Costarox (Kostarox)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceEtoricoxibEtoricoxib
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    • Dosage form: & nbspfilm coated tablets
    Composition:

    1 tablet contains:

    Name component

    Amount, mg

    30 mg

    60 mg

    90 mg

    120 mg

    Active substance

    Etoricoxib1

    30,0

    60,0

    90,0

    120,0

    Excipients

    Calcium hydrophosphate anhydrous

    13,0

    26,0

    39,0

    52,0

    Microcrystalline cellulose2

    12,75

    25,5

    38,25

    51,0

    Povidone K-30

    3,0

    6,0

    9,0

    12,0

    Magnesium stearate

    0,5

    1,0

    1,5

    2,0

    Croscarmellose sodium

    0,75

    1,5

    2,25

    3,0

    Composition of the tablet shell

    Opapray II green 32K5100013 2,0

    Opapray II green 32K5100023 4,0

    Opadrai II
    white 32K580000S3 6,0

    Opadrai II green 32K5100033 8,0

    1 Theoretical significance. The actual value of the amount of ethoricoxib used depends on the actual analysis of the active substance (used in an amount of 100% in terms of dry matter). The weight of the tablet is adjusted by the microcrystalline cellulose content.

    2 Theoretical significance. The actual value of the amount used depends on the actual value of the amount of active ingredient used.

    3 Composition lousy:

    Opaprai II green 32K510001: hypromellose 15 cPs 0.8 mg, lactose monohydrate 0.56 mg, titanium dioxide 0.462 mg, triacetin 0.16 mg, indigocarmine aluminum varnish (3-5%) 0.012 mg, iron oxide yellow 0.006 mg.

    Opadrai II green 32K510002: hypromellose 15 cPs 1.6 mg, lactose monohydrate 1.12 mg, titanium dioxide 0.628 mg, triacetin 0.32 mg, indigocarmine aluminum varnish (3-5%) 0.256 mg, iron oxide yellow 0.076 mg.

    Opadrai II white 32K580000S: hypromellose 15 cPs 2.4 mg, lactose monohydrate 1.68 mg, titanium dioxide 1.44 mg, triacetin 0.48 mg.

    Opadrai II green 32K510003: hypromellose 15 cPs 3.2 mg, lactose monohydrate 2.24 mg, titanium dioxide 1.776 mg, triacetin 0.64 mg, indigocarmine aluminum varnish (3-5%) 0.04 mg, iron oxide yellow 0.104 mg.

    Description:

    Tablets 30 mg: round biconvex tablets of bluish-green color, covered with a film membrane.

    Tablets of 60 mg: round biconvex tablets of dark green color, covered with a film membrane.

    Tablets 90 mg: round biconvex tablets of white color, covered with a film membrane.

    Tablets 120 mg: round biconvex tablets of light green color, covered with a film membrane.

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

    M.01.A.H.05   Etoricoxib

    Pharmacodynamics:

    Etorikoksib at oral intake in therapeutic concentrations is a selective inhibitor of cyclooxygenase type 2 (COX-2).

    In studies on clinical pharmacology etorikoksib dose-dependent inhibition of COX-2 without affecting COX-1 when administered at doses up to 150 mg per day. Etoricoxib did not inhibit the synthesis of prostaglandins in the gastric mucosa and did not affect the function of platelets.

    COX is responsible for the synthesis of prostaglandins. Two isoforms of this enzyme, COX-1 and COX-2, are isolated. COX-2 is an isoenzyme that is induced by the action of 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, central nervous system (induction of fever, sensation of pain, 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 (OA) etorikoksib when used at a dose of 60 mg once a day caused a significant reduction in 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 in a dose of 30 mg once a day (using similar methods of evaluation) demonstrated the effectiveness of the drug compared with placebo during the entire treatment period (12 weeks). In a study to determine the optimal dose, etorikoksib in a dose of 60 mg showed a significantly more marked improvement than a dose of 30 mg for all 3 primary endpoints after 6 weeks of treatment. The use of a dose of 30 mg for the treatment of OA joints of the hands has not been studied.

    In patients with rheumatoid arthritis (RA), taking etorikoksib in a dose of 60 mg or 90 mg once a day provided a significant reduction in pain, inflammation and improved mobility. These beneficial effects persisted for a 12-week treatment period. A comparison of the use of etorikoksib in a dose of 60 mg and 90 mg once daily for the treatment of RA showed that both dosing regimes provided superior efficacy compared with placebo. The dose of etorikoksib 90 mg once a day exceeded the dose of 60 mg once a day in assessing the effect with the Global Patient Evaluation Scale (0-100 mm visual-analog scale), the mean improvement was -2.71 mm (95 % confidence interval (CI): -4.98 mm, -0.45 mm).

    Patients with acute gouty arthritis etorikoksib in a dose of 120 mg once a day during the entire treatment period (8 days) reduced moderate and severe pain in the joints and inflammation compared with indomethacin at a dose of 50 mg 3 times a day. Reduction of pain was noted only 4 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 also improvement of motor function. The clinical efficacy of etorikoksib was already observed on the second day of treatment and persisted throughout the treatment period (52 weeks).

