Bixitor, 60 mg 10 pcs.

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drugs (NSAIDs) ATX code: M01AN05 Pharmacological properties

Pharmacodynamics

Mechanism of action

Etoricoxib is a selective cyclooxygenase-2 (COX-2) inhibitor when administered orally in therapeutic concentrations. In clinical pharmacological studies, etoricoxib inhibited COX-2 in a dose-dependent manner, with no effect on COX-1 at a daily dose up to 150 mg. The drug does not inhibit the synthesis of prostaglandins in the gastric mucosa and does not affect platelet function.

Cyclooxygenase is responsible for the formation of prostaglandins. Two isoforms of cyclooxygenase, COX-1 and COX-2, have been isolated. COX-2 is an isoenzyme that is induced by various proinflammatory mediators and is considered 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, sensation of pain, cognitive function), and may also play a certain role in the process of ulcer healing. COX-2 has been detected in the tissues surrounding gastric ulcers in humans, but its importance in ulcer healing has not been established.

Efficacy

In patients with osteoarthritis (OA), etoricoxib, administered at a dose of 60 mg once daily, provided a significant reduction in pain and improvement in patients’ assessment of their condition. These favorable effects were observed on the second day of treatment and persisted for 52 weeks. Studies of etoricoxib at a dose of 30 mg once daily (using similar evaluation methods) demonstrated efficacy compared to placebo during the treatment period of 12 weeks. In a study conducted to determine the optimal dose, etoricoxib at a dose of 60 mg demonstrated significantly greater improvement than at a dose of 30 mg for all three primary endpoints after 6 weeks of treatment. The 30 mg dose has not been studied in osteoarthritis of the hand joints.

In patients with rheumatoid arthritis (RA), etoricoxib at a dose of 90 mg once daily provided a significant reduction in pain and inflammation and improved mobility. These favorable effects persisted for a treatment period of 12 weeks.

In patients with acute gouty arthritis, etoricoxib, administered at a dose of 120 mg once daily for an eight-day treatment period, reduced moderate to severe joint pain and inflammation. The efficacy was comparable to that of indomethacin when used in a dose of 50 mg three times a day. Pain reduction was noted as early as four hours after the start of treatment.

In patients with ankylosing spondylitis, etoricoxib at a dose of 90 mg once daily provided a significant reduction in back pain, inflammation, stiffness, and improved function. The clinical efficacy of etoricoxib was observed on the second day of treatment and was sustained for the entire treatment period of 52 weeks.

In a clinical study of pain after dental surgery, etoricoxib at a dose of 90 mg was administered once daily for three days. In a subgroup of patients with moderate pain (at baseline assessment), etoricoxib had the same analgesic effect as ibuprofen at a dose of 600 mg (16.11 vs. 16.39 P=0.722), and was superior to the paracetamol/codeine combination at a dose of 600 mg/60 mg (11.00, P<0.001) and placebo (6.84, P<0.001) according to the overall assessment of pain reduction during the first 6 hours (TOPAR6). The proportion of patients who required rapid-acting pain medication within the first 24 hours of taking the study drugs was 40.8% with etoricoxib at 90 mg, 25.5% with ibuprofen at 600 mg every 6 hours, and 46.7% with the paracetamol/codein combination at 600 mg/60 mg every 6 hours, compared with 76.2% in the placebo group. In this study, the median onset of action (tangible pain reduction) with etoricoxib at a dose of 90 mg was 28 minutes after taking the drug.

Safety

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

The MEDAL Program was a multinational program that evaluated the long-term use of etoricoxib and diclofenac in arthritis. The MEDAL program was a prospective safety assessment program based on cardiovascular (CV) events from pooled data from three randomized, double-blind, active-controlled trials: MEDAL, EDGE II and EDGE.

The MEDAL study was a trial, the duration of which was determined by achieving endpoints (CC events), that included 17,804 patients with OA and 5,700 patients with RA who received etoricoxib at a dose of 60 mg (OA) or 90 mg (OA and RA) or diclofenac at a dose of 150 mg daily for an average of 20.3 months (maximum 42.3 months, median 21.3 months). Only serious adverse events and dropouts due to any adverse events were reported in this study.

