Arcoxia pills 120mg 7pcs

Composition

1 tablet contains:

Active ingredient:

Etoricoxib 120 mg.

Auxiliary substances:

Calcium hydrophosphate;

Microcrystalline cellulose;

Croscarmellose sodium, magnesium stearate.

Shell composition:

Opadray II green 39 K 11529;

Carnauba wax.

Composition of the film shell:

Lactose monohydrate;

Hypromellose;

Titanium dioxide;

Triacetin;

Aluminum varnish based on indigo carmine dye (E 132);

Iron oxide yellow dye (E 172).

Pharmacological action

Pharmaceutical group:

NSAIDs. Highly selective COX-2 inhibitor.

Pharmaceutical action:  

Arcoxia is an 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 decrease 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 COX-2 inhibition, without affecting COX-1 when used in a daily dose of up to 150 mg. Arcoxia® has no effect on the production of prostaglandins in the gastric mucosa and on the time of bleeding. In the conducted studies, there was no decrease in arachidonic acid levels and platelet aggregation caused by collagen.

Pharmacokinetics:  

Suction

After oral use, it is rapidly absorbed from the gastrointestinal tract. Oral bioavailability is about 100%. After taking the drug in adults on an empty stomach at a dose of 120 mg, Cmax is 3.6 mcg / ml, the time to reach Cmax is -1 h after use. Food intake does not significantly affect the severity and rate of absorption of etoricoxib when taken at a dose of 120 mg. At the same time, Cmax decreases by 36% and Tmax increases by 2 hours. Taking antacids does not affect the pharmacokinetics of the drug.

Distribution

The geometric mean value of AUC0-24 was 37.8 µg × h / ml. The pharmacokinetics of etoricoxib within therapeutic doses are linear. Binding to plasma proteins exceeds 92%. The Vd at steady state is about 120 liters. Etoricoxib penetrates the placental and blood-brain barrier.

Metabolism

It is intensively metabolized in the liver, with the participation of the cytochrome P450 isoenzyme (CYP) and the formation of 6-hydroxymethyl-etoricoxib. 5 metabolites of etoricoxib were detected, the main ones-6-hydroxymethyl-etoricoxib and its derivative-6-carboxy-acetyl-etoricoxib. The main metabolites do not affect COX-1 and are completely inactive or poorly active against COX-2.

Excretionthe elimination of etoricoxib occurs as metabolites by the kidneys. Less than 1% of the drug is excreted unchanged in the urine. A single intravenous use of a labeled radioactive drug containing etoricoxib at a dose of 25 mg to healthy volunteers demonstrated that 70% of the drug is excreted through the kidneys,20% – through the intestines, mainly in the form of metabolites. Less than 2% were found unchanged. The equilibrium state is reached after 7 days with a daily dose of 120 mg, with a cumulation coefficient of about 2, which corresponds to T1 / 2-about 22 hours. Plasma clearance is approximately 50 ml / min

. Pharmacokinetics In special clinical cases

, there are no pharmacokinetic differences between men and women.

Pharmacokinetics in the elderly (65 years and older)are comparable to those in the young, and there is no need to adjust the dose of the drug in the elderly.

Racial differences do not affect the pharmacokinetic parameters of etoricoxib.

In patients with minor hepatic impairment (5-6 points on the Child-Pugh scale), a single dose of etoricoxib at a dose of 60 mg / day. It was accompanied by a 16% increase in AUC compared to healthy individuals.

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 individuals who took the drug daily at the same dose.

Data from clinical and pharmacokinetic studies in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale) are not available.

The pharmacokinetic parameters of a single 120 mg dose of etoricoxib in patients with moderate to severe renal insufficiency 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 comparative pharmacokinetic studies reported comparable data in the application of etoricoxib adolescents (12 to 17 years) weighing 40-60 kg at a dose of 60 mg/day, in the same age group and with a body weight over 60 kg to 90 mg/day, in adults when receiving 90 mg/day.

Indications

Symptomatic treatment of the following diseases and conditions:

• Osteoarthritis.
• Rheumatoid arthritis.
• Ankylosing spondylitis.
• Pain and inflammatory symptoms associated with acute gouty arthritis.

Treatment of moderate to severe acute pain after dental surgery.

Use during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

The use of the drug may negatively affect female fertility and is not recommended for women planning pregnancy.

