Etoricoxib-Teva, 60 mg 14 pcs

Indications

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

Active ingredient

Etoricoxib

Composition

1 tablet contains:

Active substance:

itricoxib 60.00 mg;

Supplements: calcium hydrophosphate (anhydrous) 76.40 mg; microcrystalline cellulose (type 101) 21.80 mg; microcrystalline cellulose (type 102) 21.80 mg; crospovidone (type A) 12.00 mg; povidone-K25 6.00 mg; magnesium stearate 2.00 mg;

The 60 mg dosage capsule: Aq51B↩uarolish P green 074.23 MS (hypromellose 3.0000 mg; hydroxypropyl cellulose (hyprolose) 0.3000 mg; talc 0.6600 mg; medium-chain triglycerides 0.3000 mg; titanium dioxide (E171) 1.2000 mg; aluminum varnish based on diamond blue dye (E133) 0.1200 mg; aluminum varnish based on indigo carmine (E132) 0.1200 mg; iron oxide yellow dye (E172) 0.2400 mg; iron oxide black dye (E172) 0.0600 mg;

How to take, the dosage

Orally, regardless of meals, with a small amount of water.

The drug Etoricoxib-Teva should be used in the lowest effective dose for the shortest possible course.

Osteoarthritis

The recommended dose is 30 mg once daily or 60 mg once daily.

Rheumatoid arthritis and ankylosing spondylitis

The 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 daily may increase the therapeutic effect.

In conditions accompanied by acute pain, Etoricoxib-Teva should be used only in the acute symptomatic period.

Acute gouty arthritis

The recommended dose in the acute period is 120 mg once daily.

The duration of use of the drug in a dose of 120 mg is no more than 8 days.

Acute pain after dental surgery

The recommended dose is 90 mg once daily. When treating acute pain after dental surgery, Etoricoxib-Teva should only be used for an acute period of no more than 3 days.

Doses higher than those recommended for each indication either have no additional efficacy or have not been studied. Thus:

• daily dose for osteoarthritis should not exceed 60 mg;
• daily dose for rheumatoid arthritis should not exceed 90 mg;
• daily dose in ankylosing spondylitis should not exceed 90 mg;daily dose for acute gouty arthritis should not exceed 120 mg; for a period not to exceed 8 days;
• daily dose to relieve pain after dental surgery should not exceed 90 mg; for a period not to exceed 3 days.

Special patient groups

.Elderly

Dose adjustment in elderly patients is not necessary. As with other drugs in elderly patients, caution should be exercised when using Etoricoxib-Teva (see “Special Precautions”).

Patients with impaired liver function

. Regardless of the indication, patients with mild hepatic impairment (Child-Pugh scores 5-6) should not exceed a dose of 60 mg once daily; patients with moderate hepatic impairment (Child-Pugh scores 7-9) should not exceed 30 mg once daily.

We recommend caution when using Etoricoxib-Teva in patients with moderate hepatic impairment because clinical experience with Etoricoxib-Teva in this group of patients is limited. Due to the lack of clinical experience with Etoricoxib-Teva in patients with severe hepatic impairment (≥10 Child-Pugh score) the drug is contraindicated for this group of patients (see section “Pharmacological properties”, subsection “Pharmacokinetics” as well as sections “Contraindications” and “Cautions”).

Patients with impaired renal function

Dose adjustment in patients with creatinine clearance ≥30 ml/min is not required (see section “Pharmacological properties”, subsection “Pharmacokinetics”). The use of etoricoxib in patients with creatinine clearance < 30 ml/min is contraindicated (see sections “Contraindications” and “Special indications”).

Children

Etoricoxib is contraindicated in children and adolescents under 16 years of age (see Contraindications section).

Interaction

Pharmacodynamic interaction

Peroral anticoagulants (warfarin). In patients receiving warfarin, administration of etoricoxib at a dose of 120 mg daily was accompanied by an increase of approximately 13% in the international normalized ratio (INR) prothrombin time. In patients receiving oral anticoagulants, prothrombin time and INR should be monitored at the start of treatment or when treatment with etoricoxib is changed, 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 (e.g., patients with dehydration or elderly patients with impaired renal function), simultaneous use of ACE inhibitor or angiotensin II antagonist and drugs that inhibit cyclooxygenase may lead to additional deterioration of renal function, including possible development of acute renal failure, which is usually reversible. It should be remembered about the possibility of such interactions in patients who take etoricoxib simultaneously with ACE inhibitors or with angiotensin II antagonists. Such combination should be administered with caution, especially in elderly patients. At the beginning of combined treatment, as well as at certain intervals thereafter, fluid replacement should be performed and renal function monitoring should be considered.

