Etoricoxib-Teva pills 90mg, 7pcs

Composition

Auxiliary substances:  calcium hydrophosphate anhydrous-114.6 mg, microcrystalline cellulose PH 101-32.7 mg, microcrystalline cellulose PH 102-32.7 mg, crospovidone type A-18 mg, povidone K 25-9 mg, magnesium stearate-3 mg.

Composition of the film shell:  Aquapolish P white 014.44 MS; (hypromellose-4.5 mg; hydroxypropylcellulose (giprolose)- 0.45 mg; talc-1.35 mg; medium chain triglycerides-0.45 mg; titanium dioxide (E171) – 2.25 mg. )

Pharmacological action

Pharmacodynamics

Etoricoxib, when taken orally at therapeutic concentrations, is a selective cyclooxygenase-2 (COX-2) inhibitor. In clinical pharmacological studies, etoricoxib dose-dependently inhibited COX-2, without affecting COX-1 with a daily dose of up to 150 mg. The drug does not inhibit prostaglandin synthesis in the gastric mucosa and does not affect platelet function.

Cyclooxygenase is responsible for the formation of prostaglandins. Two isoforms of cyclooxygenase, COX – 1 and COX-2, have been identified. COX-2 is an isoenzyme that is induced by various anti-inflammatory mediators and is considered the main enzyme responsible for the synthesis of prostanoid mediators of pain, inflammation, and fever.

COX-2 is involved in the processes of ovulation, implantation and closure of the ductus arteriosus, regulation of renal function and Central nervous system (induction of fever, pain, cognitive function), and can also play a role in the process of the healing of ulcers. COX-2 was detected in the tissues surrounding gastric ulcers in humans but its relevance to ulcer healing is not installed.

Pharmacokinetics

Absorption.

Etoricoxib is rapidly absorbed when taken orally. Absolute oral bioavailability is about 100%. When using the drug in adults on an empty stomach at a dose of 120 mg once a day until equilibrium is reached, the maximum concentration (cmax) is 3.6 mcg / ml. The time to reach the maximum concentration (T_Cmax) in blood plasma is 1 hour after taking the drug.

The geometric mean AUC_{of 0-24} h is 37.8 mcg * h / ml. The pharmacokinetics of etoricoxib within therapeutic doses are linear.

When taking etoricoxib 120 mg with a meal (high-fat food), there was no clinically significant effect on the degree of absorption. The rate of absorption changed, which led to a decrease_{in Cmax} by 36% and an increase in T_Cmax by 2 h.

These results are not considered clinically significant. In clinical trials, etoricoxib was used regardless of food intake.

Distribution.

Etoricoxib is approximately 92% bound to human plasma proteins at concentrations of 0.05-5 mcg / ml. The volume of distribution (_vdss) at steady state is about 120 liters. Etoricoxib penetrates the placental barrier and the blood-brain barrier.

Metabolism.

Etoricoxib is extensively metabolized. Less than 1% of etoricoxib is excreted unchanged by the kidneys. The main pathway of metabolism is the formation of 6 ‘ – hydroxymethylethoricoxib, catalyzed by cytochrome P450 enzymes. CYP3A4 promotes the metabolism of etoricoxib in vivo. In vitro studies indicate that the isoenzymes CYP2D6, CYP2C9, CYP1A2, and CYP2C19 can also catalyze the main pathway of metabolism, but their quantitative effects in vivo have not been studied.

5 metabolites of etoricoxib were detected in humans. The main metabolite is 6′ – carboxyacetylethoricoxib, which is formed by additional oxidation of 6′ – hydroxymethylethoricoxib. These major metabolites do not have significant activity, or are weak COX-2 inhibitors. None of these metabolites inhibit COX-1.

Output.

In a single intravenous dose of 25 mg labeled radioactive etoricoxib,70% of etoricoxib was excreted via the kidneys,20% – via the intestines, mainly in the form of metabolites. Less than 2% were found unchanged.

Elimination of etoricoxib occurs mainly through metabolism, followed by elimination through the kidneys. A non-equilibrium concentration is achieved with a daily intake of 120 mg of etoricoxib after 7 days with a cumulative coefficient of about 2, which corresponds to a half-life of about 22 hours. Plasma clearance after intravenous use of 25 mg is approximately 50 ml/min.

Special patient groups

Elderly pharmacokinetics in the elderly (65 years and older) is comparable to the pharmacokinetics in the young.

The polpharmacokinetics of etoricoxib are similar in men and women.

Liver failure

In patients with mild hepatic impairment (Child-Pugh score 5-6), taking etoricoxib at a dose of 60 mg once a day was accompanied by an increase in AUC by 16% compared to healthy individuals taking the drug at the same dose.