The EDGE and EDGE II studies compared the gastrointestinal tolerability of etoricoxib and diclofenac. The EDGE study included 7111 patients with OA who received etoricoxib at a dose of 90 mg daily (1.5 times the recommended dose for OA) or diclofenac at a dose of 150 mg daily for an average of 9.1 months (maximum 16.6 months, median 11.4 months). The EDGE II study included 4,086 patients with RA who received etoricoxib at a dose of 90 mg daily or diclofenac at a dose of 150 mg daily for an average of 19.2 months (maximum 33.1 months, median 24 months).

In the combined MEDAL Program, 34,701 patients with OA or RA were treated for an average of 17.9 months (maximum 42.3 months, median 16.3 months); about 1,800 patients were treated for more than 24 months. Patients included in the MEDAL Program had a wide range of CV and gastrointestinal risk factors at baseline assessment. Patients with recent myocardial infarction, as well as those with aortocoronary bypass or percutaneous coronary intervention within 6 months before study inclusion were excluded. Gastroprotectants and low-dose aspirin were allowed in the studies.

The cardiovascular safety results

The incidence of confirmed serious thrombotic CC adverse events (which included cardiac, cerebrovascular, and peripheral vascular events) was comparable between the groups receiving etoricoxib or diclofenac (data are shown in the table below). There were no statistically significant differences in the incidence of thrombotic events between etoricoxib and diclofenac in all subgroups analyzed, including patient categories in the baseline CC risk range. The relative risk for confirmed serious thrombotic CC adverse events was similar for etoricoxib (when administered at 60 mg or 90 mg) and diclofenac (when administered at 150 mg).

Table “Frequency of Confirmed Thrombotic CC Events (MEDAL Program)”

CC mortality and overall mortality were comparable between the etoricoxib and diclofenac treatment groups.

Cardiorenal events

Approximately 50% of patients included in the MEDAL study had a history of arterial hypertension at baseline assessment. The dropout rate due to adverse events associated with arterial hypertension was statistically significantly higher for etoricoxib than for diclofenac. The frequency of adverse events related to chronic heart failure (dropouts and serious events) was similar for etoricoxib in 60 mg dose and diclofenac in 150 mg dose, but was higher for etoricoxib in 90 mg dose compared to diclofenac in 150 mg dose (and statistically significantly higher for etoricoxib in 90 mg dose compared to diclofenac in 150 mg dose in the MEDAL trial OA group). The frequency of confirmed adverse events related to chronic heart failure (events that were serious and resulted in hospitalization or emergency department visits) was slightly higher for etoricoxib compared to diclofenac in the 150 mg dose; this effect was dose-dependent. Study dropout rates due to adverse events related to edema were higher for etoricoxib compared with diclofenac at a dose of 150 mg; this effect was dose-dependent (statistically significant for etoricoxib at a dose of 90 mg, but not for etoricoxib at a dose of 60 mg).

The results of the EDGE and EDGE II cardiorenal safety assessments are consistent with the results in the MEDAL study

. In individual MEDAL studies, the absolute dropout rate in any treatment group for etoricoxib (60 mg or 90 mg) was up to 2.6% for arterial hypertension, up to 1.9% for edema, and up to 1.1% for chronic heart failure. Patients taking etoricoxib at the 90-mg dose had a higher dropout rate than patients taking etoricoxib at the 60-mg dose.

The MEDAL gastrointestinal tolerability results

In each of the three MEDAL studies, the study dropout rate for any clinical GI adverse event (e.g., dyspepsia, abdominal pain, ulcers) was significantly lower for etoricoxib compared to diclofenac. The dropout rate due to GI adverse clinical events per 100 patient-years for the entire study period was as follows: 3.23 for etoricoxib and 4.96 for diclofenac in the MEDAL study; 9.12 for etoricoxib and 12.28 for diclofenac in the EDGE study, and 3.71 for etoricoxib and 4.81 for diclofenac in the EDGE II study.

The MEDAL Gastrointestinal Safety Assessment Results

In general, upper GI adverse events were defined as perforations, ulcers and bleeding. Complicated upper GI adverse events included perforations, obstruction and complicated bleeding; uncomplicated upper GI adverse events included uncomplicated bleeding and uncomplicated ulcers. The overall incidence of upper gastrointestinal adverse events was significantly lower for etoricoxib compared with diclofenac. No significant differences between etoricoxib and diclofenac were found in the frequency of complications. No significant differences between etoricoxib and diclofenac were found for hemorrhagic adverse events from the upper gastrointestinal tract (complicated and uncomplicated in the aggregate). The advantage of etoricoxib in the upper GI tract compared with diclofenac in patients simultaneously taking low-dose aspirin (about 33% of patients) was not statistically significant.

