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Arcoxia

Arcoxia
Arcoxia is essential for the symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and pain and inflammation associated with acute gouty arthritis.

Brand: Etoricoxib

Availability: In Stock
Average Delivery Time: 9 Days
Exp. Date: September 2023
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Arcoxia 120 mg
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Product description

Pharmacodynamics of Arcoxia

Buy Arcoxia tablets in Canada

Mechanism of Action

Etoricoxib, an oral drug, is a selective inhibitor of cyclooxygenase-2 (COX-2) when used within the clinical dose range.

In clinical pharmacological studies, the drug dose-dependently inhibited COX-2 without inhibiting COX-1 when used in doses up to 150 mg per day. Etoricoxib does not inhibit the synthesis of gastric prostaglandins and does not affect platelet function. Cyclooxygenase is responsible for the formation of prostaglandins. Two isoforms have been identified - COX-1 and COX-2. COX-2 is an isoform of an enzyme that is induced by anti-inflammatory impulses and is regarded as the main factor responsible for the synthesis of prostanoid mediators of pain, inflammation and fever. COX-2 is also involved in the processes of ovulation, implantation and closure of the ductus arteriosus, regulation of renal and central nervous system function (induction of fever, pain sensation, cognitive function); also, can take part in the healing process of ulcers. COX-2 has been identified in tissue around gastric ulcers in humans, but its significance for ulcer healing has not been established.

Pharmacokinetics

Absorption. Etoricoxib is well absorbed when taken orally. The absolute bioavailability is about 100%. After taking 120 mg once a day until an equilibrium is reached, the maximum plasma concentration (geometric mean Cmax = 3.6 μg / ml) is observed approximately 1 hour (Tmax) after fasting adults. The geometric mean value AUC0-24 is 37.8 μg * h / ml. Within the clinical dose range, the pharmacokinetics of Etoricoxib are linear.

There was no clinically significant effect on absorption with Etoricoxib 120 mg with a meal (high fat meal). The absorption rate changed, which was characterized by a 36% decrease in Cmax and an increase in Tmax by 2 hours. Such data are not considered clinically relevant. In clinical studies, Etoricoxib has been used with or without food.

Distribution. Etoricoxib is approximately 92% bound to human plasma proteins at concentrations from 0.05 to 5 μg / ml. In humans, the volume of distribution at equilibrium is about 120 liters.

Etoricoxib crosses the placental barrier in rats and rabbits, as well as the blood-brain barrier in rats.

Metabolism. Etoricoxib is actively metabolized, less than 1% of the dose is excreted in the urine as the parent drug. The main metabolic pathway is the formation of the 6'-hydroxymethyl derivative by catalyzing by CYP enzymes. CYP3A4 promotes the metabolism of etoricoxib in vivo. studies In vitro indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 also can catalyze the main metabolic pathway, but their quantitative characteristics have not been studied in vivo.

Five metabolites have been identified in humans. The main metabolite is 6'-carboxylic acid, a derivative of etoricoxib, formed by further oxidation of the 6'-hydroxymethyl derivative. These major metabolites show no measurable activity, or are only weak COX-2 inhibitors. None of these metabolites inhibit COX-1.

Excretion. After a single intravenous injection of radioisotope-labeled etoricoxib at a dose of 25 mg to healthy volunteers, 70% of radioactivity was excreted in the urine and 20% in the feces, mainly in the form of metabolites. Less than 2% is excreted as an unchanged drug.

Elimination of etoricoxib occurs primarily through metabolism, followed by renal excretion. Equilibrium concentrations of etoricoxib are achieved over seven days with 120 mg once daily, with an accumulation rate of about 2, which corresponds to an elimination half-life of about 22 hours. Plasma clearance after intravenous administration of 25 mg is about 50 ml / min.

Separate groups of patients

Elderly age. Pharmacokinetics in the elderly (65 years and older) and younger patients are similar.

Floor. The pharmacokinetics of etoricoxib are similar in men and women.

Liver dysfunction. In patients with mild liver dysfunction (5-6 points on the Child-Pugh scale), when using etoricoxib at a dose of 60 mg once a day, the average AUC is approximately 16% higher than in healthy individuals with the same dosage of the drug. In patients with moderate liver dysfunction (7-9 points on the Child-Pugh scale) when using etoricoxib at a dose of 60 mg once every two days, the average AUC was similar to that in healthy individuals who took the drug at a dose of 60 mg once per day every day; the use of etoricoxib at a dose of 30 mg has not been studied in this group of patients. There are no clinical or pharmacokinetic data on patients with severe liver dysfunction (≥10 points on the Child-Pugh scale).