In patients with moderate hepatic impairment (Child-Pugh score 7-9) who took etoricoxib at a dose of 60 mg every other day, the average AUC value was the same as in healthy individuals who took etoricoxib daily at the same dose. Etoricoxib 30 mg once daily has not been studied in this population.

Data from clinical and pharmacokinetic studies in patients with severe hepatic impairment (≥10 points on the Child-Pugh scale) are not available.

Renal insufficiency

The pharmacokinetic parameters of a single 120 mg dose of etoricoxib in patients with moderate to severe renal impairment and end-stage chronic renal failure (CRF) undergoing hemodialysis did not differ significantly from those in healthy individuals. Hemodialysis had little effect on excretion (dialysis clearance was about 50 ml / min).

The pharmacokinetic parameters of etoricoxib in children under 12 years of age have not been studied. In a pharmacokinetic study (n=16) conducted in adolescents aged 12 to 17 years, the pharmacokinetics in adolescents with a body weight of 40 to 60 kg when taking etoricoxib at a dose of 60 mg once a day and in adolescents with a body weight of more than 60 kg when taking etoricoxib at a dose of 90 mg once a day were similar to the pharmacokinetics in adults when taking etoricoxib at a dose of 90 mg once a day.

The safety and efficacy of etoricoxib in children has not been established.

Indications

Symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, pain and inflammation associated with acute gouty arthritis. Short-term treatment of moderate acute pain after dental surgery.

Use during pregnancy and lactation

Pregnancy

There are no clinical data on the use of etoricoxib during pregnancy. Toxic effects on the reproductive system have been observed in animal studies.

The potential risk in women during pregnancy is unknown. The use of etoricoxib, as well as other drugs that inhibit prostaglandin synthesis, during the last trimester of pregnancy can lead to suppression of uterine contractions and premature closure of the ductus arteriosus. Etoricoxib is contraindicated during pregnancy. If pregnancy occurs during treatment, etoricoxib should be discontinued.

Breast-feeding

In lactating rats, etoricoxib is excreted in milk. Studies confirming the release of etoricoxib in breast milk in women have not been conducted. Women who take etoricoxib should stop breastfeeding.

Contraindications

• Hypersensitivity to any component of the drug.
• Peptic ulcer of the stomach and duodenum 12 in the acute stage, active gastrointestinal bleeding.
• Complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (including in the anamnesis).
• Pregnancy, breast-feeding period.
• Severe hepatic impairment (serum albumin
• Severe renal insufficiency (creatinine clearance less than 30 ml / min).
• Children under 16 years of age.
• Inflammatory bowel diseases.
• Chronic heart failure (NYHA functional class II-IV).
• Uncontrolled arterial hypertension, in which blood pressure consistently exceeds 140/90 mm Hg.
• Confirmed coronary artery disease, peripheral artery disease, and / or cerebrovascular disease.
• Confirmed hyperkalemia.
• Progressive kidney diseases.

With caution

Caution should be exercised when using the drug in the following groups of patients:

• patients with a high risk of complications from the gastrointestinal tract due to NSAIDs; the elderly, at the same time taking other NSAIDs, including acetylsalicylic acid or patients with diseases of the gastrointestinal tract in history, such as peptic ulcer disease or gastrointestinal bleeding.
• patients with a history of risk factors for cardiovascular complications such as dyslipidemia/hyperlipidemia, diabetes mellitus, hypertension, Smoking, heart failure, impaired left ventricular function, swelling, and fluid retention;
• patients with impaired liver function of mild severity (5-6 points on a scale child-Pugh) should not exceed 60 mg once daily, patients with impaired liver function moderate (7-9 points on a scale child-Pugh) 30 mg once daily;
• patients with dehydration;
• patients with impaired renal function, at the same time using ACE inhibitors, diuretics, angiotensin II, especially the elderly;
• patients with a creatinine clearance of <60 ml/min;
• patients with previous significant decrease in renal function, with impaired renal function, decompensated heart failure or cirrhosis, are at risk with long-term use of NSAIDs.

Side effects

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

Nervous system disorders: 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 side of 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 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.

Respiratory system disorders: sometimes-cough, shortness of breath, nosebleeds; very rarely-bronchospasm.

Dermatological reactions: often – ecchymosis; sometimes-facial swelling, itching, 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 services: often-flu-like syndrome; sometimes – chest pain.

Interaction

Oral anticoagulants (warfarin). In patients receiving warfarin, etoricoxib 120 mg daily was associated with an increase of approximately 13% in the international normalized ratio (INR) of prothrombin time. In patients receiving oral anticoagulants, prothrombin time and INR should be monitored at the beginning of treatment or when changing treatment with etoricoxib, especially in the first few days.

Diuretics, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II antagonists. NSAIDs may weaken the effect of diuretics and other antihypertensive drugs.

