Expiration date: 09/2026

Form of issue and composition:

Tablets, film-coated green, biconvex, yablonovite form, with embossed ARCOXIA 60 on one side and embossed with the 200 on the other.

1 tablet contains: etoricoxib 60 mg

Auxiliary substances: calcium hydrophosphate, microcrystalline cellulose, sodium croscarmellose, magnesium stearate.

The composition of the shell: Opadry II Green 39K11520, Carnauba wax.

The composition of the film coating: lactose monohydrate, hypromellose, titanium dioxide, triacetin, aluminium lacquer based on indigokarmin dye (E132), iron oxide yellow dye (E172).

Tablets, film-coated white color, lenticular, yablonovite form, with embossed ARCOXIA 90 on one side and embossed with the 202 on the other.

1 tablet contains: etoricoxib 90 mg

Auxiliary substances: calcium hydrophosphate, microcrystalline cellulose, sodium croscarmellose, magnesium stearate.

The composition of the shell: Opadry II White 39K18305, Carnauba wax.

The composition of the film coating: lactose monohydrate, hypromellose, titanium dioxide, triacetin.

Film-coated tablets of light green color, biconvex, Apple-shaped, embossed ARCOXIA 120 on one side, and embossed 204 on the other.

1 tablet contains: etoricoxib 120 mg

Auxiliary substances: calcium hydrophosphate, microcrystalline cellulose, sodium croscarmellose, magnesium stearate.

The composition of the shell: Opadry II Green 39K11529, Carnauba wax.

The composition of the film coating: lactose monohydrate, hypromellose, titanium dioxide, triacetin, aluminium lacquer based on indigokarmin dye (E132), iron oxide yellow dye (E172).

Pharmacological action:

NPVS. Selective inhibitor COX-2, in therapeutic concentrations inhibits 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 inflammation, with no effect on platelet function and gastrointestinal mucosa.

Ethericoxib has a dose-dependent effect of inhibiting COX-2, without affecting COX-1 when used in a daily dose of 150 mg. Arcoxia® has no effect on the production of prostaglandins in the gastric mucosa and bleeding time. In these studies, there was no decrease in arachidonic acid and platelet aggregation caused by collagen.

Pharmacokinetics:

Suction

After ingestion is rapidly absorbed from the gastrointestinal tract. Bioavailability when administered is about 100%. After taking the drug adults on an empty stomach at a dose of 120 mg Cmax is 3.6 µg / ml, Tmax -1 h after administration.

Food intake has no significant effect on the severity and rate of absorption etoricoxib when taken in a dose of 120 mg. however, the values of Cmax reduced by 36% and Tmax increased by 2 hours.

Taking antacids does not affect the pharmacokinetics of the drug.

Distribution

The average geometric mean value of AUC0-24 was 37.8 µg x h/ml. etoricoxib Pharmacokinetics within the therapeutic dose is linear.

Plasma protein binding exceeds 92%. Vd at steady state is approximately 120 L. Etoricoxib crosses the placental and blood-brain barrier.

Metabolism

Extensively metabolized in the liver with participation of isoenzyme of cytochrome P450 (CYP) and the formation of 6-gidroksimetil-etoricoxib. Detected 5 metabolites etoricoxib, basic - 6-gidroksimetil-etoricoxib and its derivative 6-carboxy-acetyl-etoricoxib. The main metabolites do not affect COX-1 and completely inactive or inactive against COX-2.

Breeding

Etoricoxib excretion occurs in the form of metabolites via the kidneys. Less than 1% of the drug is excreted in the urine unchanged.

With a single on / in the introduction of healthy volunteers labeled radioactive drug containing etorikoksib dose of 25 mg, it was shown that 70% of the drug is excreted through the kidneys, 20% - through the intestine, mainly in the form of metabolites. Less than 2% is detected in an unmodified form.

The equilibrium state is achieved after 7 days at 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

Pharmacokinetic differences between men and women are absent.

Pharmacokinetics in the elderly (65 years and older) is comparable with 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 etoricoxib.

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

In patients with moderate hepatic impairment (7-9 points on the Chid-Pugh scale), taking the drug at a dose of 60 mg every other day, the value of AUC was the same as in healthy individuals, taking the drug daily at the same dose.

Data of clinical and pharmacokinetic studies in patients with severe hepatic impairment (more than 9 points on the Chid-Pugh scale) are absent.

The pharmacokinetic parameters of single use etoricoxib at a dose of 120 mg in patients with moderate and severe renal impairment and end-stage chronic renal failure (CRF), hemodialysis did not differ significantly from that of healthy individuals. Hemodialysis significantly influenced by the elimination (dialysis clearance approximately 50 ml/min).