Impaired renal function. The pharmacokinetics of a single dose of Etoricoxib 120 mg in patients with moderate to severe renal impairment, as well as in patients with end-stage kidney disease undergoing hemodialysis, did not differ significantly from that in healthy patients. Hemodialysis has little effect on drug elimination (dialysis clearance is about 50 ml / min).

Children. The pharmacokinetics of etoricoxib in children (under 12 years of age) has not been studied.

In a pharmacokinetic study (N = 16), conducted with the participation of adolescents (aged 12 to 17 years), the pharmacokinetics in adolescents weighing 40 to 60 kg when taking etoricoxib at a dose of 60 mg once a day and in adolescents weighing body over 60 kg when taking etoricoxib at a dose of 90 mg once a day was similar to the pharmacokinetics in adults when taking etoricoxib at a dose of 90 mg once a day. The safety and effectiveness of etoricoxib in children have not been established.

Preclinical Safety Data of Arcoxia

Packaging of Arcoxia tablets

In preclinical studies, etoricoxib has been shown to be free of genotoxicity. Etoricoxib was non-carcinogenic in mice. Rats developed hepatocellular and thyroid follicular cell adenomas at doses more than 2 times the daily human dose [90 mg], based on systemic exposure, with daily administration for about 2 years. Hepatocellular adenomas and adenomas of the follicular cells of the thyroid gland in rats are a consequence of a mechanism specific for this animal species associated with the induction of CYP enzymes. In humans, Etoricoxib does not induce the hepatic CYP3A enzyme.

In rats, the gastrointestinal toxicity of etoricoxib increased with increasing dose and exposure time. In a 14-week toxicity study, etoricoxib resulted in gastrointestinal ulcers at exposures exceeding those in humans at therapeutic doses. The 53- and 106-week toxicity studies also observed the occurrence of gastrointestinal ulcers at exposures comparable to those in humans at therapeutic doses. In dogs, pathological changes in the kidneys and gastrointestinal tract were observed at high drug exposures.

Etoricoxib was non-teratogenic in reproductive toxicity studies conducted in rats at a dose of 15 mg / kg / day (approximately 1.5 times the daily human dose [90 mg] based on systemic exposure). In rabbits, an increase in the incidence of cardiovascular malformation associated with treatment was observed at exposure levels below the clinical exposure of the daily human dose (90 mg). However, there were no fetal skeletal malformations associated with treatment. In rats and rabbits, a dose-dependent increase in post-implantation losses was observed at exposures exceeding the exposure in humans by 1.5 times or more.

Etoricoxib passes into the milk of lactating rats at concentrations approximately 2 times higher than those in blood plasma. There was a decrease in body weight in the offspring when lactating females were injected with etoricoxib during lactation.

Indications for Use Arcoxia tablets

For the relief of symptoms in osteoarthritis (OA), rheumatoid arthritis (PA) and ankylosing spondylitis, and for relieving pain and signs of inflammation in acute gouty arthritis.

For the short-term treatment of moderate pain due to dental surgery.

The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of all individual risks to the patient.

Method of administration and dosage

Arcoxia tablet plate

The drug ARKOKSIA is taken orally. The drug can be taken with or without food. The onset of effect occurs more quickly if the drug is taken before meals, which should be taken into account if a quick relief of symptoms is required.

Since the risk of cardiovascular complications with the use of etoricoxib may increase with increasing dose and duration of use, the minimum effective dose should be used for the shortest possible period of time. The need for symptom relief and response to treatment should be periodically re-evaluated, especially in patients with osteoarthritis.

Osteoarthritis (OA)

The maximum recommended dose is 60 mg once a day. If there is no improvement in the effect, other possible treatments should be considered.

Rheumatoid arthritis (RA)

The recommended dose is 60 mg or 90 mg once a day. The minimum effective daily dose is 60 mg once a day. In some patients, a dose of 90 mg once a day may enhance the therapeutic effect.

