Etorelex pills 60mg, 28pcs

Composition

One film-coated tablet contains:

Active ingredient:

Etoricoxib 60.0 mg;

Auxiliary substances:

Core: hypromellose E 15-2.00 mg; calcium hydrophosphate dihydrate-60.00 mg; croscarmellose sodium-4.00 mg; colloidal silicon dioxide-1.00 mg; sodium stearyl fumarate-3.00 mg; microcrystalline cellulose 200-70.00 mg.

Film coating: hypromellose E 15-4.80 mg; copovidone (Collidone VA64) – 0.64 mg; macrogol 6000-0.96 mg; iron oxide yellow dye-0.16 mg; talc-0.16 mg; titanium dioxide-1.28 mg

Pharmacological action

Pharmacotherapy group: nonsteroidal anti-inflammatory drugs (NSAIDs).

ATX Code: M01 AN 05

Pharmacological properties

Pharmacodynamics

Etoricoxib, when taken orally at therapeutic concentrations, is a selective cyclooxygenase-2 (COX-2) inhibitor. In clinical pharmacological studies, etoricoxib dose-dependently inhibited COX-2, without affecting COX-1 with a daily dose of up to 150 mg. The drug does not inhibit prostaglandin synthesis 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 identified. COX-2 is an isoenzyme that is induced by various pro-inflammatory 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 ductus arteriosus, regulation of kidney and CNS function (fever induction, pain sensation, cognitive function), and may also play a role in the healing of ulcers. COX-2 has been found in the tissues surrounding human gastric ulcers, but its significance for ulcer healing has not been established.

Efficiency

In patients with osteoarthritis (OA), etoricoxib, when administered at a dose of 60 mg 1 time/day, provided a significant reduction in pain and improved the assessment of their condition by patients. These beneficial effects were observed as early as the second day of treatment and persisted for 52 weeks. Studies of etoricoxib administered at a dose of 30 mg 1 time / day (using similar assessment methods) demonstrated efficacy compared to placebo over a 12-week treatment period. In a study conducted to determine the optimal dose, etoricoxib at a dose of 60 mg showed significantly more pronounced improvement than at a dose of 30 mg for all three primary endpoints after 6 weeks of treatment. A dose of 30 mg has not been studied for osteoarthritis of the hand joints.

In patients with rheumatoid arthritis (RA), etoricoxib, when administered at a dose of 90 mg 1 time/day, significantly reduced pain and inflammation and improved mobility. These beneficial effects persisted during the 12-week treatment period.

In patients with acute gouty arthritis, etoricoxib, when administered at a dose of 120 mg 1 time / day for the entire treatment period of 8 days, reduced moderate to severe joint pain and inflammation. The efficacy was comparable to that of Indometacin when administered at a dose of 50 mg 3 times a day. Pain reduction was noted as early as 4 hours after the start of treatment.

In patients with ankylosing spondylitis, etoricoxib, when administered at a dose of 90 mg 1 time / day, significantly reduced back pain, inflammation, rigidity, and improved functions. Clinical efficacy of etoricoxib was observed as early as the second day of treatment and was maintained throughout the entire 52-week treatment period.

In a clinical study of pain after dental surgery, etoricoxib 90 mg was administered once a day for 3 days. In the subgroup of patients with moderate pain (at baseline), etoricoxib, when administered at a dose of 90 mg, had the same analgesic effect as ibuprofen at a dose of 600 mg (16.11 vs. 16.39; P=0.722), and was superior in effectiveness to the combination of paracetamol/codeine at a dose of 600 mg / 60 mg (11.00; P<0.001) and placebo (6.84; P The proportion of patients who required rapid-acting pain medications within the first 24 hours after taking the study drugs was 40.8% with etoricoxib at a dose of 90 mg,25.5% with ibuprofen at a dose of 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 with 76.2% in the placebo group. In this study, the median onset of action (measurable pain reduction) with etoricoxib 90 mg was 28 minutes after the drug was administered.

Pharmacokinetics

Absorption rate

Etoricoxib is rapidly absorbed when taken orally. Absolute oral bioavailability is about 100%. After taking the drug in adults on an empty stomach at a dose of 120 mg 1 time/day, the maximum concentration (Cmax) is 3.6 mcg/ml, the time to reach Cmax is 1 hour after use. Geometric mean AUC0-24 h – 37.8 mcg×h / ml. The pharmacokinetics of etoricoxib within therapeutic doses are linear.