Pharmacokinetic parameters etoricoxib in children under 12 years has not been studied. In comparative pharmacokinetic studies to obtain comparable data when using etoricoxib adolescents (12 to 17 years) weighing 40-60 kg dose of 60 mg/day, in the same age group with body weight over 60 kg - 90 mg/day, and adults when taking 90 mg/day.

Indications:

Symptomatic therapy of the following diseases and conditions:

• osteoarthrosis
  
• rheumatoid arthritis
  
• ankylosing spondylitis
  
• pain and inflammatory symptoms associated with acute gouty arthritis.
  

Dosage regimen:

The drug is taken orally, regardless of the meal, drinking a small amount of water.

In osteoarthritis, the recommended dose is 60 mg 1 time / day.

With rheumatoid arthritis and ankylosing spondylitis, the recommended dose is 90 mg 1 time/day.

In acute gouty arthritis, the recommended dose in the acute period is 120 mg 1 time / day.

The duration of use of the drug at a dose of 120 mg is not more than 8 days. You should use the minimum effective dose of the shortest possible course.

The average therapeutic dose for pain is once 60 mg.

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

Side effect:

The frequency of adverse reactions is presented in accordance with the following gradation: very often (gt10%), often (1-10%) sometimes (0.1-1%) rarely (0.01-0.1%) very rarely (t 0.01%), including individual cases.

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, ulcers of the mucous membrane of the stomach or duodenal ulcers, irritable bowel syndrome, esophagitis, ulcers of the mucous membrane of the mouth, vomiting very rare - gastrointestinal ulcers (bleeding or perforation), hepatitis.

From the nervous system: often - headache, dizziness, weakness sometimes - violation of taste, drowsiness, sleep disorders, sensitivity disorders, including paresthesia/hyperesthesia, anxiety, depression, concentration disorders are very rare - hallucinations, confusion.

From the senses: sometimes - blurred vision, conjunctivitis, tinnitus, vertigo.

From the urinary system: sometimes-proteinuria is very rare-renal failure, usually reversible when you cancel the drug.

Allergic reactions: very rarely-anaphylactic / anaphylactoid reactions, including severe decrease in blood PRESSURE and shock.

From the cardiovascular system: often-palpitation, increase in blood PRESSURE sometimes-tides, impaired cerebral circulation, atrial fibrillation, congestive heart failure, non - specific ECG changes myocardial infarction, very rarely-hypertensive crisis.

From the respiratory system: sometimes - cough, shortness of breath, nasal bleeding is very rare - bronchospasm.

Dermatological reactions: often - ecchymosis sometimes-swelling of the face, itching, rash very rare-urticaria, Stevens-Johnson syndrome, Lyell syndrome.

Infectious complications: sometimes-gastroenteritis, infections of the upper respiratory tract, urinary tract.

From the musculoskeletal system: sometimes-muscle cramps, arthralgia, myalgia.

From the metabolic: often - swelling, fluid retention and sometimes changes in appetite, increase of body weight.

From laboratory studies: often - increased activity of hepatic transaminases sometimes - increased nitrogen in the blood and urine, increased activity of CFC, reduced hematocrit, hemoglobin, hyperkalemia, leukopenia, thrombocytopenia, increased serum creatinine, increased uric acid rarely - increased sodium in the blood serum.

Other: often-flu-like syndrome sometimes-chest pain.

Contraindications:

• complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or sinuses and intolerance of acetylsalicylic acid and other NSAIDs (including history)
  
• erosive and ulcerative changes in the mucous membrane of the stomach or duodenum, active gastrointestinal bleeding, cerebrovascular or other bleeding
  
• inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the phase of exacerbation
  
• hemophilia and other blood clotting disorders
  
• severe heart failure (II-IV functional classes according to NYHA classification)
  
• severe hepatic insufficiency (more than 9 points on the child-Pugh scale) or active liver disease
  
• severe renal insufficiency (CC less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia
  
• the period after coronary artery bypass grafting peripheral artery disease, cerebrovascular disease, clinically expressed IBS
  
• persistent persistent blood pressure values exceeding 140/90 mm Hg. article with uncontrolled hypertension
  
• pregnancy,
  
• lactation (breastfeeding))
  
• children under 16 years of age
  
• hypersensitivity to any component of the drug.
  