Ankylosing spondylitis (AS)

The recommended dose is 60 mg or 90 mg once a day. The minimum effective daily dose is 60 mg once a day. In some patients, a dose of 90 mg once a day may enhance the therapeutic effect.

Conditions accompanied by acute pain.

For conditions with acute pain, etoricoxib should be used only during the acute period.

Acute gouty arthritis

The recommended dose is 120 mg once a day. In clinical trials for the treatment of acute gouty arthritis, etoricoxib was used for 8 days. Postoperative pain in dentistry The recommended dose is 90 mg once daily for a maximum of 3 days. For some patients, additional postoperative pain relief may be necessary.

Doses in excess of those recommended for each indication either have no additional efficacy or have not been studied.

Therefore:

the dose for OA should not exceed 60 mg per day;

the dose for RA and ankylosing spondylitis should not exceed 90 mg per day;

the dose for acute gout should not exceed 120 mg per day, and the treatment is carried out for a maximum of 8 days;

the dose for acute pain after dental surgery should not exceed 90 mg per day, and the treatment should be carried out for a maximum of 3 days.

Elderly patients

There is no need for dose adjustment for elderly patients. As with other drugs in elderly patients, caution should be exercised.

Liver dysfunction

Regardless of the indication for the use of the drug, in patients with mild liver dysfunctions (5-6 points on the Child-Pugh scale), a dose of 60 mg once a day should not be exceeded. In patients with moderate liver dysfunction (7-9 points on the Child-Pugh scale), regardless of the indication for the use of the drug, do not exceed the dose of 60 mg 1 time in 2 days; you can also consider using the drug at a dose of 30 mg 1 time per day.

Clinical experience with the drug is limited, in particular in patients with moderate liver dysfunction, therefore, it is recommended to exercise caution. There is no clinical experience of using the drug in patients with severely impaired liver function (≥10 points on the Child-Pugh scale); therefore, the drug is contraindicated for use in these patients.

Renal dysfunction

There is no need for dose adjustment in patients with creatinine clearance ≥30 ml / min. The use of etoricoxib is contraindicated in patients with creatinine clearance <30 ml / min.


Contraindications

  • Hypersensitivity to the active substance or any other component of the drug.
  • Active peptic ulcer or gastrointestinal bleeding.
  • Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioedema, urticaria or other allergic reactions after using acetylsalicylic acid or NSAIDs, including cyclooxygenase-2 (COX-2) inhibitors.
  • During pregnancy and breastfeeding.
  • Severe liver dysfunction (serum albumin <25 g / L or ≥10 points on the Child-Pugh scale).
  • Established renal creatinine clearance <30 ml / min.
  • Children and adolescents under the age of 16.
  • Inflammatory bowel disease.
  • Congestive heart failure (NYHA II-IV).
  • Patients with arterial hypertension, whose blood pressure values ​​are constantly above 140/90 mm Hg. Art. and are not sufficiently monitored.
  • Identified ischemic heart disease, peripheral arterial disease and / or cardiovascular disease.

Overdose

In clinical trials, the use of etoricoxib in single doses up to 500 mg or repeated administration in doses up to 150 mg / day for 21 days was not accompanied by significant toxicity. Acute overdose of etoricoxib has been reported, although in most cases no adverse reactions have been reported. The most commonly observed adverse reactions were consistent with the safety profile of etoricoxib (eg, gastrointestinal reactions, cardiorenal reactions).

In the event of an overdose, it is advisable to apply the usual supportive measures, such as removing the unabsorbed drug from the gastrointestinal tract, to conduct clinical observation and, if necessary, carry out supportive therapy.

Etoricoxib is not dialyzed by hemodialysis; it is not known whether the drug is dialyzed by peritoneal dialysis.

Precautions

Effect on the gastrointestinal tract

Complications from the gastrointestinal tract (perforation, ulcers or bleeding), sometimes fatal, have been reported in patients who used etoricoxib.

It is recommended to use NSAIDs with caution in the treatment of patients with a high risk of developing complications from the gastrointestinal tract (patients who simultaneously use any other NSAIDs or acetylsalicylic acid, patients with a history of gastrointestinal diseases such as ulcers or gastrointestinal bleeding).

