Etoria 60mg tablets, No. 14

- Symptomatic therapy of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain and inflammatory symptoms associated with acute gouty arthritis.

- Treatment of moderate to severe acute pain after dental operations.

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

Osteoarthritis:

The recommended dose is 60 mg once a day.

Rheumatoid arthritis and ankylosing spondylitis:

The recommended dose is 90 mg once a day.

Acute gouty arthritis:

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

The duration of use of the drug at a dose of 120 mg should not exceed 8 days.

The minimum effective dose should be used in the smallest possible short course.

The average therapeutic dose for pain syndrome is 60 mg once a day.

Acute pain after dental surgery:

The recommended dose is 90 mg once a day.

In the treatment of acute pain, Etoria should be used only in the acute period, limited to a duration of no more than 8 days.

The daily dose for relief of pain after dental surgery should not exceed 90 mg

Film-coated tablets

1 tab.

etoricoxib

Excipients: calcium hydrogen phosphate anhydrous (calcium hydrogen phosphate anhydrous disubstituted), microcrystalline cellulose, povidone K 30, croscarmellose sodium, magnesium stearate.

• Hypersensitivity to any component of the drug;

• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose or paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including a history);

• erosive and ulcerative changes in the mucous membrane of the stomach or duodenum 12, active gastrointestinal bleeding;

• cerebrovascular or other bleeding;

• inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the acute phase;

• hemophilia and other blood clotting disorders;

• severe heart failure (NYHA functional class II-IV);

• severe liver failure (more than 9 points on the Child-Pugh scale) or active liver disease;

• severe renal failure (creatinine clearance less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia;

• period after coronary artery bypass grafting;

• peripheral arterial disease, cerebrovascular disease, clinically expressed ischemic heart disease;

• persistent blood pressure values ??exceeding 140/90 mm Hg. Art. with uncontrolled arterial hypertension;

• pregnancy, breastfeeding period;

• children under 16 years of age.

Carefully

Anamnestic data on the development of ulcerative lesions of the gastrointestinal tract (GIT), the presence of Helicobacter pylori infection, advanced age, prolonged use of NSAIDs, frequent alcohol consumption, severe somatic diseases, dyslipidemia / hyperlipidemia, diabetes mellitus, arterial hypertension, edema and fluid retention, smoking , creatinine clearance less than 60 ml / min, concomitant therapy with the following drugs: - anticoagulants (for example, warfarin), - antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), - oral glucocorticosteroids (for example, prednisolone), - selective serotonin reuptake inhibitors (for example , citalopram, fluoxetine, paroxetine, sertraline). In patients with hepatic impairment (5-9 points on the Child-Pugh scale), it is recommended not to exceed a daily dose of 60 mg.

Pharmacodynamics

Etoricoxib is a selective inhibitor of cyclooxygenase-2 (COX-2), in therapeutic concentrations blocks the formation of prostaglandins and has anti-inflammatory, analgesic and antipyretic effects. Selective inhibition of COX-2 with etoricoxib is accompanied by a decrease in the severity of clinical symptoms associated with the inflammatory process, while there is no effect on platelet function and the mucous membrane of the gastrointestinal tract. Etoricoxib has a dose-dependent effect of inhibition of COX-2 without affecting COX-1 when a daily dose of up to 150 mg is used. The drug has no effect on the production of prostaglandins in the gastric mucosa and bleeding time. In the studies conducted, there was no decrease in the level of arachidonic acid and platelet aggregation caused by collagen.

Pharmacokinetics

Absorption

It is rapidly absorbed when taken orally. Oral bioavailability is about 100%. When using the drug in adults on an empty stomach at a dose of 120 mg, the maximum concentration (Cmax) is 3.6 ?g / ml, the time to reach the maximum concentration (TCmax) in the blood plasma is 1 hour after administration. The geometric mean area under the concentration-time curve AUC0 - 24 hours was 37.8 ?g * h / ml. The pharmacokinetics of etoricoxib within therapeutic doses is linear. Food intake does not significantly affect the severity and rate of absorption of etoricoxib at a dose of 120 mg. At the same time, there is a decrease in Cmax values ??by 36% and an increase in TCmax by 2 hours. Taking antacids does not affect the pharmacokinetics of the drug.