Acetylsalicylic acid. In a study involving healthy volunteers, etoricoxib at a dose of 120 mg daily at equilibrium had no effect on the antiplatelet activity of acetylsalicylic acid (81 mg once daily). Etoricoxib can be used concomitantly with acetylsalicylic acid in low doses designed for prevention of CC diseases. However, concomitant administration of low doses of acetylsalicylic acid and etoricoxib may result in an increased incidence of GI ulcers and other complications compared with etoricoxib administration alone. Concomitant use of etoricoxib with acetylsalicylic acid in doses higher than those recommended for prevention of CC complications, as well as with other NSAIDs is not recommended (see section “Pharmacological properties”, subsection “Pharmacodynamics”, as well as section “Cautions”).

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 concomitant use of etoricoxib with any of these drugs.

Pharmacokinetic interaction

.Effect of etoricoxib on other drugs

Lithium. NSAIDs reduce renal excretion of lithium and therefore increase plasma lithium concentrations. If necessary, frequent monitoring of lithium concentration in blood is performed and the dose of lithium is adjusted during concomitant use with NSAIDs, as well as when NSAIDs are withdrawn.

Methotrexate. Two studies examined the effects of etoricoxib in doses of 60, 90 and 120 mg once daily for seven days in patients receiving once-weekly methotrexate in doses of 7.5 to 20 mg for rheumatoid arthritis. Etoricoxib at doses of 60 and 90 mg had no effect on plasma concentrations and renal clearance of methotrexate. In one study, etoricoxib at a dose of 120 mg had no effect on the pharmacokinetic parameters of methotrexate. In another study, plasma concentrations of methotrexate were increased by 28% and renal clearance of methotrexate was decreased by 13%. When etoricoxib and methotrexate are prescribed concomitantly, monitoring for possible toxic effects of methotrexate should be conducted.

Peroral contraceptives. Taking etoricoxib for 21 days at a dose of 60 mg with oral contraceptives containing 35 mcg ethinylestradiol (EE) and 0.5 to 1 mg norethindrone increases the AUC_0-24h for EE by 37%. Taking etoricoxib at a dose of 120 mg with the above oral contraceptives (simultaneously or 12 hours apart) increases the equilibrium AUC_0-24h for EE by 50-60%. This increase in AE concentration should be taken into account when choosing an appropriate oral contraceptive for concomitant use with etoricoxib. This fact can lead to an increased incidence of adverse events associated with oral contraceptive use (e.g., venous thromboembolism in women at risk).

Hormone replacement therapy (HRT). Administration of etoricoxib at a dose of 120 mg concomitantly with hormone replacement therapy containing conjugated estrogens at a dose of 0.625 mg for 28 days increases the mean equilibrium AUC_0-24h of unconjugated estrone (41%), equiline (76%) and 17-β-estradiol (22%). The effects of the doses of etoricoxib recommended for long-term use (30, 60, and 90 mg) have not been studied. Etoricoxib at a dose of 120 mg changed the exposure (AUC_0-24h) of these estrogenic components less than twice as much as monotherapy with a drug containing conjugated estrogens when the latter dose was increased from 0.625 to 1.25 mg. The clinical significance of such increases is unknown. The use of a combination of etoricoxib and a drug containing higher doses of conjugated estrogens has not been studied. Increased estrogen concentrations should be considered when choosing a hormone medication for use in the postmenopause when concomitantly prescribed with etoricoxib because increased estrogen exposure may increase the risk of adverse events associated with MHT.

Prednisone/prednisolone. In drug interaction studies, etoricoxib had no clinically significant effect on the pharmacokinetics of prednisone/prednisolone. Digoxin. When etoricoxib was administered at a dose of 120 mg once daily for 10 days in healthy volunteers, there was no change in AUC_0-24h at equilibrium or effect on renal excretion of digoxin. There was an increase in the C_max of digoxin (approximately 33%). This increase is generally not significant in most patients. However, concomitant use of etoricoxib and digoxin should be monitored in patients at high risk of digoxin toxicity.