When taking etoricoxib 120 mg with a meal (high-fat food), 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 by 2 h. These results are not considered clinically significant. In clinical trials, etoricoxib was used regardless of food intake.

Distribution

Etoricoxib is approximately 92% bound to human plasma proteins at concentrations of 0.05-5 mcg / ml. The volume of distribution (Vdss) at steady state is about 120 liters. Etoricoxib penetrates the placental barrier and the blood-brain barrier.

Metabolism

Etoricoxib is extensively metabolized. Less than 1% of etoricoxib is excreted unchanged by the kidneys. The main pathway of metabolism is the formation of 6 ‘ – hydroxymethylethoricoxib, catalyzed by cytochrome P450 enzymes. CYP3A4 promotes the metabolism of etoricoxib in vivo. In vitro studies indicate that the isoenzymes CYP2D6, CYP2C9, CYP1A2, and CYP2C19 can also catalyze the main pathway of metabolism, but their quantitative effects in vivo have not been studied.

5 metabolites of etoricoxib were detected in humans. The main metabolite is 6′ – carboxyacetylethoricoxib, which is formed by additional oxidation of 6′ – hydroxymethylethoricoxib. These major metabolites do not have significant activity, or are weak COX-2 inhibitors. None of these metabolites inhibit COX-1.

Deduction

With a single intravenous use of labeled radioactive etoricoxib at a dose of 25 mg to healthy volunteers,70% of etoricoxib was excreted by the kidneys,20% – through the intestine, mainly in the form of metabolites. Less than 2% were found unchanged.

Elimination of etoricoxib occurs mainly through metabolism, followed by elimination by the kidneys.

The steady-state concentration is reached with a daily intake of 120 mg of etoricoxib after 7 days with a cumulative coefficient of about 2, which corresponds to a half-life of about 22 hours. Plasma clearance after intravenous use of 25 mg is approximately 50 ml/min.

Special patient groups

Elderly

Pharmacokinetics in elderly patients (65 years and older) is comparable to the pharmacokinetics in young patients.

The

pharmacokinetics of etoricoxib are similar in men and women.

Liver failure

In patients with mild hepatic impairment (Child-Pugh score 5-6), taking etoricoxib at a dose of 60 mg 1 time / day was accompanied by an increase in AUC by 16% compared to healthy individuals taking the drug at the same dose.

In patients with moderate hepatic impairment (Child-Pugh score 7-9) who took etoricoxib at a dose of 60 mg every other day, the average AUC value was the same as in healthy individuals who took etoricoxib daily at the same dose. Etoricoxib 30 mg once daily has not been studied in this population.

Data from clinical and pharmacokinetic studies in patients with severe hepatic impairment (≥10 points on the Child-Pugh scale) are not available.

Renal insufficiency

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

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

In a pharmacokinetic study (n=16) conducted in adolescents aged 12 to 17 years, the pharmacokinetics in adolescents with a body weight of 40 to 60 kg when taking etoricoxib at a dose of 60 mg 1 time/day and in adolescents with a body weight of more than 60 kg when taking etoricoxib at a dose of 90 mg 1 time/day were similar to the pharmacokinetics in adults when taking etoricoxib at a dose of 90 mg 1 time/day. The safety and efficacy of etoricoxib in children has not been established.

Indications

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.

Use during pregnancy and lactation

Pregnancy

There are no clinical data on the use of etoricoxib during pregnancy. Toxic effects on the reproductive system have 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, during the last trimester of pregnancy can lead to suppression of uterine contractions and premature closure of the ductus arteriosus. Etoricoxib is contraindicated during pregnancy. If pregnancy occurs during treatment, etoricoxib should be discontinued.

Breast-feeding

In lactating rats, etoricoxib is excreted in milk. Studies confirming the release of etoricoxib in breast milk in women have not been conducted. Women taking etoricoxib should stop breastfeeding (see section “Contraindications”).

Fertility

The use of etoricoxib, as well as other drugs that inhibit COX-2 and prostaglandin synthesis, is not recommended for women who are planning pregnancy.

