Arkoksia® (Arcoxia®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceEtoricoxibEtoricoxib
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  • Arkoksia®
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    Merck Sharp and Doum B.V.     Netherlands
  • Arkoksia®
    pills inwards 
    Merck Sharp and Doum B.V.     Netherlands
  • Costarox
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    Sandoz d.     Slovenia
    • Dosage form: & nbspfilm coated tablets
    Composition:

    One tablet, film-coated, contains:

    Dosage of 60 mg: active substance: etorikoksib 60.0 mg;

    Excipients: calcium hydrophosphate 60.0 mg, cellulose microcrystalline 74.0 mg, croscarmellose sodium 4.0 mg, magnesium stearate 2.0 mg; film sheath tablet: Opadrai II Green 39K11520 8.0 mg, which contains: lactose monohydrate 35.0% (wt), hypromellose 33.0% (wt), titanium dioxide 16.6% (wt), triacetip 8.0 % (wt.), aluminum lacquer based on indigo carmine dye (E132) 5.4% (wt.), Iron dye yellow oxide (E172) 1.9% (wt.); carnauba wax 0.02 mg.

    Dosage of 90 mg: active substance: etorikoksib 90.0 mg;

    Excipients: calcium hydrophosphate 90.0 mg, cellulose microcrystalline 111.0 mg, croscarmellose sodium 6.0 mg, magnesium stearate 3.0 mg; film sheath tablet: Opadrai II White 39K18305 12.0 mg, which contains: lactose monohydrate 35.0% (wt), hypromellose 33.0% (wt), titanium dioxide 24.0% (wt), triacetip 8.0 % (the weight.); carnauba wax 0.03 mg.

    Dosage of 120 mg: active substance: etorikoksib 120.0 mg; Excipients: calcium hydrophosphate 120.0 mg, cellulose microcrystalline 148.0 mg, croscarmellose sodium 8.0 mg, magnesium stearate 4.0 mg; film sheath tablet: Opadrai II Green 39K11529 16.0 mg, which contains: lactose monohydrate 35.0% (wt), hypromellose 33.0% (wt), titanium dioxide 21.6% (wt), triacetip 8.0 % (wt.), aluminum lacquer based on indigo carmine dye (E132) 1.6% (wt.), iron dye oxide yellow (E172) 0.9% (wt.); carnauba wax 0.04 mg.

    Description:

    Dosage of 60 mg: green biconvex tablets of apple-shaped, film-coated, embossed ARCOXIA 60 on one side and with an embossing 200 on the other side.

    Dosage of 90 mg: white biconvex tablets, apple-shaped, film-coated, embossed ARCOXIA 90 on one side and with an embossing 202 on the other side.

    Dosage of 120 mg: light green biconvex tablets apple-shaped, film-coated, embossed ARCOXIA 120 on one side and with embossing 204 on the other side.

    Pharmacotherapeutic group:Non-steroidal anti-inflammatory drugs (NSAIDs)
    ATX: & nbsp

    M.01.A.H.05   Etoricoxib

    Pharmacodynamics:Etoricoxib when administered orally at therapeutic concentrations, is a selective inhibitor of cyclooxygenase-2 (COX-2). In clinical pharmacological studies etorikoksib dose-dependent inhibition of COX-2 without affecting COX-1 with a daily dose of up to 150 mg. The drug does not inhibit the synthesis of prostaglandins in the gastric mucosa and does not affect the function of platelets.

    Cyclooxygenase is responsible for the formation of prostaglandins. Two isoforms of cyclooxygenase - COX-1 and COX-2 - are isolated. COX-2 is an isoenzyme that is induced by various proinflammatory mediators and is considered as the main enzyme responsible for the synthesis of prostanoid mediators of pain, inflammation and fever. COX-2 is involved in the processes of ovulation, implantation and closure of the arterial duct, regulation of kidney function and the central nervous system (induction of fever, pain sensations, cognitive function), and may play a role in the healing of ulcers. COX-2 was found in the tissues surrounding the stomach ulcer in humans, but its significance for ulcer healing is not established.

    Efficiency

    In patients with osteoarthritis (OD) etorikoksib When applied at a dose of 60 mg once a day, a reliably reduced pain and an improvement in the assessment of their condition by patients.These beneficial effects were observed on the second day of treatment and persisted for 52 weeks. Studies of etorikoksib when used at a dose of 30 mg once daily (using similar methods of evaluation) showed efficacy compared with placebo during the 12-week treatment period. In a study to determine the optimal dose, etorikoksib when administered at a dose of 60 mg, showed a significantly greater improvement than a 30 mg dose for all three primary endpoints after 6 weeks of treatment. A dose of 30 mg has not been studied with osteoarthritis of the joints of the hands.

    In patients with rheumatoid arthritis (RA) etorikoksib when used in a dose of 90 mg alone once a day provided a reliable reduction of pain and inflammation and improved mobility. These beneficial effects persisted during the treatment period of 12 weeks.

    Patients with acute gouty arthritis etorikoksib when administered at a dose of 120 mg once a day during the entire treatment period of eight days, reduced moderate and severe pain in the joints and inflammation.The efficacy was comparable to that of indomethacin when administered at a dose of 50 mg three times a day. Reduction of pain was noted already four hours after the start of treatment.

    In patients with ankylosing spondylitis etorikoksib when applied at a dose of 90 mg once a day, provided a reliable reduction in back pain, inflammation, stiffness, and improved functions. The clinical efficacy of etorikoksib was already observed on the second day of treatment and persisted throughout the treatment period of 52 weeks.

    In a clinical study on pain after dental surgery etorikoksib in a dose of 90 mg was administered once a day for three days. In a subgroup of patients with moderate pain (with baseline assessment) etorikoksib when used at a dose of 90 mg had the same analgesic effect as ibuprofen in a dose of 600 mg (16.11 versus 16.39; P = 0.722) and was superior in efficiency to a combination of paracetamol / codeine 600 mg / 60 mg (11.00, P <0.001) and placebo (6.84, P <0.001) according to the overall pain reduction score for the first 6 hours (TOPAR6). The proportion of patients who needed fast-acting analgesics within the first 24 hours after taking the study drugs,was 40.8% with etorikoksiba at a dose of 90 mg, 25.5% with ibuprofen 600 mg every 6 hours and 46.7% with a combination of paracetamol / codeine at a dose of 600 mg / 60 mg every 6 hours compared to from 76.2% in the placebo group. In this study, the median onset of action (a measurable reduction in pain) with etoricoxib 90 mg was 28 minutes after taking the drug.