Distribution

The connection with plasma proteins when taking the drug exceeds 92%. The volume of distribution (Vdss) at equilibrium is about 120 liters. Etoricoxib has been shown to cross the placental and blood-brain barrier.

Metabolism

It is extensively metabolized in the liver with the participation of the cytochrome P450 isoenzyme (CYP) and the formation of 6-hydroxymethylethoricoxib. Less than 1% of the drug is excreted in the urine unchanged. Found 5 metabolites of etoricoxib, the main ones: 6-hydroxymethylethoricoxib and its derivative - 6-carboxyacetylethoricoxib. The main metabolites do not affect COX-1 and are completely inactive or inactive with respect to COX-2.

Withdrawal

With a single intravenous administration of a labeled radioactive preparation containing etoricoxib at a dose of 25 mg to healthy volunteers, it was demonstrated that 70% of the drug is excreted through the kidneys, 20% through the intestines, mainly in the form of metabolites. Less than 2% was found unchanged. Etoricoxib is administered primarily by metabolism via the kidneys. The equilibrium concentration of the drug is achieved with a daily intake of 120 mg of the drug after 7 days with a cumulation coefficient of about 2, which corresponds to a half-life of about 22 hours. Plasma clearance is approximately 50 ml / min.

Special patient groups

Floor

There are no pharmacokinetic differences between men and women.

Elderly patients

Pharmacokinetics in the elderly (65 years and older) are comparable to those in younger patients. There is no need to adjust the dose of the drug in elderly patients. Racial differences do not affect the pharmacokinetic parameters of etoricoxib.

Patients with liver disorders

In patients with minor liver dysfunctions (5-6 points on the Child-Pugh scale), a single dose of etoricoxib at a dose of 60 mg / day was accompanied by a 16% increase in the AUC index compared with healthy individuals.

In patients with moderate hepatic impairment (7-9 points on the Child-Pugh scale) who took the drug at a dose of 60 mg every other day, the AUC value was the same as in healthy individuals who took the drug daily at the same dose. There are no data from clinical and pharmacokinetic studies in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale).

Patients with impaired renal function

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

Application in children

The pharmacokinetic parameters of etoricoxib in children under 12 years of age have not been studied. In comparative pharmacokinetic studies, comparable data were obtained when using etoricoxib in a group of adolescents (from 12 to 17 years old) weighing 40-60 kg at a dose of 60 mg / day, in a similar age group and weighing more than 60 kg - 90 mg / day, as well as in adults when taken 90 mg / day.

Side effect

Infectious and parasitic diseases

Uncommon - gastroenteritis, upper respiratory tract infections, urinary tract infections.

Blood and lymphatic system disorders

Uncommon - leukopenia, thrombocytopenia.

Immune system disorders:

Very rarely - hypersensitivity reaction, anaphylactic / anaphylactoid reactions, including shock.

Metabolic and nutritional disorders

Often - edema, fluid retention;

Uncommon - changes in appetite, weight gain.

Mental disorder

Uncommon - anxiety, depression, concentration disorders;

Very rarely - hallucinations, confusion, anxiety.

Nervous system disorders Often - headache, dizziness, weakness;

Infrequently - taste disturbance, drowsiness, insomnia, sensory disturbances, incl. paresthesia / hyperesthesia.

Violation of the organ of vision Uncommon - conjunctivitis, blurred vision.

Hearing and labyrinth disorders

Infrequently - tinnitus, vertigo.

Heart disorders

Often - palpitations;

Infrequently - atrial fibrillation, congestive heart failure, nonspecific ECG changes, angina pectoris, myocardial infarction;

Very rarely - tachycardia, arrhythmia.

