Etorikoksib Velpharm (Tablets) Instructions for Use

Marketing Authorization Holder

Elzapharm, LLC (Russia)

Manufactured By

Velpharm, LLC (Russia)

Or

Velpharm-M, LLC (Russia)

ATC Code

M01AH05 (Etoricoxib)

Active Substance

Etoricoxib (Rec.INN registered by WHO)

Dosage Forms

	Etoricoxib Velpharm	Film-coated tablets 30 mg: 7, 10, 14, 20, 21, 28, 30, 40, 42 or 56 pcs.
		Film-coated tablets 60 mg: 7, 10, 14, 20, 21, 28, 30, 40, 42 or 56 pcs.
		Film-coated tablets 90 mg: 7, 10, 14, 20, 21, 28, 30, 40, 42 or 56 pcs.
		Film-coated tablets 120 mg: 7, 10, 14, 20, 21, 28, 30, 40, 42 or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex; on the cross-section – a core of white or white with a yellowish tint.

Excipients: calcium hydrogen phosphate anhydrous, microcrystalline cellulose 102, croscarmellose sodium (primellose), magnesium stearate.

Shell composition dry mix for film coating containing hypromellose, titanium dioxide, macrogol or hypromellose (hydroxypropyl methylcellulose), titanium dioxide, macrogol 6000 (polyethylene glycol 6000, polyethylene oxide 6000).

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

Film-coated tablets white or almost white, round, biconvex; on the cross-section – a core of white or white with a yellowish tint.

Excipients: calcium hydrogen phosphate anhydrous, microcrystalline cellulose 102, croscarmellose sodium (primellose), magnesium stearate.

Shell composition dry mix for film coating containing hypromellose, titanium dioxide, macrogol or hypromellose (hydroxypropyl methylcellulose), titanium dioxide, macrogol 6000 (polyethylene glycol 6000, polyethylene oxide 6000).

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

Film-coated tablets white or almost white, round, biconvex; on the cross-section – a core of white or white with a yellowish tint.

Excipients: calcium hydrogen phosphate anhydrous, microcrystalline cellulose 102, croscarmellose sodium (primellose), magnesium stearate.

Shell composition dry mix for film coating containing hypromellose, titanium dioxide, macrogol or hypromellose (hydroxypropyl methylcellulose), titanium dioxide, macrogol 6000 (polyethylene glycol 6000, polyethylene oxide 6000).

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

Film-coated tablets white or almost white, round, biconvex; on the cross-section – a core of white or white with a yellowish tint.

Excipients: calcium hydrogen phosphate anhydrous, microcrystalline cellulose 102, croscarmellose sodium (primellose), magnesium stearate.

Shell composition dry mix for film coating containing hypromellose, titanium dioxide, macrogol or hypromellose (hydroxypropyl methylcellulose), titanium dioxide, macrogol 6000 (polyethylene glycol 6000, polyethylene oxide 6000).

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

Clinical-Pharmacological Group

NSAID. Highly selective COX-2 inhibitor

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs; non-steroidal anti-inflammatory and antirheumatic drugs; coxibs

Pharmacological Action

NSAID. 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 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 h 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 h. 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.

It is 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 detected, 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 inactive or have low activity against COX-2.

It is excreted by the kidneys in the form of 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 in the form of 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 ratio of about 2, which corresponds to a T_1/2 of about 22 h. 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 symptoms of inflammation associated with acute gouty arthritis; short-term treatment of pain associated with dental surgery.

ICD codes

Dosage Regimen

Take the tablet orally once daily, with or without food.

For osteoarthritis, the recommended dose is 30 mg or 60 mg once daily. The maximum daily dose for this indication is 60 mg.

For rheumatoid arthritis, the recommended dose is 60 mg or 90 mg once daily. The maximum daily dose for this indication is 90 mg.

For ankylosing spondylitis, the recommended dose is 60 mg or 90 mg once daily. The maximum daily dose for this indication is 90 mg.

For acute gouty arthritis, the recommended dose is 120 mg once daily. Use this dose only for the acute symptomatic period, with a maximum treatment duration of 8 days.

For acute pain following dental surgery, the recommended dose is 90 mg once daily. Limit use to a maximum of 3 days.

Use the lowest effective dose for the shortest duration necessary to control symptoms.

In patients with mild to moderate hepatic impairment (Child-Pugh score 5-9), do not exceed a daily dose of 60 mg.

For patients with moderate hepatic impairment (Child-Pugh score 7-9), consider an initial dose of 60 mg every other day.

Contraindicated in patients with severe hepatic impairment (Child-Pugh score greater than 9).

Contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min). Use with caution in patients with creatinine clearance less than 60 mL/min.

Contraindicated in children and adolescents under 16 years of age.

Monitor blood pressure within two weeks of initiation and periodically thereafter during therapy.

Adverse Reactions

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

From the nervous system often – headache, dizziness, weakness; sometimes – taste disturbance, drowsiness, sleep disorders, sensory 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 upon drug withdrawal.

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

From the cardiovascular system often – palpitations, increased blood pressure; sometimes – hot flashes, cerebrovascular accident, atrial fibrillation, congestive heart failure, nonspecific ECG changes, myocardial infarction; very rarely – hypertensive crisis.

From the respiratory system sometimes – cough, shortness of breath, nosebleed; very rarely – bronchospasm.

Dermatological reactions often – ecchymosis; 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.

From the musculoskeletal system sometimes – muscle cramps, arthralgia, myalgia.

From metabolism often – edema, fluid retention; sometimes – changes in appetite, weight gain.

From 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.

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

Contraindications

Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal 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 disease, 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 infection, in elderly persons, in patients receiving long-term NSAID therapy, 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 the treatment period, 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 when starting therapy or changing the 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 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 acetylsalicylic acid in low doses 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 an increase in plasma methotrexate concentration by 28% (based on AUC) and a decrease in its renal clearance by 13% under the influence of etoricoxib.

Administration of etoricoxib at a dose of 120 mg with oral contraceptives containing 35 mcg of ethinyl estradiol and from 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 extent. 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 the elimination of digoxin. However, Etoricoxib increases C_max (on average by 33%), which may be significant in the event 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 etoricoxib is co-administered with rifampicin.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.