitution: COX-2 selective inhibitors are not a substitute for aspirin for cardiovascular prophylaxis because of their lack of effect on platelets. Because etoricoxib, a member of this class, does not inhibit platelet aggregation, antiplatelet therapies should not be discontinued.
Gastrointestinal effects: Physicians should be aware that individual patients may develop upper gastrointestinal (GI) ulcers/ulcer complications irrespective of treatment. Although the risk of upper GI toxicity is not eliminated with Etoricoxib, the results of the MEDAL Program demonstrate that in patients treated with Etoricoxib, the risk of upper GI toxicity with Etoricoxib 60mg or 90mg once daily is significantly less than with diclofenac 150mg daily.
In clinical studies with ibuprofen and naproxen, the risk of endoscopically detected upper GI ulcers was lower in patients treated with Etoricoxib 120mg once daily than in patients treated with the non-selective NSAIDs. While the risk of endoscopically detected ulcers was low in patients treated with Etoricoxib 120mg it was higher than in patients treated with placebo. Upper GI ulcers/ulcer complications have occurred in patients treated with Etoricoxib. These events can occur at any time during use and without warning symptoms. Independent of treatment, patients with a prior history of GI perforation, ulcers and bleeding (PUB) and patients greater than 65 years of age are known to be at a higher risk for a PUB.
Patients should be informed about the signs and/or symptoms of serious GI toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. It has been demonstrated that upper GI ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue, thus increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
There is a further increase in the risk of gastrointestinal adverse effects (gastrointestinal ulceration or other gastrointestinal complications) when etoricoxib is taken concomitantly with acetylsalicylic acid (even at low doses). A significant difference in GI safety between selective COX-2 inhibitors + acetylsalicylic acid vs. NSAIDs + acetylsalicylic acid has not been demonstrated in long-term clinical trials.
Renal effects: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal prostaglandins may play a compensatory role in the maintenance of renal perfusion. Therefore, under conditions of compromised renal perfusion, administration of Etoricoxib may cause a reduction in prostaglandin formation and, secondarily, in renal blood flow, and thereby impair renal function. Patients at greatest risk of this response are those with pre-existing significantly impaired renal function, uncompensated heart failure, or cirrhosis. Monitoring of renal function in such patients should be considered.
Caution should be used when initiating treatment with Etoricoxib in patients with considerable dehydration. It is advisable to rehydrate patients prior to starting therapy with Etoricoxib.
Fluid retention, oedema, hypertension: As with other drugs known to inhibit prostaglandin synthesis, fluid retention, oedema and hypertension have been observed in patients taking Etoricoxib. All Nonsteroidal Antiinflammatory Drugs (NSAIDs), including etoricoxib, can be associated with new onset or recurrent congestive heart failure. For information regarding a dose related response for etoricoxib.
Caution should be exercised in patients with a history of cardiac failure, left ventricular dysfunction, or hypertension and in patients with pre-existing oedema from any other reason. If there is clinical evidence of deterioration in the condition of these patients, appropriate measures including discontinuation of etoricoxib should be taken.
Etoricoxib may be associated with more frequent and severe hypertension than some other NSAIDs and selective COX-2 inhibitors, particularly at high doses. Therefore, hypertension should be controlled before treatment with etoricoxib (see CONTRAINDICATIONS) and special attention should be paid to blood pressure monitoring during treatment with etoricoxib. Blood pressure should be monitored within two weeks after initiation of treatment and periodically thereafter. If blood pressure rises significantly, alternative treatment should be considered.
Hepatic effects: Elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials treated for up to one year with Etoricoxib 90 mg and 120mg daily. In active comparator portions of clinical trials, the incidence of elevated AST and/or ALT in patients treated with Etoricoxib 90mg daily was similar to that of patients treated with naproxen 1000mg daily, but notably less than the incidence in the diclofenac 150mg daily group. These elevations resolved in patients treated with etoricoxib, with approximately half resolving while patients remained on therapy.
