Etaria (Tablets) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

ATC Code

M01AH05 (Etoricoxib)

Active Substance

Etoricoxib (Rec.INN registered by WHO)

Dosage Forms

	Etaria	Film-coated tablets, 60 mg: 2, 4, 6, 7, 8, 10, 12, 14, 16, 20, 21, 28, 30, 40, 42 or 56 pcs.
		Film-coated tablets, 90 mg: 2, 4, 6, 7, 8, 10, 12, 14, 16, 20, 21, 28, 30, 40, 42 or 56 pcs.
		Film-coated tablets, 120 mg: 2, 4, 6, 7, 8, 10, 12, 14, 16, 20, 21, 28, 30, 40, 42 or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets green in color, round, biconvex; the core on the cross-section is white or almost white.

Excipients: anhydrous calcium hydrogen phosphate (dibasic anhydrous calcium phosphate) – 60 mg, microcrystalline cellulose – 68 mg, povidone K30 – 6 mg, croscarmellose sodium – 4 mg, magnesium stearate – 2 mg.

Film coating composition Opadry^® II green 32K210011 coating system – 8 mg (hypromellose 2910 – 39%, lactose monohydrate – 28%, titanium dioxide – 17.33%, triacetin – 8%, aluminum lake based on indigo carmine dye – 5.67%, yellow iron oxide dye – 2%).

2 pcs. – contour cell packaging (1) – cardboard packs.
2 pcs. – contour cell packaging (2) – cardboard packs.
2 pcs. – contour cell packaging (3) – cardboard packs.
2 pcs. – contour cell packaging (4) – cardboard packs.
4 pcs. – contour cell packaging (1) – cardboard packs.
4 pcs. – contour cell packaging (2) – cardboard packs.
4 pcs. – contour cell packaging (3) – cardboard packs.
4 pcs. – contour cell packaging (4) – cardboard packs.
7 pcs. – contour cell packaging (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (3) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
14 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (3) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.
20 pcs. – dark glass jars (1) – cardboard packs.
30 pcs. – dark glass jars (1) – cardboard packs.

Film-coated tablets white in color, round, biconvex; the core on the cross-section is white or almost white.

Excipients: anhydrous calcium hydrogen phosphate (dibasic anhydrous calcium phosphate) – 90 mg, microcrystalline cellulose – 102 mg, povidone K30 – 9 mg, croscarmellose sodium – 6 mg, magnesium stearate – 3 mg.

Film coating composition Opadry^® II white 32K280000 coating system – 12 mg (hypromellose 2910 – 39%, lactose monohydrate – 28%, titanium dioxide – 25%, triacetin – 8%).

2 pcs. – contour cell packaging (1) – cardboard packs.
2 pcs. – contour cell packaging (2) – cardboard packs.
2 pcs. – contour cell packaging (3) – cardboard packs.
2 pcs. – contour cell packaging (4) – cardboard packs.
4 pcs. – contour cell packaging (1) – cardboard packs.
4 pcs. – contour cell packaging (2) – cardboard packs.
4 pcs. – contour cell packaging (3) – cardboard packs.
4 pcs. – contour cell packaging (4) – cardboard packs.
7 pcs. – contour cell packaging (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (3) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
14 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (3) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.
20 pcs. – dark glass jars (1) – cardboard packs.
30 pcs. – dark glass jars (1) – cardboard packs.

Film-coated tablets light green in color, oval, biconvex, with a score on one side; the core on the cross-section is white or almost white.

Excipients: anhydrous calcium hydrogen phosphate (dibasic anhydrous calcium phosphate) – 120 mg, microcrystalline cellulose – 136 mg, povidone K30 – 12 mg, croscarmellose sodium – 8 mg, magnesium stearate – 4 mg.

Film coating composition Opadry^® II green 32K210012 coating system – 16 mg (hypromellose 2910 – 39%, lactose monohydrate – 28%, titanium dioxide – 22.45%, triacetin – 8%, aluminum lake based on indigo carmine dye – 1.6%, yellow iron oxide dye – 0.95%).