    In another study, which compared the efficacy of using etorikoksiba at a dose of 90 mg once a day and 60 mg once a day, this drug showed equal efficacy compared with naproxen 1000 mg once a day. Among patients who did not achieve an adequate clinical response to therapy for 6 weeks with the use of etorikoksiba at a dose of 60 mg once daily, an increase a daily dose of up to 90 mg allowed to improve the results of treatment,evaluated with the intensity scale of back pain (0-100 mm visual analogue scale), compared with the continuation of therapy with etoricoxib at a dose of 60 mg once a day. The mean improvement was -2.70 mm (95% CI: 4.88 mm, -0.52 mm).

    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 in a dose of 90 mg showed an analgesic effect similar to ibuprofen at a dose of 600 mg (16.11 compared with 16.39, P = 0.722) and greater than with a combination of paracetamol / codeine at a dose of 600 mg / 60 mg (11.00 ; P <0.001) and placebo (6.84; P <0.001) according to a general assessment of pain reduction during the first 6 h (TOPAR6). The proportion of patients requiring rapid-action analgesics during the first 24 hours after taking the study drugs was 40.8% for etorikoksiba at a dose of 90 mg, 25.5% for ibuprofen 600 mg every 6 hours and 46.7% for paracetamol / codeine combinations at a dose of 600 mg / 60 mg every 6 hours compared with 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.

    Security

    Program MEDAL (Multinational Evaluation Program for Long-Term Prescribing of Etoricoxib and Diclofenac in Arthritis)

    Program MEDAL was a prospective safety assessment program based on cardiovascular events 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 (cardiovascular events), it included 17,804 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 phenomenon.

    In studies EDGE and EDGE II compared the safety of taking etorikoksib and diclofenac for the gastrointestinal tract (GIT). In the study EDGE 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 for an average of 9.1 months (a maximum of 16.6 months, a median of 11.4 months).In the study EDGE II included 4086 patients with RA who received etorikoksib in a dose of 90 mg per day or diclofenac in a dose of 150 mg per day for an average of 19.2 months (a maximum of 33.1 months, a median of 24 months).

    In the joint program MEDAL analyzed data on the treatment of 34701 patients with OA or RA, the average duration of treatment was 17.9 months (maximum 42.3 months, median 16.3 months), with approximately 12 800 patients receiving treatment for more than 24 months. Patients included in the program, with the initial evaluation, had a wide range of cardiovascular and gastrointestinal risk factors. Patients who had a recent history of myocardial infarction (MI), coronary artery bypass grafting, or percutaneous coronary intervention for 6 months prior to enrollment were excluded. In studies, it was permitted to use gastroprotectors and low doses of aspirin.

    General security

    There were no significant differences between etorikoksibom and diclofenac with respect to the incidence of cardiovascular thrombotic events. Cardiorenal adverse events were more often observed with etorikoksib compared with diclofenac, the effect was dose-dependent (see results below). Adverse events from the gastrointestinal tract and liver significantly more often with diclofenac than with etorikoksib.

    Frequency of adverse events in studies EDGE and EDGE II and undesirable phenomena recognized as serious or requiring withdrawal of treatment, in the study MEDAL was higher when taking etorikoksiba compared with diclofenac.

    Results of the safety study for the cardiovascular system

    The incidence of confirmed serious thrombotic cardiovascular 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). There were no statistically significant differences in the incidence of thrombotic events between etorikoksibom and diclofenac in all of the subgroups analyzed, including those in patients with an increased risk of cardiovascular complications. The relative risk for confirmed serious cardiovascular thrombotic adverse events was similar when taking etorikoksiba at a dose of 60 mg or 90 mg and diclofenac at a dose of 150 mg.

    The incidence of confirmed thrombotic cardiovascular serious adverse events (Joint Program MEDAL)

    		Etoricoxib
    (N = 16819)
    25,836 patient-years

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

    Comparison between treatments

    Frequency1 (95% CI)

    Frequency1 (95% CI)

    Relative risk (95% CI)

    Confirmed thrombotic cardiovascular serious adverse events

    When fulfilling protocol requirements (Per protocol)

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

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

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

    Depending on the treatment prescribed (Intent-to-treat)

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

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

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

    Evidence from the heart

    When fulfilling protocol requirements (Per protocol)

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

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

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

    Depending on the treatment prescribed (Intent-to-treat)

    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 (Per protocol)

    0,34 (0,28; 0,42)

    0,32 (0,25; 0,40)

    1,08 (0,80; 1,46)

    Depending on the treatment prescribed (Intent-to-treat)

    0,33 (0,28; 0,39)

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

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

    Confirmed phenomena from the peripheral vascular system

    When fulfilling protocol requirements (Per protocol)

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

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

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

    Depending on the treatment prescribed (Intent-to-treat)

    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 number 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 took <75% of the study drug or 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 (including patients who may have been subjected to non-intervention interventions after discontinuing the study medications). Total number of randomized patients: n = 17 412 for etoricoxib and n = 17 289 for diclofenac.