    Bsafety

    Program MEDAL (Multinational Long-Term Appointment Evaluation Program Thisoricoxib and Diclofenac in Arthritis)

    Program MEDAL was a prospective safety assessment program on based cardiovascular (CS) phenomena from the combined data of three randomized, double-blind, actively-controlled studies: MEDAL, EDGE II and EDGE.

    Study MEDAL was a study, the duration of which was determined by the achievement of end points (SS phenomena), which included 17804 patients with OA and 5,700 patients with RA who received etorikoksib in a dose of 60 mg (OA) or 90 mg (OA and RA) or diclofenac in a dose of 150 mg per day on average for 20.3 months (a maximum of 42.3 months, a median of 21.3 months). In this study, only serious adverse events and cases of drop-out from the study were recorded due to any undesirable events.

    In studies EDGE and EDGE II compared the gastrointestinal tolerance of etorikoksib and diclofenac. Study EDGE included 7111 patients with OA who received etorikoksib in a dose of 90 mg per day (1.5 times the dose recommended for OA) or diclofenac in a dose of 150 mg per day on average for 9.1 months (a maximum of 16.6 months, a median of 11.4 months). Study EDGE II included 4,086 patients with RA who committed etorikoksib in a dose of 90 mg per day or diclofenac in a dose of 150 mg per day on average for 19.2 months (a maximum of 33.1 months, a median of 24 months).

    In the joint Program MEDAL 34701 patients with OA or RA received treatment for an average of 17.9 months (a maximum of 42.3 months, a median of 16.3 months), and about 12 800 patients received treatment for more than 24 months. Included in the Program MEDAL of patients at baseline, a wide spectrum of CC and gastrointestinal risk factors was recorded. Patients with recent myocardial infarction, as well as with coronary artery bypass grafting or percutaneous coronary intervention for 6 months prior to enrollment were excluded. In studies, it was allowed to use gastroprotectors and low doses acpIrina.

    General security

    There were no significant differences between etorikoksib and diclofenac with regard to the frequency of thrombotic SS events. Cardiorenal adverse events were more frequently observed with etoricoxib than with diclofenac; this effect was dose-dependent (some results are presented below). Undesirable effects from the gastrointestinal tract (GIT) and liver were significantly more often observed with diclofenac than with etorikoksib. Frequency of adverse events in studies EDGE and EDGE II, as well as adverse events recognized as serious or requiring withdrawal of treatment, in the study MEDAL was higher in the appointment of etorikoksiba than with the appointment of diclofenac.

    Results of safety assessment for cardiovascular system

    The incidence of confirmed severe thrombotic SS adverse events (including cardiac, cerebrovascular and peripheral vascular events) was comparable between the groups receiving etorikoksib or diclofenac (the data are given in the table below). The frequency of thrombotic events did not reveal statistically significant differences between etorikoksibom and diclofenac in all the analyzed subgroups,including categories of patients in the range of the initial CC risk. The relative risk for confirmed serious thrombotic SS adverse events was similar for etorikoksib (when taken at a dose of 60 mg or 90 mg) and diclofenac (when taken in a dose of 150 mg).

    Table "Frequency of confirmed thrombotic SS events (Program MEDAL)"

    Etoricoxib (N = 16819) 25836 patient-years

    Diclofenac (N = 16483) 24,766 patient-years

    Comparison between treatments

    Frequency1 (95% CI)

    Frequency1 (95% CI)

    Relative risk (95% CI)

    Confirmed thrombotic SS serious adverse events

    When fulfilling protocol requirements

    1,24 (1,11, 1,38)

    1,30(1,17, 1,45)

    0,95 (0,81, 1,11)

    Depending on the treatment prescribed

    1,25 (1,14, 1,36)

    1,19 (1,08, 1,30)

    1,05 (0,93,1,19)

    Confirmed cardiac events

    When fulfilling protocol requirements

    0,71 (0,61,0,82)

    0,78 (0,68, 0,90)

    0,90 (0,74, 1,10)

    In dependence on the prescribed treatment

    0,69 (0,61,0,78)

    0,70 (0,62, 0,79)

    0,99 (0,84, 1,17)

    Confirmed cerebrovascular events

    When fulfilling protocol requirements

    0,34 (0,28. 0,42)

    0,32 (0,25, 0.40)

    1.08 (0,80, 1,46)

    Depending on the treatment prescribed

    0,33 (0.28, 0,39)

    0,29 (0,24, 0,35)

    1,12 (0,87, 1,44)

    Confirmed peripheral vascular phenomena

    When fulfilling protocol requirements

    0,20 (0,15,0,27)

    0,22 (0,17, 0,29)

    0,92 (0,63, 1,35)

    Depending on the treatment prescribed

    0,24 (0,20, 0.30)

    0,23 (0,18, 0.28)

    1.08 (0.81, 1,44)

    1 - The number of phenomena per 100 patient-years; CI = confidence interval; N= total the number of patients included in the population of patients who fulfilled the protocol requirements.

    When fulfilling the requirements of the protocol, all the phenomena that developed against the background of the therapy being studied or within 14 days after its termination (patients who received <75% of the study drug and patients who took non-NSAIDs> 10% of the time were excluded).

    Depending on the treatment prescribed, all confirmed events that developed before the end of the study (patients included who could be subjected to unintended interventions after stopping the study drug were included). General information number of randomized patients: n = 17412 for etoricoxib and n= 17289 for diclofenac.

    MOP mortality and total mortality were comparable between the treatment groups etorikoksibom and diclofenac.

    Kardiorenal phenomena

    Approximately 50% of patients included in the study MEDAL, at an initial estimation the arterial hypertensia in the anamnesis has been registered. The frequency of elimination due to adverse events associated with hypertension was statistically significantly higher for etorikoksiba than for diclofenac. The incidence of adverse events associated with chronic heart failure (drop-out and serious events) was similar for etorikoksiba at a dose of 60 mg and diclofenac 150 mg,but it was higher for etoricoxib 90 mg compared with diclofenac at a dose of 150 mg (statistically significantly higher for etoricoxib 90 mg compared with diclofenac at a dose of 150 mg in study group OA MEDAL). The frequency of confirmed adverse events associated with congestive heart failure (phenomena which were severe and resulted in hospitalization or emergency room visit) was slightly higher for etoricoxib compared with diclofenac at a dose of 150 mg; this effect was dose-dependent. The frequency of dropout cases due to adverse events associated with edema was higher for etorikoksib compared with diclofenac at a dose of 150 mg; this effect was dose-dependent (statistically significant for etorikoksiba in a dose of 90 mg, but not for etorikoksiba in a dose of 60 mg).