The incidence of confirmed complicated and uncomplicated upper GI clinical adverse events per 100 patient-years (perforations, 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, based on which the relative risk was 0.69 (95% CI 0.57, 0.83).

The incidence of confirmed upper gastrointestinal adverse events in older patients was examined; the maximum reduction 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 etoricoxib and diclofenac, respectively.

The incidence of confirmed lower GI adverse events (small or large bowel perforation, obstruction, or bleeding) did not differ significantly between the groups receiving etoricoxib and diclofenac.

The results of the MEDAL liver safety assessment

Etoricoxib had a statistically significantly lower dropout rate due to liver adverse events compared to diclofenac. In the combined MEDAL Program, 0.3% of patients receiving etoricoxib and 2.7% of patients receiving diclofenac dropped out of the study due to liver adverse events. 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 liver adverse events in the MEDAL Program were not serious.

Additional safety data related to thrombotic CC events

In clinical trials other than the MEDAL Program trials, approximately 3,100 patients received etoricoxib at a dose of ≥60 mg daily for 12 weeks or longer. There were no notable differences in the incidence of confirmed serious thrombotic CC events in patients receiving etoricoxib ≥60 mg, placebo, or naproxen-free NSAIDs. However, compared with patients receiving naproxen at a dose of 500 mg twice daily, the incidence of these events was higher in patients receiving etoricoxib. The difference in antiplatelet activity between some COX-1 inhibiting DAAs and COX-2 selective inhibitors may be of clinical significance in patients at risk for thromboembolic events. Selective COX-2 inhibitors inhibit systemic (and possibly endothelial) prostacyclin formation without affecting platelet thromboxane. The clinical significance of these observations has not been established.

Additional Gastrointestinal Safety Data

. In two double-blind, 12-week endoscopic studies, the cumulative incidence of gastroduodenal ulcers was significantly lower in patients receiving etoricoxib at a dose of 120 mg once daily than in patients receiving naproxen at a dose of 500 mg twice daily or ibuprofen at a dose of 800 mg three times daily. The incidence of ulcers was higher with etoricoxib compared to placebo.

The study of renal function in the elderly

. A randomized, double-blind, placebo-controlled, parallel-group study evaluated the effects of 15 days of therapy with etoricoxib (90 mg), celecoxib (200 mg twice daily), naproxen (500 mg twice daily) and placebo on renal sodium excretion, blood pressure (BP) and other measures of renal function in patients aged 60 to 85 years who received a sodium diet of 200 mEq/day. Etoricoxib, celecoxib, and naproxen had similar effects on renal sodium excretion after 2 weeks of treatment. All active comparison drugs increased systolic BP relative to placebo, but etoricoxib therapy resulted in a statistically significant increase in systolic BP at day 14 compared with celecoxib and naproxen (mean change for systolic BP compared with baseline: etoricoxib 7.7 mmHg, celecoxib 2.4 mmHg, naproxen 3.6 mmHg).

Pharmacokinetics

Absorption

Etoricoxib is rapidly absorbed when administered orally. Absolute bioavailability when taken orally is about 100%. Administration in adults on an empty stomach in a dose of 120 mg once a day until reaching equilibrium state the maximum concentration (Cmax) is 3.6 µg/ml. Time of reaching maximum concentration (TCmax) in blood plasma is 1 h after drug administration. Geometric mean AUC0-24 is 37.8 µg/h/ml. Pharmacokinetics of etoricoxib within therapeutic doses is linear.
When taking etoricoxib at a dose of 120 mg with meals (high-fat meals) there was no clinically significant effect on the degree of absorption. The rate of absorption was altered, resulting in a 36% decrease in Cmax and a 2 h increase in TCmax. These results are not considered clinically significant. In clinical trials etoricoxib was used independently from food intake.

Distribution

Etoricoxib is approximately 92% bound to human plasma proteins at concentrations of 0.05-5 µg/ml. The volume of distribution (Vdss) in equilibrium is about 120 l.
Etoricoxib penetrates through the placental and blood-brain barriers.