    Mortality from cardiovascular events, as well as overall mortality in treatment groups with ethoricoxib and diclofenac were comparable.

    Cardiorenal phenomena

    Approximately 50% of patients included in the study MEDAL, at an initial assessment in the history the arterial hypertensia has been registered. In the study, the dropout rate due to adverse events associated with hypertension was statistically significantly higher with etorikoksib compared with diclofenac. The incidence of adverse events associated with chronic heart failure (dropout or serious adverse events) was similar in the 60 mg and 56 mg diclofenac groups, but was higher for etoricoxib 90 mg than diclofenac indose 150 mg (and statistically significantly higher for etorikoksiba at a dose of 90 mg compared with diclofenac at a dose of 150 mg in the study MEDAL in patients with OA). The incidence of confirmed adverse events associated with chronic heart failure (serious, leading to hospitalization or the need for emergency care) was slightly higher for etorikoksiba compared with diclofenac at a dose of 150 mg, the effect was dose-dependent. The frequency of dropout cases due to adverse events associated with edema was higher for etorikoksiba compared with diclofenac 150 mg, the effect was dose-dependent (statistically significant for etorikoksiba at a dose of 90 mg, but not for etorikoksiba at a dose of 60 mg).

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

    In separate studies of the program MEDAL The absolute drop-out rate in any treatment group with etorikoksib (60 mg or 90 mg) was 2.6% with arterial hypertension, 1.9% with edema, and 1.1% with chronic heart failure. In patients who took etorikoksib in a dose of 90 mg, the drop-out rate was higher than in patients taking etorikoksib in a dose of 60 mg.

    Results of the evaluation of gastrointestinal tolerance in the Program MEDAL

    In each of the three studies included in the program MEDAL, the frequency of dropout from the study for any clinical adverse events on the part of the digestive tract (for example, dyspepsia, abdominal pain, ulcers) was significantly lower for etorikoksiba compared with diclofenac. The dropout rate due to undesirable GIT clinical events per 100 patient-years for the entire study period was 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; 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

    To undesirable phenomena from the upper part of the gastrointestinal tract were perforations, ulcers and bleeding. Complicated undesirable phenomena from the upper gastrointestinal tract included perforation, obstruction and complicated bleeding; uncomplicated phenomena included uncomplicated bleeding and uncomplicated ulcers.When taking etorikoksiba compared with diclofenac, the overall incidence of adverse events from the upper gastrointestinal tract was significantly lower. There were no significant differences between etorikoksibom and diclofenac in the frequency of complicated adverse events. For cases of bleeding from the upper gastrointestinal tract (complicated and uncomplicated), there were no significant differences between etorikoksib and diclofenac. The advantage of etorikoksib compared with diclofenac for complications from the upper gastrointestinal tract was not statistically significant in patients taking aspirin at low doses (about 33% of patients).

    The incidence of confirmed complicated and uncomplicated clinical adverse events from the upper gastrointestinal 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, the relative risk was 0.69 (95% CI: 0.57, 0.83).

    In assessing the incidence of confirmed clinical adverse events from the upper GI tract in elderly patients, a maximum reduction was observed in patients aged ≥75 years in the etorikoksib group compared with diclofenac 1.35 (95% CI: 0.94, 1.87) and 2.78 (95% CI: 2.14, 3.56) per 100 patient-years, respectively.

    The incidence of confirmed adverse events from the lower part of the digestive tract (perforation of the small or large intestine, obstruction, bleeding) did not differ significantly between the groups taking etorikoksib and diclofenac.

    The results of the liver safety assessment in the Program MEDAL

    When taking etorikoksiba compared with diclofenac, a statistically significantly lower incidence of dropout from the study due to adverse events on the part of the liver was observed. In the joint program MEDAL 0.3% of patients taking etorikoksib, and 2.7% of patients taking 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 compared to 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 cardiovascular events

    In clinical trials, with the exception of the Program MEDAL, approximately 3100 patients received etorikoksib in a dose of ≥60 mg per day for 12 weeks or longer. In these studies, there were no significant differences in the incidence of confirmed serious thrombotic cardiovascular 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 some NSAIDs that inhibit COX-1 and selective inhibitors of COX-2 may be of clinical importance in patients at risk of 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 12-week, double-blind endoscopic studies, 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 500 mg twice daily or ibuprofen 800 mg three times a day. The frequency of ulceration in the appointment of etorikoksib was higher compared with placebo.

    The study of renal function in elderly patients

    In a randomized, double-blind, placebo-controlled study in parallel groups, the effect of 15-day therapy with etoricoxib (90 mg), celecoxib (200 mg twice daily), naproxen (500 mg twice daily), compared with placebo for kidney sodium excretion , blood pressure (BP) and other parameters of kidney function in patients aged 60 to 85 years who received a diet with limited sodium intake up to 200 meq / day.