Contraindications

·  Hypersensitivity to any component of the drug;

·  Acute peptic ulcer of the stomach and duodenum, active gastrointestinal bleeding·

* Complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to acetylsalicylic acid or other NSAIDs (including in the anamnesis).

* Pregnancy, breast-feeding period.

·  Severe hepatic impairment (serum albumin <25 g / l or ≥10 points on the Child-Pugh scale);

·  Severe renal insufficiency (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 consistently exceeds 140/90 mm Hg.

·  Confirmed coronary artery disease, peripheral artery disease, and / or cerebrovascular diseases·

* Lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

·  Confirmed hyperkalemia·

* Progressive kidney disease.

With caution

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

– patients with a high risk of complications from the gastrointestinal tract due to NSAIDs; the elderly, at the same time taking other NSAIDs, including acetylsalicylic acid, or patients with diseases of the gastrointestinal tract in history, such as peptic ulcer disease and gastrointestinal bleeding;

– patients with a history of risk factors for cardiovascular complications such as dyslipidemia/hyperlipidemia, diabetes mellitus, hypertension, Smoking, heart failure, impaired left ventricular function, swelling, and fluid retention;

– patients with impaired liver function of mild severity (5-6 points on a scale child-Pugh) should not exceed 60 mg 1 time/day, patients with impaired liver function moderate (7-9 points on a scale child-Pugh) – 30 mg 1 time/day;

– patients with dehydration;

– patients with impaired renal function, at the same time using ACE inhibitors, diuretics, angiotensin II, especially the elderly;

patients with creatinine clearance <60 ml/min;

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

Caution should be exercised when concomitant therapy with the following medications::

– anticoagulants (for example, warfarin);

– antiplatelet agents (for example, acetylsalicylic acid, clopidogrel);

– drugs metabolized by sulfotransferases.

Side effects

The safety of etoricoxib was evaluated in clinical trials involving 9295 participants, including 6757 patients with OA, RA, chronic lower back pain, and ankylosing spondylitis (approximately 600 patients with OA or RA were treated for one year or longer).

In clinical trials, the adverse effect profile was similar in patients with OA or RA who had been taking etoricoxib for 1 year or longer.

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

In the Cardiovascular Safety Assessment Program, which included data from three active-controlled trials,17,412 patients with OA or RA received etoricoxib at a dose of 60 mg or 90 mg for an average of 18 months (see section “Pharmacological properties”, subsection”Pharmacodynamics”).

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

The following adverse reactions were reported more frequently with the drug than with placebo, in clinical trials involving patients with OA, RA, chronic lower back pain or ankylosing spondylitis who took etoricoxib at a dose of 30 mg,60 mg or 90 mg with an increase in the recommended dose for 12 weeks, in MEDAL Studies lasting up to 3.5 years, in short-term acute pain studies, and in post-marketing use (determination of the frequency registered in the clinical trial database: very often (≥1/10), often (≥1/100 to <1/10), infrequently (≥1/1000 to <1/100), rarely (≥1/10,000 to <1/1000), very rarely (:

Infectious and parasitic diseases: often – alveolar ostitis; infrequently-gastroenteritis, upper respiratory tract infections, urinary tract infections.

Disorders of the blood and lymphatic system: infrequently-anemia (mainly as a result of gastrointestinal bleeding), leukopenia, thrombocytopenia.

Immune system disorders: infrequently-hypersensitivity reactions 1,3; rarely-angioedema, anaphylactic / anaphylactoid reactions, including shock 1.

Metabolic and nutritional disorders: often – edema/ fluid retention; infrequently-decreased or increased appetite, weight gain.

Mental disorders: infrequently-anxiety, depression, concentration disorders, hallucinations 1; rarely-confusion 1, anxiety 1.

Nervous system disorders: often – dizziness, headache; infrequently – taste disorders, insomnia, paresthesia/ hypesthesia, drowsiness.

Visual disturbances: infrequently – blurred vision, conjunctivitis.

Hearing disorders and labyrinth disorders: infrequently-tinnitus, vertigo.

Disorders of the cardiovascular system: often-palpitation, arrhythmia 1, arterial hypertension; infrequently-atrial fibrillation, tachycardia 1, chronic heart failure, non-specific ECG changes, angina pectoris 1, myocardial infarction 4, hot flashes, cerebrovascular accident 4, transient ischemic attack, hypertensive crisis 1, vasculitis 1.