Influence of etoricoxib on drugs metabolized by sulfotransferases. Etoricoxib is an inhibitor of human sulfotransferase (specifically SULT1E1) and can increase serum EE concentrations. Because there are currently insufficient data on the effects of various sulfotransferases and their clinical relevance to the use of many drugs is still being studied, it is prudent to prescribe etoricoxib with caution concomitantly with other drugs that are metabolized primarily by human sulfotransferases (e.g., oral salbutamol and minoxidil).

The effect of etoricoxib on drugs metabolized by isoenzymes of the cytochrome system. Based on in vitro studies, etoricoxib is not expected to inhibit cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and WA4. In a study involving healthy volunteers, daily use of etoricoxib at a dose of 120 mg had no effect on the activity of the CYP WA4 isoenzyme in the liver, according to the erythromycin breath test.

Influence of other drugs on the pharmacokinetics of etoricoxib

The main route of metabolism of etoricoxib depends on enzymes of the cytochrome system.

The CYP3A4 isoenzyme contributes to the metabolism of etoricoxib in vivo. in vitro studies suggest that the CYP2D6, CYP2C9, CYP1A2, and CYP2CI9 isoenzymes may also catalyze the major metabolic pathway, but their quantitative characteristics in vivo have not been studied.

Ketoconazole. Ketoconazole is a potent inhibitor of CYP3A4 isoenzyme. When administered to healthy volunteers at a dose of 400 mg once daily for 11 days, ketoconazole had no clinically significant effect on the pharmacokinetics of a single dose of etoricoxib 60 mg (increase in AUC by 43%).

Voriconazole and myconazole. Concomitant administration of strong CYP3A4 isoenzyme inhibitors (oral voriconazole or topical myconazole, oral gel) and etoricoxib caused a slight increase in etoricoxib exposure, which was not considered clinically significant based on published data.

Rifampicin. Concomitant administration of etoricoxib and rifampicin (a potent inducer of the cytochrome system) resulted in a 65% decrease in plasma concentration of etoricoxib. This interaction may be accompanied by relapse of symptoms when concomitant use of etoricoxib with rifampicin. These data may indicate the need to increase the dose; however, etoricoxib should not be used in doses that are higher than recommended for each indication (see section “Dosage and administration”), since the combined use of rifampicin and etoricoxib in such doses has not been studied.

Antacids. Antacids have no clinically significant effect on the pharmacokinetics of etoricoxib.

Special Instructions

Influence on the gastrointestinal tract

There have been cases of upper gastrointestinal complications (perforations, ulcers or bleeding), sometimes with fatal outcome, in patients who received etoricoxib.

We recommend caution when treating patients with a high risk of GI complications when using NSAIDs, particularly in the elderly, patients who use other NSAIDs, including acetylsalicylic acid, and in patients with a history of GI disease such as ulceration or gastrointestinal bleeding.

There is an additional risk of adverse gastrointestinal reactions (gastrointestinal ulcers or other gastrointestinal complications) when etoricoxib and acetylsalicylic acid are used concomitantly (even at low doses). In long-term clinical trials, no significant differences were observed with respect to 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”).

Influence on cardiovascular system

The results of clinical studies indicate that the use of drugs of class 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 SS disease with 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. The patient’s need for symptomatic treatment and response to therapy should be periodically evaluated, especially for patients with osteoarthritis (see section “Pharmacological properties”, subsection “Pharmacodynamics” as well as sections “Contraindications”, “Administration and doses” and “Side effects”).

Patients with known risk factors for CC complications (such as: arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) should only be prescribed etoricoxib after a careful assessment of benefits and risks (see section “Pharmacological properties”, subsection “Pharmacodynamics”).

The selective COX-2 inhibitors are not a substitute for acetylsalicylic acid in the prevention of SS because they have no effect on platelets. Therefore, the use of antiplatelet agents should not be discontinued (see section “Pharmacological properties”, subsection “Pharmacodynamics”, and section “Interaction with other medicinal products”).

Influence on renal function

The renal prostaglandins may play a compensatory role in maintaining renal perfusion. In the presence of conditions that adversely affect renal perfusion, administration of etoricoxib may cause decreased formation of prostaglandins and decreased renal blood flow, and thereby reduce renal function. The greatest risk of developing this reaction is in patients with a significant decrease in renal function, decompensated heart failure, or a history of cirrhosis. In these patients, renal function should be monitored.

