Etoriax 60 mg, 14 film-coated tablets

Pharmacodynamics and pharmacokinetics

Etoricoxib inhibits the activity of COX-2 through a selective mechanism and interferes with the biosynthesis of inflammatory mediators prostaglandins . There is a decrease in the severity of symptoms of the inflammatory process. In this case, the substance does not affect the functional activity of platelets and does not damage the mucous membrane of the digestive tract. The degree of inhibition of cyclooxygenase-2 is dose-dependent. The drug does not affect COX-1 (if the daily dosage does not exceed 150 mg).

This substance significantly reduces the degree of vascular permeability, improves blood microcirculation and the intensity of production of prostaglandins , kinins and leukotrienes . The energy supply to the inflammatory process is blocked.

Pain relief is achieved by reducing the intensity of inflammation and reducing the amount of bradykinin . Due to the ability of the drug to reduce the excitability of the thermoregulation center in the diencephalon, it has an antipyretic effect.

After oral administration of the drug, the substance is quickly absorbed in the digestive tract and penetrates into the blood. The medicine has almost 100% bioavailability. After taking 120 mg of Etoricoxib, its maximum concentration in the blood is observed after 60 minutes. Eating reduces the maximum concentration by 35%, and the time to reach it increases to 2 hours.

Degree of binding to plasma proteins = 92%. The drug overcomes the blood-brain and placental barriers . Metabolism occurs with the participation of microsomal liver enzymes, forming inactive metabolites: 6-hydroxymethyl-etoricoxib , 6-carboxy-acetyl-etoricoxib and others.

Daily administration of the drug at a dosage of 120 mg leads to the establishment of an equilibrium concentration within a week. The half-life is about 22 hours. The medicine is excreted through the kidneys and with feces, in the form of metabolites and unchanged (less than 2%).

It has been established that age, renal and liver failure slightly change the pharmacokinetic parameters of the substance. Studies have not been conducted in patients under 12 years of age or with severe hepatic impairment.

Arcoxia tab 60mg N14 (MSD)

Pharmacodynamic interaction: In patients receiving warfarin, taking Arcoxia® at a dose of 120 mg/day was accompanied by an increase of approximately 13% in MHO and prothrombin time. In patients receiving warfarin or similar drugs, MHO levels should be monitored when initiating therapy or changing the dosage regimen of Arcoxia®, especially in the first few days. There are reports that non-selective NSAIDs and selective COX-2 inhibitors may weaken the hypotensive effect of ACE inhibitors . This interaction should be taken into account when treating patients taking Arcoxia® concomitantly with ACE inhibitors. In patients with impaired renal function (for example, with dehydration or in old age), such a combination may aggravate renal failure. Arcoxia® can be used simultaneously with acetylsalicylic acid in low doses intended for the prevention of cardiovascular diseases. However, simultaneous administration of acetylsalicylic acid in low doses and Arcoxia® may lead to an increase in the incidence of gastrointestinal ulcers and other complications compared to taking Arcoxia® alone. After reaching a steady state, taking etoricoxib at a dose of 120 mg 1 time / day does not affect the antiplatelet activity of acetylsalicylic acid in low doses (81 mg / day). The drug does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases. Cyclosporine and tacrolimus increase the risk of developing nephrotoxicity while taking Arcoxia®. Pharmacokinetic interaction There is evidence that 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 Arcoxia® concomitantly with lithium. Two studies examined the effects of Arcoxia® at a dose of 60, 90 and 120 mg 1 time / day for seven days in patients receiving methotrexate once a week in dose from 7.5 to 20 mg for rheumatoid arthritis. Arcoxia® at a dose of 60 and 90 mg had no effect on the plasma concentration (according to AUC) and renal clearance of methotrexate. In one study, Arcoxia® at a dose of 120 mg had no effect on the plasma concentration (AUC) and renal clearance of methotrexate. In another study, Arcoxia® at a dose of 120 mg increased the plasma concentration of methotrexate by 28% (based on AUC) and decreased the renal clearance of methotrexate by 13%. When prescribing Arcoxia® at doses above 90 mg/day and methotrexate simultaneously, monitor for the possible occurrence of toxic effects of methotrexate. Oral contraceptives: taking Arcoxia® at a dose of 120 mg with oral contraceptives containing 35 mcg ethinyl estradiol and 0.5 to 1 mg norethindrone administered for 21 days, simultaneously or 12 hours apart, increases the steady-state AUC0-24 of ethinyl estradiol by 50-60%. However, norethisterone concentrations usually do not increase to a clinically significant extent. This increase in ethinyl estradiol concentrations should be taken into account when selecting the appropriate oral contraceptive for concomitant use with Arcoxia®. This fact may lead to an increased incidence of thromboembolism due to increased exposure to ethinyl estradiol. No significant pharmacokinetic interaction with GCS was detected. Etoricoxib does not affect AUC0-24 at steady state or the elimination of digoxin. At the same time, etoricoxib increases Cmax (by an average of 33%), which may be important in the event of digoxin overdose. Simultaneous administration of Arcoxia® and rifampicin (a powerful inducer of hepatic metabolism) leads to a 65% decrease in the AUC of etoricoxib in plasma. This interaction should be taken into account when prescribing Arcoxia® with rifampicin. Antacids and ketoconazole (a potent inhibitor of CYP3A4) do not have a clinically significant effect on the pharmacokinetics of Arcoxia®.