Respiratory system disorders: often-bronchospasm 1; infrequently-cough, shortness of breath, nosebleeds.

Violations of the gastrointestinal tract: often – abdominal pain; often – constipation, flatulence, gastritis, heartburn/gastroesophageal reflux, diarrhea, dyspepsia/ epigastric discomfort, nausea, vomiting, esophagitis, ulcers of the mucous membrane of the mouth; rarely, bloating, changes in motility, dryness of the mucous membrane of the oral cavity, gastro-duodenal ulcer, gastric ulcer, including gastrointestinal perforation and bleeding, irritable bowel syndrome, pancreatitis 1.

Liver and biliary tract disorders: often-increased ALT activity, increased ACT activity; rarely-hepatitis 1; rarely 2-liver failure 1, jaundice 1.

Skin and subcutaneous tissue disorders: often-ecchymosis; infrequently-facial swelling, pruritus, rash, erythema 1, urticaria 1; rarely 2-Stevens-Johnson syndrome 1, toxic epidermal necrolysis 1, fixed drug erythema 1.

Musculoskeletal and connective tissue disorders: infrequently-muscle spasms / cramps, musculoskeletal pain/stiffness.

Renal and urinary tract disorders: infrequently-proteinuria, increased serum creatinine, renal insufficiency 1.

General disorders and disorders at the injection site: often-asthenia/ weakness, flu-like syndrome; infrequently-chest pain.

Influence on the results of laboratory and instrumental studies: infrequently-increased blood urea nitrogen, increased creatine phosphokinase, hyperkalemia, increased uric acid; rarely-decreased blood sodium.

1 This adverse reaction was reported during post-marketing surveillance.The frequency of reports for it is estimated based on the highest frequency observed in clinical studies combined depending on the dose and indication.

2 The frequency category “rare” was determined based on an estimated upper bound of the 95% confidence interval for 0 events, taking into account the number of patients treated with etoricoxib in the Phase III data analysis combined according to dose and indication (n=15,470).

3 Hypersensitivity includes the terms “allergy”, “drug allergy”, ” drug hypersensitivity”, ” hypersensitivity”, ” unspecified hypersensitivity”, ” hypersensitivity reaction “and”non-specific allergy”.

4 Based on data from long-term placebo-controlled and active-controlled clinical trials, the use of selective COX-2 inhibitors increases the risk of serious arterial thrombotic events, including myocardial infarction and stroke. Based on the available data, it is unlikely that the absolute risk of these events exceeds 1% per year (infrequently).

The following serious adverse events have been reported with NSAIDs and cannot be excluded for etoricoxib: nephrotoxicity, including interstitial nephritis and nephrotic syndrome.

Interaction

Pharmacodynamic interaction

Oral anticoagulants (warfarin). In patients receiving warfarin, etoricoxib 120 mg / day was associated with an approximately 13% increase in MHO and prothrombin time. In patients receiving warfarin or similar medications, MHO values should be monitored at the time of starting therapy or changing the dosage regimen of etoricoxib, especially in the first few days.

Diuretics, ACE inhibitors, and angiotensin II antagonists. NSAIDs may weaken the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (for example, in patients with dehydration or in elderly patients with impaired renal function), the simultaneous use of an ACE inhibitor or angiotensin II antagonist and drugs that inhibit cyclooxygenase may lead to additional deterioration of renal function, including the possible development of acute renal failure, which is usually reversible. Patients taking etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists should be aware of the possibility of such interactions. This combination should be used with caution, especially in elderly patients. At the beginning of combined treatment, as well as at certain intervals in the future, fluid deficiency should be replenished and monitoring of renal function should be considered.

Acetylsalicylic acid. In a study involving healthy volunteers, etoricoxib at a dose of 120 mg/day at steady state did not affect the antiplatelet activity of acetylsalicylic acid (81 mg 1 time/day). Etoricoxib can be used simultaneously with acetylsalicylic acid in low doses intended for the prevention of cardiovascular diseases. However, concomitant use of low-dose acetylsalicylic acid and etoricoxib may lead to an increased incidence of gastrointestinal ulceration and other complications compared to etoricoxib alone. Concomitant use of etoricoxib with acetylsalicylic acid in doses exceeding those recommended for the prevention of cardiovascular complications, as well as with other NSAIDs, is not recommended.