Metabolism

Etoricoxib is extensively metabolized. Less than 1% of etoricoxib is excreted unchanged by the kidneys. The main route of metabolism is the formation of 6′-hydroxymethylethoricoxib, catalyzed by enzymes of the cytochrome system. CYP3A4 isoenzyme contributes to the metabolism of etoricoxib in vivo. In vitro studies indicate that the CYP2D6, CYP2C9, CYP1A2, and CYP2C19 isoenzymes can also catalyze the major metabolic pathway, but their quantitative effects in vivo have not been studied.

In humans, 5 metabolites of etoricoxib have been identified. The main metabolite is 6′-carboxyacetyl etoricoxib, which is formed by additional oxidation of 6′-hydroxymethyl etoricoxib. These major metabolites have no appreciable activity or are weak COX-2 inhibitors. None of these metabolites inhibits COX-1.

On single intravenous administration of labeled radioactive etoricoxib to healthy volunteers at a dose of 25 mg, 70% of etoricoxib was excreted through the kidneys, 20% – through the intestine, mostly as metabolites. Less than 2% was found unchanged.

The excretion of etoricoxib is mainly by metabolism, followed by excretion through the kidneys.

The equilibrium concentration is reached when 120 mg of etoricoxib is taken daily after 7 days with a cumulation coefficient 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.

Pharmacokinetics in selected patient groups

Elderly patients

Pharmacokinetics in the elderly (65 years and older) are comparable with those in the young.

Paul

The pharmacokinetics of etoricoxib are similar in men and women.

Hepatic disorders

In patients with mild hepatic impairment (Child-Pugh score of 5-6), administration of etoricoxib in a dose of 60 mg once daily was associated with a 16% increase in AUC compared to healthy subjects taking the drug in the same dose.

In patients with moderate hepatic dysfunction (Child-Pugh score 7-9) taking etoricoxib at a dose of 60 mg once daily, the average AUC was the same as in healthy subjects taking etoricoxib daily at the same dose. Etoricoxib in a dose of 30 mg once daily has not been studied in this population.
No data from clinical and pharmacokinetic studies in patients with severe hepatic impairment (≥10 Child-Pugh score) are available.

Renal dysfunction

The pharmacokinetic parameters of a single dose of etoricoxib 120 mg in patients with moderate to severe renal impairment and with end-stage chronic renal failure (CKF) on hemodialysis were not significantly different from those in healthy subjects. Hemodialysis had little effect on excretion (dialysis clearance was about 50 ml/min).

Children
Pharmacokinetic parameters of etoricoxib in children younger than 12 years have not been studied.

In a pharmacokinetic study (n=16) conducted in adolescents aged 12 to 17 years, the pharmacokinetics in adolescents weighing 40 to 60 kg when taking etoricoxib at a dose of 60 mg once daily and in those weighing more than 60 kg when taking etoricoxib at a dose of 90 mg once daily were similar to the pharmacokinetics in adults when taking etoricoxib at a dose of 90 mg once daily.

The safety and effectiveness of etoricoxib in children has not been established.

Indications

Treatment of chronic low back pain.
Symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain and inflammation associated with acute gouty arthritis.
Short-term treatment of moderate acute pain after dental surgery. The decision to prescribe a selective COX-2 inhibitor should be justified taking into account the general risks for each individual patient (see sections “Contraindications” and “Special instructions”).

Pharmacological effect

Pharmacotherapeutic group:

Special instructions

Effect on the gastrointestinal tract

Cases of upper gastrointestinal complications (perforation, ulceration or bleeding), sometimes fatal, have been reported in patients receiving etoricoxib. It is recommended to exercise caution when treating patients at high risk of developing gastrointestinal complications when using NSAIDs, in particular in the elderly, patients who are simultaneously using other NSAIDs, incl. acetylsalicylic acid, as well as in patients with a history of gastrointestinal diseases such as ulcers or gastrointestinal bleeding.

There is an additional increase in the risk of developing GI adverse events (gastrointestinal ulcers or other GI complications) with concomitant use of etoricoxib and acetylsalicylic acid (even at low doses). In long-term clinical studies, there were no significant differences in gastrointestinal safety when using selective COX-2 inhibitors + acetylsalicylic acid compared with the use of NSAIDs + acetylsalicylic acid (see section “Pharmacological properties”, subsection “Pharmacodynamics”).