With caution, the drug is used in the presence of anamnostic data on the development of ulcerative lesions of the gastrointestinal tract, heicbacter pyri infection, in elderly patients who have long-term use of NSAIDs, often consuming alcohol, in severe somatic diseases, dyslipidemia / hyperlipidemia, diabetes, hypertension, edema and fluid retention, Smoking, in patients with CC less than 60 ml/ min, with concomitant therapy with the following drugs: anticoagulants (eg, warfarin), antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), GCS (e.g., prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline).

Pregnancy and lactation:

The drug is contraindicated in pregnancy and lactation.

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

Special instruction:

Taking the drug Arcoxia® requires careful monitoring of blood PRESSURE. All patients in the appointment of the drug should monitor blood pressure DURING the first two weeks of treatment and periodically thereafter.

Liver and kidney function should also be monitored regularly.

In the case of an increase in liver transaminases 3 times or more relative to VGN drug should be canceled.

Given the increasing risk of adverse effects with an increase in the duration of the reception, 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 in conjunction with other NSAIDs.

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

Influence on the ability to drive vehicles and management mechanisms

During treatment, caution should be exercised when driving and engaging in other potentially hazardous activities that require high concentration and speed of psychomotor reactions. Patients who have had episodes of dizziness, drowsiness, or weakness should refrain from activities that require concentration.

Overdose:

In clinical trials of arcoxia ® overdose was not reported. In clinical trials, a single dose of Arcoxia® 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. 

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

Treatment: symptomatic therapy. Etoricoxib does not appear in hemodialysis, elimination of the drug in peritoneal dialysis has not been studied.

Drug interaction:

Pharmacodynamic interaction

In patients receiving warfarin, the dose of Arcoxia ® 120 mg / day was accompanied by an increase of about 13% of the international normalized ratio (MHO) and prothrombin time. In patients receiving warfarin or similar medicines, MHO should be monitored during 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 are reported to weaken the anti-hypertensive effect of ACE inhibitors. This interaction should be taken into account when treating patients receiving Arcoxia® at the same time with ACE inhibitors. In patients with impaired renal function (eg, dehydration or in old age), such a combination can exacerbate functional renal failure.

Arcoxia® can be used simultaneously with acetylsalicylic acid in low doses, intended for the prevention of cardiovascular diseases. However, the simultaneous administration of acetylsalicylic acid in low doses and Arcoxia® can lead to an increase in the frequency of ulcerative lesions of the gastrointestinal tract and other complications compared to taking one Arcoxia® . After reaching the equilibrium state of the reception etoricoxib at a dose of 120 mg 1 time/day has no effect on the antiplatelet activity of acetylsalicylic acid in low doses (81 mg/day). The drug does not replace the preventive action of acetylsalicylic acid in cardiovascular diseases. Cyclosporine and tacrolimus increase the risk of nephrotoxicity in patients receiving Arcoxia®.

Pharmacokinetic interaction

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

Two studies examined the effects of Arcoxia® at a dose of 60, 90 and 120 mg 1 time / day for seven days in patients receiving once a week methotrexate at a dose of 7.5 to 20 mg for rheumatoid arthritis. Arcoxia® at a dose of 60 and 90 mg had no effect on plasma concentrations (AUC) and renal clearance of methotrexate. In one study, arcoxia® at a dose of 120 mg had no effect on plasma concentrations (AUC) and renal clearance of methotrexate. In another study, Arcoxia® the dose of 120 mg increased the concentration of methotrexate in plasma by 28% (for AUC) and reduced renal clearance of methotrexate by 13%. At the same time the appointment Arkoksia® doses above 90 mg / day and methotrexate should be monitored for the possible occurrence of toxic effects of methotrexate.

Oral contraceptives: taking Arcoxia® 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, simultaneously or with a difference of 12 hours increases the stationary AUC0-24 of ethinyl estradiol by 50-60%. However, the concentration of norethisterone usually does not increase to a clinically significant degree. This increase in the concentration of ethinyl estradiol should be taken into account when choosing the appropriate oral contraceptive for simultaneous use with Arcoxia®. Such a fact can lead to an increase in the frequency of thromboembolism, due to an increase in the exposure of ethinyl estradiol. No significant pharmacokinetic interaction with GCS was found.

Etoricoxib not affect the AUC0-24 at steady state or the elimination of digoxin. However, etoricoxib increases Cmax (an average of 33%), which may be important in the development of overdose digoxin.

Simultaneous reception of Arcoxia® and rifampicin (potent inducer of hepatic metabolism) leads to a decrease of 65% etoricoxib AUC in plasma. This interaction should be taken into account when concomitant administration of Arcoxia® with rifampicin.

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

Storage terms and conditions:

The drug should be stored out of reach of children at a temperature not higher than 30°C. shelf life - 2 years, do not use after expiration date.