Kostarox, 60 mg 28 pcs.

NSAIDs. Selective COX-2 inhibitor, in therapeutic concentrations blocks 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, with no effect on platelet function and gastrointestinal mucosa.

Etoricoxib has a dose-dependent effect on COX-2 inhibition with no effect on COX-1 when used in daily doses up to 150 mg. It has no effect on the production of prostaglandins in the gastric mucosa and on bleeding time. In the conducted studies, no reduction in arachidonic acid levels and collagen-induced platelet aggregation was observed.

Pharmacokinetics

After oral administration it is rapidly absorbed from the gastrointestinal tract. Bioavailability when taken orally is about 100%. After adults on an empty stomach at a dose of 120 mg, Cmax is 3.6 mcg/ml, Tmax is 1 hour after intake. Food intake has no significant effect on the severity and absorption rate of etoricoxib at a dose of 120 mg. At the same time, Cmax values are decreased by 36% and Tmax is increased by 2 h. The geometric mean AUC0-24 was 37.8 µg x h/ml. The pharmacokinetics of etoricoxib within therapeutic doses is linear.

The binding to plasma proteins exceeds 92%. Vd in equilibrium is about 120 l. Etoricoxib penetrates through the placental and the HEB.

Intensively metabolized in the liver, with the participation of cytochrome P450 isoenzymes and the formation of 6-hydroxymethyl etoricoxib. Five metabolites of etoricoxib have been detected, the main ones being 6-hydroxymethyl-etoricoxib and its derivative, 6-carboxy-acetyl-etoricoxib. The main metabolites have no effect on COX-1 and are inactive or inactive against COX-2.

Extracted by the kidneys as metabolites. Less than 1% is excreted unchanged in the urine.

In a single intravenous injection, 70% is excreted by the kidneys, 20% is excreted through the intestine, mainly as metabolites. Less than 2% is found unchanged.

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

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

In patients with moderate hepatic impairment (Child-Pugh score 7-9) who received the drug in a dose of 60 mg every other day, the AUC was the same as in healthy subjects who took the drug daily in the same dose.

Hemodialysis had little effect on excretion (dialysis clearance was approximately 50 mL/min).

Indications

Active ingredient

How to take, the dosage

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

In patients with hepatic impairment (Child-Pugh score 5-9) it is recommended not to exceed the daily dose of 60 mg.

Interaction

In patients receiving warfarin, an etoricoxib dose of 120 mg/day was associated with an increase of approximately 13% in MHO and prothrombin time. In patients receiving warfarin or similar drugs, MHO values should be monitored during initiation of therapy or change of etoricoxib dosing regimen, 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 simultaneously with ACE inhibitors. In patients with impaired renal function (e.g., if dehydrated or elderly), this combination may exacerbate functional impairment of the kidneys.

Etoricoxib may be used concomitantly with acetylsalicylic acid at low doses intended for the prevention of cardiovascular disease. However, concomitant administration of low-dose acetylsalicylic acid and etoricoxib may result in an increased incidence of GI ulceration and other complications compared to etoricoxib administration alone. After reaching equilibrium, administration of etoricoxib at a dose of 120 mg once daily has no effect on the antiplatelet activity of low-dose acetylsalicylic acid (81 mg/day). The drug does not replace the prophylactic effect of acetylsalicylic acid in cardiovascular diseases. Cyclosporine and tacrolimus increase the risk of nephrotoxicity with etoricoxib.

There is evidence that non-selective NSAIDs and selective COX-2 inhibitors may increase the plasma concentration of lithium. This interaction should be taken into account when treating patients taking etoricoxib concomitantly with lithium.

There is evidence of a 28% increase in plasma concentration of methotrexate (by AUC) and a 13% decrease in its renal clearance with etoricoxib.

Taking etoricoxib at a dose of 120 mg with oral contraceptives containing 35 µg of ethinylestradiol and 0.5 to 1 mg of norethindrone for 21 days simultaneously or 12 h apart increases the steady-state AUC0-24 of ethinylestradiol by 50-60%. However, norethisterone concentrations are not usually increased to a clinically significant degree. This increase in ethinylestradiol concentration should be taken into account when choosing an appropriate oral contraceptive for concomitant use with etoricoxib. This fact may lead to an increased incidence of thromboembolism by increasing ethinylestradiol exposure.

Etoricoxib has no effect on the AUC0-24 in equilibrium or elimination of digoxin. However, etoricoxib increases Cmax (by an average of 33%), which may be important in the development of digoxin overdose.