Contraindications

• Erosive and ulcerative changes in the gastric or duodenal mucosa, active gastrointestinal bleeding, cerebrovascular or other bleeding.
• Complete or incomplete combination of bronchial asthma, recurrent nasal or paranasal sinus polyposis, and intolerance to acetylsalicylic acid and other NSAIDs (including in the anamnesis).
• Inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute phase.
• Hemophilia and other blood clotting disorders.
• Severe heart failure (NYHA functional classes II-IV).
• Severe liver failure (more than 9 points on the Child-Pugh scale) or active liver disease.
• Severe renal insufficiency (creatinine clearance less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia.
• Period after coronary artery bypass grafting; peripheral artery diseases, cerebrovascular diseases, clinically pronounced coronary heart disease.
• Persistent BP values exceeding 140/90 mm Hg in patients with uncontrolled arterial hypertension.
• Pregnancy.
• The period of lactation (breastfeeding).
• Children under 16 years of age.
• Hypersensitivity to any component of the drug.

With caution: use the drug in the presence of anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, Helicobacter pylori infection, in the elderly, in patients who have used NSAIDs for a long time, often use alcohol, with severe somatic diseases, dyslipidemia/hyperlipidemia, with diabetes mellitus, arterial hypertension, edema and fluid retention, smoking, in patients with creatinine clearance less than 60 ml/min, with concomitant therapy with the following drugs: anticoagulants (for example antiplatelet agents (e. g., acetylsalicylic acid, clopidogrel), corticosteroids (e. g., prednisone), selective serotonin reuptake inhibitors (e. g., citalopram, fluoxetine, paroxetine, sertraline).

Side effects

The frequency of adverse reactions is presented in accordance with the following gradation:

• Very often (≥10%).
• Often (1-10%).
• Infrequently (0.1-1%).
• Rarely (0.01-0.1%).
• Very rare (

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

From the nervous system: often-headache, dizziness, weakness; infrequently-taste disorders, drowsiness, sleep disorders, sensitivity disorders, including paresthesia/hyperesthesia, anxiety, depression, concentration disorders; very rarely-hallucinations, confusion.

From the sensory organs: infrequently-blurred vision, conjunctivitis, tinnitus, vertigo.

From the urinary system: infrequently-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; infrequently-hot flashes, impaired cerebral circulation, atrial fibrillation, congestive heart failure, non-specific ECG changes; myocardial infarction; very rarely-hypertensive crisis.

From the respiratory system: infrequently-cough, shortness of breath, nosebleeds; very rarely – bronchospasm.

Dermatological reactions: often-ecchymosis; infrequently-facial swelling, pruritus, rash; very rarely-urticaria, Stevens-Johnson syndrome, Lyell’s syndrome.

Infectious complications: infrequently-gastroenteritis, upper respiratory tract infections, urinary tract infections.

Musculoskeletal disorders: infrequently-muscle cramps, arthralgia, myalgia.

From the side of metabolism: often-edema, fluid retention; infrequently-changes in appetite, increased body weight.

From laboratory tests: often-increased activity of hepatic transaminases; infrequently-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: often-flu-like syndrome; infrequently-chest pain.

Interaction

Pharmacodynamic interaction

In patients receiving warfarin, Arcoxia® 120 mg / day was associated with an approximately 13% increase in MHO and prothrombin time. In patients receiving warfarin or similar medications, MHO values should be monitored at the time of initiation of therapy or changes in the dosage regimen of Arcoxia®, especially in the first few days.

Non-selective NSAIDs and selective COX-2 inhibitors have been reported to weaken the antihypertensive effect of ACE inhibitors. This interaction should be taken into account when treating patients taking Arcoxia concomitantly with ACE inhibitors. In patients with impaired renal function (for example, with dehydration or in the elderly), such a combination may worsen the functional insufficiency of the kidneys.

Arcoxia® can be used simultaneously with acetylsalicylic acid in low doses intended for the prevention of cardiovascular diseases. However, concomitant use of low-dose acetylsalicylic acid and Arcoxia may lead to an increased incidence of gastrointestinal ulceration and other complications compared to Arcoxia alone. After reaching an equilibrium state, taking etoricoxib at a dose of 120 mg 1 time/day does not affect the antiplatelet activity of acetylsalicylic acid in low doses (81 mg/day). The drug does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases.

Cyclosporine and tacrolimus increase the risk of nephrotoxicity when taking Arcoxia®.