Fluid retention, edema and arterial hypertension

As with other prostaglandin synthesis inhibiting drugs, fluid retention, edema and arterial hypertension have been observed in patients using etoricoxib. The use of all NSAIDs, including etoricoxib, may be associated with the occurrence or recurrence of chronic heart failure. Information about the dose-dependent effect of etoricoxib is given in section “Pharmacological properties”, subsection “Pharmacodynamics”. Caution should be exercised when prescribing etoricoxib in patients with a history of heart failure, left ventricular dysfunction or arterial hypertension, as well as in patients with pre-existing edema due to any other reason. If there are clinical signs of deterioration in such 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 some other NSAIDs and COX-2 selective inhibitors. During treatment with etoricoxib, special attention should be paid to BP control (see section “Contraindications”), which should be monitored for 2 weeks after the start of treatment and periodically thereafter. Alternative treatment should be considered if there is a significant increase in BP.

Influence on liver function

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

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

The use of etoricoxib should be discontinued if persistent abnormal liver function is detected (three times the upper limit of normal).

General Instructions

If a patient experiences deterioration in any of the organ systems listed above during treatment, appropriate action should be taken and consideration should be given to discontinuing etoricoxib. Appropriate medical monitoring is necessary when using etoricoxib in elderly patients and in patients with impaired renal, hepatic or cardiac function.

With caution, treatment with etoricoxib should be initiated in patients who are dehydrated. Rehydration is recommended before starting etoricoxib.

During postmarketing surveillance, serious skin reactions have very rarely been reported with NSAIDs and some selective COX-2 inhibitors. Some of them (including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis) were fatal (see section “Adverse effects”). The risk of 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 receiving etoricoxib (see section “Adverse effects”). The use of some selective COX-2 inhibitors was accompanied by an increased risk of skin reactions in patients with a history of any drug allergy. 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 used concomitantly with warfarin or other oral anticoagulants (see section “Interaction 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 plan pregnancy (see section “Pharmacological properties”, subsection “Pharmacodynamics” and section “Use in pregnancy and during breastfeeding, effects on fertility”).

Influence on driving and operating machinery

Patients who have experienced dizziness, drowsiness or weakness while using etoricoxib should refrain from driving and operating machinery.

Synopsis

Round biconvex film-coated tablets, dark green, engraved “60” on one side, the other side is smooth.

Contraindications

• High sensitivity to any component of the drug.
• Gastric and duodenal ulcer in the acute stage, active gastrointestinal bleeding.
• The complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and sinuses, and intolerance to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (including a history).
• Pregnancy, breastfeeding.
• Severe liver dysfunction (serum albumin < 25 g/L or ≥10 Child-Pugh score).
• Severe renal failure (CK less than 30 ml/min).
• Children under 16 years of age.
• Inflammatory bowel disease.
• Cronic heart failure (NYHA functional class II-IV).
• Uncontrolled arterial hypertension, in which BP values persistently exceed 140/90 mm Hg.
• Confirmed coronary heart disease, peripheral artery disease and/or cerebrovascular disease
• Confirmed hyperkalemia.
• Progressive renal disease.

Cautions

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

• patients with an increased risk of gastrointestinal complications due to taking NSAIDs; elderly, concomitantly taking other NSAIDs including acetylsalicylic acid or patients with a history of gastrointestinal conditions such as peptic ulcer disease and gastrointestinal bleeding;
• patients with a history of cardiovascular risk factors such as dyslipidemia/hyperlipidemia, diabetes mellitus, arterial hypertension, smoking, heart failure, left ventricular dysfunction, edema and fluid retention;
• Patients with dehydration;
• Patients with renal dysfunction concomitantly using ACE inhibitors, angiotensin II diuretics, especially the elderly;
• Patients with creatinine clearance < 60 ml/min;
patients with a previous significant decrease in renal function, with impaired renal function, decompensated heart failure, or cirrhosis of the liver, who are at risk for long-term use of NSAIDs.

Caution should be exercised with concomitant therapy with the following drugs:

• anticoagulants (e.g., warfarin);
• anti-aggregants (e.g., acetylsalicylic acid, clopidogrel);
• drugs metabolized by sulfotransferases.