    Results of assessing cardiorenal safety in studies EDGE and EDGE II consistent with the results in the study MEDAL

    In some studies of the Program MEDAL absolute frequency drop-out in any treatment group for etoricoxib (60 mg or 90 mg) amounted to 2.6% due to hypertension, up to 1.9% due to swelling and to 1.1% in relation to chronic heart insufficiency.In patients taking ethornecoxib at a dose of 90 mg, the dropout rate was higher in the study than in patients taking etrncoxib at a dose of 60 mg.

    The results of the evaluation of gastrointestinal tolerance in the Program MEDAL

    In each of the three studies included in the Program MEDAL, the drop-out rate for any clinical adverse gastrointestinal event (eg, dyspepsia, abdominal pain, ulcers) was significantly lower for etorikoxib than diclofenac. The dropout rate from the study due to undesirable GIT clinical events for 100 patient-years for the entire study period was as follows: 3.23 for etoricoxib and 4.96 for diclofenac in the study MEDAL; 9.12 for etoricoxib and 12.28 for diclofenac in the study EDGE, and 3.71 for etoricoxib and 4.81 for diclofenac in the study EDGE II.

    The results of the evaluation of GI safety in the Program MEDAL

    In general, undesirable phenomena from the upper gastrointestinal tract were defined as perforations, ulcers and bleeding. Complicated undesired side effects from the upper gastrointestinal tract included perforation, obstruction and complicated bleeding; uncomplicated adverse events from the upper gastrointestinal tract included uncomplicated bleeding and uncomplicated ulcers.The overall incidence of adverse events from the upper gastrointestinal tract was significantly lower for etorikoksib in comparison with diclofenac. There were no significant differences between etorikoksib and diclofenac in the frequency of complicated events. For hemorrhagic adverse events on the part of the upper gastrointestinal tract (complicated and uncomplicated in the aggregate), there were no significant differences between etorikoksibom and diclofenac. The advantage of etorikoksib in relation to the upper gastrointestinal tract compared with diclofenac in patients taking aspirin at low doses (about 33% of patients) was not statistically significant.

    The incidence of confirmed complicated and uncomplicated clinical adverse events from the upper GI tract for 100 patient-years (perforation, ulcers and bleeding) was 0.67 (95% CI 0.57, 0.77) for etoricoxib and 0.97 (95% CI 0.85, 1.10) for diclofenac, on the basis of which the relative risk was 0.69 (95% CI 0.57.0.83).

    The frequency of confirmed adverse events on the part of the upper GI tract in elderly patients was studied; the maximum reduction in frequency was observed in patients aged ≥75 years-1.35 (95% CI 0.94, 1.87) compared with 2.78 (95% CI 2.14, 3.56) events per 100 patient- years for etorikoksib and diclofenac, respectively.The incidence of confirmed adverse events from the lower gastrointestinal tract (small or large intestine perforation, obstruction or bleeding) did not differ significantly between the groups receiving etorikoksib and diclofenac.

    The results of the liver safety assessment in the Program MEDAL

    Etorikoksib was statistically significantly lower at the drop-out rate because of undesirable liver side effects compared with diclofenac. In the joint Program MEDAL 0.3% of patients who received etorikoksib, and 2.7% of patients who received diclofenac, withdrew from the study due to adverse events on the part of the liver. The incidence of adverse events per 100 patient-years was 0.22 for etoricoxib and 1.84 for diclofenac (p <0.001 for etoricoxib versus diclofenac). Most of the adverse events on the part of the liver in the Program MEDAL were not serious.

    Additional safety data associated with thrombotic CC events

    In clinical trials, with the exception of research programs MEDAL, approximately 3100 patients received etorikoksib in a dose of ≥60 mg per day for 12 weeks or longer. Hc, there were significant differences in the incidence of confirmed serious thrombotic SS events in patients who received etorikoksib in a dose ≥60 mg, placebo or NSAIDs that do not contain naproxen. However, in comparison with patients receiving naproxen in a dose of 500 mg twice a day, the frequency of these events was higher in patients who received etorikoksib. The difference in antiaggregant activity between certain NSAIDs that inhibit COX-1 and selective inhibitors of COX-2 may be of clinical importance in patients at risk of developing thromboembolic events. Selective inhibitors of COX-2 inhibit the formation of systemic (and, possibly, endothelial) prostacyclin without affecting platelet thromboxane. The clinical significance of these observations is not established.

    Additional safety data for the digestive tract

    In two double-blind endoscopic studies lasting 12 weeks, the cumulative incidence of gastroduodenal ulcers was significantly lower in patients receiving etorikoksib in a dose of 120 mg once a day than in patients who received naproxen in a dose of 500 mg twice a day or ibuprofen in a dose of 800 mg three times a day. The frequency of ulceration in the appointment of etorikoksib was higher compared with placebo.

    Research of kidney function in the elderly

    In a randomized, double-blind, placebo-controlled parallel group study evaluated the effects of 15-day therapy etoricoxib (90 mg), celecoxib (200 mg twice daily), naproxen (500 mg twice daily) and placebo on the excretion of sodium by the kidneys, blood pressure (BP) and other indicators of kidney function in patients aged 60 to 85 years who received a diet with a sodium content of 200 meq / day. Etoricoxib, celecoxib and naproxen after 2 weeks of treatment had a similar effect on the excretion of sodium by the kidneys. All active comparators led to an increase in systolic blood pressure relative to placebo, however, etoricoxib therapy resulted in a statistically significant increase in systolic blood pressure at Day 14 compared to celecoxib and naproxen (mean change in systolic blood pressure compared to baseline: 7.7 etorikoksib- mmHg., celecoxib - 2.4 mm of mercury. Art. naproxen - 3.6 mm of mercury. st.).