Contraindications

The medicine is contraindicated for use:

• if allergic to the active substance or group of substances;
• if the patient has bronchial asthma , recurrent polyposis and intolerance to NSAIDs or aspirin (previously observed);
• for ulcers and erosions in the stomach and duodenum;
• in patients with inflammatory bowel diseases, Crohn's disease , ulcerative colitis , bleeding in the gastrointestinal tract;
• in patients with hemophilia , with impaired blood clotting processes;
• with cerebrovascular or other types of bleeding;
• if the patient has severe chronic or acute heart failure (class 2-4);
• for serious liver diseases;
• in patients with severe renal failure , hyperkalemia , and progressive kidney disease;
• for diseases of peripheral arteries;
• in patients with ischemia ;
• in pregnant women at any stage;
• if the patient has recently undergone coronary artery bypass grafting ;
• with high blood pressure, if hypertension reaches more than 140 mm Hg. Art. at 90 mm Hg. Art.;
• in children under 16 years of age;
• when breastfeeding.

Etoriax 60 mg, 14 film-coated tablets

Registration Certificate Holder

KRKA dd, Novo mesto (Slovenia)

Dosage form

Medicine - Etoriax

Description

Film-coated tablets

light brownish-yellow in color, round, biconvex, chamfered; with "60" engraving on one side; appearance at the fracture - a white or almost white rough mass with a filmy shell of a light brownish-yellow color.

1 tab.

etoricoxib 60 mg

Excipients

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

Tablet shell composition:

Opadry 85F28751 II white* (polyvinyl alcohol, titanium dioxide (E171), macrogol-3000, talc), yellow iron oxide dye (E172). * Opadry 85F28751 II white - ready-to-use mixture of polyvinyl alcohol, titanium dioxide (E171), macrogol-3000 and talc.

7 pcs. - blisters (1) from a combined material - cardboard packs. 7 pcs. - blisters (2) made of combined material - cardboard packs. 7 pcs. - blisters (4) made of combined material - cardboard packs. 7 pcs. - blisters (8) made of combined material - cardboard packs. 7 pcs. - blisters (12) made of combined material - cardboard packs. 10 pieces. - blisters (1) from a combined material - cardboard packs. 10 pieces. - blisters (3) made of combined material - cardboard packs. 10 pieces. - blisters (6) made of combined material - cardboard packs. 10 pieces. - blisters (10) made of combined material - cardboard packs.

Indications

Symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis; pain and inflammatory symptoms associated with acute gouty arthritis; short-term treatment of pain associated with dental surgery.

Contraindications for use

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 diseases (Crohn's disease, ulcerative colitis) in the acute phase.

Hemophilia and other bleeding disorders.