Cyclosporine and tacrolimus. The interaction of etoricoxib with these drugs has not been studied, but the simultaneous use of NSAIDs with cyclosporine and tacrolimus may increase the nephrotoxic effect of these drugs. Renal function should be monitored when etoricoxib is co-administered with any of these medications.

Pharmacokinetic interaction

Effect of etoricoxib on other medications

Lithium. NSAIDs reduce the excretion of lithium by the kidneys and, consequently, increase the concentration of lithium in the blood plasma. If necessary, frequent monitoring of blood lithium concentrations is performed and the dose of lithium is adjusted during concomitant use with NSAIDs, as well as when NSAIDs are discontinued.

Methotrexate. Two studies examined the effects of etoricoxib at doses of 60,90, and 120 mg once daily for 7 days in patients treated with 7.5 to 20 mg methotrexate once weekly for rheumatoid arthritis. Etoricoxib at doses of 60 and 90 mg had no effect on the plasma concentration and renal clearance of methotrexate. In one study, etoricoxib 120 mg had no effect on the pharmacokinetic parameters of methotrexate. In another study, the concentration of methotrexate in plasma increased by 28%, and the renal clearance of methotrexate decreased by 13%. Co-use of etoricoxib and methotrexate should be monitored for possible toxic effects of methotrexate.

Oral contraceptives. Taking etoricoxib for 21 days at a dose of 60 mg with oral contraceptives containing 35 mcg of ethinyl estradiol (EE) and 0.5 to 1 mg of norethindrone increases the AUC0-24 hours for EE by 37%. Taking etoricoxib 120 mg with the above-mentioned oral contraceptives (simultaneously or at 12-hour intervals) increases the steady-state AUC0-24 hours for EE by 50-60%. This increase in EE concentration should be taken into account when selecting an appropriate oral contraceptive for concomitant use with etoricoxib. This fact may lead to an increase in the incidence of adverse events associated with the use of oral contraceptives (for example, venous thromboembolism in women at risk).

Hormone replacement therapy (HRT). use of etoricoxib at a dose of 120 mg concomitantly with hormone replacement therapy containing conjugated estrogens at a dose of 0.625 mg for 28 days increases the mean steady-state AUC0-24 hours of unconjugated estrone (41%), equilin (76%) and 17-P-estradiol (22%). The effect of the recommended long-term doses of etoricoxib (30,60, and 90 mg) has not been studied. Etoricoxib at a dose of 120 mg changed the exposure (AUC0-24 h) of these estrogenic components by less than half compared to monotherapy with a drug containing conjugated estrogens, with an increase in the dose of the latter from 0.625 to 1.25 mg. The clinical significance of such increases is unknown. The use of a combination of etoricoxib and a drug containing higher doses of conjugated estrogens has not been studied. Increased estrogen concentrations should be taken into account when choosing a hormone preparation for use in the postmenopausal period when administered concomitantly with etoricoxib, since increased estrogen exposure may increase the risk of HRT-related adverse events.

Prednisone/prednisone. In drug interaction studies, etoricoxib did not have a clinically significant effect on the pharmacokinetics of prednisone/prednisolone.

Digoxin. When using etoricoxib at a dose of 120 mg 1 time/day for 10 days in healthy volunteers, there was no change in AUC 0-24 hours at steady state or effect on the excretion of digoxin by the kidneys. There was an increase in digoxin Cmax (approximately 33%). Such an increase, as a rule, is not significant in most patients. However, patients at high risk of developing digoxin toxicity should be monitored when etoricoxib and digoxin are co-administered.

Effect of etoricoxib on drugs metabolized by sulfotransferases. Etoricoxib is an inhibitor of human sulfotransferase (in particular SULT1E1) and can increase serum EE concentrations. Due to the current lack of data on the effects of various sulfotransferases, and their clinical significance for the use of many drugs is still being studied, it is advisable to prescribe etoricoxib with caution simultaneously with other drugs that are mainly metabolized by human sulfotransferases (for example, oral salbutamol and minoxidil).