    Pharmacokinetics:
    Absorbition

    Erythikoxib is rapidly absorbed when taken orally. Absolute bioavailability when ingestion is about 100%. When using the drug in adults on an empty stomach at a dose of 120 mg once a day until the equilibrium state is reached, the maximum concentration (Cmax) is 3.6 mkt / ml. The time to reach the maximum concentration (TCmax) in blood plasma - 1 hour after taking the drug. Average geometric AUC0-24h - 37.8 μg * h / ml. The pharmacokinetics of etorikoksib within the therapeutic dose is linear.

    When taking etorikoksiba at a dose of 120 mg during meals (high-fat foods), there was no clinically significant effect on the degree of absorption. The rate of absorption changed, which led to a decrease in Cmax by 36% and an increase in TCmax pa 2 hours. These results are not considered clinically relevant. In clinical trials etorikoksib was used regardless of food intake.

    Distribution

    Etorikoksib approximately 92% binds to plasma proteins in humans at concentrations of 0.05-5 μg / ml. Volume of distribution (Vdss) in the equilibrium state is about 120 liters.

    Etorikoksib is intensively metabolized. Less than 1% of etorikoksib is excreted by the kidneys unchanged. The main pathway of metabolism is the formation of 6'-hydroxymethylethricoxib, catalyzed by enzymes of the cytochrome system. CYP3A4 promotes the metabolism of etorikoksiba in vivo. Research in vitro indicate that isoenzymes CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyze the suture pathway of metabolism, but their quantitative impact in vivo not studied.

    In humans, 5 metabolites of ethoricoxib were found. The main metabolite is 6'-carboxyacetyl etorikoxib, which is formed by additional oxidation of 6'-hydroxymethylethoricoxib. These major metabolites have no appreciable origin, or are weak inhibitors of COX-2. None of these metabolites lie inhibits COX-1.

    Excretion

    With a single intravenous injection of radiolabeled etorikoksib in a dose of 25 mg, 70% of etorikoksib was excreted through the kidneys, 20% through the intestine, mainly in the form of metabolites. Less than 2% was found unchanged.

    Elimination of etorikoksib occurs mainly by metabolism, followed by excretion through the kidneys.

    The equilibrium concentration is achieved with daily intake of 120 mg etorikoksib after 7 days with a cumulation factor of about 2, which corresponds to a half-life of about 22 hours. Plasma clearance after intravenous administration of 25 mg is approximately 50 ml / min.

    Special patient groups

    Elderly

    Pharmacokinetics in the elderly (65 years and older) is comparable with the pharmacokinetics in young people.

    FarThe makokinetics of etorikoksib is similar in men and women.

    Liver failure

    In patients with violations of mild liver function (5-6 points on the Child-Pugh scale), taking etorikoksiba at a dose of 60 mg once a day was accompanied by an increase in the index AUC on 16% in comparison with the healthy persons accepting a preparation in the same dose.

    In patients with impaired liver function of moderate severity (7-9 on the Child-Pugh scale) who took etorikoksib in a dose of 60 mg every other day, the average LPS value was the same as in healthy individuals who received etorikoksib daily in the same dose. Etoricoxib in a dose of 30 mg once a day has not been studied in this population.

    Data of clinical and pharmacokinetic studies in patients with severe impairment of liver function (≥10 points on the Child-Pugh scale) are absent.

    Renal insufficiency

    The pharmacokinetic parameters of a single application of etorikoksib in a dose of 120 mg in patients with impaired renal function of medium and severe degree and with terminal stage of chronic renal failure (CRF) on hemodialysis did not differ significantly from those of healthy individuals. Hemodialysis slightly affected the excretion (clearance of dialysis - about 50 ml / min).

    Children

    The pharmacokinetic parameters of etorikoksib in children under 12 years of age have not been studied.

    In the pharmacokinetic study (n= 16), conducted in adolescents aged 12 to 17 years, pharmacokinetics in adolescents with a body weight of 40 to 60 kg with taking etorikoksiba at a dose of 60 mg once a day and in adolescents with a body weight of more than 60 kg with taking etorikoksiba in a dose 90 mg once a day was similar to pharmacokinetics in adults when taking etorikoksiba at a dose of 90 mg once a day. Safety and effectiveness of etorikoksiba in children is not established.

    Indications:Symptomatic therapy of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain and inflammation associated with acute gouty arthritis. Short-term therapy of moderate acute pain after dental operations.
    Contraindications:

    Hypersensitivity to any component of the drug.

    Stomach ulcer and duodenal ulcer in the acute stage, active gastrointestinal bleeding.

    Full or partial combination of asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including history).

    Pregnancy, the period of breastfeeding.

    Severe violations of the liver function (serum albumin <25 g / l or ≥10 points on the Child-Pugh scale).

    Severe renal failure (CC less than 30 ml / min).

    Children under 16 years.

    Inflammatory bowel disease.

    Chronic heart failure (II-IV functional class but NYHA). Uncontrolled arterial hypertension, in which the blood pressure values ​​persistently exceed 140/90 mm Hg. Art.

    Confirmed ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease.

    Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

    Confirmed hyperkalemia.

    Progressive kidney disease.

    Carefully:

    Care should be taken when using the drug in the following groups of patients:

    - patients with an increased risk of complications from the gastrointestinal tract due to NSAID administration; the elderly, simultaneously taking other NSAIDs, including acetylsalicylic acid or patients with gastrointestinal diseases in history, such as peptic ulcer and gastrointestinal bleeding;

    - patients with a history of cardiovascular risk factors such as dyslipidemia / hyperlipidemia, diabetes mellitus, hypertension, smoking, heart failure, left ventricular dysfunction, edema and fluid retention;

    - patients with impaired liver function of mild severity (5-6 points on the Child-Pyo scale) should not exceed a dose of 60 mg once a day, in patients with violations of liver function of moderate severity (7-9 on the Child-Pugh scale) 30 mg once a day;

    - patients with dehydration;

    - patients with impaired renal function concomitantly using ACE inhibitors, angiotensin II diuretics, especially the elderly;

    - patients with creatinine clearance <60 ml / min;

    - patients with previous significant decrease in kidney function, with impaired renal function,decompensated heart failure or cirrhosis of the liver, at risk of long-term use of NSAIDs.

    Care should be taken with concomitant therapy with the following drugs:

    - anticoagulants (for example, warfarin);

    -antiaggregants (for example, acetylsalicylic acid, clopidogrel);

    - drugs, destabilized by sulfotransferases.