2 pcs. – contour cell packaging (1) – cardboard packs.
2 pcs. – contour cell packaging (2) – cardboard packs.
2 pcs. – contour cell packaging (3) – cardboard packs.
2 pcs. – contour cell packaging (4) – cardboard packs.
4 pcs. – contour cell packaging (1) – cardboard packs.
4 pcs. – contour cell packaging (2) – cardboard packs.
4 pcs. – contour cell packaging (3) – cardboard packs.
4 pcs. – contour cell packaging (4) – cardboard packs.
7 pcs. – contour cell packaging (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (3) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
14 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (3) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.
20 pcs. – dark glass jars (1) – cardboard packs.
30 pcs. – dark glass jars (1) – cardboard packs.

Clinical-Pharmacological Group

NSAID. Selective COX-2 inhibitor

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID. Selective COX-2 inhibitor, at therapeutic concentrations blocks the formation of prostaglandins and has anti-inflammatory, analgesic and antipyretic effects. Selective inhibition of COX-2 is accompanied by a reduction 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 does not affect the production of prostaglandins in the gastric mucosa and bleeding time. In conducted studies, no decrease in arachidonic acid levels and collagen-induced platelet aggregation was observed.

Pharmacokinetics

After oral administration, it is rapidly absorbed from the gastrointestinal tract. Oral bioavailability is about 100%. After a single 120 mg dose taken by adults on an empty stomach, C_max is 3.6 µg/ml, T_max – 1 hour after administration. Food intake does not have a significant effect on the extent and rate of absorption of etoricoxib when taken at a dose of 120 mg. However, C_max values decrease by 36% and T_max increases by 2 hours. The mean geometric value of AUC_0-24 was 37.8 µg × h/ml. The pharmacokinetics of etoricoxib within therapeutic doses is linear.

Plasma protein binding exceeds 92%. V_d at steady state is about 120 L. Etoricoxib crosses the placental and blood-brain barriers.

Extensively metabolized in the liver, with the participation of cytochrome P450 isoenzymes and the formation of 6-hydroxymethyl-etoricoxib. Five metabolites of etoricoxib have been identified, the main ones being 6-hydroxymethyl-etoricoxib and its derivative, 6-carboxy-acetyl-etoricoxib. The main metabolites do not affect COX-1 and are either completely inactive or have low activity against COX-2.

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

After a single intravenous administration, 70% is excreted by the kidneys, 20% – through the intestine, mainly as metabolites. Less than 2% was found unchanged.

Steady state is reached after 7 days with daily administration at a dose of 120 mg, with an accumulation factor of about 2, which corresponds to a T_1/2 of about 22 hours. Plasma clearance is approximately 50 ml/min.

In patients with mild hepatic impairment (5-6 points on the Child-Pugh scale), a single dose of etoricoxib 60 mg/day was accompanied by 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 subjects taking the drug daily at the same dose.

Hemodialysis had little effect on excretion (dialysis clearance – 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.

ICD codes

Dosage Regimen

Take the drug orally once daily. The recommended dose for osteoarthritis is 60 mg once daily. The recommended dose for rheumatoid arthritis is 90 mg once daily. The recommended dose for ankylosing spondylitis is 90 mg once daily. For acute gouty arthritis, take 120 mg once daily, but only for the acute symptomatic period, not exceeding 8 days. For postoperative dental pain, take 120 mg once daily, limited to short-term use for a maximum of 3 days.

Select the lowest effective dose for the shortest duration necessary to control symptoms. Do not exceed the maximum daily dose of 120 mg. The total daily dose for chronic conditions like osteoarthritis or rheumatoid arthritis should not exceed 120 mg. For acute gouty arthritis, the maximum daily dose is 120 mg.

Take tablets with or without food. Swallow tablets whole with a sufficient amount of water. The 120 mg tablet is scored and can be split for easier swallowing, but not for dose division.

In patients with mild to moderate hepatic impairment (Child-Pugh score 5-9), do not exceed a daily dose of 60 mg. The drug is contraindicated in severe hepatic impairment (Child-Pugh score greater than 9).

Use with caution in patients with mild renal impairment (creatinine clearance 30-60 ml/min). The drug is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 ml/min). Monitor renal function in at-risk patients.

Use the lowest effective dose in elderly patients and monitor for adverse effects, particularly those related to fluid retention, renal function, and gastrointestinal bleeding. No initial dosage adjustment is generally required for elderly patients with normal renal and hepatic function.

Regularly reassess the need for continued treatment, especially for chronic conditions. Discontinue treatment if no therapeutic benefit is achieved.

