Etoriax tablets 120mg, No. 7

• Symptomatic therapy of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis;

• pain and inflammation symptoms associated with acute gouty arthritis;

• short-term treatment of pain associated with dental surgery.

The drug is taken orally at a dose of 60-120 mg 1 time / day.

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.

Pink film-coated tablets

1 tab.

etoricoxib

Excipients: microcrystalline cellulose, type KG-802, microcrystalline cellulose, type PH-200 LM, calcium hydrogen phosphate, croscarmellose sodium, sodium stearyl fumarate, colloidal silicon dioxide.

• 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, 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 classes II-IV).

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

• Severe renal failure (CC less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia.

• The period after coronary artery bypass grafting; peripheral arterial disease, cerebrovascular disease, clinically severe coronary artery disease.

• Persistent arterial hypertension with blood pressure values ??over 140/90 mm Hg. Art.

• Pregnancy, lactation (breastfeeding).

• Children and adolescents up to 16 years old.

• Hypersensitivity to Etoricoxib.

pharmachologic effect

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.

Pharmacokinetics

After oral administration, it is rapidly absorbed from the gastrointestinal tract. Oral bioavailability is about 100%. After taking by adults on an empty stomach at a dose of 120 mg, Cmax is 3.6 ?g / ml, Tmax - 1 hour after administration. Food intake does not significantly affect the severity and rate of absorption of etoricoxib when taken in a dose of 120 mg. At the same time, Cmax values ??decrease by 36% and Tmax increases by 2 hours. The geometric mean AUC0-24 was 37.8 ?g? h / ml. The pharmacokinetics of etoricoxib within therapeutic doses is linear. Plasma protein binding exceeds 92%. Vd in equilibrium is about 120 liters. Etoricoxib crosses the placental and BBB. It is extensively metabolized in the liver, with the participation of cytochrome P450 isoenzymes and the formation of 6-hydroxymethyl-etoricoxib. Found 5 metabolites of etoricoxib,the main ones are 6-hydroxymethyl-etoricoxib and its derivative, 6-carboxy-acetyl-etoricoxib. The main metabolites do not affect COX-1 and are completely inactive or inactive with respect to COX-2. It is excreted by the kidneys in the form of metabolites. Less than 1% is excreted in the urine unchanged. With a single intravenous injection, 70% is excreted by the kidneys, 20% through the intestines, mainly in the form of metabolites. Less than 2% was found unchanged. The equilibrium state is reached after 7 days with a daily intake of 120 mg, with a cumulation coefficient of about 2, which corresponds to T1 / 2 - about 22 hours. Plasma clearance is approximately 50 ml / min. 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 an increase in AUC by 16% compared to healthy individuals.In patients with moderate liver dysfunction (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. Hemodialysis had little effect on excretion (dialysis clearance - about 50 ml / min).

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.

Application during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation. Etoricoxib may adversely affect female fertility and is not recommended for women planning a pregnancy.

Application for violations of liver function

Contraindicated in severe liver failure (more than 9 points on the Child-Pugh scale) or active liver disease. In patients with moderate hepatic impairment (5-9 points on the Child-Pugh scale), it is recommended not to exceed a daily dose of 60 mg.

Application for impaired renal function

Contraindicated in severe renal failure (CC less than 30 ml / min), progressive kidney disease. Application in children

Contraindicated in children and adolescents under 16 years of age.

Use in elderly patients

Use with caution in the elderly.

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.