Etorikoksib - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

NSAIDs - Coxiba

Included in the formulation

Arkoksia®

pills inwards

Merck Sharp and Doum B.V. Netherlands

Arkoksia®

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Merck Sharp and Doum B.V. Netherlands

Costarox

pills inwards

Sandoz d. Slovenia

АТХ:

M.01.A.H.05 Etoricoxib

Pharmacodynamics:

Non-steroidal anti-inflammatory drug. The selective inhibitor of COX-2, at therapeutic concentrations, blocks the formation of prostaglandins and has anti-inflammatory, analgesic and antipyretic effects. Selective oppression of COX-2 is accompanied by a decrease in the severity of clinical symptoms associated with the inflammatory process, with no effect on the function of platelets and the mucosa of the gastrointestinal tract.

Etorikoksib has a dose-dependent effect of COX-2 inhibition, without affecting COX-1 when administered at a daily dose of up to 150 mg. Has no effect on the production of prostaglandins in the mucous membrane of the stomach and at the time of bleeding. In the conducted studies, there was no decrease in the level of arachidonic acid and platelet aggregation caused by collagen.

Pharmacokinetics:

When ingested quickly absorbed from the digestive tract, bioavailability - about 100%. When taken in adults fasting (120 mg) reaches the maximum concentration through1 hour. Food intake does not affect the severity and absorption rate of etorikoksib in a dose of 120 mg, while the maximum concentration is reduced by 36%, and the time of its increase is increased by 2 hours.Binding to plasma proteins is more than 92%. Volume of distribution- 120 liters. It penetrates the placental barrier and the blood-brain barrier. Metabolized by microsomal enzymes of the liver with the formation of 6-hydroxymethyl-etorikoksib. Detected 5 etorikoksiba metabolites, the most important of which - 6-hydroxymethyl-etoricoxib and its derivative - 6-carboxy-acetyl-etoricoxib. Metabolites no effect on COX-1 are inactive or inactive against COX-2. The equilibrium concentration is reached after 7 days (with daily intake of 120 mg). Plasma clearance - 50 ml / min. Half-life-. 22 hours Return (after a single intravenous 25 mg) Kidney - 70% (less than 1% - unchanged), intestine - 20% (predominantly in the form of metabolites, less than 2% - unchanged).

Indications:

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.

ICD-10

XIII.M05-M14.M05 Seropositive rheumatoid arthritis

XIII.M05-M14.M10 Gout

XIII.M15-M19.M15 Polyarthrosis

XIII.M45-M49.M45 Ankylosing spondylitis

Contraindications:

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

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 phase of exacerbation.

Hemophilia and other bleeding disorders.

Severe heart failure (NYHA class II-IV functional classes).

Severe hepatic insufficiency (more than 9 on the Child-Pugh scale) or active liver disease.

Renal failure of severe degree (creatinine clearance less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia.

Period after aortocoronary bypass surgery; diseases of peripheral arteries, cerebrovascular diseases, clinically expressed CHD.

Stable arterial hypertension with values of blood pressure more than 140/90 mm Hg. Art.

Pregnancy, lactation (breastfeeding).

Children and adolescence under 16 years.

Hypersensitivity to etorikoksibu.

Carefully:

In patients with moderate hepatic insufficiency (5-9 points on the Child-Pugh scale) it is recommended not to exceed the daily dose of 60 mg.

With caution apply when indicated in an anamnesis for ulcerative lesions of the digestive tract, infection Helicobacter pylori, in elderly patients, in patients receiving long-term NSAIDs, in severe somatic diseases, dyslipidemia / hyperlipidemia, in diabetes mellitus, hypertension, swelling and fluid retention, smoking, in patients with creatinine clearance less than 60 ml / min, with concomitant therapy the following drugs: anticoagulants (eg, warfarin), antiplatelet agents (eg, acetylsalicylic acid, clopidogrel), glucocorticosteroids (eg, prednisolone), selective reuptake inhibitors serotonin (for example, citalopram, fluoxetine, paroxetine, sertraline), with chronic alcoholism.

Pregnancy and lactation:

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

Dosing and Administration:

The drug is taken orally in a dose of 60-120 mg once a day.

In patients with hepatic insufficiency (5-9 points on the Child-Pugh scale), it is recommended not to exceed the daily dose of 60 mg.

Side effects:

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

From the side nervous system: often - headache, dizziness, weakness; sometimes - a violation of taste, drowsiness, sleep disturbances, sensitivity disorders, including paresthesia / hyperesthesia, anxiety, depression, concentration disorders; very rarely - hallucinations, confusion.

From the side sense organs: sometimes - blurred vision, conjunctivitis, tinnitus, vertigo.