Vascular disorders

Often - increased blood pressure (BP); Infrequently - hot flashes, impaired cerebral circulation; Very rarely - hypertensive crisis.

Respiratory, Chest and Mediastinal Disorders

Uncommon - cough, shortness of breath, epistaxis;

Very rarely - bronchospasm.

Gastrointestinal disorders

Often - epigastric pain, heartburn, nausea, diarrhea, dyspepsia, flatulence;

Uncommon - bloating, belching, increased peristalsis, constipation, dryness of the oral mucosa, gastritis, gastric or duodenal ulcer, irritable bowel syndrome, esophagitis, oral mucosa ulcers, vomiting;

Very rarely - gastrointestinal ulcers (with bleeding or perforation).

Liver and biliary tract disorders

Often - an increase in the activity of 'hepatic' transaminases;

Very rarely - hepatitis, jaundice; frequency not established - liver failure.

Violation of the skin and subcutaneous tissue

Often - ecchymosis;

Uncommon - facial swelling, itching, rash;

Rarely, erythema;

Very rarely - urticaria, Stevens-Johnson syndrome, Lyell's syndrome;

Frequency not established - fixed drug erythema.

Musculoskeletal and connective tissue disorders Uncommon - muscle cramps, arthralgia, myalgia.

Kidney and urinary tract disorders

Infrequently - proteinuria;

Very rarely - renal failure.

General disorders and disorders at the injection site

Often - flu-like syndrome;

Infrequently - chest pain.

Laboratory and instrumental data

Infrequently - an increase in nitrogen in the blood and urine, an increase in the activity of creatine phosphokinase, a decrease in hematocrit, a decrease in hemoglobin, hyperkalemia, an increase in serum creatinine, an increase in uric acid;

Rarely - a decrease in serum sodium.

Overdose

Etoricoxib overdose has not been reported in clinical trials. In clinical trials, single doses of up to 500 mg etoricoxib or repeated doses of up to 150 mg / day for 21 days did not cause significant toxic effects. In case of an overdose of the drug, undesirable effects from the gastrointestinal tract, cardiovascular system and kidneys may occur. In case of an overdose, symptomatic therapy is performed. Etoricoxib is not excreted by hemodialysis, and the elimination of the drug by peritoneal dialysis has not been studied.

Interaction with other medicinal products

Pharmacodynamic interaction

Oral anticoagulants (warfarin): Etoricoxib 120 mg daily was associated with an approximately 13% increase in the International Normalized Ratio (INR) prothrombin time in patients receiving warfarin. In patients receiving warfarin or similar drugs, INR should be monitored when starting or changing treatment with etoricoxib, especially in the first few days. Diuretics, angiotensin-converting enzyme (ACE) inhibitors: There are reports that non-selective NSAIDs and selective COX-2 inhibitors can weaken the antihypertensive effect of ACE inhibitors. This interaction should be taken into account when treating patients taking etoricoxib concomitantly with ACE inhibitors. In patients with impaired renal function (for example,with dehydration or in old age), such a combination can aggravate functional kidney failure. Acetylsalicylic acid: Etoricoxib can be used concomitantly with acetylsalicylic acid in low doses for the prevention of cardiovascular disease. However, the simultaneous administration of low doses of acetylsalicylic acid and etoricoxib can lead to an increase in the incidence of gastrointestinal ulcers and other complications compared to taking etoricoxib alone. In the equilibrium state, etoricoxib at a dose of 120 mg once a day does not affect the antiplatelet activity of acetylsalicylic acid in low doses (81 mg per day). The drug does not replace the prophylactic action of acetylsalicylic acid in cardiovascular diseases.Cyclosporine and tacrolimus increase the risk of developing nephrotoxicity when taking the drug.