    Etoricoxib, celecoxib and naproxen had similar effects on the excretion of sodium by the kidneys after 2 weeks of treatment. All active comparators showed an increase in systolic blood pressure compared with placebo, however, etorikoksib caused a statistically significant increase in systolic blood pressure on the 14th day compared with celecoxib and naproxen (mean change in systolic blood pressure compared to baseline: etorikoksib 7.7 mm Hg. Art. celecoxib 2.4 mm Hg. Art. naproxen 3.6 mm of mercury. st.).

    Pharmacokinetics:

    Suction

    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 in the blood plasma (Cmax) is 3.6 μg / ml. Time to reach CmOh (TmOh) is approximately 1 hour after taking the drug. The average geometric area under the curve "concentration - time" (AUC0-24h) was 37.8 μg * h / ml. The pharmacokinetics of etorikoksib in the range of therapeutic doses is linear.

    When taking etorikoksiba at a dose of 120 mg during meals (food with a high fat content), there was no clinically significant effect on the degree of absorption. The rate of absorption thus varied, which led to a decrease in CmOh at 36 % and an increase in TmOh for 2 hours. These data are not clinically relevant. In clinical trials etorikoksib was used regardless of food intake.

    Distribution

    Etorikoksib approximately 92% binds to plasma proteins in humans in the concentration range from 0.05 to 5 μg / ml.The volume of distribution in the equilibrium state (VdSS) is about 120 liters.

    Etoricoxib penetrates the placental barrier in rats and rabbits and the blood-brain barrier in rats.

    Metabolism

    Etiricoxib is extensively metabolized, <1% of the dose is excreted by the kidneys unchanged. The main pathway of metabolism is the formation of 6'-hydroxymethylethricoxib, catalyzed by enzymes of the cytochrome system. The main role in metabolism in vivo belongs to the isoenzyme CYP3A4. Research in vitro show that isoenzymes CYP2D6, CYP2C9, CYP1A2, CYP2C19 can also catalyze the main pathway of metabolism, but their quantitative impact in vivo not studied.

    Five metabolites of ethoricoxib were found in humans. The main metabolite is 6'-carboxyacetyl etorecoxib, formed in resulting in the further oxidation of 6'-hydroxymethylethorecoxy. These major metabolites have no appreciable activity or poorly inhibit COX-2. None of these metabolites inhibit COX-1.

    Excretion

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

    Elimination of etorikoksib occurs mainly by metabolism in the liver with subsequent excretion by the kidneys.

    Equilibrium concentrations of etorikoksib achieved with daily intake of 120 mg for 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

    Floor: pharmacokinetic parameters of the drug in men and women do not differ.

    Elderly patients: the pharmacokinetics of the drug in patients older than 65 years is comparable with pharmacokinetics in patients younger than the age.

    Children: the pharmacokinetics of etorikoksib in children (<12 years) has not been studied. In the pharmacokinetic study (N=16), conducted in a group of adolescents aged 12 to 17 years, pharmacokinetics in adolescents with a body weight of 40 kg to 60 kg, taking etorikoksib in a dose of 60 mg once a day, and in adolescents with a body weight> 60 kg, taking etorikoksib in a dose of 90 mg once a day, was similar to pharmacokinetics in adults taking etorikoksib in a dose of 90 mg once a day. Safety and effectiveness of the use of etorikoksib in children is not established.

    Liver failure: in patients with mild hepatic insufficiency (5-6 points on the Child-Pugh scale), taking etorikoksib in a dose of 60 mg once a day was accompanied by an increase in the index AUC about by 16% compared to healthy volunteers taking the drug at the same dose. In patients with moderate hepatic impairment (7-9 on the Child-Pugh scale) who received etorikoksib in a dose of 60 mg once a day every other day, the mean AUC was the same as in healthy volunteers who took etorikoksib in a dose of 60 mg once a day every day. The use of etorikoksib in a dose of 30 mg once a day has not been studied in this group of patients. Clinical and pharmacokinetic data of studies in patients with severe hepatic insufficiency (> 10 points on the Child-Pugh scale) are absent.

    Renal insufficiency: pharmacokinetic parameters of a single application of etorikoksib at a dose of 120 mg in patients with moderate and severe renal insufficiency and in patients with terminal stage of chronic renal failure on hemodialysis do not differ significantly from those of healthy volunteers. Hemodialysis slightly affects the excretion of the drug (clearance in dialysis - about 50 ml / min).

    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 etorikoksibu or any of the excipients of the drug.

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

    - Bronchial asthma, bronchospasm, acute rhinitis, polyposis of the nose, angioedema, hives, or allergic reactions after taking acetylsalicylic acid or non-steroidal anti-inflammatory drugs (NSAIDs), including inhibitors of COX-2, in the anamnesis.

    - Pregnancy and 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 (CK <30 mL / min).

    - Children and adolescents under 16 years.

    - Inflammatory bowel disease.

    - Chronic heart failure (II-IV functional class by classification NYHA).

    - Uncontrolled arterial hypertension (blood pressure is stably higher than 140/90 mm Hg).

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

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

    - Confirmed hyperkalemia.