Severe heart failure (II-IV functional classes according to the NYHA classification).

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.

The period after coronary artery bypass surgery; peripheral arterial diseases, cerebrovascular diseases, clinically significant ischemic heart disease.

Sustained arterial hypertension with blood pressure values ​​​​more than 140/90 mm Hg. Art.

Pregnancy, lactation period (breastfeeding).

Children and teenagers up to 16 years of age.

Hypersensitivity to etoricoxib.

pharmachologic effect

NSAIDs. A selective COX-2 inhibitor, 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. It has no effect on the production of prostaglandins in the gastric mucosa and on bleeding time. In the studies conducted, there was no decrease in arachidonic acid levels and platelet aggregation caused by collagen.

Drug interactions

In patients receiving warfarin, administration of etoricoxib at a dose of 120 mg/day was accompanied by an increase of approximately 13% in MHO and prothrombin time. In patients receiving warfarin or similar drugs, MHO levels should be monitored when initiating therapy or changing the dosage regimen of etoricoxib, especially in the first few days.

There are reports that non-selective NSAIDs and selective COX-2 inhibitors can 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, dehydration or old age), this combination may worsen renal failure.

Etoricoxib can be used concomitantly with acetylsalicylic acid in low doses intended for the prevention of cardiovascular diseases. However, simultaneous administration of acetylsalicylic acid in low doses and etoricoxib may lead to an increased incidence of gastrointestinal ulcers and other complications compared to taking etoricoxib alone. After reaching a steady state, taking etoricoxib at a dose of 120 mg 1 time / day does not affect the antiplatelet activity of acetylsalicylic acid in low doses (81 mg / day). The drug does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases. Cyclosporine and tacrolimus increase the risk of nephrotoxicity while taking etoricoxib.

There is evidence that non-selective NSAIDs and selective COX-2 inhibitors may increase plasma lithium concentrations. 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 120 mg with oral contraceptives containing 35 mcg ethinyl estradiol and 0.5 to 1 mg norethindrone for 21 days, either simultaneously or 12 hours apart, increased the steady-state AUC0-24 of ethinyl estradiol by 50-60%. However, norethisterone concentrations usually do not increase to a clinically significant extent. This increase in ethinyl estradiol concentrations should be taken into account when selecting the appropriate oral contraceptive for concomitant use with etoricoxib. This fact may lead to an increased incidence of thromboembolism due to increased exposure to ethinyl estradiol.

Etoricoxib does not affect AUC0-24 at steady state or digoxin elimination. However, etoricoxib increases Cmax (by an average of 33%), which may be important in the development of digoxin overdose.

Concomitant use of etoricoxib and rifampicin (a potent inducer of hepatic metabolism) leads to a 65% decrease in plasma etoricoxib AUC. This interaction should be considered when etoricoxib is coadministered with rifampicin.

Dosage regimen

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

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

Side effect

From the digestive system:

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

From the nervous system:

often - headache, dizziness, weakness; sometimes - taste disturbance, 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 pronounced decrease in blood pressure and shock.

From 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, itching, 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 - swelling, fluid retention;
sometimes - changes in appetite, weight gain. From laboratory tests
: often - increased activity of liver transaminases; sometimes - increased nitrogen in the blood and urine, increased CPK activity, decreased hematocrit, decreased hemoglobin, hyperkalemia, leukopenia, thrombocytopenia, increased serum creatinine, increased uric acid; rarely - increased sodium in the blood serum.

Other:

often - flu-like syndrome; sometimes - chest pain.

special instructions

Use with caution when there is a history of ulcerative lesions of the gastrointestinal tract, Helicobacter pylori infections, in the elderly, in patients who have been receiving NSAIDs for a long time, with severe somatic diseases, dyslipidemia/hyperlipidemia, with 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), corticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline), for chronic alcoholism.

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

During treatment, liver and kidney function indicators should be regularly monitored. If the activity of liver transaminases increases by 3 times or more relative to ULN, treatment should be discontinued.