Pharmacokinetic interaction

Ћитий: имеютс¤ данные, что неселективные Ќѕ¬ѕ и селективные ингибиторы ?ќv-2 могут повышать концентрацию лити¤ в плазме. Ёто взаимодействие следует принимать во внимание при лечении больных, принимающих эторикоксиб одновременно с литием. ћетотрексат: в двух исследовани¤х изучались эффекты препарата в дозе 60 мг, 90 мг и 120 мг 1 раз в день в течение семи дней у больных, получавших 1 раз в неделю метотрексат в дозе от 7,5 до 20 мг по поводу ревматоидного артрита. Ёторикоксиб в дозе 60 мг и 90 мг не оказывал вли¤ни¤ на концентрацию в плазме (по AUC) и почечный клиренс метотрексата. ¬ одном исследовании эторикоксиб в дозе 120 мг не оказывал вли¤ни¤ на концентрацию в плазме (по AUC) и почечный клиренс метотрексата. ¬ другом исследовании эторикоксиб в дозе 120 мг повышал концентрацию метотрексата в плазме на 28 % (по AUC) и снижала почечный клиренс метотрексата на 13 %. ѕри одновременном назначении эторикоксиба в дозах выше 90 мг в день и метотрексата следует вести наблюдение за возможным по¤влением токсических эффектов метотрексата. ѕероральные контрацептивы: прием эторикоксиба в дозе 120 мг с пероральными контрацептивами, содержащими 35 мкг этинилэстрадиола (ЁЁ) и от 0,5 до 1 мг норэтиндрона в течение 21 дн¤, одновременно или с разницей в 12 часов увеличивает стационарную AUC0-24ч дл¤ ЁЁ на 50-60 %. ќднако, концентраци¤ норэтистерона обычно не увеличиваетс¤ до клинически значимой степени. Ёто увеличение концентрации ЁЁ следует принимать во внимание при выборе соответствующего перорального контрацептива дл¤ одновременного применени¤ с эторикоксибом. ѕодобный факт может приводить к увеличению частоты тромбоэмболий за счет увеличени¤ экспозиции ЁЁ. «начимого фармакокинетического взаимодействи¤ с глюкокортикостероидами не обнаружено. ?игоксин: эторикоксиб не вли¤ет на равновесную AUC0-24ч или элиминацию дигоксина. ¬месте с тем, эторикоксиб повышает —mах (в среднем на 33 %), что может иметь значение при развитии передозировки дигоксина. –ифампицин: одновременный прием эторикоксиба и рифампицина Ч мощного индуктора печеночного метаболизма Ч приводит к снижению на 65 % AUC дл¤ эторикоксиба в плазме. Ёто взаимодействие следует учитывать при одновременном назначении эторикоксиба с рифампицином. јнтациды и кетоконазол (мощный ингибитор CYP3A4) не оказывают клинически значимого действи¤ на фармакокинетику эторикоксиба.

ќсобые указани¤

ѕрием препарата Ётори¤ требует тщательного контрол¤ артериального давлени¤. ¬сем пациентам при назначении препарата следует проводить мониторирование артериального давлени¤ в течение первых двух недель лечени¤ и периодически в дальнейшем. “акже следует регул¤рно контролировать показатели функции печени и почек. ¬ случае повышени¤ уровн¤ активности Ђпеченочныхї трансаминаз в 3 раза и более, относительно верхней границы нормы, препарат должен быть отменен. ”читыва¤ возрастание риска развити¤ нежелательных эффектов с увеличением продолжительности приема, необходимо периодически оценивать необходимость продолжени¤ приема препарата и возможность снижени¤ дозы. Ќе следует примен¤ть препарат одновременно с другими Ќѕ¬ѕ. ѕрименение препарата может отрицательно вли¤ть на женскую фертильность и не рекомендуетс¤ женщинам, планирующим беременность. ќболочка препарата Ётори¤ содержит лактозу в незначительном количестве, что следует учитывать при назначении препарата больным с лактазной недостаточностью. ѕациенты, у которых отмечались эпизоды головокружений, сонливости или слабости, должных воздержатьс¤ от зан¤тий, требующих концентрации внимани¤.

Influence on the ability to drive vehicles and mechanisms

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.