Effect on the cardiovascular system

Clinical trial results suggest that the use of selective COX-2 inhibitor drugs may be associated with a risk of thrombotic events (especially myocardial infarction (MI) and stroke) relative to placebo and some NSAIDs. Because the risk of developing cardiovascular disease with etoricoxib may increase with increasing dose and duration of use, it is necessary to choose the shortest possible duration of use and the lowest effective daily dose. It is necessary to periodically assess the patient’s need for symptomatic treatment in response to therapy, especially for patients with osteoarthritis (see section “Pharmacological properties”, subsection “Pharmacodynamics”, as well as sections “Contraindications”, “Dosage and Administration” and “Side effects”).

Patients with significant risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) should be prescribed etoricoxib only after careful assessment of benefit (see section “Pharmacological properties”, subsection “Pharmacodynamics”).

Selective COX-2 inhibitors are not a replacement for acetylsalicylic acid in the prevention of cardiovascular thromboembolic diseases due to their insufficient effect on platelets. Therefore, you should not stop using antiplatelet drugs (see section “Pharmacological properties”, subsection “Pharmacodynamics”, as well as section “Interaction with other drugs”).

Effect on kidney function

Renal prostaglandins may play a compensatory role in maintaining renal perfusion. Therefore, in the presence of conditions that adversely affect renal perfusion, the use of etoricoxib may cause a decrease in prostaglandin formation and, secondarily, a decrease in renal blood flow, and thus impair renal function. The greatest risk of developing this reaction is in patients with a significant decrease in renal function, decompensated heart failure, or a history of cirrhosis. In such patients, it is necessary to monitor renal function.

Fluid retention, edema and hypertension

As with other drugs that inhibit prostaglandin synthesis, fluid retention, edema, and hypertension have been reported in patients treated with etoricoxib.

All NSAIDs, including etoricoxib, may be associated with the onset or recurrence of chronic heart failure. Information on the dose dependence of the effect of etoricoxib is given in the “Pharmacological properties” section, subsection “Pharmacodynamics”. Caution should be exercised in patients with a history of heart failure, left ventricular dysfunction or hypertension, as well as in patients with pre-existing edema due to any other cause. If clinical signs of deterioration occur in such patients, appropriate measures should be taken, including discontinuation of etoricoxib.

The use of etoricoxib, especially at high doses, may be associated with more frequent and severe hypertension than with some other NSAIDs and selective COX-2 inhibitors. During treatment with etoricoxib, special attention should be paid to blood pressure control (see section “Contraindications”). Blood pressure should be monitored for two weeks after starting treatment and periodically thereafter. If there is a significant increase in blood pressure, alternative treatment should be considered.

Effect on liver function

In clinical studies lasting up to one year, approximately 1% of patients treated with etoricoxib at doses of 30 mg, 60 mg and 90 mg per day experienced increases in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately three or more times the upper limit of normal).

All patients with symptoms and/or signs of liver dysfunction, as well as patients with abnormal liver function tests, should be monitored. If there are signs of liver failure or persistent abnormalities in liver function tests (three times the upper limit of normal), use of Bixitor should be discontinued.

General instructions

If the patient experiences deterioration in the function of any of the organ systems listed above during treatment, appropriate measures should be taken and discontinuation of etoricoxib therapy should be considered. When using etoricoxib in elderly patients and in patients with impaired renal, hepatic or cardiac function, appropriate medical supervision is required.

Caution should be exercised when initiating treatment with etoricoxib in patients with dehydration. Rehydration is recommended before starting etoricoxib therapy.

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

Etoricoxib may mask fever or other signs of inflammation.

Caution should be exercised when concomitantly prescribing etoricoxib with warfarin or other oral anticoagulants (see section “Interactions with other drugs”).

The use of etoricoxib, like other drugs that inhibit the synthesis of cyclooxygenase/prostaglandins, is not recommended for women who are planning pregnancy (see section “Pharmacological properties”, subsection “Pharmacodynamics” and section “Use during pregnancy and breastfeeding, effects on fertility”).

Bixitor® contains lactose monohydrate. Patients with rare congenital diseases such as lactose intolerance, congenital lactase deficiency and glucose-galactose malabsorption should not use this drug.

Impact on the ability to drive vehicles and machinery

Patients who have experienced spatial disorientation, dizziness, or drowsiness while taking etoricoxib should refrain from driving or operating machinery.