Effect of etoricoxib on drugs metabolized by cytochrome isoenzymes. Based on the results of in vitro studies, etoricoxib is not expected to inhibit cytochrome P 450 isoenzymes 1A2,2C9,2C19,2D6,2E1, and 3A4. In a study involving healthy volunteers, daily use of etoricoxib at a dose of 120 mg did not affect the activity of the CYP3A4 isoenzyme in the liver, according to the results of an erythromycin breath test.

Effect of other drugs on the pharmacokinetics of etoricoxib

The main pathway of etoricoxib metabolism depends on cytochrome P450 enzymes. The CYP3A4 isoenzyme promotes etoricoxib metabolism in vivo. In vitro studies suggest that the isoenzymes CYP2D6, CYP2C9, CYP1A2, and CYP2C19 can also catalyze the main pathway of metabolism, but their quantitative characteristics in vivo have not been studied.

Ketoconazole. Ketoconazole is a potent inhibitor of the CYP3A4 isoenzyme. When ketoconazole was administered to healthy volunteers at a dose of 400 mg 1 time/day for 11 days, it did not have a clinically significant effect on the pharmacokinetics of a single dose of etoricoxib 60 mg (an increase in AUC by 43%).

Voriconazole and miconazole. Concomitant use of strong inhibitors of the CYP3A4 isoenzyme (voriconazole for oral use or topically miconazole, oral gel) and etoricoxib caused a slight increase in etoricoxib exposure, which, based on published data, was not considered clinically significant.

Rifampicin.Concomitant use of etoricoxib and rifampicin (a potent inducer of the cytochrome system) resulted in a 65% reduction in etoricoxib plasma concentrations. This interaction may be accompanied by a relapse of symptoms when etoricoxib is co-administered with rifampicin. These data may indicate the need to increase the dose, but etoricoxib should not be used at doses that exceed the recommended values for each indication, since the combined use of rifampicin and etoricoxib at such doses has not been studied.

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

How to take, course of use and dosage

Inside, regardless of food intake, with a small amount of water.

The drug Etorelex should be used in the minimum effective dose in the shortest possible 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 60 mg or 90 mg once a day. The minimum effective daily dose is 60 mg once a day. In some patients, taking a dose of 90 mg once a day may lead to increased therapeutic effects.

For conditions with acute pain, etoricoxib should only be used during 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 in a dose of 120 mg is no more than 8 days.

Acute pain after dental surgery

The recommended dose is 90 mg once a day. In the treatment of acute pain, etoricoxib should only be used in the acute period of no more than 3 days.

Doses that exceed the recommended dose for each indication either do not have additional efficacy or have not been studied. Thus:

– daily dose of osteoarthritis should not exceed 60 mg;

– daily dose in rheumatoid arthritis should not exceed 90 mg;

daily dose for ankylosing spondylitis should not exceed 90 mg;

– daily dose for acute gouty arthritis should not exceed 120 mg; for a period of not more than 8 days;

– 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 people

No dose adjustment is required in elderly patients. As with other medications used in elderly patients, caution should be exercised when using etoricoxib (see section “Special Instructions”).

Patients with impaired liver function.

Regardless of the indication, patients with mild hepatic impairment (5-6 points on the Child-Pugh scale) should not exceed the dose of 60 mg 1 time per day, patients with moderate hepatic impairment (7-9 points on the Child-Pugh scale) – 30 mg 1 time per day.

Caution is recommended when using etoricoxib in patients with moderate hepatic impairment, as the clinical experience of using etoricoxib in this group of patients is limited. Due to the lack of clinical experience with the use of etoricoxib 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.

No dose adjustment is required in patients with creatinine clearance ≥30 ml / min (see section “Pharmacological properties”, subsection”Pharmacokinetics”). Use of etoricoxib in patients with creatinine clearance

Children

Etoricoxib is contraindicated in children and adolescents under 16 years of age (see section “Contraindications”).

Overdose

In clinical studies, taking etoricoxib at a single dose of up to 500 mg or multiple doses of up to 150 mg / day for 21 days did not cause significant toxic effects. Acute overdose with etoricoxib has been reported, but no adverse reactions have been reported in most cases.

Symptoms: The most frequent adverse reactions were consistent with the safety profile of etoricoxib (e. g. gastrointestinal disorders, cardiorenal events).

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

Description

Round biconvex tablets covered with a yellow film coating. On a cross-section, the core is almost white to light yellow in color.