    Carefully:

    - Patients with an increased risk of complications from the gastrointestinal tract (peptic ulcer of the gastrointestinal tract or gastrointestinal bleeding in the anamnesis, the presence of infection Helicobacter Pylori, simultaneous use of other NSAIDs, including acetylsalicylic acid, elderly age).

    - Patients with a history of risk factors for cardiovascular complications (dyslipidemia / hyperlipidemia, diabetes mellitus, hypertension, smoking, heart failure, left ventricular dysfunction, edema and fluid retention in the body).

    - Hepatic insufficiency (5-9 points according to the Child-Pugh classification). See section "Dosing and Administration").

    - Patients with dehydration.

    - Patients with impaired renal function (CC <60 mL / min), especially the elderly, using concomitant angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, diuretics.

    - Patients with a previous significant decrease in renal function, with impaired renal function, decompensated heart failure, or cirrhosis of the liver, who are at risk with prolonged use of NSAIDs.

    - Concomitant therapy with anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), drugs metabolized by sulfotransferases (cm section "Interaction with other drugs").

    Pregnancy and lactation:

    Pregnancy

    At present, there are no clinical data on the use of etorikoxib in pregnancy. In animal studies, toxic effects on the reproductive system were observed. The potential risk for women during pregnancy is unknown. The use of etorikoksib, as well as other drugs that inhibit the synthesis of prostaglandins, in the III trimester of pregnancy can lead to suppression of uterine contractions and premature closure of the arterial duct. Etoricoxib contraindicated in pregnancy. 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 etorikoksiba with breast milk in women have not been carried out. Women who take etorikoksib, should stop breastfeeding.

    Fertility

    The use of etorikoksib, as well as other drugs that inhibit COX-2 or 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. The effect of the drug is realized faster when taken on an empty stomach. Due to the likely increase in the risk of developing cardiovascular complications, the minimum effective dose should be used as little as possible.

    Osteoarthritis: the recommended dose of etorikoksib is 30 mg once a day. In case of insufficient effect, the daily dose of the drug can be increased to 60 mg per day. The daily dose for osteoarthritis should not exceed 60 mg.

    Rheumatoid arthritis and ankylosing spondylitis: the recommended dose of etorikoksib is 60 mg 1 time per day. In patients with insufficient clinical effect, an increase in the daily dose of the drugup to 90 mg once a day. After clinical stabilization of the disease, it is possible to reduce the dose to 60 mg once a day. If there are no signs of clinical improvement, other methods of treatment should be considered. The daily dose should not exceed 90 mg.

    Acute gouty arthritis: the recommended dose of etorikoksib in the acute period is 120 mg once a day. The duration of the drug at a dose of 120 mg is not more than 8 days. The daily dose should not exceed 120 mg.

    Acute pain after dental operations: the recommended dose of etorikoksib is 90 mg once a day. Etoricoxib should be used only in an acute symptomatic period lasting no more than 3 days. The daily dose for pain relief after dental operations should not exceed 90 mg. Some patients may need additional funds to provide an adequate level of anesthesia in postoperative period during the three-day period of therapy with etoricoxib.

    Special patient groups

    Elderly patients: dose adjustment is not required. As with the use of other drugs, etorikoksib should be used with caution.

    Children: the use of etorikoksiba in patients younger than 16 years is contraindicated.

    Impaired liver function: regardless of the indication for use in patients with mild liver function disorders (5-6 points on the Child-Pugh scale), do not exceed the dose of 60 mg once a day, in patients with violations of the liver function of moderate severity (7-9 points on the Child-Pugh scale) - 30 mg once a day. It is advisable to use caution when using the drug in patients with impaired liver function of moderate severity, as the clinical experience of using the drug in this group of patients is limited.

    Due to the lack of clinical experience in the use of the drug in patients with severe impairment of liver function (≥10 points on the Child-Pugh scale), the drug is contraindicated for this group of patients.

    Impaired renal function: dosage adjustment is not required when administered in patients with CC ≥ 30 mL / min. The use of the drug in patients with QC <30 ml / min is contraindicated.

    Side effects:

    Security Profile Summary

    The safety of the use of etorikoksib was evaluated in clinical trials involving 9295 patients, including 6757 patients with OA, RA,chronic low back pain and ankylosing spondylitis (approximately 600 patients with OA or RA received treatment for one year or more). The profile of adverse reactions was similar in patients with OA or RA who received etorikoksib for one year or longer.

    In a clinical study of acute gouty arthritis, patients received etorikoksib in a dose of 120 mg once a day for 8 days. Profile The adverse events in this study were generally the same as in the combined studies of OA, RA and chronic low back pain.

    For the evaluation of cardiovascular safety, data from three active controlled trials were combined in which 17412 patients with OA or RA received etorikoksib in a dose of 60 mg or 90 mg, the average duration of the study was approximately 18 months.

    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.

    A tabular summary of unwanted reactions

    The table lists undesirable reactions that were registered with greater frequency with the drug than in the placebo group in clinical trials involving patients with OA, RA, chronic low back pain, or ankylosing spondylitis (etorikoksib was administered at a dose of 30 mg, 60 mg or 90 mg with an increase in the dose to the recommended dose for 12 weeks), in the program MEDAL, where studies lasted up to 3.5 years, in short-term studies of acute pain (within 7 days), as well as those obtained during post-marketing application.