Active ingredient

Etoricoxib

Composition

1 tablet contains:

Active ingredient: etoricoxib – 60 mg / or 90 mg / or 120 mg;

Excipients: anhydrous calcium hydrogen phosphate, microcrystalline cellulose, povidone K 30, croscarmellose sodium, magnesium stearate; shell – hypromellose, lactose monohydrate, titanium dioxide, triacetin, indigo carmine aluminum varnish (for dosages of 60 mg and 120 mg), yellow iron oxide (for dosages of 60 mg and 120 mg).

Pregnancy

Pregnancy
There are no clinical data on the use of etoricoxib during pregnancy. Reproductive toxicity has been observed in animal studies. The potential risk in women during pregnancy is unknown. The use of etoricoxib, as well as other drugs that inhibit prostaglandin synthesis, can lead to suppression of uterine contractions in the last trimester of pregnancy – to premature closure of the ductus arteriosus in the fetus.
Etoricoxib is contraindicated during pregnancy (see section “Contraindications”). If a woman becomes pregnant during treatment, etoricoxib should be discontinued.

Breastfeeding
It is unknown whether etoricoxib is excreted into human milk. In lactating rats, etoricoxib is excreted in milk. Women taking etoricoxib should stop breastfeeding (see Contraindications section).

Fertility
The use of etoricoxib, like other drugs known to inhibit COX-2, is not recommended for women planning pregnancy.

Contraindications

Hypersensitivity to any component of the drug;
peptic ulcer of the stomach and duodenum in the acute stage, active gastrointestinal bleeding;
complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including a history);
pregnancy, breastfeeding period;
severe liver dysfunction (serum albumin <25 g/l or ≥10 points on the Child-Pugh scale); severe renal failure (creatinine clearance less than 30 ml/min); children under 16 years of age; inflammatory bowel diseases; chronic heart failure (NYHA functional class II-IV); uncontrolled arterial hypertension, in which blood pressure levels consistently exceed 140/90 mm Hg. Art.; confirmed coronary heart disease, peripheral arterial disease and/or cerebrovascular disease. lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the drug contains lactose); confirmed hyperkalemia; progressive kidney diseases. With caution

Caution should be exercised when using the drug in the following groups of patients:

patients with an increased risk of developing complications from the gastrointestinal tract due to taking NSAIDs; elderly patients concomitantly taking other NSAIDs, including acetylsalicylic acid, or patients with a history of gastrointestinal diseases such as peptic ulcers and gastrointestinal bleeding:
patients with a history of risk factors for cardiovascular complications, such as dyslipidemia/hyperlipidemia, diabetes mellitus, hypertension, smoking, heart failure, left ventricular dysfunction, edema and fluid retention:
patients with mild liver dysfunction (5-6 points on the Child-Pugh scale) should not exceed a dose of 60 mg once a day, patients with moderate liver dysfunction (7-9 points on the Child-Pugh scale) should not exceed 30 mg once a day:
patients with dehydration:
patients with impaired renal function who are simultaneously using ACE inhibitors, diuretics, angiotensin II receptor antagonists, especially the elderly;
patients with creatinine clearance <60 ml/min; patients with a previous significant decrease in renal function, with weakened renal function, decompensated heart failure or cirrhosis, who are at risk with long-term use of NSAIDs.

Caution should be exercised during concomitant therapy with the following drugs:

anticoagulants (for example, warfarin),
antiplatelet agents (for example, acetylsalicylic acid, clopidogrel),
drugs metabolized by sulfotransferases.

Side Effects

Brief description of the security profile

Interaction

Pharmacodynamic interaction

Overdose

In clinical studies, single doses of etoricoxib up to 500 mg or multiple doses of up to 150 mg/day for 21 days did not cause significant toxic effects. There have been reports of acute overdose with etoricoxib, but in most cases no adverse reactions were reported. The most commonly observed adverse reactions were consistent with the safety profile of etoricoxib (eg, gastrointestinal disorders, cardiorenal events).

In case of overdose, it is advisable to use the usual supportive measures, such as removal of unabsorbed drug from the gastrointestinal tract, clinical observation and, if necessary, supportive therapy.
Etoricoxib is not eliminated by hemodialysis, and elimination of etoricoxib by peritoneal dialysis has not been studied.

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf life

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

Manufacturer

AET Laboratories Private Limited/Hemofarm LLC, India