Special instructions

Effect on the gastrointestinal tract

Upper gastrointestinal complications (perforations, ulcers, or bleeding), sometimes fatal, have been reported in patients treated with etoricoxib. Caution is recommended 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, including acetylsalicylic acid, as well as in patients with a history of gastrointestinal diseases such as ulcers or gastrointestinal bleeding.

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

Impact on the cardiovascular system

The results of clinical studies indicate that the use of drugs of the class of selective COX-2 inhibitors is associated with an increased risk of thrombotic events (especially myocardial infarction and stroke) relative to placebo and some NSAIDs. Since the risk of developing cardiovascular diseases when taking selective COX-2 inhibitors 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 and response to therapy, especially for patients with osteoarthritis (see the section “Pharmacological properties”, subsection “Pharmacodynamics”, as well as the sections “Contraindications”, “Dosage and use” and “Side effects”).

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

Selective COX-2 inhibitors are not a substitute for acetylsalicylic acid in the prevention of cardiovascular diseases, since they do not affect platelets. Therefore, the use of antiplatelet drugs should not be discontinued (see the section “Pharmacological properties”, subsection “Pharmacodynamics”, as well as the section “Interaction with other drugs”).

Effects on kidney function

Renal prostaglandins may play a compensatory role in maintaining renal perfusion. In the presence of conditions that negatively affect renal perfusion, the use of etoricoxib may cause a decrease in prostaglandin formation and a decrease in renal blood flow, and thus reduce renal function. The greatest risk of developing this reaction exists for 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, patients taking etoricoxib experienced fluid retention, edema, and hypertension. The use of all NSAIDs, including etoricoxib, may be associated with the occurrence or recurrence of chronic heart failure. For information on the dose-dependent effect of etoricoxib, see the section “Pharmacological properties”, subsection”Pharmacodynamics”. Caution should be exercised when prescribing etoricoxib to patients with a history of heart failure, left ventricular dysfunction, or hypertension, as well as to patients with pre-existing edema that has occurred for any other reason. If there are clinical signs of deterioration in these patients, appropriate measures should be taken, including discontinuation of etoricoxib.

The use of etoricoxib, especially in high doses, may be associated with more frequent and severe arterial hypertension than with certain other NSAIDs and selective COX-2 inhibitors. During treatment with etoricoxib, special attention should be paid to blood pressure control, which should be monitored for 2 weeks after the start of treatment and periodically thereafter. If there is a significant increase in blood pressure, alternative treatment should be considered.

Effects on liver function

In clinical trials lasting up to one year, approximately 1% of patients treated with etoricoxib at doses of 30 mg,60 mg and 90 mg per day showed an increase in the activity of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) (approximately 3 or more times relative to the upper limit of normal).

All patients with symptoms and/or signs of liver dysfunction, as well as patients with abnormal liver function indicators, should be monitored. If permanent abnormalities in liver function parameters are detected (three times higher than the upper limit of normal), the use of etoricoxib should be discontinued.

General instructions

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

Caution should be exercised when starting treatment with etoricoxib in patients with dehydration. Rehydration is recommended before starting the use of etoricoxib.

Serious skin reactions have been reported very rarely during post-marketing surveillance with NSAIDs and some selective COX-2 inhibitors. Some of them (including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) were fatal. The risk of developing such reactions 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 treated with etoricoxib. The use of some selective COX-2 inhibitors was associated with an increased risk of skin reactions in patients with a history of drug allergies. Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

The use of etoricoxib may mask fever or other signs of inflammation.

Caution should be exercised when etoricoxib is co-administered with warfarin or other oral anticoagulants (see section “Interactions with other medicinal products”).

The use of etoricoxib, as well as other drugs that inhibit COX and prostaglandin synthesis, is not recommended for women who are planning pregnancy (see the section “Pharmacological properties”, subsection “Pharmacodynamics” and the section “Use during pregnancy and lactation, effects on fertility”).

Influence on the ability to drive vehicles and mechanisms

Patients who have experienced dizziness, drowsiness or weakness during the use of etoricoxib should refrain from driving vehicles and working with mechanisms.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Active ingredient

Etoricoxib

Conditions of release from pharmacies

By prescription

Dosage form

Tablets