Pharmacokinetic interaction

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

Two studies examined the effects of Arcoxia 60,90, and 120 mg once daily for seven days in patients treated with 7.5 to 20 mg methotrexate once weekly for rheumatoid arthritis. Arcoxia® at doses of 60 and 90 mg did not affect the plasma concentration (AUC) and renal clearance of methotrexate. In one study, Arcoxia® at a dose of 120 mg did not affect the plasma concentration (AUC) and renal clearance of methotrexate. In another study, Arcoxia® 120 mg increased the concentration of methotrexate in plasma by 28% (AUC) and reduced the renal clearance of methotrexate by 13%. Concomitant use of Arcoxia® at doses above 90 mg / day and methotrexate should be monitored for possible toxic effects of methotrexate.

Oral contraceptives: taking Arcoxia® at a dose of 120 mg with oral contraceptives containing 35 mcg of ethinyl estradiol and 0.5 to 1 mg of norethindrone for 21 days, simultaneously or with a difference of 12 hours increases the steady-state AUC_{of 0-24} 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 Arcoxia. This fact can lead to an increase in the frequency of thromboembolism, due to increased exposure to ethinyl estradiol. There was no significant pharmacokinetic interaction with corticosteroids.

Etoricoxib does not affect steady-state AUC_0-24 or digoxin elimination. However, etoricoxib increases_cmax (by an average of 33%), which may be important in the development of digoxin overdose.

Concomitant use of Arcoxia® and rifampicin (a potent inducer of hepatic metabolism) resulted in a 65% reduction in the plasma AUC of etoricoxib. This interaction should be considered when Arcoxia is co-administered with rifampicin.

Antacids and ketoconazole (a potent CYP3A4 inhibitor) do not have a clinically significant effect on the pharmacokinetics of Arcoxia®.

How to take, course of use and dosage

The drug is taken orally, regardless of food intake, with a small amount of water.

In osteoarthritis, the recommended dose is 60 mg 1 time/day. The daily dose for osteoarthritis should not exceed 60 mg.

For rheumatoid arthritis and ankylosing spondylitis, the recommended dose is 90 mg once a day. The daily dose for rheumatoid arthritis and ankylosing spondylitis should not exceed 90 mg.

In acute gouty arthritis, the recommended dose in the acute period is 120 mg 1 time/day. The daily dose for acute gouty arthritis should not exceed 120 mg.

The duration of use of the drug in a dose of 120 mg is no more than 8 days. The minimum effective dose should be used in the shortest possible course.

The average therapeutic dose for pain syndrome is 60 mg once.

Acute pain after dental surgery: the recommended dose is 90 mg 1 time / day. In the treatment of acute pain, Arcoxia® should be used only in the acute symptomatic period, limited to a maximum of 8 days. The daily dose for pain relief after dental surgery should not exceed 90 mg.

In patients with hepatic insufficiency (5-9 points on the Child-Pugh scale), it is recommended not to exceed the daily dose of 60 mg.

Overdose

No overdose of Arcoxia® has been reported in clinical trials. In clinical trials, a single dose of Arcoxia® up to 500 mg or multiple doses up to 150 mg / day for 21 days did not cause significant toxic effects.

Symptoms: an overdose of the drug may cause undesirable effects from the gastrointestinal tract, cardiovascular system and kidneys.

Treatment: perform symptomatic therapy. Etoricoxib is not eliminated by hemodialysis, and elimination of the drug by peritoneal dialysis has not been studied.

Special instructions

Taking Arcoxia ® requires careful monitoring of blood pressure. All patients receiving the drug should be monitored for blood pressure during the first two weeks of treatment and periodically thereafter.

Liver and kidney function indicators should also be monitored regularly.

If the level of hepatic transaminases increases by 3 times or more relative to the ULN, the drug should be discontinued.

Taking into account the increasing risk of adverse effects with increasing duration of use, it is necessary to periodically assess the need to continue taking the drug and the possibility of reducing the dose.

Do not use the drug simultaneously with other NSAIDs.

The shell of Arcoxia® contains a small amount of lactose, which should be taken into account when prescribing the drug to patients with lactase deficiency.

Influence on the ability to drive motor vehicles and manage mechanisms

During the treatment period, care should be taken when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. Patients who have experienced episodes of dizziness, drowsiness, or weakness should refrain from activities that require concentration.

Form of production

Film-coated tablets.

Storage conditions

Store in a dry place, protected from light, at a temperature of 18-22 °C.

Shelf

life is 3 years.

Active ingredient

Etoricoxib

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor, Children over 16 years of age

Indications

Arthritis, Rheumatoid Arthritis, Gout, Osteoarthritis, Osteoarthritis