Adverse Reactions

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

Nervous system frequently – headache, dizziness, weakness; sometimes – taste disturbance, drowsiness, sleep disorders, sensory disturbances, including paresthesia/hyperesthesia, anxiety, depression, concentration disorders; very rarely – hallucinations, confusion.

Sensory organs sometimes – blurred vision, conjunctivitis, tinnitus, vertigo.

Urinary system sometimes – proteinuria; very rarely – renal failure, usually reversible upon drug withdrawal.

Allergic reactions very rarely – anaphylactic/anaphylactoid reactions, including pronounced decrease in blood pressure and shock.

Cardiovascular system frequently – palpitations, increased blood pressure; sometimes – flushing, cerebrovascular accident, atrial fibrillation, congestive heart failure, nonspecific ECG changes, myocardial infarction; very rarely – hypertensive crisis.

Respiratory system sometimes – cough, dyspnea, epistaxis; very rarely – bronchospasm.

Dermatological reactions frequently – ecchymoses; sometimes – facial swelling, skin itching, rash; very rarely – urticaria, Stevens-Johnson syndrome, Lyell’s syndrome.

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

Musculoskeletal system sometimes – muscle cramps, arthralgia, myalgia.

Metabolism frequently – edema, fluid retention; sometimes – changes in appetite, weight gain.

Laboratory tests: frequently – 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.

Other frequently – flu-like syndrome; sometimes – chest pain.

Contraindications

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

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 bleeding disorders.

Severe heart failure (NYHA functional class II-IV).

Severe hepatic insufficiency (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 diseases, confirmed hyperkalemia.

Period after coronary artery bypass surgery; peripheral arterial disease, cerebrovascular disease, clinically significant coronary artery disease.

Persistent arterial hypertension with blood pressure values above 140/90 mm Hg.

Pregnancy, lactation (breastfeeding).

Children and adolescents under 16 years of age.

Hypersensitivity to etoricoxib.

Use in Pregnancy and Lactation

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

Use in Hepatic Impairment

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

Use in Renal Impairment

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

Pediatric Use

Contraindicated in children and adolescents under 16 years of age.

Geriatric Use

Use with caution in elderly persons.

Special Precautions

Use with caution in patients with a history of gastrointestinal ulcers, Helicobacter pylori infections, in elderly persons, in patients receiving NSAIDs for a long time, in patients with 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, during concomitant therapy with the following drugs: anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel), glucocorticosteroids (e.g., prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline), in chronic alcoholism.

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

During treatment, liver and kidney function parameters should be regularly monitored. If liver transaminase activity increases by 3 times or more relative to the upper limit of normal, treatment should be discontinued.

Given the increased risk of adverse effects with increasing duration of use, it is necessary to periodically assess the need for continued treatment and the possibility of dose reduction.

Should not be used concomitantly with other NSAIDs.

Effect on ability to drive vehicles and operate machinery

During treatment, caution must be exercised 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.

Drug Interactions

In patients receiving warfarin, administration of etoricoxib at a dose of 120 mg/day was accompanied by an increase in INR and prothrombin time by approximately 13%. In patients receiving warfarin or similar drugs, INR should be monitored during the initiation of therapy or when changing the etoricoxib dosage 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 concomitantly with ACE inhibitors. In patients with impaired renal function (e.g., dehydration or elderly patients), such a combination may worsen functional renal failure.

Etoricoxib can be used concomitantly with low-dose acetylsalicylic acid intended for the prevention of cardiovascular diseases. However, the concomitant administration of low-dose acetylsalicylic acid and etoricoxib may lead to an increased frequency of gastrointestinal ulceration and other complications compared to taking etoricoxib alone.

After reaching a steady state, the administration of etoricoxib at a dose of 120 mg once daily does not affect 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 during the administration of 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 a 28% increase in plasma methotrexate concentration (based on AUC) and a 13% decrease in its renal clearance under the influence of etoricoxib.

Administration of etoricoxib 120 mg with oral contraceptives containing 35 mcg of ethinyl estradiol and 0.5 to 1 mg of norethindrone for 21 days, either simultaneously or 12 hours apart, increases the steady-state AUC_0-24 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 may lead to an increased frequency of thromboembolism due to increased exposure to ethinyl estradiol.

Etoricoxib does not affect the steady-state AUC_0-24 or elimination of digoxin. However, Etoricoxib increases C_max (on average by 33%), which may be significant in cases of digoxin overdose.

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

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.