In some patients with impaired renal function (for example, in patients with dehydration or in elderly patients with impaired renal function), the simultaneous use of an ACE inhibitor or angiotensin II antagonist and drugs that inhibit cyclooxygenase may lead to additional deterioration of renal function, including the possible development of acute renal failure, which is usually reversible.

Patients taking etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists should be aware of the possibility of such interactions. This combination should be used with caution, especially in elderly patients. At the beginning of combined treatment, as well as at certain intervals in the future, fluid deficiency should be replenished and monitoring of renal function should be considered.

Acetylsalicylic acid. In a study involving healthy volunteers, etoricoxib 120 mg daily at steady state did not affect the antiplatelet activity of acetylsalicylic acid (81 mg once daily). Etoricoxib can be used simultaneously with acetylsalicylic acid in low doses intended for the prevention of SS 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. Concomitant use of etoricoxib with acetylsalicylic acid in doses exceeding those recommended for the prevention of SS complications, as well as with other NSAIDs, is not recommended.

Cyclosporine and tacrolimus. The interaction of etoricoxib with these drugs has not been studied, but the simultaneous use of NSAIDs with cyclosporine and tacrolimus may increase the nephrotoxic effect of these drugs. Renal function should be monitored when etoricoxib is co-administered with any of these medications.

How to take, course of use and dosage

Inside, regardless of food intake, with a small amount of water. The drug Etoricoxib-Teva should be used in the lowest effective dose in the shortest possible course.

OsteoarthritisThe recommended dose is 30 mg once a day or 60 mg once a day.

Rheumatoid arthritis and ankylosing spondylitisThe recommended dose is 60 mg or 90 mg once daily. The minimum effective daily dose is 60 mg once daily. In some patients, taking a dose of 90 mg once a day may lead to increased therapeutic effects.

In cases of acute pain, Etoricoxib-Teva should be used only during the acute symptomatic period.

Acute gouty arthritisThe recommended dose in the acute period is 120 mg once a day. The duration of use of the drug in a dose of 120 mg is no more than 8 days.

Acute pain after dental surgeryThe recommended dose is 90 mg once daily. In the treatment of acute pain after dental surgery, Etoricoxib-Teva should be used only in the acute period of no more than 3 days.

Overdose

In clinical studies, taking etoricoxib at a single dose of up to 500 mg or multiple doses of up to 150 mg / day for 21 days did not cause significant toxic effects.

Acute overdose with etoricoxib has been reported, but no adverse reactions have been reported in most cases.

The most frequent adverse reactions were consistent with the safety profile of etoricoxib (for example, gastrointestinal disorders, cardiorenal events).

In case of overdose, it is advisable to apply the usual supportive measures, such as: removal of the non-absorbed drug from the gastrointestinal tract, clinical observation and, if necessary, maintenance therapy. Etoricoxib is not eliminated by hemodialysis, and the elimination of etoricoxib by peritoneal dialysis has not been studied.

Description

Round biconvex tablets, film-coated in white, with the inscription “90” on one side, the other side is smooth.

Special instructions

Effect on the gastrointestinal tract

Upper gastrointestinal complications (perforations, ulcers, or bleeding), sometimes fatal, have been reported in patients treated with etoricoxib. Caution is recommended when treating patients at high risk of developing gastrointestinal complications when using NSAIDs, in particular in the elderly, patients who are simultaneously using other NSAIDs, including acetylsalicylic acid, as well as in patients with a history of gastrointestinal diseases such as ulcers or gastrointestinal bleeding.

There is an additional risk of gastrointestinal adverse reactions (gastrointestinal ulcers or other gastrointestinal complications) when etoricoxib and acetylsalicylic acid are co-administered (even at low doses).

In long-term clinical studies, there were no significant differences in gastrointestinal safety when using selective COX-2 inhibitors in combination with acetylsalicylic acid compared to the use of NSAIDs in combination with acetylsalicylic acid (see section “Pharmacological properties”, subsection “Pharmacodynamics”).

Impact on the cardiovascular system

The results of clinical studies indicate that the use of drugs of the class of selective COX-2 inhibitors is associated with an increased risk of thrombotic events (especially myocardial infarction and stroke) relative to placebo and some NSAIDs.

Since the risk of developing SS diseases when taking selective COX-2 inhibitors may increase with increasing dose and duration of use, it is necessary to choose the shortest possible duration of use and the lowest effective daily dose.

It is necessary to periodically assess the patient’s need for symptomatic treatment and response to therapy, especially for patients with osteoarthritis (see the section “Pharmacological properties”, subsection “Pharmacodynamics”, as well as the sections “Contraindications”, “Dosage and use” and “Side effects”). Patients with known risk factors for the development of SS complications (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) should be prescribed etoricoxib only after careful assessment of the benefit and risk (see section “Pharmacological properties”, subsection “Pharmacodynamics”).