Given the increasing risk of adverse effects with increasing duration of use, it is necessary to periodically evaluate the need to continue treatment and the possibility of dose reduction.

Should not be used simultaneously with other NSAIDs.
Effect on the ability to drive vehicles and operate machinery
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 experienced episodes of dizziness, drowsiness or weakness should refrain from activities requiring concentration.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated. The drug is contraindicated during pregnancy and lactation. Etoricoxib may adversely affect female fertility and is not recommended for women planning pregnancy.

Use for renal impairment

Restrictions for impaired renal function - Contraindicated. Contraindicated in severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney diseases.

Use for liver dysfunction

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

Use in elderly patients

Restrictions for elderly patients - Use with caution.

Use with caution in elderly people.

Use in children

Restrictions for children - Contraindicated. Contraindicated in children and adolescents under 16 years of age.

Side effects

The following adverse reactions may occur during treatment with Etoricoxib:

• dizziness , palpitations, general weakness, headache , high blood pressure ;
• diarrhea , cough, nausea, indigestion , increased gas formation;
• pain in the epigastric region;
• ecchymosis , increased levels of liver enzymes;
• swelling, flu .

Rarely (in less than 1% of patients) the following are observed:

• distortion of taste and smell, drowsiness , paresthesia , insomnia , hyperesthesia , disorders of the blood supply to the brain;
• depressive disorders , anxiety, decreased concentration, hot flashes ;
• leukopenia , visual impairment, tinnitus, vertigo , conjunctivitis ;
• heart failure, atrial fibrillation ;
• shortness of breath , nosebleeds, cough, development of upper respiratory tract infections;
• gastritis , esophagitis hemoglobin and hematocrit levels , myocardial infarction , thrombocytopenia ;
• constipation , heaviness in the abdomen, hiccups, dry oral mucosa;
• decreased or increased appetite, duodenal and stomach ulcers, vomiting;
• gastroenteritis , urinary tract infections, proteinuria , myalgia ;
• decreased seizure threshold, arthralgia , skin rashes, itching, allergic swelling of the face ;
• weight gain, pain in the chest and behind the sternum, hyperkalemia ;
• hyperuricemia , increased urea in the blood.

Very rarely occur:

• renal failure (the condition normalizes when the drug is discontinued);
• hypernatremia , shock , anaphylactic reactions ;
• Stevens-Johnson syndrome , urticaria ;
• perforation and bleeding in the gastrointestinal tract;
• Lyell's syndrome , hepatitis , bronchospasm ;
• hypertensive crisis , confusion and hallucinations .

Interaction

Combine treatment with this substance with caution when taking oral contraceptives ( norethindrone and ethinyl estradiol ) for a long time (from 3 weeks). This combination significantly increases the risk of thromboembolism .

If a patient takes acetylsalicylic acid in a small dosage for the prevention of cardiovascular diseases, then treatment with Etoricoxib should be done with caution. ulcers and erosions increases .

In patients taking warfarin , the drug may increase the prothrombin index and INR . Therefore, it is recommended to monitor these indicators before starting therapy and during treatment. You can also adjust the daily dosage (not higher than 60 mg), especially at the beginning of treatment.

Medicines included in the groups of non-selective NSAIDs and selective cyclooxygenase-2 reduce the effectiveness of ACE inhibitors. In patients with renal failure, this combination is extremely undesirable and can lead to functional renal failure and increased blood pressure.

The combined use of Etoricoxib, cyclosporine and tacrolimus increases the load on the kidneys.

This drug may increase plasma lithium levels when combined with lithium preparations.

Etoricoxib increases plasma concentrations of methotrexate and reduces its renal clearance.

The combination of the drug with digoxin is acceptable. The drug does not affect the AUC value and the process of excretion of digoxin . However, the maximum concentration of cardiotonic in the blood increases, this can cause an overdose of the drug.

The combination of etoricoxib and rifampicin .

Instructions for use ARCOXIA® (ARCOXIA)

Pharmacodynamic interactions

Oral anticoagulants.