    Classification of organ systems

    Unwanted reaction

    Frequency1

    Infectious and parasitic diseases

    alveolar ostitis

    often

    gastroenteritis, upper respiratory tract infections, urinary tract infections

    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

    increased or decreased appetite, weight gain

    infrequently

    Disorders of the psyche

    anxiety, depression, decreased clarity of thinking, 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

    Hearing disorders and labyrinthine 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, dyspepsia / epigastric discomfort, nausea, vomiting, esophagitis, ulcers of the oral mucosa

    often

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

    infrequently

    Disturbances from the liver and bile ducts

    increased ALT and ACT activity

    often

    hepatitis2

    rarely

    liver failure2, jaundice2

    rarely3

    Disturbances from the skin and subcutaneous tissues

    ecchymosis

    often

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

    infrequently

    Stevens-Johnson syndrome2, toxic epidermal necrolysis2, fixed drug erythema2

    rarely3

    Infringements from musculoskeletal and connective tissue

    muscle cramps / spasm, musculoskeletal pain / stiffness

    infrequently

    Disorders from the kidneys and urinary tract

    proteinuria, increased serum creatinine concentration, renal failure2,3,4

    infrequently

    General disorders and disorders at the site of administration

    asthenia / weakness, flu-like syndrome

    often

    chest pain

    infrequently

    Laboratory and

    instrumental

    data

    increased blood urea nitrogen concentration, increased activity of creatine phosphokinase, hyperkalemia, increased uric acid concentration

    infrequently

    hyponatremia

    rarely

    1 According to the frequency considered in clinical trials: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥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 was evaluated on the basis of the highest frequency observed in clinical studies taking into account the indications and the approved dose.

    3 The frequency category "rarely" was determined in accordance with the guidelines (version 2, September 2009) for a Brief Characterization of the Drug based on the calculated upper limit of 95% confidence interval for 0 events, given the number of patients receiving etorikoksib in the analysis of phase III data combined according to dose and indication (n = 15470).

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

    5 Based on the results of this analysis of long-term placebo and actively controlled clinical trials using selective COX-2 inhibitors, the risk of developing serious arterial thrombotic events, including myocardial infarction and stroke, increases. 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 NGTLD and can not be excluded for etorikoksiba: nephrotoxicity, including interstitial nephritis and nephrotic syndrome.

    Overdose:

    In clinical trials, taking etorikoksib in a single dose up to 500 mg and repeatedly taking up to 150 mg / day for 21 days did not cause significant toxic effects. Reports of acute overdose with etoricoxib have been received, however, 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 take routine maintenance measures, such as removal of the non-sucking drug from the digestive tract, clinical observation and, if necessary, maintenance therapy. Etoricoxib not excreted in hemodialysis; excretion of etorikoksiba with peritoneal dialysis was not studied.

    Interaction:

    Pharmacodynamic interactions

    Oral anticoagulants (warfarin). In patients who are constantly taking warfarin, taking etorikoksib in a dose of 120 mg per day was accompanied by an increase in the international normalized ratio (INR) / prothrombin time by approximately 13%. Therefore, patients receiving oral anticoagulants should be monitored by INR / prothrombin time at the beginning of treatment or when changing the dose of etorikoksib, especially in the first few days.

    Diuretics, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists. NSAIDs can reduce the effect of diuretics and other antihypertensive medications. In some patients with impaired renal function (eg, in patients with dehydration or in elderly patients with impaired renal function), simultaneous usean ACE inhibitor or an angiotensin II receptor antagonist and preparations that inhibit COX can lead to an additional impairment in kidney function, including the possible development of acute renal failure, which is usually reversible. This should be taken into account in patients taking both etorikoksib with ACE inhibitors or angiotensin II receptor antagonists. Such combinations should be administered with caution, especially in elderly patients. Patients should be properly hydrated, while monitoring the kidney function at the beginning of the combination therapy and periodically thereafter.

    Acetylsalicylic acid. In a study in healthy volunteers etorikoksib in a dose of 120 mg once a day in an equilibrium state did not affect the antiplatelet activity of acetylsalicylic acid (81 mg once a day). Etoricoxib can simultaneously be used with acetylsalicylic acid in low doses, intended for the prevention of cardiovascular diseases. However, simultaneous use of low doses of acetylsalicylic acid and etorikoksib can lead to an increase in the frequency of ulcerative lesions of the gastrointestinal tract or other complications compared with the intake of only etorikoksiba.The simultaneous use of etorikoksiba with acetylsalicylic acid in doses exceeding those recommended for prevention of cardiovascular complications, as well as with other NSAIDs is not recommended.

    Cyclosporine and tacrolimus. The interaction of etorikoksib with these drugs has not been studied, however, the simultaneous use of cyclosporine or tacrolimus with any NSAID may enhance the nephrotoxic effect of cyclosporin or tacrolimus. When taking etorikoksib in combination with any of these drugs should monitor the kidney function.

