Etoricoxib-Teva 60mg tablets, No. 14

• Symptomatic therapy of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain and inflammation associated with acute gouty arthritis.

• Short-term therapy for moderate acute pain after dental surgery.

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

The drug Etoricoxib-Teva should be used in the minimum effective dose for the minimum possible short course.

Osteoarthritis

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

Rheumatoid arthritis and ankylosing spondylitis

The recommended dose is 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 increase the therapeutic effect. In conditions accompanied by acute pain, Etoricoxib-Teva should be used only in the acute symptomatic period. Acute gouty arthritis The recommended dose in the acute period is 120 mg once a day.

The duration of use of the drug at a dose of 120 mg is 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 after dental operations, Etoricoxib-Teva should be used only in an acute period of no more than 3 days. Doses in excess of those recommended for each indication either have no additional efficacy or have not been studied.

Thus:

- the daily dose for osteoarthritis should not exceed 60 mg;

- the daily dose for rheumatoid arthritis should not exceed 90 mg;

- the daily dose for ankylosing spondylitis should not exceed 90 mg;

- the daily dose for acute gouty arthritis should not exceed 120 mg; for a period not exceeding 8 days;

- the daily dose for relief of pain after dental operations should not exceed 90 mg; for a period not exceeding 3 days.

Special patient groups

Elderly

No dose adjustment is required in elderly patients. As with the use of other drugs in elderly patients, caution should be exercised when using Etoricoxib-Teva (see section 'Special instructions').

Patients with impaired liver function

Regardless of the indication for the use of the drug, 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) - 30 mg once a day.

It is recommended to be careful when using Etoricoxib-Teva in patients with moderate hepatic dysfunction, since the clinical experience of using Etoricoxib-Teva in this group of patients is limited. Due to the lack of clinical experience with the use of the drug Etoricoxib-Teva in patients with severe liver dysfunction (?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 sections 'Contraindications' and 'Special instructions').

Patients with impaired renal function

Dose adjustment in patients with creatinine clearance ?30 ml / min is not required (see the section 'Pharmacological properties', subsection 'Pharmacokinetics'). The use of etoricoxib in patients with creatinine clearance <30 ml / min is contraindicated (see sections 'Contraindications' and 'Special instructions').

Film-coated tablets

1 tab.

etoricoxib

Excipients: calcium hydrogen phosphate anhydrous, microcrystalline cellulose PH101, microcrystalline cellulose PH 102, crospovidone type A, povidone K25, magnesium stearate.

• Hypersensitivity to any component of the drug.

• Peptic ulcer and 12 duodenal ulcer 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

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

• Children under the age of 16.

• Inflammatory bowel disease.

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

• Uncontrolled arterial hypertension, in which blood pressure indicators persistently exceed 140/90 mm Hg. Art.

• Confirmed coronary artery disease, peripheral arterial disease and / or cerebrovascular disease.

• Confirmed hyperkalemia.

• Progressive kidney disease.

  Carefully

• 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; the elderly, concomitantly taking other NSAIDs, including acetylsalicylic acid, or patients with a history of gastrointestinal tract diseases such as peptic ulcer and gastrointestinal bleeding;

• patients with a history of risk factors for cardiovascular complications, such as: dyslipidemia / hyperlipidemia, diabetes mellitus, arterial 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) - 30 mg once a day;

• patients with dehydration;

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

• patients with creatinine clearance <60 ml / min;

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

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

• anticoagulants (such as warfarin);

• antiplatelet agents (eg, acetylsalicylic acid, clopidogrel);

• drugs metabolized by sulfotransferases.

Pharmacodynamics

NSAIDs. Selective inhibitor of COX-2, in therapeutic concentrations, blocks the formation of prostaglandins and has anti-inflammatory, analgesic and antipyretic effects. Selective inhibition of COX-2 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 gastrointestinal mucosa. Etoricoxib has a dose-dependent effect of inhibiting COX-2 without affecting COX-1 when used in a daily dose of up to 150 mg. Does not affect 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.

Pharmokinetics

Absorption.

Etoricoxib is rapidly absorbed when taken orally. Absolute oral bioavailability is about 100%. When using the drug in adults on an empty stomach at a dose of 120 mg once a day until an equilibrium state is reached, the maximum concentration (Cmax) is 3.6 ?g / ml. The time to reach the maximum concentration (TCmax) in blood plasma is 1 hour after taking the drug. Geometric mean AUC0-24h - 37.8 ?g * h / ml. The pharmacokinetics of etoricoxib within therapeutic doses is linear. There was no clinically significant effect on absorption with Etoricoxib 120 mg with a meal (high fat meal). The absorption rate changed, which led to a decrease in Cmax by 36% and an increase in TCmax by 2 hours. These results are not considered clinically significant.In clinical trials, Etoricoxib has been used with or without food.