General: When using etoricoxib in the elderly and in patients with renal, hepatic, or cardiac dysfunction, medically appropriate supervision should be maintained. If these patients deteriorate during treatment, appropriate measures should be taken, including discontinuation of therapy.
Serious skin reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance. These serious events may occur without warning. Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients receiving etoricoxib. Some selective COX-2 inhibitors have been associated with an increased risk of skin reactions in patients with a history of any drug allergy. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Use in patients with Inflammatory Bowel Disease (IBD): NSAIDs have been associated with an exacerbation of IBD associated with spondyloarthropathies. There has only been limited study of etoricoxib in patients with IBD.
Use in patients with fever and infection: Etoricoxib may mask fever, which is a sign of infection. The physician should be aware of this when using etoricoxib in patients being treated for infection.
Effects on ability to drive and operate machinery: The effect of etoricoxib on the ability to drive or use machinery has not been studied. However, based on its pharmacodynamic properties and overall safety profile it is unlikely to have an effect on these activities.
Genotoxicity: Etoricoxib was not genotoxic in assays for gene mutations (in vitro bacterial and human lymphoblast [TK locus] cell assays), chromosomal damage (CHO cells in vitro, rat bone marrow in vivo) and other genotoxic effects (alkaline elution assay of DNA damage in vitro and in vivo, DNA adduct formation in vitro).
Carcinogenicity: When etoricoxib at doses ≥30mg/kg/day (>6 times the daily human dose [90mg]) was administered orally for up to 2 years in rats liver adenomas were observed in the males and females and thyroid follicular cell adenomas were observed in the males, as well. At the lower dose tested in this species (10mg/kg/day) hepatic cell and thyroid follicular cell hypertrophy were observed in both sexes, and were associated with systemic exposure (AUC0-24h) lower than that expected in humans at the maximum recommended dose of 120mg.
Etoricoxib was not carcinogenic in mice given oral doses up to 400mg/kg/day for males and up to 600mg/kg/day for females for two years. Systemic exposure (AUC0-24h) at these dose levels was similar to that in humans at the maximum recommended dose of 120mg.
Effects on fertility: Etoricoxib administered to male rats at oral doses up to 100mg/kg/day (systemic exposure about 4-fold greater than that in humans at the maximum recommended dose of 120mg/day, based on AUC0-24h) had no effects on mating performance, fertility, testicular/epididymal weights, or histology, or sperm count and motility. Etoricoxib produced post-implantation losses in female rats at oral doses of 30mg/kg/day (approximately 3-fold human exposure at 120mg daily based on the AUC0-24hr). These changes are expected with inhibition of prostaglandin synthesis and are not the result of permanent alteration of female reproductive function (see PRECAUTIONS, Use in pregnancy as follows).
Use in pregnancy: Category C: Medicines which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis and, when given during the latter part of pregnancy, may cause closure of the foetal ductus arteriosis, foetal renal impairment, inhibition of platelet aggregation, and delay labour and birth.
There are no adequate and well-controlled studies in pregnant women. Etoricoxib should not be used during the first two trimesters of pregnancy unless the potential benefit justifies the potential risk to the foetus. As with other agents that inhibit prostaglandin synthesis, treatment with etoricoxib during the third trimester should be avoided because it may cause closure of the foetal ductus arteriosus.