    Pharmacokinetic interactions

    The effect of other drugs on the pharmacokinetics of etorikoksiba

    The main pathway of the metabolism of etorikoksib depends on the enzymes of the system CYP. Isozyme CYP3A4 promotes the metabolism of etorikoksiba in vivo. Research in vitro show that isoenzymes CYP2D6, CYP2C9, CYP1A2 and CYP2C19 can also catalyze the main pathway of metabolism, but their quantitative characteristics in vivo not studied.

    Ketoconazole. Ketoconazole, a potent inhibitor of isoenzyme CYP3A4, when taken by healthy volunteers at a dose of 400 mg once a day for 11 days did not have a clinically significant effect on the pharmacokinetics of a single dose of etorikoksib 60 mg (increase AUC on 43%).

    Voriconazole and miconazole. Simultaneous administration of strong inhibitors of isoenzyme CYP3A4 (voriconazole for oral administration or miconazole topically, in the form of gel for oral administration) and etoricoxib etoricoxib caused a slight increase in exposure is not considered clinically significant based upon published data.

    Rifampicin. Simultaneous application etoricoxib and rifampicin (a potent inducer of cytochrome system) resulted in a reduction in plasma concentration etoricoxib 65%. This interaction can lead to a relapse of symptoms with the simultaneous administration of etorikoksiba with rifampicin. This information suggests a need to increase the dose, but apply etorikoksib in doses exceeding recommended for each indication, is not recommended, 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 etorikoksib.

    Effect of etorikoksib on other drugs

    Lithium. NSAIDs decrease the excretion of lithium by the kidneys, therefore, 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 simultaneous admission with NSAIDs, as well as with the abolition of NSAIDs.

    Methotrexate. Two studies examined the effects of etorikoksib in doses of 60, 90 or 120 mg once a day for seven days in patients who received 1 time per week methotrexate in a dose of 7.5 to 20 mg for the treatment of RA. Etoricoxib in doses of 60 and 90 mg had no effect on plasma methotrexate concentration and renal clearance of methotrexate. In one study etorikoksib in a dose of 120 mg did not exert a pharmacokinetic effect on methotrexate, but in another study the plasma methotrexate concentration increased by 28%, and the renal clearance of methotrexate decreased by 13%. When taking etorikoksib and methotrexate concomitantly, it is recommended to observe for possible appearance of toxic effects of methotrexate.

    Oral contraceptives. Etoricoxib in a dose of 60 mg with simultaneous intake for 21 days with oral contraceptives containing 35 μg of ethinyl estradiol (EE) and 0.5 mg to 1 mg of norethindrone, increased AUC0-24h EE is 37% in the equilibrium state.Reception etorikoksiba in a dose of 120 mg in combination with the above oral contraceptives (simultaneously or at an interval of 12 hours) increased AUC0-24h EE on 50-60% in the equilibrium state. This increase in EE concentration should be considered when choosing an oral contraceptive for simultaneous use with etorikoksibom. Such interaction can 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 etorikoksib in a dose of 120 mg concomitantly with preparations for HRT containing conjugated estrogens at a dose of 0.625 mg for 28 days increases the average value of the equilibrium AUC0-24h unconjugated estrone (41%), equilin (76%) and 17-r-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 monotherapy with conjugated estrogens with increasing dose from 0.625 to 1.25 mg.The clinical significance of such increases is unknown, the use of higher doses of conjugated estrogens in combination with etorikoksib has not been studied. The increase in estrogen concentration should be taken into account when choosing hormone therapy during the postmenopausal period with concomitant administration with etorikoksib, 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 etorikoksib was used at a dose of 120 mg once a day for 10 days in healthy volunteers, there was no change in the equilibrium AUC0-24h digoxin in the blood plasma or influence on its excretion by the kidneys. There was an increase in Cmax digoxin by approximately 33%. This increase, as a rule, is not significant for most patients. However, with simultaneous use of etorikoksib and digoxin, patients with a high risk of toxic effects of digoxin should be monitored.

    Effect of etorikoksib on drugs metabolized by sulfotransferases. Etorikoksib is an inhibitor of sulfotransferase person (in particular, SULT1E1) and can increase the concentration of EE in the serum. Due to the fact that currently there is insufficient data on the effects of various sulfotransferases, and their clinical relevance for the use of many drugs is still being studied, it is advisable to use caution in prescribing etorikoksib simultaneously with other drugs metabolized by human sulfhydrases (eg, oral salbutamol and minoxidil).

    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 cytochrome P450 isoenzymesCYP) 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4. In a study in healthy volunteers, the daily use of etorikoksib in a dose of 120 mg did not affect the activity of the isoenzyme CYP3A4 liver when evaluated with the erythromycin respiratory test.