    Pregnancy and lactation:Pregnancy

    There are no clinical data on the use of etorikoxib during pregnancy. In animal studies, toxic effects on the reproductive system were observed. The potential risk in women during pregnancy is unknown. The use of etorikoksib, as well as other drugs that inhibit the synthesis of prostaglandins, during the last trimester of pregnancy can lead to suppression of uterine contractions and premature closure of the arterial duct.

    Etiorikoxib is contraindicated during pregnancy (see section "Contraindications"). If during pregnancy there was a pregnancy, etorikoksib necessary cancel.

    Breast-feeding

    In lactating rats etorikoksib is excreted with milk.Studies confirming the isolation of etorikokenb with breast milk in women have not been carried out. Women who take etorikoksib, should stop breastfeeding (see section "Contraindications").

    Fertility

    The use of etorikoksib, as well as other drugs that inhibit COX-2 and the synthesis of prostaglandins, is not recommended for women who are planning a pregnancy.
    Dosing and Administration:

    Inside, regardless of meals, squeezed a small amount of water.

    A drug ARCOXIA® should be applied at the lowest effective dose with the minimum possible short course.

    Osteoarthritis

    The recommended dose is 30 mg once a day or 60 mg once a day.

    Rheumatoid arthritis and ankylosing spondylitis

    The recommended dose is 90 mg once a day.

    In conditions accompanied by acute pain, the drug ARCOXIA® should be used only in the acute symptomatic period.

    Acute gouty arthritis

    The recommended dose in the acute period is 120 mg once a day.

    The duration of use of the drug at a dose of 120 mg is not more than 8 days.

    Acute pain after dental operations

    The recommended dose is 90 mg once a day. In the treatment of acute pain after dental operations ARCOXIA® preparation should be used only in the acute period not more than 3 days.

    Doses in excess of those recommended for each indication either do not have additional efficacy or have not been studied. Thus: the daily dose for osteoarthritis should not exceed 60 mg; the daily dose for rheumatoid arthritis should not exceed 90 mg; daily dose for ankylosing spondylitis should not exceed 90 mg; the daily dose for acute gouty arthritis should not exceed 120 mg; for a period not exceeding 8 days; the daily dose for relief of pain after dental operations should not exceed 90 mg; for a period of not more than 3 days.

    Special patient groups

    Elderly

    Dose adjustments in elderly patients are not required. As with the use of other drugs in elderly patients, care should be taken when using ARCOXIA "(see section" Special instructions ").

    Patients with impaired hepatic function

    Regardless of the indications for use of the drug for patients with mild liver function disorders (5-6 points on the Child-Pugh scale), do not exceed doses / 60 mg once a day,patients with violations of the liver of moderate severity (7-9 points on the scale Child-Pugh) - 30 mg once a day.

    It is advisable to use caution when using ARCOXIA® in patients with impaired liver function of moderate severity, as the clinical experience with ARCOXIA® in this group of patients is limited. Due with oThe lack of clinical experience with ARCOXIA® in patients with severe hepatic impairment (≥10 points on the Child-Pugh scale) the drug is contraindicated for this group of patients (see the section "Pharmacological properties", subsection "Pharmacokinetics", as well as the sections "Contraindications" and "Special instructions").

    Patients with impaired renal function

    Dose Correction in Patients with Creatinine Clearance ≥30 ml / min is not required (see section "Pharmacological properties", subsection "Pharmacokinetics"). The use of etericcoxib in patients with creatinine clearance <30 ml / min is contraindicated (see the sections "Contraindications" and "Special instructions").

    Children

    Etiorikoxib is contraindicated for children and adolescents under 16 years of age (see section "Contraindications").

    Side effects:
    The safety of the use of etorikoksib was evaluated in clinical trials involving 7152 participants, including 4614 patients with OA, RA, chronic lower back pain and ankylosing spondylitis (approximately 600 patients with OA or RA received treatment for one year or longer). In clinical studies, the profile of adverse effects was similar in patients with OA or RA who were taking etorikoksib for 1 year or longer.

    In a clinical study of acute gouty arthritis, patients received etorikoksib in a dose of 120 mg / day for 8 days. The profile of unwanted effects in this studywas generally the same as at combined studies of OA, RA and chronic pain in the lower back.

    In the Safety Assessment Program for MOP of the system, which included data from three actively-controlled studies, 17412 patients with OA or RA received etorikoksib in a dose of 60 mg or 90 mg on average for 18 months (see the section "Pharmacological properties", subsection "Pharmacodynamics").

    In clinical studies of acute postoperative pain associated with dental surgery, in which 614 patients received etorikoksib in a dose of 90 mg or 120 mg, the adverse effects profile was generally similar to the profile in pooled studies of OA, RA and chronic lower back pain.

    The following undesirable reactions were recorded more frequently with the drug than with placebo in clinical trials involving patients with OA, RA, chronic low back pain, or ankylosing spondylitis who were taking etorikoksib in a dose of 30 mg, 60 mg or 90 mg with an increase in the dose to the recommended dose within 12 weeks, in the studies of the Program MEDAL duration of up to 3.5 years, in short-term studies of acute pain, as well as during post-marketing use.

    Class system / organ

    Unwanted phenomenon

    Frequency1

    Infectious and parasitic diseases

    alveolar ostitis

    often

    gastroenteritis, upper respiratory tract infection, urinary tract infection

    infrequently

    Violations of the blood and lymphatic system

    anemia (mainly as a result of gastrointestinal bleeding), leukopenia, thrombocytopenia

    infrequently

    Immune system disorders

    hypersensitivity reactions2,4

    infrequently

    angioedema, anaphylactic / anaphylactoid reactions, including shock2

    rarely

    Disorders from the metabolism and nutrition

    swelling / fluid retention

    often

    decreased or increased appetite, weight gain

    infrequently

    Disorders of the psyche

    anxiety, depression, concentration disorders, hallucinations2

    infrequently

    confusion2, anxiety2

    rarely

    Disturbances from the nervous system

    dizziness, headache

    often

    impaired taste, insomnia, paresthesia / hypoesthesia, drowsiness

    infrequently

    Disturbances on the part of the organ of sight

    blurred vision, conjunctivitis

    infrequently

    Disturbances from the organ of hearing and ps of violent disorders

    ringing in the ears, vertigo

    infrequently

    Heart Disease

    palpitation, arrhythmia2

    often

    atrial fibrillation, tachycardia2, chronic heart failure, nonspecific changes on the ECG, angina pectoris2, myocardial infarction5