Selective COX-2 inhibitors are not a substitute for acetylsalicylic acid in the prevention of SS diseases, since they do not affect platelets. Therefore, the use of antiplatelet drugs should not be discontinued (see the section “Pharmacological properties”, subsection “Pharmacodynamics”, as well as the section “Interaction with other drugs”).

Effects on kidney function

Renal prostaglandins may play a compensatory role in maintaining renal perfusion. In the presence of conditions that negatively affect renal perfusion, the use of etoricoxib may cause a decrease in prostaglandin formation and a decrease in renal blood flow, and thus reduce renal function.

The greatest risk of developing this reaction exists for patients with a significant decrease in renal function, decompensated heart failure, or a history of cirrhosis. In such patients, it is necessary to monitor renal function.

Fluid retention, edema, and hypertension

As with other drugs that inhibit prostaglandin synthesis, patients taking etoricoxib experienced fluid retention, edema, and hypertension. The use of all NSAIDs, including etoricoxib, may be associated with the occurrence or recurrence of chronic heart failure. For information on the dose-dependent effect of etoricoxib, see the section “Pharmacological properties”, subsection”Pharmacodynamics”.

Caution should be exercised when prescribing etoricoxib to patients with a history of heart failure, left ventricular dysfunction, or hypertension, as well as to patients with pre-existing edema that has occurred for any other reason. If there are clinical signs of deterioration in these patients, appropriate measures should be taken, including discontinuation of etoricoxib.

The use of etoricoxib, especially in high doses, may be associated with more frequent and severe arterial hypertension than with certain other NSAIDs and selective COX-2 inhibitors. During treatment with etoricoxib, special attention should be paid to blood pressure control (see section “Contraindications”), which should be monitored for 2 weeks after the start of treatment and periodically thereafter. If there is a significant increase in blood pressure, alternative treatment should be considered.

Effects on liver function

In clinical trials lasting up to one year, approximately 1% of patients treated with etoricoxib at doses of 30 mg,60 mg and 90 mg per day showed an increase in the activity of alanine aminotransferase (ALT) and/or aspartate aminotransferase (ACT) (approximately three or more times relative to the upper limit of normal).

All patients with symptoms and/or signs of liver dysfunction, as well as patients with abnormal liver function indicators, should be monitored.

If permanent abnormalities in liver function parameters are detected (three times higher than the upper limit of normal), the use of etoricoxib should be discontinued.

General instructions

If the patient experiences a deterioration in the function of any of the organ systems listed above during treatment, appropriate measures should be taken and discontinuation of etoricoxib should be considered. When using etoricoxib in elderly patients and in patients with impaired renal, liver or heart function, appropriate medical supervision is necessary.

Caution should be exercised when starting treatment with etoricoxib in patients with dehydration. Rehydration is recommended before starting the use of etoricoxib.

Serious skin reactions have been reported very rarely during post-marketing surveillance with NSAIDs and some selective COX-2 inhibitors. Some of them (including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis) were fatal (see the section “Side effects”). The risk of developing such reactions is highest at the beginning of therapy, in most cases during the first month of treatment.

Serious hypersensitivity reactions, such as anaphylaxis and angioedema, have been reported in patients treated with etoricoxib (see section “Side effects”). The use of some selective COX-2 inhibitors was associated with an increased risk of skin reactions in patients with a history of drug allergies.

Etoricoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

The use of etoricoxib may mask fever or other signs of inflammation. Caution should be exercised when etoricoxib is co-administered with warfarin or other oral anticoagulants (see section “Interactions with other medicinal products”).

The use of etoricoxib, as well as other drugs that inhibit COX and prostaglandin synthesis, is not recommended for women who are planning pregnancy.

Influence on the ability to drive vehicles and work with mechanisms

Patients who have experienced dizziness, drowsiness or weakness during the use of etoricoxib should refrain from driving vehicles and working with mechanisms.

Form of production

Film-coated tablets,30 mg,60 mg,90 mg,120 mg. Dosage of 30 mg:7 or 14 tablets in foil blisters (OPA/Al/PVC-Al).1 blister of 7 tablets,2 blisters of 14 tablets,4 blisters of 14 tablets or 7 blisters of 14 tablets together with the instructions for use are placed in a cardboard box. Dosages of 60 mg,90 mg,120 mg:2,7 or 14 tablets in foil blisters (OPA/Al/PVC-Al).1 blister of 2 or 7 tablets,1 blister of 14 tablets,2 blisters of 14 tablets,4 blisters of 14 tablets or 7 blisters of 14 tablets together with the instructions for use are placed in a cardboard box.

Storage conditions

Store at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date.

Active ingredient

Etoricoxib

Conditions of release from pharmacies

By prescription

Dosage form

Tablets