The simultaneous use of etoricoxib and rifampicin (a potent inducer of hepatic metabolism) leads to a 65% reduction of the AUC of etoricoxib in plasma. This interaction should be considered when concomitant administration of etoricoxib with rifampicin.

Special Instructions

With caution when there is a history of gastrointestinal ulcers, Helicobacter pylori infection, in elderly patients, in patients who have received long-term NSAIDs, severe somatic diseases, dyslipidemia/hyperlipidemia, diabetes, arterial hypertension, edema and fluid retention, smoking, in patients with IQ less than 60 ml/min, concomitant therapy with the following medicines anticoagulants (e.g., warfarin), antiaggregants (e.g., acetylsalicylic acid, clopidogrel), GCS (e.g., prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline), in chronic alcoholism.

At the time of treatment, close monitoring of BP during the first 2 weeks and periodically thereafter is required.

Hypatic and renal function parameters should be regularly monitored during treatment. If hepatic transaminase activity increases by a factor of 3 or more relative to VHF, treatment should be discontinued.

With increasing risk of adverse effects with increasing duration of therapy, the need for continued treatment and the possibility of reducing the dose should be periodically assessed.

Do not use simultaneously with other NSAIDs.

Impact on driving and operating machinery

At the time of treatment, caution should be exercised when driving motor vehicles and engaging in other potentially hazardous activities requiring increased concentration and rapid psychomotor reactions. Patients who have had episodes of dizziness, drowsiness or weakness should refrain from activities that require concentration.

Contraindications

The complete or incomplete combination of bronchial asthma, recurrent nasal or paranasal sinus polyposis and intolerance to acetylsalicylic acid and other NSAIDs (including history).

Erotic ulcerative changes of the mucous membrane of the stomach or duodenum, active gastrointestinal bleeding, cerebrovascular or other bleeding.

Inflammatory bowel disease (Crohn’s disease, nonspecific ulcerative colitis) in the acute phase.

Hemophilia and other disorders of blood clotting.

Developed heart failure (functional class II-IV according to NYHA classification).

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

Severe renal failure (CKR less than 30 ml/min), advanced renal disease, confirmed hyperkalemia.

The period after coronary artery bypass grafting; peripheral artery disease, cerebrovascular disease, clinically significant CHD.

Sustained 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

Digestive system disorders: frequent – epigastric pain, nausea, diarrhea, dyspepsia, flatulence; sometimes – bloating, belching, increased peristalsis, constipation, dry oral mucosa, gastritis, gastric or duodenal ulcer, irritable bowel syndrome, esophagitis, oral mucosa ulcers, vomiting; very rarely – GI ulcers (with bleeding or perforation), hepatitis.

Nervous system disorders: frequently – headache, dizziness, weakness; sometimes – taste disorders, drowsiness, sleep disorders, sensitivity disorders, including paraesthesia/hyperesthesia, anxiety, depression, concentration disorders; very rarely – hallucinations, confusion.

Sensory system disorders: sometimes – blurred vision, conjunctivitis, tinnitus, vertigo.

The urinary system: sometimes – proteinuria; very rare – renal failure, usually reversible upon drug withdrawal.

Allergic reactions: very rare – anaphylactic/anaphylactoid reactions, including marked BP decrease and shock.

Cardiovascular system disorders: often – palpitations, increased BP; sometimes – hot flashes, impaired cerebral circulation, atrial fibrillation, congestive heart failure, non-specific ECG changes, myocardial infarction; very rarely – hypertensive crisis.

Respiratory system: sometimes – cough, dyspnea, nasal bleeding; very rare – bronchospasm.

Dermatological reactions: often – ecchymosis; sometimes – swelling of the face, skin itching, rash; very rare – urticaria, Stevens-Johnson syndrome, Lyell syndrome.

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

Muscular system disorders: sometimes – muscle cramps, arthralgia, myalgia.

Metabolism disorders: often – edema, fluid retention; sometimes – changes in appetite, weight gain.

Laboratory tests: often – increased activity of liver transaminases; sometimes – increased blood and urine nitrogen, increased CPK activity, decreased hematocrit, decreased hemoglobin, hyperkalemia, leukopenia, thrombocytopenia, increased serum creatinine, increased uric acid; rarely – increased serum sodium.

Others: often – flu-like syndrome; sometimes – pain in the chest.

Similarities