Distribution.

Etoricoxib is approximately 92% bound to plasma proteins in humans at concentrations of 0.05-5 ?g / ml. The volume of distribution (Vdss) at equilibrium is about 120 liters. Etoricoxib crosses 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 metabolic pathway is the formation of 6'-hydroxymethylethoricoxib, catalyzed by enzymes of the cytochrome system. 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 metabolic pathway, but their quantitative effect in vivo has not been studied. 5 metabolites of etoricoxib have been found in humans. The main metabolite is 6'-carboxyacetylethoricoxib, which is formed upon additional oxidation of 6'-hydroxymethylethoricoxib. These main metabolites have no significant activity, or are weak inhibitors of COX-2. None of these metabolites inhibit COX-1.

Excretion.

With a single intravenous injection of labeled radioactive etoricoxib in a dose of 25 mg to healthy volunteers, 70% of etoricoxib was excreted through the kidneys, 20% through the intestines, mainly in the form of metabolites. Less than 2% was found unchanged. The elimination of etoricoxib occurs mainly by metabolism, followed by excretion through the kidneys. Equilibrium concentration is achieved with a daily intake of 120 mg of etoricoxib 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.

Special patient groups

Elderly

Pharmacokinetics in the elderly (65 years and older) is comparable to the pharmacokinetics in young people. Gender Etoricoxib pharmacokinetics are similar in men and women. Hepatic impairment In patients with mild liver dysfunction (5-6 points on the Child-Pugh scale), taking etoricoxib at a dose of 60 mg once a day was accompanied by an increase in AUC by 16% compared with healthy individuals taking the drug in the same dose. In patients with moderate liver dysfunction (7-9 points on the Child-Pugh scale), who took etoricoxib at a dose of 60 mg every other day, the average AUC 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.There are no data from clinical and pharmacokinetic studies in patients with severe hepatic impairment (?10 points on the Child-Pugh scale).

Renal failure

The pharmacokinetic parameters of a single use of Etoricoxib at a dose of 120 mg in patients with moderate and severe renal impairment 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).

Children

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, pharmacokinetics in adolescents weighing 40 to 60 kg when taking etoricoxib at a dose of 60 mg once a day and in adolescents weighing more than 60 kg with etoricoxib 90 mg once daily was similar to the pharmacokinetics in adults with etoricoxib 90 mg once daily. The safety and effectiveness of etoricoxib in children has not been established.

Side effect

From the digestive system: often - epigastric pain, nausea, diarrhea, dyspepsia, flatulence; sometimes - bloating, belching, increased peristalsis, constipation, dryness of the oral mucosa, gastritis, ulcers of the gastric or duodenal mucosa, irritable bowel syndrome, esophagitis, oral mucosa ulcers, vomiting; very rarely - gastrointestinal ulcers (with bleeding or perforation), hepatitis.

From the nervous system: often - headache, dizziness, weakness; sometimes - taste disturbances, drowsiness, sleep disturbances, sensory disturbances, incl. paresthesia / hyperesthesia, anxiety, depression, concentration disorders; very rarely - hallucinations, confusion.

From the senses: sometimes - blurred vision, conjunctivitis, tinnitus, vertigo.

From the urinary system: sometimes - proteinuria; very rarely - renal failure, usually reversible when the drug is discontinued. Allergic reactions: very rarely - anaphylactic / anaphylactoid reactions, including a marked decrease in blood pressure and shock.

From the side of the cardiovascular system: often - palpitations, increased blood pressure; sometimes - hot flashes, cerebrovascular accident, atrial fibrillation, congestive heart failure, nonspecific ECG changes, myocardial infarction; very rarely - hypertensive crisis.

From the respiratory system: sometimes - cough, shortness of breath, nosebleeds; very rarely - bronchospasm. Dermatological reactions: often - ecchymosis; sometimes - swelling of the face, itchy skin, rash; very rarely - urticaria, Stevens-Johnson syndrome, Lyell's syndrome. Infectious complications: sometimes - gastroenteritis, infections of the upper respiratory tract, urinary tract. From the musculoskeletal system: sometimes - muscle cramps, arthralgia, myalgia.

From the side of metabolism: often - edema, fluid retention; sometimes - changes in appetite, weight gain.