    infrequently

    Vascular disorders

    arterial hypertension

    often

    "hot flashes", cerebrovascular accident5, transient ischemic attack, hypertensive crisis2, vasculitis2

    infrequently

    Disturbances from the respiratory system, chest and mediastinal organs

    bronchospasm2

    often

    cough, shortness of breath, nosebleeds

    infrequently

    Disorders from the gastrointestinal tract

    abdominal pain

    Often

    Constipation, flatulence, gastritis, heartburn / gastroesophageal reflux, diarrhea, indigestion / discomfort in epigastrium, nausea, vomiting, esophagitis, ulcers of the oral mucosa

    often

    bloating, changes in peristalsis, dryness of the oral mucosa, gastroduodenal ulcer, gastric ulcer, including gastrointestinal perforation and bleeding, irritable bowel syndrome, pancreatitis2

    infrequently

    Disturbances from the liver and bile ducts

    increased ALT activity, increased ACT activity

    often

    hepatitis2

    rarely

    liver failure2, jaundice2

    rarely2

    Disturbances from the skin and subcutaneous tissues

    ecchymosis

    often

    swelling of the face, itching, rash, erythema2, urticaria2

    infrequently

    Stevens-Johnson syndrome2, toxic epidermal nsrolysis2, fixed drug erythema2

    rarely2

    Disturbances from musculoskeletal and connective tissue

    Cramps / muscle spasms, musculoskeletal pain / stiffness

    infrequently

    Disorders from the kidneys and urinary tract

    proteinuria, increased serum creatinine, renal failure2

    infrequently

    General disorders and disorders in the place of attention

    asthenia / weakness, flu-like syndrome

    often

    chest pain

    infrequently

    Impact on the results of laboratory and instrumental studies

    increased blood urea nitrogen, increased creatine phosphokinase, hyperkalemia, increased uric acid

    infrequently

    decrease in sodium in the blood

    rarely
    1 According to the frequency recorded in the clinical trial database: very often (> 1/10), often (> 1/100 to <1/10), infrequently (> 1/1000 to <1/100), rarely (from > 1/10000 to <1/1000), very rarely (<1/10000).

    2 This undesirable reaction was recorded during post-marketing surveillance. The frequency of messages for it is estimated based on the highest frequency observed in clinical studies combined according to dose and indication.

    3 The frequency category "Rarely" has been determined in accordance with the guidelines (version 2, September 2009) for the Brief Characteristics of the Preparation (SmPC) on the basis of the estimatedThe upper boundary of the 95% confidence interval for 0 events, given the number of patients receiving the drug ARCOXIA® in the analysis of phase III data combined according to the dose and the indication (n = 15470).

    4 Hypersensitivity includes the terms "allergy", "drug allergy," "hypersensitivity to the drug," "hypersensitivity," "hypersensitivity, unspecified," "hypersensitivity reaction," and "nonspecific allergy."

    5Pthe results of this analysis of long-term placebo-controlled and actively controlled clinical trials using selective COX-2 inhibitors increase the risk of developing serious arterial thrombotic events, including a heart attack miocard and stroke. Based on the available data, it is unlikely that the absolute risk of developing these events exceeds 1% per year (infrequently).

    The following serious adverse events have been reported in connection with the administration of NSAIDs and ns can be excluded for etorikoksiba: nephrotoxicity, including interstitial nephritis and nephrotic syndrome.

    Overdose:In clinical trials, the drug ARCOXIA ® in a single dose of up to 500 mg or repeated intake of up to 150 mg / day for 21 days, all caused significant toxic effects. Reports of acute overdose with etoricoxib have been reported, but in most cases no adverse reactions have been reported. The most frequent adverse reactions corresponded to the safety profile of etorikoksib (for example, gastrointestinal disorders, cardiorenal phenomena).

    In case of an overdose, it is advisable to use usual supportive measures, such as removal of the non-sucking drug from the digestive tract, clinical observation and, if necessary, maintenance therapy. Etoricoxib it is not excreted in hemodialysis, etorikoksib was not studied for peritoneal dialysis.

    Interaction:
    Pharmacodynamic interaction

    Oral anticoagulants (warfarin). In patients receiving warfarin, taking ARCOXIA ® in a dose of 120 mg per day was accompanied by an increase of approximately 13% of the international normalized ratio (INR) prothrombin time. Patients receiving oral anticoagulants should monitor prothrombin time and INR at the beginning of treatment or when changing ARKOXIA treatment ®, especially in the first few days.

    Diuretic drugs, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists. NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg, in patients with dehydration or in elderly patients with impaired renal function), simultaneous use of an ACE inhibitor or an angiotensin II antagonist and preparations inhibiting cyclooxygenase may lead to an additional impairment of kidney function, including the possible development of acute renal disease deficiency, which is usually reversible. You should remember about the possibilityThe emergence of such interactions in patients who take etorikoksib simultaneously with ACE inhibitors or with angiotensin II antagonists. This combination should be administered with caution, especially in elderly patients. At the beginning of the combined treatment, as well as with a certain periodicity in farEyshem should fill the deficiency of fluid and consider monitoring the function of the kidneys.

    Acetylsalicylic acid. In a study involving healthy volunteers etorikoksib at a dose of 120 mg per day in the equilibrium state did not affect the angioprombocytic activity of acetylsalicylic acid (81 mg once a day). The drug ARKOKSIA ® can be used concomitantly with acetylsalicylic acid in low doses, intended for the prevention of CC diseases. However, simultaneous administration of low doses of acetylsalicylic acid and ARCOXIA ® may lead to an increase in the frequency of ulcerative lesions of the gastrointestinal tract and other complications compared with the use of one drug ARKOXIA ®. Simultaneous use of etorikoksiba with acetylsalicylic acid at doses exceeding the recommended for prevention of MI complications, as well as with other NSAIDs is not recommended (see the section "Pharmacological properties", subsection "Pharmacodynamics", as well as the section "Special instructions").

    Cyclosporine and tacrolimus. The interaction of etorikoksib with these drugs has not been studied, but the simultaneous use of NSAIDs with cyclosporine and tacrolimus may enhance the neurotoxic effect of these drugs. If you simultaneously use etorikoksiba with any of these drugs should monitor kidney function.