There is an additional risk of side reactions from the gastrointestinal tract (gastrointestinal ulcers or other complications from the gastrointestinal tract) with the simultaneous use of etoricoxib and acetylsalicylic acid (even in low doses). In long-term clinical studies, there was no pronounced difference regarding safety for the gastrointestinal tract when using a selective COX-2 inhibitor + acetylsalicylic acid and NSAIDs + acetylsalicylic acid.

Effects on the cardiovascular system

Clinical studies indicate that the use of selective COX-2 inhibitors may be associated with the risk of thrombotic complications (especially myocardial infarction and stroke), when compared with placebo and some NSAIDs. Since the risk of cardiovascular complications can increase with increasing dose and duration of Etoricoxib use, the drug should be used in the lowest effective doses for the shortest possible period of time.

The need for symptom relief and response to treatment should be periodically re-evaluated, especially in patients with osteoarthritis.

Patients with severe risk factors for cardiovascular complications (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) should be treated with etoricoxib only after careful consideration of this possibility.

Selective COX-2 inhibitors are not a substitute for aspirin for the prevention of cardiovascular disease, since they do not affect platelets. Therefore, you should not stop using antiplatelet drugs.

Effects on the kidneys

Renal prostaglandins may play a compensatory role in maintaining renal perfusion. Therefore, when renal perfusion is weakened, taking etoricoxib can cause a decrease in the formation of prostaglandins and, as a result, a decrease in renal blood flow and a weakening of renal function. The risk of such a reaction is highest in patients with pre-existing significant impairment of renal function, uncompensated heart failure, or cirrhosis. Consideration should be given to monitoring renal function in these patients.

Fluid retention, edema and arterial hypertension.

As with other drugs that inhibit prostaglandin synthesis, some patients taking etoricoxib have experienced fluid retention, edema, and hypertension. All NSAIDs, including etoricoxib, can lead to the onset or recurrence of congestive heart failure. The drug is prescribed with caution to patients who have a history of heart failure, impaired left ventricular function or arterial hypertension, as well as to patients with edema arising from any other reason. If there are clinical signs of deterioration in such patients, appropriate measures should be taken, including the withdrawal of etoricoxib.

The use of etoricoxib, especially in high doses, may be associated with more frequent and severe hypertension than the use of some other NSAIDs and selective COX-2 inhibitors. Therefore, hypertension should be monitored before starting treatment with etoricoxib, and special attention should be paid to controlling blood pressure during treatment with etoricoxib. With a significant increase in pressure, alternative treatment should be prescribed. Blood pressure (BP) should be monitored for 2 weeks after starting treatment, and then periodically. If blood pressure rises significantly, alternative treatment should be considered.

Effects on the liver

Approximately 1% of patients treated with etoricoxib at doses of 30 mg, 60 mg and 90 mg per day in clinical studies of up to one year, there was an increase in the activity of alanine aminotransferase (ALT) and / or aspartate aminotransferase (ACT) (approximately three and more times compared to the upper limit of the norm).

All patients with symptoms and / or signs of liver dysfunction should be monitored, as well as patients with abnormal liver function tests. If there are signs of liver dysfunction or persistent pathological changes in liver function indicators (three times higher than the upper limit of the norm), etoricoxib should be canceled.

General instructions

If, during treatment, the patient experiences deterioration in the function of any of the organ systems mentioned above, appropriate measures should be taken and the question of discontinuation of etoricoxib should be considered. Appropriate medical supervision should be carried out when using etoricoxib in elderly patients and in patients with impaired renal, hepatic or cardiac function. Caution should be exercised when initiating treatment with etoricoxib in patients with dehydration. Rehydration is recommended before starting Etoricoxib.


The occurrence of serious skin reactions, in some cases with a fatal outcome, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have very rarely been reported with the use of NSAIDs and some selective COX-2 inhibitors during post-marketing surveillance. The risk of such reactions is highest at the beginning of therapy, with the onset of manifestations, in most cases, during the first month of treatment. Serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported in patients using etoricoxib. Some selective COX-2 inhibitors may increase the risk of skin reactions in patients with a history of allergic reactions to a drug. Etoricoxib should be discontinued at the first manifestations of a skin rash, mucosal lesions, or other signs of hypersensitivity.

Etoricoxib can suppress the manifestations of fever or other signs of infection.

Etoricoxib and warfarin or other oral anticoagulants should be used with caution.

The use of etoricoxib, like other drugs that inhibit COX and prostaglandin synthesis, is not recommended for women planning a pregnancy.