On the part of laboratory studies: often - an increase in the activity of hepatic transaminases; sometimes - an increase in nitrogen in the blood and urine, an increase in CPK activity, a decrease in hematocrit, a decrease in hemoglobin, hyperkalemia, leukopenia, thrombocytopenia, an increase in serum creatinine, an increase in uric acid; rarely - an increase in sodium in the blood serum. Others: often - flu-like syndrome; sometimes - chest pains.

special instructions

Use with caution if there is a history of ulcerative lesions of the gastrointestinal tract, Helicobacter pylori infection, in the elderly, in patients who have been receiving NSAIDs for a long time, in severe somatic diseases, dyslipidemia / hyperlipidemia, in diabetes mellitus, arterial hypertension, edema and fluid retention, smoking , in patients with CC less than 60 ml / min, with concomitant therapy with the following drugs: anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), GCS (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline), with chronic alcoholism. During the treatment period, careful monitoring of blood pressure is required during the first 2 weeks and periodically thereafter.During the period of treatment, the indicators of liver and kidney function should be regularly monitored. In the case of an increase in the activity of hepatic transaminases by 3 times or more relative to VGN, treatment should be discontinued. Given the increased risk of undesirable effects with increasing duration of admission, it is necessary to periodically assess the need to continue treatment and the possibility of reducing the dose. Should not be used concomitantly with other NSAIDs.

Influence on the ability to drive vehicles and use 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. Patients who have experienced episodes of dizziness, drowsiness or weakness should refrain from activities that require concentration.

Drug interactions

In patients receiving warfarin, taking etoricoxib at a dose of 120 mg / day was accompanied by an approximately 13% increase in MHO and prothrombin time. In patients receiving warfarin or similar drugs, MHO should be monitored during initiation of therapy or changes in the dosage regimen of etoricoxib, especially in the first few days. There are reports that non-selective NSAIDs and selective COX-2 inhibitors are able to weaken the hypotensive 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), this combination can aggravate functional renal failure.Etoricoxib can be used concomitantly with acetylsalicylic acid in low doses for the prevention of cardiovascular disease. However, concomitant administration of low-dose acetylsalicylic acid and etoricoxib may increase the incidence of gastrointestinal ulcers and other complications compared with etoricoxib alone. After reaching an equilibrium state, taking etoricoxib at a dose of 120 mg 1 time / day does not affect the antiplatelet activity of acetylsalicylic acid at low doses (81 mg / day). The drug does not replace the prophylactic action of acetylsalicylic acid in cardiovascular diseases. Cyclosporine and tacrolimus increase the risk of nephrotoxicity while taking etoricoxib. There is evidence thatthat non-selective NSAIDs and selective COX-2 inhibitors can increase the concentration of lithium in plasma. This interaction should be taken into account when treating patients taking etoricoxib concomitantly with lithium. There is evidence of an increase in the concentration of methotrexate in plasma by 28% (according to AUC) and a decrease in its renal clearance by 13% under the influence of etoricoxib. Taking etoricoxib at a dose of 120 mg with oral contraceptives containing 35 ?g of ethinylestradiol and 0.5 to 1 mg of norethindrone for 21 days, simultaneously or with a difference of 12 hours, increases the steady-state AUC0-24 of ethinyl estradiol by 50-60%. However, the concentration of norethisterone usually does not increase to a clinically significant degree.This increase in ethinyl estradiol concentration should be taken into account when choosing an appropriate oral contraceptive for concomitant use with etoricoxib. This fact can lead to an increase in the incidence of thromboembolism, due to an increase in the exposure of ethinylestradiol. Etoricoxib does not affect steady state AUC0-24 or digoxin elimination. At the same time, etoricoxib increases Cmax (by an average of 33%), which may be important in the development of an overdose of digoxin. The simultaneous administration of etoricoxib and rifampicin (a powerful inducer of hepatic metabolism) leads to a 65% decrease in the plasma AUC of etoricoxib. This interaction should be considered when concomitant administration of etoricoxib with rifampicin.by increasing the exposure of ethinyl estradiol. Etoricoxib does not affect steady state AUC0-24 or digoxin elimination. At the same time, etoricoxib increases Cmax (by an average of 33%), which may be important in the development of an overdose of digoxin. The simultaneous administration of etoricoxib and rifampicin (a powerful inducer of hepatic metabolism) leads to a 65% decrease in the plasma AUC of etoricoxib. This interaction should be considered when concomitant administration of etoricoxib with rifampicin.by increasing the exposure of ethinyl estradiol. Etoricoxib does not affect steady state AUC0-24 or digoxin elimination. At the same time, etoricoxib increases Cmax (by an average of 33%), which may be important in the development of an overdose of digoxin. The simultaneous administration of etoricoxib and rifampicin (a powerful inducer of hepatic metabolism) leads to a 65% decrease in the plasma AUC of etoricoxib. This interaction should be considered when concomitant administration of etoricoxib with rifampicin.This interaction should be considered when concomitant administration of etoricoxib with rifampicin.This interaction should be considered when concomitant administration of etoricoxib with rifampicin.