    Pharmacokinetic interaction

    Effect of the drug ARCOXIA ® on other medications

    Lithium. NSAIDs decrease the excretion of lithium by the kidneys and, consequently, increase the concentration of lithium in the blood plasma. If necessary, frequent monitoring of the concentration of lithium in the blood and adjust the dose of lithium during the period of simultaneous use with NSAIDs, as well as with the abolition of NSAIDs.

    Metrenksat. Two studies examined the effects of ARCOXIA® at doses of 60, 90 and 120 mg once a day for seven days in patients who received once a week methotrexate in a dose of 7.5 to 20 mg but for rheumatoid arthritis. The drug ARCOXIA® in doses of 60 and 90 mg did not affect the plasma concentration and renal clearance of methotrexate. In one study, the ARCOXIA® preparation in a dose of 120 mg did not affect the pharmacokinetics of methotrexate. In another study, the plasma methotrexate concentration increased by 28%, and the renal clearance of methotrexate decreased by 13%. With the simultaneous administration of ARCOXIA ® and methotrexate should be monitored for possible toxic effects of methotrexate.

    Oral contraceptives. Taking ARCOXIA® for 21 days at a dose of 60 mg with oral contraceptives containing 35 μg of ethyiyl estradiol (EE) and 0.5 to 1 mg of norethindrone increases the AUC0-24h for energy efficiency by 37%.Taking ARCOXIA in a dose of 120 mg with the above oral contraceptives (at the same time or with an interval of 12 hours) increases the equilibrium AUC0-24h for EE on 50-60%. This increase in EE concentration should be taken into account when choosing the appropriate oral contraceptive for simultaneous use with ARCOXIA®. This fact may lead to an increase in the incidence of adverse events associated with the use of oral contraceptives (eg, venous thromboembolism in women at risk).

    Hormone replacement therapy (HRT). The administration of etoricoxib in a dose of 120 mg concurrently with hormone replacement therapy containing conjugated estrogens at a dose of 0.625 mg increases the mean value of the equilibrium AUC for 28 days0-24h unconjugated estrone (41%), equilin (76%) and 17-β-estradiol (22%). The effect of doses of etorikoksib recommended for long-term use (30, 60 and 90 mg) has not been studied. Etoricoxib in a dose of 120 mg changed the exposure (AUC0-24h) of these estrogen components is less than twice that of ionotherapy with a preparation containing conjugated estrogens, with an increase in the dose of the latter from 0.625 to 1.25 mg. The clinical significance of such enhancements is unknown.The use of a combination of etorikoksib and a preparation containing higher doses of conjugated estrogens has not been studied. The increase in estrogen concentration should be taken into account when choosing a hormone drug for use in the postmenopausal period, while concomitant administration with etorikokenb, as increasing the exposure of estrogens may increase the risk of developing adverse events associated with HRT.

    Prednisone / Prednisolone. In studies of drug interactions etorikoksib had no clinically significant effect on the pharmacokinetics of prednisone / prednisolone.

    Digoxin. When using etorikoksiba at a dose of 120 mg once a day for 10 days in healthy volunteers there was no change in AUC0-24h at equilibrium state or influence on excretion of digoxin by the kidneys. An increase in the indicator Cmax digoxin (approximately 33%). This increase, as a rule, is not significant in the majority of patients. However, with simultaneous use of etorikoksib and digoxin, patients with a high risk of toxic action of digoxin should be monitored.

    Vliyaof etorikoksib on drugs metabolized by sulfotransferases. Etorikoksib is an inhibitor of human sulfhydrase (in particular SULT1E1) and can increase the concentration of EE in the blood serum. Due to the fact that insufficient data are now available on the effect of various sulfotransferases, and their clinical significance for the use of many drugs is still being studied, it is advisable to use caution in prescribing etorikoksib simultaneously with other drugs metabolized mainly by human sulfhydrases (eg, oral salbutamol and mnnoksidil).

    Effect of etorikoksib on drugs metabolized by isoenzymes of the cytochrome system. Based on research results in vitro It is not expected that etorikoksib will inhibit isoenzymes of cytochrome P450 1A2, 2C9, 2C19, 2D6, 2E1 FOR4. In a study involving healthy volunteers, the daily use of etorikoksib in a dose of 120 mg did not affect the activity of the isoenzyme CYP 4 in the liver, according to the results of the erythromycin respiratory test.

    The effect of other drugs on the pharmacokinetics of etorikoksiba

    The main pathway of the metabolism of etorikoksib depends on the enzymes of the cytochrome system. Isozyme CYP3A4 promotes the metabolism of etorikoksiba in vivo. Research P vitro give reason to believe that isoenzymes CYP2D6, CYP2C9, CYP1A2 and 2YP2C19 can also catalyze the main pathway of metabolism, but their quantitative characteristics in vivo not studied.

    Ketoconazole. Ketoconazole is a potent inhibitor of isoenzyme CYP3A4. In appointing ketocoiazole to healthy volunteers at a dose of 400 mg once daily for 11 days, it had no clinically significant effect on the pharmacokinetics of a single dose of etoricoxib 60 mg (increase AUC on 43%).

    Voriconazole and miconazole. Simultaneous administration of strong inhibitors of isoenzyme CYP3A4 (voriconazole for oral or topical use miconazole, oral gel) and etorikoksib caused a slight increase in etorikoksib exposure, which was not clinically significant on the basis of published data.

    Rifampicin. Simultaneous administration of etorikoksib and rifampicin (a powerful inducer of the cytochrome system) led to a decrease in the concentration of etorikoksib in blood plasma by 65%.This interaction may be accompanied by a relapse of symptoms with the simultaneous use of etorikoksiba with rifampicin. These data may indicate the need to increase the dose, but apply etorikoksib in doses that exceed recommended for each indication (see the section "Method of administration and dose") should not be used, since the combined use of rifampicin and etorikoksib in such doses has not been studied.

    Antacids. Antacids do not have a clinically significant effect on the pharmacokinetics of ARCOXIA®.

    Special instructions:
    Effect on the gastrointestinal tract

    There were cases of complications from the upper GI tract (perforation, ulcers or bleeding), sometimes fatal, in patients who received etorikoksib. It is advisable to use caution in the treatment of patients with a high risk of complications from the gastrointestinal tract when using NSAIDs, in particular in the elderly, patients who simultaneously use other NSAIDs, including. acetylsalicylic acid, as well as in patients with such a history of gastrointestinal disease, as an ulcer or gastrointestinal bleeding.