In patients whose condition is stabilized on chronic warfarin, etoricoxib 120 mg/day is associated with an approximately 13% increase in the international normalized ratio (INR) prothrombin time. Therefore, patients receiving oral anticoagulants should have their prothrombin time (IHO) monitored frequently, especially during the first days of etoricoxib use or when its dose is changed.

Diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists.

NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg, dehydrated patients or elderly patients with compromised renal function), concomitant use of an ACE inhibitor or angiotensin II antagonist and COX-inhibiting drugs may result in subsequent deterioration of renal function, including possible acute renal failure. , which is usually reversible. The possibility of such interactions should be kept in mind in patients who use etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, this combination should be prescribed with caution, especially in elderly patients. Adequate hydration should be provided and consideration should be given to monitoring renal function at the start of combination treatment and at regular intervals thereafter.

Acetylsalicylic acid.

In a study involving healthy volunteers, under steady state conditions, the use of etoricoxib at a dose of 120 mg 1 time/day did not affect the antiplatelet activity of acetylsalicylic acid (81 mg 1 time/day). Etoricoxib can be prescribed concomitantly with acetylsalicylic acid, used in doses for the prevention of cardiovascular complications (low doses). However, simultaneous use of low doses of acetylsalicylic acid and etoricoxib may lead to an increased incidence of gastrointestinal ulcers or other complications compared to etoricoxib monotherapy. The simultaneous use of etoricoxib with acetylsalicylic acid in doses exceeding those established for the prevention of cardiovascular complications, as well as with other NSAIDs, is not recommended.

Cyclosporine and tacrolimus.

Although the interaction of etoricoxib with these drugs has not been studied, concomitant use of NSAIDs with cyclosporines and tacrolimus may enhance the nephrotoxic effect of the latter. Monitor renal function when etoricoxib is used concomitantly with any of these drugs.

Pharmacokinetic interactions

Effect of etoricoxib on the pharmacokinetics of other drugs

Lithium.

NSAIDs reduce the renal excretion of lithium, thereby increasing plasma lithium levels. If necessary, frequently monitor lithium blood levels and adjust the dose of lithium while these drugs are being used concomitantly, as well as when NSAIDs are discontinued.

Methotrexate.

Two studies examined the effects of etoricoxib at doses of 60 mg, 90 mg, and 120 mg once daily for seven days in patients receiving once-weekly methotrexate 7.5 mg to 20 mg for rheumatoid arthritis. Etoricoxib 60 mg and 90 mg did not affect plasma concentrations or renal clearance of methotrexate. In one study, etoricoxib 120 mg had no effect on methotrexate levels, but in another study, methotrexate plasma concentrations increased by 28% and methotrexate renal clearance decreased by 13%. If etoricoxib is used concomitantly with methotrexate, appropriate monitoring for methotrexate toxicity should be performed.

Oral contraceptives.

Etoricoxib 60 mg, when coadministered with oral contraceptives containing 35 mcg ethinyl estradiol and 0.5-1 mg norethindrone for 21 days, resulted in a 37% increase in ethinyl estradiol AUC0-24. Etoricoxib at a dose of 120 mg, when used with the above oral contraceptives simultaneously or at intervals of 12 hours, increased the AUC0-24 value of ethinyl estradiol at steady state by 50-60%. This increase in ethinyl estradiod concentrations should be kept in mind when selecting an oral contraceptive to be used concomitantly with etoricoxib. Increased exposure to ethinyl estradiol may increase the incidence of adverse reactions associated with the use of oral contraceptives (for example, venous thromboembolism in women at risk).

Hormone replacement therapy. Taking 120 mg of etoricoxib with hormone replacement drugs including conjugated estrogens (Premarin™ 0.625 mg) for 28 days increased the average AUC0-24 at steady state of unconjugated estrone (by 41%), equilin (by 76%) and 17-β- estradiol (by 22%). The effects of etoricoxib doses recommended for long-term use (30, 60 and 90 mg) have not been studied.