High placental transfer of etoricoxib has been demonstrated in pregnant rats and rabbits. Etoricoxib treatment at oral doses ≥ 30mg/kg/day prior to or during gestation in pregnant rats or rabbits caused an increase in embryofetal resorptions and reduced the number of foetuses. Exposure to etoricoxib at the no-effect dose for increased resorption (10mg/kg/day in either species) was lower than that expected in humans after 120mg, based on AUC. Etoricoxib was not teratogenic in rats at oral doses of 45mg/kg/day (approximately 4-fold the expected human exposure at a dose of 120mg/day, based on AUC). A low incidence of ventricular septal defects and other cardiovascular malformations has been observed in rabbits given etoricoxib at oral doses producing exposure levels comparable to that expected in humans. Increased post-natal pup mortality with etoricoxib was observed at doses of 15 and 45mg/kg/day in rats. Maternal drug exposure at the no-effect dose for increased pup mortality (5mg/kg/day) was lower than human exposure at a dose of 120mg/day, based on AUC. In addition, reduced pup weights were observed after oral treatment of pregnant rats with etoricoxib doses of 45mg/kg/day during gestation and lactation.
Use in lactation: Etoricoxib is excreted in the milk of lactating rats at concentrations up to two-fold greater than the maximal maternal plasma concentration. Because many drugs are excreted in human milk and because of the possible adverse effects of drugs that inhibit prostaglandin synthesis on nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Use in children: The pharmacokinetics of etoricoxib in paediatric patients (<12 years of age) have not been studied.
The pharmacokinetics in adolescents (aged 12 to 17) weighing 40 to 60kg given etoricoxib 60mg once daily and in adolescents >60kg given etoricoxib 90mg once daily were similar to the pharmacokinetics in adults given etoricoxib 90mg once daily.
Safety and effectiveness in patients aged below 18 years have not been established.
Use in the elderly: In each of these datasets, a higher incidence of adverse events was seen in older patients compared to younger patients; the relative differences between the etoricoxib and control groups were similar in the elderly and the young. Greater sensitivity of some older individuals cannot be ruled out. As with any NSAID, caution should be exercised in treating the elderly (65 years and older).

Hypersensitivity reactions including anaphylaxis and angioedema have occurred in patients receiving etoricoxib; it should be stopped at the first signs of hypersensitivity. Etoricoxib should be avoided in patients with severe hepatic impairment (Child-Pugh score of 10 or more).
The following are some of the side effects that are known to be associated with this medicine.
Common (affect between 1 in 10 and 1 in 100 people): Excessive fluid retention in the body tissues, resulting in swelling (oedema).
Dizziness.
Headache.
High blood pressure (hypertension).
Awareness of your heartbeat (palpitations).
Disturbances of the gut such as diarrhoea, nausea, indigestion, flatulence or abdominal pain.
Feeling weak or fatigued.
Cold or flu-like symptoms.
Uncommon (affect between 1 in 100 and 1 in 1000 people): Change in appetite, weight gain.
Anxiety or depression.
Difficulty sleeping (insomnia).
Change in taste.
Changes in sensation, eg pins and needles or tingling sensations.
Blurred vision.
Nosebleeds (epistaxis).
Cough or shortness of breath (dyspnoea).
Skin reactions such as rash and itch.
Muscle cramps.
Chest pain.
Heart failure, heart attack, stroke or mini-stroke (see Precautions).
Very rare (affect less than 1 in 10,000 people): Ulceration or bleeding in the stomach or intestine (see Precautions).
Liver or kidney disorders.
Confusion.

General: Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1 and has been shown to increase the serum concentrations of ethinyl oestradiol (see INTERACTIONS, Oral Contraceptives as follows).
Diuretics, Angiotensin Converting Enzyme (ACE) Inhibitors and Angiotensin II Antagonists (AIIAs): Reports suggest that NSAIDs including selective COX-2 inhibitors may diminish the antihypertensive effect of diuretics, ACE inhibitors and AIIAs. This interaction should be given consideration in patients taking etoricoxib concomitantly with these products. In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors, the co-administration of ACE inhibitors or AIIAs may result in a further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, the combination should be administered with caution, especially in the elderly.