    There is an additional risk of developing unwanted reactions from the gastrointestinal tract (gastrointestinal ulcers or other complications from the gastrointestinal tract) with simultaneous use of etorikoksiba and acetylsalicylic acid (even in low doses). In long-term clinical trials, there have been significant differences in safety of the gastrointestinal tract with the use of selective COX-2 inhibitors in acetylsalicylic acid storage compared to the use of NSAIDs in combination with acetylsalicylic acid (see the section Pharmacological properties, subsection Pharmacodynamics).

    Influence on the cardiovascular system

    The results of clinical studies indicate that the use of drugs of class selective inhibitors of COX-2 is associated with an increased risk of thrombotic events (especially myocardial infarction and stroke) with respect to placebo and certain NSAIDs. Since the risk of developing CC diseases when taking selective COX-2 inhibitors may increase with increasing dose and duration of application, it is necessary to choose the shortest duration of administration and the lowest effective daily dose.It is necessary to periodically evaluate the patient's need for symptomatic treatment and response to therapy, especially for patients with osteoarthritis (see the section "Pharmacological properties", subsection "Pharmacodynamics", as well as the sections "Contraindications", "Dosage and administration" and "Side effect" ).

    Patients with known risk factors for developing MI complications (such as hypertension, hyperlipidemia, diabetes, smoking) should be assigned this etorikoksib only after a thorough evaluation of the benefits and risks (see the section "Pharmacological properties", subsection "Pharmacodynamics").

    Selective inhibitors of COX-2 are not a substitute for acetylsalicylic acid in the prevention of CC disease, since they do not affect platelets. Therefore, one should not stop the use of antiplatelet drugs (see the section "Pharmacological properties", subsection "Pharmacodynamics", as well as the section "Interaction with other medicinal products").

    Effect on renal function

    Renal prostaglandins can play a compensatory role in maintaining renal perfusion. In the presence of conditions that adversely affect renal perfusion, w the value of ARCOXIA ® can cause a decrease in the formation of prostaglandins and a decrease in renal blood flow, and thus reduce kidney function. The greatest risk of this reaction exists for patients with a significant decrease in renal function, decompensated heart failure or cirrhosis in a history. In such patients, it is necessary to monitor kidney function.

    Fluid retention, edema and hypertension

    As with the use of other drugs that inhibit the synthesis of prostaglandins, fluid retention and swelling of arterial hypertension were observed in patients using ARCOXIA®. The use of all PPAI, including etorikoksib, can be associated with the onset or relapse of chronic heart failure. Information on the dependence of the effect of etorikoksiba on dose is given in the section Pharmacological properties ", subsection" Pharmacodynamics. "Caution should be used when prescribing ARCOXIA ® patients who have a history of heart failure, a violation of left ventricular function or hypertension, as well as patients with existing swelling that have arisen for any other reason.When clinical signs of deterioration appear in such patients, appropriate measures should be taken, including the abolition of etorikoksib.

    The use of etorikoksib, especially in high doses, can beь is associated with more frequent and severe arterial hypertension than with some other NSAIDs and selective COX-2 inhibitors. During treatment with etorikoksibom, special attention should be paid to the control of blood pressure (see the section "Contraindications"), which should be monitored for 2 weeks after the start of treatment and periodically thereafter. With a significant increase in blood pressure, alternative treatment should be considered.

    Effects on liver function

    In clinical studies of up to one year, an increase in alanine aminotransferase (ALT) and / or aspartate aminotransferase activity was observed in approximately 1% of patients treated with etoricoxib at doses of 30 mg, 60 mg and 90 mg / day (ACT) (approximately three or more times the upper limit of the norm).

    It is necessary to monitor the condition of all patients with symptoms and / or signs of liver dysfunction, as well as patients with pathological liver function.In case of detection of permanent deviations of liver function parameters (three times higher than the upper limit of the norm), ARCOXIA ® must be terminated.

    General instructions

    If, during treatment, the patient experiences a worsening of the function of any of the organ systems mentioned above, appropriate measures should be taken and the issue of abolition of etorikoxib should be considered. When etorikoksiba is used in elderly patients and patients with impaired renal, hepatic or cardiac function, appropriate medical supervision is necessary.

    Caution should be started with etorikoksib treatment in patients with dehydration. Before starting the use of etorikoksib recommended rehydration.

    During the post-marketing observation, NSAIDs and some selective COX-2 inhibitors very rarely reported the development of serious skin reactions. Some of them (including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis) were fatal (section "Side effect" section). The risk of developing such reactions is highest at the beginning of therapy, in most cases during the first month of treatment.There have been reports of the development of serious hypersensitivity reactions, such as anaphylaxis and angioedema, in patients receiving ethornoxib (see "Side effect"). The use of selective COX-2 inhibitors has been associated with an increased risk of skin reactions in patients with a history of any drug allergy. Etoricoxib should be abolished at the first appearance of a skin rash, lesions of the mucosa or any other sign of hypersensitivity.

    The use of etorikoksib can mask a fever or other signs of inflammation.

    Caution should be exercised in the simultaneous administration of etorikoksiba with warfarin or other oral anticoagulants (see section "Interaction with other drugs")

    The use of etorikoksib, as well as other drugs that inhibit COX and the synthesis of prostaglandins, is not recommended for women who plan pregnancy (see the section "Pharmacological properties", subsection "Pharmacodynamics" and the section "Application in pregnancy and during breastfeeding, the effect on fertility" ),

    The drug ARCOXIA contains lactose.Patients with such rare congenital diseases as lactose intolerance, congenital insufficiency of lactose and impaired absorption of glucose-galactose, should not use this drug.

    Effect on the ability to drive transp. cf. and fur:Patients who experienced cases of dizziness, drowsiness, or weakness during the use of etorikoxib should refrain from driving and working with machinery.
    Form release / dosage:Tablets film-coated 60 mg, 90 mg, 120 mg.
    Packaging:By 2, 4, 7 or 14 tablets in sterilized from a PVC film and aluminum foil. For 1, 2 or 4 blisters together with the use of the structure in a cardboard box.
    Storage conditions:Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.
    Shelf life:3 years. Do not use after expiry date.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-009511/08
    Date of registration:28.11.2008 / 30.04.2013
    Expiration Date:Unlimited
    The owner of the registration certificate:Merck Sharp and Doum B.V.Merck Sharp and Doum B.V. Netherlands
    Manufacturer: & nbsp
    Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.
    Information update date: & nbsp13.09.2017
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