.

Side effects

The safety of etoricoxib has been evaluated in clinical studies involving 9,295 participants, including 6,757 patients with OA, RA, chronic low back pain and ankylosing spondylitis (approximately 600 patients with OA or RA have been treated for one year or longer).

In clinical trials, the adverse effect profile was similar in patients with OA or RA who received etoricoxib for 1 year or longer.

In a clinical trial of acute gouty arthritis, patients received etoricoxib at a dose of 120 mg/day for 8 days. The adverse effect profile in this study was generally the same as in the pooled studies of OA, RA and chronic low back pain.

In the SS Safety Assessment Program, which included data from three active-controlled studies, 17412 patients with OA or RA received etoricoxib at a dose of 60 mg or 90 mg for an average of 18 months (see “Pharmacological Properties,” subsection “Pharmacodynamics”).

In clinical trials of acute postoperative pain associated with dental surgery in which 614 patients received etoricoxib at a dose of 90 mg or 120 mg, the profile of adverse effects was generally similar to that in the pooled studies of OA, RA and chronic low back pain. The following adverse reactions were reported with greater frequency with the drug than with placebo in clinical trials involving patients with OA, RA, chronic low back pain, or ankylosing spondylitis who were taking etoricoxib at 30 mg, 60 mg, or 90 mg with dose increases to the recommended dose over 12 weeks, in MEDAL Program trials lasting up to 3.5 years, in short-term acute pain trials, and during postmarketing use.

Infectious and parasitic diseases

Alveolar ostitis often
Gastroenteritis, upper respiratory tract infections, urinary tract infections infrequent

Anemia (mainly due to gastrointestinal bleeding), leukopenia, thrombocytopenia infrequently

Disorders of the immune system reactions

hypersensitivity 2,4 infrequent
angioedema, anaphylactic/anaphylactoid reactions, including shock2 infrequent

Metabolic and nutritional disorders

pedema/ fluid retention often
decreased or increased appetite, increased body weight infrequently

Mental disorders

anxiety, depression, concentration disorders, hallucinations2 infrequent
confusion2, anxiety2 rare

Nervous system disorders

dizziness, headache often
Taste disorder, insomnia, paresthesia/hypoesthesia, somnolence infrequent

Visual disturbances

blurred vision, conjunctivitis infrequent

Hearing organ and labyrinth disorders

Tinnitus, vertigo infrequent

Cardiac disorders

palpitations, arrhythmias2 frequently
atrial fibrillation, tachycardia2, chronic heart failure, nonspecific changes on ECG, angina pectoris2, myocardial infarction5 infrequently

vascular disorders

arterial hypertension often
“hot flashes”, impaired cerebral circulation5, transient ischemic attack, hypertensive crisis2, vasculitis2 infrequent

Relatory system, organ disorders
thorax and mediastinum

bronchospasm2 often
cough, shortness of breath, nasal bleeding infrequent

Gastrointestinal tract disorders

p> abdominal pain very common
constipation, flatulence, gastritis, heartburn/gastroesophageal reflux, diarrhea, dyspepsia/ epigastric discomfort, nausea, vomiting, esophagitis, oral mucosal ulcers often
bloating, changes in peristalsis, dry mouth, gastroduodenal ulcer, peptic ulcer, including gastrointestinal perforations and bleeding, irritable bowel syndrome, pancreatitis2 infrequent

gastric ulcerLiver and biliary tract disorders increased ALT activity, increased ACT activity often
hepatitis2 rare
liver failure 2br> hepatic failure 2, jaundice2 rarely3

dermal and subcutaneous tissue disorders

ecchymosis often
facial swelling, itching, rash, erythema2, urticaria2 infrequently
Stevens-Johnson syndrome2, toxic epidermal necrolysis2, fixed drug erythema2 rarely3

Skeletal, muscular and connective tissue disorders

Muscle spasms/ cramps, skeletal-muscular pain/scarcity infrequent

Repnal and urinary tract disorders proteinuria, increased serum creatinine, renal failure2 infrequent

/p>

General disorders and disorders at the site of administration

weakness, flu-like syndrome often
chest pain infrequent

Influence on laboratory and instrumental results
studies

increased blood urea nitrogen, increased creatine phosphokinase, hyperkalemia, increased uric acid infrequently
decreased blood sodium rarely