From the side urinary system: sometimes - proteinuria; very rarely - renal failure, usually reversible when the drug is withdrawn.

Allergic reactions: very rarely - anaphylactic / anaphylactoid reactions, including a marked decrease in blood pressure and shock.

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

From the side respiratory system: sometimes - cough, shortness of breath, nosebleed; very rarely - bronchospasm.

Dermatological reactions: often - ecchymosis; sometimes - puffiness of the face, skin itch, rash; very rarely - hives, Stevens-Johnson syndrome, Lyell's syndrome.

Infectious complications: sometimes - gastroenteritis, infections of the upper respiratory tract, urinary tract.

From the side musculoskeletal system: sometimes - muscle cramps, arthralgia, myalgia.

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

From the side laboratory research: often - increased activity of liver transaminases; sometimes - increased nitrogen in the blood and urine, increased activity of creatine phosphokinase,lower hematocrit, hemoglobin decrease, Hyperkalemia, leukopenia, thrombocytopenia, increased serum creatinine, increased uric acid; rarely - increased sodium in the blood serum.

Other: often - the flu-like syndrome; sometimes - pains in the chest.

Overdose:

Symptoms: increased side effects, including on the part of the gastrointestinal tract, cardiovascular system, kidneys.

Treatment: symptomatic therapy. It is not excreted in hemodialysis, excretion in peritoneal dialysis has not been studied.

Interaction:

In patients receiving warfarin, Etoricoxib receiving a dose of 120 mg daily was accompanied by an increase of approximately 13% MHO and prothrombin time. In patients receiving warfarin or similar drugs should be monitored indicators MHO during the beginning of therapy or changing dosage regimen etoricoxib, especially in the first few days.

There are reports that nonselective NSAIDs and selective COX-2 inhibitors can attenuate the antihypertensive effect of ACE inhibitors. This interaction should be taken into account in the treatment of patients receiving etorikoksib simultaneously with ACE inhibitors.In patients with impaired renal function (eg, with dehydration or in old age), a similar combination can aggravate functional kidney failure.

Etorikoksib can be used simultaneously with acetylsalicylic acid in low doses, designed to prevent cardiovascular diseases. However, simultaneous administration of low-dose acetylsalicylic acid and etorikoksib may lead to an increase in the frequency of ulcerative gastrointestinal lesions and other complications compared with the administration of a single etorikoksib. After reaching the equilibrium state, taking etorikoksib in 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 preventive effect of acetylsalicylic acid in cardiovascular diseases. Cyclosporin and tacrolimus increase the risk of developing nephrotoxicity against the background of taking etorikoksiba.

There is evidence that nonselective NSAIDs and selective inhibitors of COX-2 can increase the concentration of lithium in plasma. This interaction should be taken into account in the treatment of patients receiving etorikoksib simultaneously with lithium.

There is evidence of an increase in plasma methotrexate concentration by 28% (according to AUC) and a decrease in its renal clearance by 13% under the influence of etorikoksib.

Taking etorikoksib in a dose of 120 mg with oral contraceptives containing 35 μg of ethinyl estradiol and 0.5 to 1 mg of norethindrone for 21 days, simultaneously or 12 hours apart, increases the steady-state AUC0-24 of ethinylestradiol by 50-60%. However, the concentration of norethisterone usually does not increase to a clinically significant extent. This increase in the concentration of ethinyl estradiol should be taken into account when choosing the appropriate oral contraceptive for simultaneous use with etorikoksibom. This fact can lead to an increase in the frequency of thromboembolism, by increasing the exposure of ethinylestradiol.

Etorikoksib does not affect AUC0-24 in the equilibrium state or the elimination of digoxin. At the same time, etorikoksib increases the maximum concentration (on average by 33%), which may be important in the development of an overdose of digoxin.

Simultaneous reception of etorikoksiba and rifampicin (a powerful inducer of hepatic metabolism) leads to a 65% decrease in AUC etorikoksiba in plasma.This interaction should be considered with the simultaneous administration of etorikoksiba with rifampicin.

Special instructions:

During the treatment, careful monitoring of blood pressure is required during the first 2 weeks and periodically thereafter.

During the treatment period, the liver and kidney function should be monitored regularly. In case of increased activity of hepatic transaminases in 3 times or more relative to the upper limit of the norm, treatment should be stopped.

Given the increased risk of developing unwanted effects with increasing duration of admission, it is necessary to periodically assess the need for continued treatment and the possibility of dose reduction.

Do not use simultaneously with other NSAIDs.

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. Patients who have had episodes of dizziness, drowsiness, or weakness, due to refrain from occupations requiring concentration.

Instructions

Etoricoxib (Etoricoxibum)