Etoricoxib 120 mg reduced exposure (AUC0-24) to the estrogenic components of Premarin by less than half compared with Premarin monotherapy; the dose of the latter was increased from 0.625 to 1.25 mg. The clinical significance of these increases is unknown, and higher doses of Premarin in combination with etoricoxib have not been studied. These increases in estrogen concentrations should be taken into account when choosing a hormonal drug for postmenopausal use during concomitant use of etoricoxib, as increased estrogen exposure may increase the risk of adverse reactions during hormone replacement therapy.

Prednisone/prednisolone.

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

Digoxin.

When etoricoxib was used at a dose of 120 mg 1 time / day for 10 days by healthy volunteers, there was no effect on AUC0-24 at steady state and on the excretion of digoxin by the kidneys. An increase in digoxin Cmax was observed (approximately 33%). This increase is usually not significant for most patients. However, patients at high risk for digoxin toxicity should be monitored when receiving etoricoxib and digoxin concomitantly.

Effect of etoricoxib on drugs metabolized by sulfotransferases

Etoricoxib is an inhibitor of human sulfotransferase activity, particularly SULT1E1, and may also increase serum ethinyl estradiol concentrations. Because there is currently limited data on the effects of various sulfotransferases and the clinical relevance for many drugs is still being studied, it is prudent to use caution when coadministering etoricoxib with other drugs that are metabolized primarily by human sulfotransferases (eg, oral salbutamol and minoxidil).

Effect of etoricoxib on drugs metabolized by CYP isoenzymes

Based on in vitro data, etoricoxib is not expected to inhibit cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. In a study of healthy volunteers, daily use of etoricoxib 120 mg had no effect on hepatic CYP3A4 activity as determined by the erythromycin breath test.

Effect of other drugs on the pharmacokinetics of etoricoxib

The main route of metabolism of etoricoxib is dependent on CYP enzymes. CYP3A4 contributes to the metabolism of etoricoxib in vivo. In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 can also catalyze the major metabolic pathway, but their quantitative characteristics have not been studied in vivo.

Ketoconazole.

Ketoconazole is a potent CYP3A4 inhibitor. When administered to healthy volunteers in doses of 400 mg once daily for 11 days, ketoconazole did not have a clinically significant effect on the pharmacokinetics of a single dose of etoricoxib 60 mg (43% increase in AUC).

Rifampicin.

Concomitant use of etbricoxib and rifampicin (a strong CYP enzyme inducer) resulted in a 65% decrease in etoricoxib plasma concentrations. This interaction may be accompanied by relapse of symptoms if etoricoxib is used concomitantly with rifampicin. While these data may indicate a need for dose escalation, it is not recommended to use etoricoxib in doses higher than those indicated for each indication as the combination 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.

special instructions

During treatment with this drug, all risks and limitations associated with taking NSAIDs (bleeding in the gastrointestinal tract, cerebrovascular disorders) should be taken into account.

It is recommended to prescribe the substance with caution:

• with diabetes or smoking;
• elderly patients;
• patients who have previously been treated with NSAIDs for a long time;
• in combination with anticoagulants , glucocorticosteroids , antiplatelet agents , selective serotonin reuptake inhibitors ;
• with alcoholism (chronic, in combination with liver failure).

During the first 14 days of therapy, it is recommended to monitor blood pressure and liver function.

It is better not to combine the drug with other non-steroidal anti-inflammatory drugs.

You are required to drive with caution and perform potentially dangerous activities that require high concentration.

Reviews

There are many reviews about the use of the medicine. It mainly helps relieve pain and inflammation with long-term use. You can also find many reports of the development of adverse reactions from the digestive system. Some patients chose to switch to safer analogues and substitutes for this medicine.

Some reviews about Etoricoxib:

• “... I took this drug for 3 weeks, it was prescribed to me after surgery for a herniated disc. I got stomach erosion from it. Now the hernia doesn’t bother me, but I had to treat the erosion”;
• “... A private paid doctor prescribed this drug to me. I should note that it is quite expensive and did not help me at all. The pain went away only after taking another time-tested medicine”;
• “... An effective remedy, the pain has decreased significantly, the inflammation has subsided. I think that if the doctor prescribed it, then you should drink it.”