Aspirin: Etoricoxib can be used concomitantly with low-dose aspirin at doses for cardiovascular prophylaxis. At steady state, etoricoxib 120mg once daily had no effect on the anti-platelet activity of low-dose aspirin (81mg once daily), as assessed by ex vivo platelet aggregation and serum TXB2 generation in clotting blood. However, concomitant administration of low-dose aspirin with etoricoxib increases the rate of GI ulceration or other complications, compared to use of etoricoxib alone.
Digoxin: Etoricoxib 120mg once daily for 10 days did not alter the steady state plasma AUC0-24hr or renal elimination of digoxin. Therefore, digoxin and etoricoxib may be co-administered without dose adjustment.
Frusemide: Clinical studies have shown that NSAIDs can reduce the natriuretic effect of frusemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.
Ketoconazole: Ketoconazole, a potent inhibitor of CYP3A4, dosed at 400mg once a day increased the AUC of etoricoxib by 43%. The clinical significance of this increase is not known.
Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Thus, when etoricoxib and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
Methotrexate: Two studies investigated the effects of etoricoxib 60, 90 or 120mg administered once daily for seven days in patients receiving once-weekly methotrexate doses of 7.5 to 20mg for rheumatoid arthritis. etoricoxib at 60 and 90mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In one study, etoricoxib 120mg had no effect on methotrexate plasma concentrations (as measured by AUC) or renal clearance. In the other study, etoricoxib 120mg increased methotrexate plasma concentrations by 28% (as measured by AUC) and reduced renal clearance of methotrexate by 13%. In these two studies, at 24 hours post-dose, a similar proportion of patients treated with methotrexate alone (approximately 93%) and subsequently treated with methotrexate co-administered with etoricoxib 120mg (approximately 82%) had methotrexate plasma concentrations below the measurable limit (5ng/mL). Standard monitoring for methotrexate-related toxicity should be considered when etoricoxib at doses greater than 90mg daily and methotrexate are administered concomitantly.
Oral Contraceptives: Etoricoxib 60mg given concomitantly with an oral contraceptive containing 35mcg ethinyl estradiol (EE) and 0.5 to 1mg norethindrone for 21 days increased the steady state AUC0-24hr of EE by 37%. Etoricoxib 120mg given with the same oral contraceptive, concomitantly or separated by 12 hours, increased the steady state AUC0-24hr of EE by 50 to 60%. This increase in EE concentration should be considered when selecting an oral contraceptive for use with etoricoxib. An increase in EE exposure can increase the incidence of adverse events associated with oral contraceptives (e.g. venous thromboembolic events in women at risk).
Hormone Replacement Therapy: Administration of etoricoxib 120mg with hormone replacement therapy consisting of conjugated oestrogens (0.625mg PREMARIN) for 28 days, increased the mean steady state AUC0-24hr of unconjugated estrone (41%), equilin (76%), and 17-β-oestradiol (22%). The effects of etoricoxib 120mg on the exposure (AUC0-24) to these oestrogenic components of PREMARIN were less than half of those observed when PREMARIN was administered alone and the dose was increased from 0.625 to 1.25mg. The clinical significance of these increases is unknown, and higher doses of PREMARIN were not studied in combination with etoricoxib. These increases in oestrogenic concentration should be taken into consideration when selecting post-menopausal hormone replacement therapy for use with etoricoxib.
Prednisone/prednisolone: Etoricoxib did not have any clinically important effect on the pharmacokinetics of prednisolone or prednisone.
Rifampicin: Co-administration of etoricoxib with rifampicin, a potent inducer of hepatic metabolism, 600mg daily, produced a 65% decrease in etoricoxib plasma AUC. This interaction should be taken into consideration when etoricoxib is co-administered with rifampicin.
Warfarin: Anticoagulant activity should be monitored, particularly in the first few days after initiating or changing etoricoxib therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding complications. In a multiple dose study in healthy subjects receiving both warfarin and etoricoxib 120mg, the steady state prothrombin time (measured as INR) was increased by approximately 13%.

Store at temperatures not exceeding 30°C.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AH05 - etoricoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.

Rx