    Special instructions:Effect on the digestive tract

    In patients who received etorikoksib, there were complications from the upper parts of the digestive tract (perforation, ulcers or bleeding), sometimes with a fatal outcome. It is advisable to use caution in the treatment of patients at high risk for complications from the gastrointestinal tract when using NSAIDs, in particular in elderly patients who simultaneously use other NSAIDs, acetylsalicylic acid, or in patients with a history of gastrointestinal disease such as ulcers and 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 studies, there were no significant differences in safety for the gastrointestinal tract with the use of selective COX-2 inhibitors in combination with acetylsalicylic acid in comparison with the use of NSAIDs in combination with acetylsalicylic acid.

    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 withincreased risk of thrombosis (especially myocardial infarction (MI) and stroke) compared with placebo and some NSAIDs. The risk of developing cardiovascular complications with the use of selective COX-2 inhibitors may increase with increasing dose and duration of treatment, therefore, etorikoksib for the shortest period of time and at the lowest effective daily dose. It is necessary to periodically assess the patient's need for symptomatic treatment and response to therapy, especially in patients with OA.

    Patients with known risk factors for developing cardiovascular complications (eg, hypertension, hyperlipidemia, diabetes, smoking) etorikoksib It is necessary to appoint only after a careful preliminary assessment of the benefit-risk relationship.

    Selective COX-2 inhibitors are not a substitute for acetylsalicylic acid in the prevention of cardiovascular disease due to the absence of an antiplatelet effect, so antiplatelet drugs should not be discontinued.

    Effect on kidney function

    Renal prostaglandins can play a compensatory role in maintaining renal perfusion.Therefore, in the presence of conditions that adversely affect renal perfusion, the appointment of etorikoksib can lead to a decrease in the formation of prostaglandins and, as a result, decrease in renal blood flow, and thereby lead to impaired renal function. The greatest risk of this reaction occurs in patients with a significant decrease in kidney function, uncompensated heart failure or cirrhosis of the liver in the anamnesis. 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, in patients taking etorikoksib, fluid retention, edema and hypertension were observed. The use of any NSAID, including etorikoksib, can be associated with the onset or relapse of chronic (congestive) heart failure. Information on the dose-response for etorikoksib is given in section "Pharmacological properties". Caution should be exercised when prescribing etoricoxib for patients with a history of heart failure, left ventricular dysfunction, hypertension, and 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, may be associated with the development of more severe arterial hypertension than with the use of some other NSAIDs and selective inhibitors of COX-2. Therefore, during treatment with etorikoksibom, special attention should be paid to monitoring of blood pressure, which should be monitored within two weeks after initiation of treatment and periodically thereafter. With a significant increase in blood pressure, alternative treatment should be considered.

    Effects on liver function

    Increased activity of alanine aminotransferase (ALT) and / or aspartate aminotransferase (ACT) (approximately three or more times the upper limit of the norm) was reported in clinical studies in approximately 1% of patients who received etorikoksib for a period of up to one year at doses of 30 mg, 60 mg and 90 mg per day.

    It is necessary to monitor the condition of all patients with symptoms and / or signs of liver dysfunction, as well as patients with altered laboratory indicators of liver function.If there are signs of liver failure or liver function indicators deviate significantly from the norm (three times higher than the upper limit of the norm), etorikoksib should be discontinued.

    General recommendations

    If, during treatment, any of the functions of the organs or systems of organs described above deteriorate in patients, appropriate measures should be taken and the issue of abolition of etorikoxib is considered. When using etorikoksib in elderly patients and patients with impaired renal, hepatic or cardiac function, appropriate medical supervision is necessary.

    With care, begin treatment with etorikoksibom patients with dehydration. Before the start of therapy with etorikoksibom it is recommended to rehydrate.

    During post-marketing follow-up, when using NSAIDs and some selective inhibitors of COX-2, very little was reported about the development of serious skin reactions. Some of them, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, were fatal. The risk of developing these reactions is highest at the beginning of the course 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 who received etorikoksib. 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 fever and other signs of inflammation.

    The use of etorikoksib, as well as other drugs that inhibit COX and the synthesis of prostaglandins, is not recommended for women who are planning a pregnancy (cf. section "Application during pregnancy and during breast-feeding").

    The shell of the tablet contains lactose. Patients with such rare congenital diseases as lactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medication.

    Effect on the ability to drive transp. cf. and fur:

    Patients who, on the background of the use of etorikoksib, have episodes of dizziness, drowsiness, or weakness,should refrain from driving and working with machinery.

    Form release / dosage:

    The film-coated tablets are 30 mg, 60 mg, 90 mg and 120 mg.

    Packaging:

    7 tablets in Al/Al blister. 1 blister with instructions for application in a cardboard box.

    10 tablets in Al/Al blister. For 1, 2, 3, 5, 6, 9, 10 blisters together with instructions for use in a cardboard box.

    For 14 tablets in Al/Al blister. By 1,2, 4, 6, 7 blisters together with instructions for use in cardboard pack.

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 of the year.

    Do not use after the expiration date stated on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004581
    Date of registration:12.12.2017
    Expiration Date:12.12.2022
    The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia
    Manufacturer: & nbsp
    Representation: & nbspSANDOZ SANDOZ Switzerland
    Information update date: & nbsp16.01.2018
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