Kostarox pills 60mg, 28pcs

Composition

of 1 tab. : etoricoxib 60 mg. Auxiliary substances: calcium hydrophosphate anhydrous-26 mg, microcrystalline cellulose-25.5 mg, povidone K 30-6 mg, magnesium stearate-1 mg, croscarmellose sodium-1.5 mg. Composition of the tablet shell: Opadray II green 32 K 510002-4 mg: hypromellose 15 cPs 1.6 mg, lactose monohydrate 1.12 mg, titanium dioxide 0.628 mg, triacetin 0.32 mg, indigo carmine aluminum varnish (3-5%) 0.256 mg, iron oxide yellow 0.076 mg

Pharmacological action

of NSAIDs. 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 COX-2 inhibition, 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 the time of bleeding. In the conducted studies, there was no decrease in arachidonic acid levels and platelet aggregation caused by collagen.

Pharmacokinetics

After oral use, it is rapidly absorbed from the gastrointestinal tract. Oral bioavailability is about 100%. After taking adults on an empty stomach at a dose of 120 mg, Cmax is 3.6 mcg / ml, Tmax-1 h after use. Food intake does not significantly affect the severity and rate of absorption of etoricoxib when taken at a dose of 120 mg. At the same time, Cmax values decrease by 36% and Tmax increases by 2 h. The average geometric value of AUC0-24 was 37.8 mcg x h / ml. The pharmacokinetics of etoricoxib within therapeutic doses are linear.

Binding to plasma proteins exceeds 92%. The Vd at steady state is about 120 liters. Etoricoxib penetrates through the placental and BBB.

It is intensively metabolized in the liver, with the participation of cytochrome P 450 isoenzymes and the formation of 6-hydroxymethyl-etoricoxib. 5 metabolites of etoricoxib were detected, the main ones-6-hydroxymethyl-etoricoxib and its derivative-6-carboxy-acetyl-etoricoxib. The main metabolites do not affect COX-1 and are completely inactive or poorly active against COX-2.

It is excreted by the kidneys in the form of metabolites. Less than 1% is excreted unchanged in the urine.

With a single intravenous injection,70% is excreted by the kidneys,20% – through the intestines, mainly in the form of metabolites. Less than 2% were found unchanged.

The equilibrium state is reached after 7 days with a daily dose of 120 mg, with a cumulation coefficient of about 2, which corresponds to T1 / 2-about 22 hours. The plasma clearance is approximately 50 ml/min.

In patients with mild hepatic impairment (Child-Pugh score 5-6), a single dose of 60 mg/day of etoricoxib was associated with a 16% increase in AUC compared to healthy subjects.

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.

Hemodialysis had little effect on excretion (dialysis clearance was about 50 ml / min).

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

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

Erosive and ulcerative changes in the gastric or duodenal mucosa, active gastrointestinal bleeding, cerebrovascular or other bleeding.

Inflammatory bowel diseases (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 insufficiency (creatinine clearance less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia.

Period after coronary artery bypass grafting; peripheral artery diseases, cerebrovascular diseases, clinically pronounced coronary heart disease.

Persistent arterial hypertension with BP values greater than 140/90 mm Hg.

Pregnancy, lactation (breast-feeding).

Children and adolescents under 16 years of age.

Hypersensitivity to etoricoxib.

Side effects

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

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

From the sensory organs: 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 cardiovascular system: often-palpitations, increased blood pressure; sometimes-hot flashes, impaired cerebral circulation, atrial fibrillation, congestive heart failure, non-specific 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-facial swelling, pruritus, rash; very rarely-urticaria, Stevens-Johnson syndrome, Lyell’s syndrome.

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

Musculoskeletal disorders: sometimes-muscle cramps, arthralgia, myalgia.

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

From laboratory tests: often-increased activity of hepatic 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.

Interaction

In patients receiving warfarin, etoricoxib 120 mg / day was associated with an approximately 13% increase in MHO and prothrombin time. In patients receiving warfarin or similar medications, MHO values should be monitored at the time of starting therapy or changing the dosage regimen of etoricoxib, especially in the first few days.

Non-selective NSAIDs and selective COX-2 inhibitors have been reported to reduce 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 the elderly), such a combination may worsen the functional insufficiency of the kidneys.

Etoricoxib can be used simultaneously with acetylsalicylic acid in low doses intended for the prevention of cardiovascular diseases. However, concomitant use of low-dose acetylsalicylic acid and etoricoxib may lead to an increased incidence of gastrointestinal ulceration and other complications compared to 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 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 when taking etoricoxib.

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 etoricoxib concomitantly with lithium.

There are data on an increase in the concentration of methotrexate in plasma by 28% (AUC) and a decrease in its renal clearance by 13% under the influence of etoricoxib.

Taking etoricoxib 120 mg with an oral contraceptive containing 35 mcg of ethinyl estradiol 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 selecting an appropriate oral contraceptive for concomitant use with etoricoxib.This fact can lead to an increase in the frequency 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) resulted in a 65% reduction in the plasma AUC of etoricoxib. This interaction should be considered when etoricoxib is co-administered with rifampicin.

How to take, course of use and dosage

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

Special instructions

Use with caution when indicated in the anamnesis for 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 creatinine clearance 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, prednisone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline), in chronic alcoholism.

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

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

Taking into account the increasing risk of adverse effects with increasing duration of use, it is necessary to periodically assess the need for continuing treatment and the possibility of reducing the dose.

Do not use concomitantly with other NSAIDs.

Influence on the ability to drive motor vehicles and manage mechanisms

During the treatment period, care should be taken when driving vehicles and engaging in other potentially dangerous 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.

Form of production

Film-coated tablets

Active ingredient

Etoricoxib

Conditions of release from pharmacies

By prescription

Dosage form

Tablets