Arcoxia contains lactose. Patients with rare congenital diseases such as galactose intolerance, Lapp lactase deficiency and glucose-galactose malabsorption should not use this drug.

Use in children

The use of etoricoxib in children and adolescents under the age of 16 is contraindicated.

Application during pregnancy and lactation

Pregnancy. The use of etoricoxib, like other COX-2 inhibiting drugs, is not recommended for women planning a pregnancy.

There are no clinical data on the use of etoricoxib during pregnancy. Reproductive toxicity has been observed in animal studies. The potential risk in women during pregnancy is unknown. The use of etoricoxib during the last trimester of pregnancy, as well as other drugs that inhibit the synthesis of prostaglandins, can lead to the absence of uterine contractions and premature closure of the Botallo duct. Etoricoxib is contraindicated during pregnancy. If pregnancy occurs during treatment, etoricoxib should be discontinued.

Lactation. It is not known whether etoricoxib passes into breast milk in women. It is known that in rats the drug is excreted in milk. Women who are using etoricoxib should not breastfeed.

Effects on the ability to drive vehicles and other mechanisms

No studies have been conducted on the effect of etoricoxib on the ability to drive vehicles and other mechanisms. Patients who develop dizziness, vertigo or drowsiness during the use of etoricoxib should not drive vehicles and machinery.

Interaction with other medicinal products

Pharmacodynamic interactions

Oral anticoagulants. In patients whose condition has been stabilized by chronic use of warfarin, taking etoricoxib at a dose of 120 mg per day is accompanied by an increase of approximately 13% in the prothrombin time of the International Normalized Ratio (INR). Therefore, in patients receiving oral anticoagulants, the prothrombin time INR should be checked frequently, especially during the first days of taking etoricoxib or when its dose is changed.

Diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists. NSAIDs can weaken the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg, patients with dehydration or elderly patients with impaired renal function), concomitant use of an ACE inhibitor or angiotensin II antagonist and COX inhibiting drugs may result in subsequent deterioration of renal function, including possible acute renal failure , which is usually reversible. It should be remembered that such interactions may occur in patients who use etoricoxib concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, this combination should be prescribed with caution, especially in elderly patients. Adequate hydration should be carried out and monitoring of renal function should be considered at the beginning of combination treatment, as well as at regular intervals thereafter.

Acetylsalicylic acid. In a study involving healthy volunteers, under steady state conditions, the use of etoricoxib at a dose of 120 mg once a day did not affect the antiplatelet activity of acetylsalicylic acid (81 mg once a day). Etoricoxib can be administered concomitantly with acetylsalicylic acid, which is used in doses to prevent cardiovascular complications (low doses). However, the simultaneous use of low doses of acetylsalicylic acid and etoricoxib may lead to an increased incidence of gastrointestinal ulcers or other complications compared with etoricoxib monotherapy. The simultaneous use of etoricoxib with acetylsalicylic acid in doses exceeding those established for the prevention of cardiovascular complications, as well as with other NSAIDs, is not recommended.

Cyclosporine and tacrolimus. Although the interaction of etoricoxib with these drugs has not been studied, the simultaneous use of NSAIDs with cyclosporins and tacrolimus may enhance the nephrotoxic effect of the latter. Renal function should be monitored while the use of etoricoxib with any of these drugs.

Pharmacokinetic interactions

Effect of etoricoxib on the pharmacokinetics of otherdrugs

lithium. NSAIDs decrease renal excretion of lithium, thereby increasing plasma lithium levels. If necessary, blood lithium levels are monitored frequently and the dose of lithium is adjusted during the period of concomitant use of these drugs, as well as when NSAIDs are discontinued.

Methotrexate. Two studies examined the effects of etoricoxib at doses of 60 mg, 90 mg, and 120 mg once daily for seven days in patients receiving methotrexate once a week at a dose of 7.5 mg to 20 mg for rheumatoid arthritis. Etoricoxib at a dose of 60 mg and 90 mg had no effect on plasma concentrations and renal clearance of methotrexate. In one study, Etoricoxib at a dose of 120 mg did not affect methotrexate, but in another study, the concentration of methotrexate in blood plasma increased by 28%, and the renal clearance of methotrexate was decreased by 13%. With the simultaneous use of etoricoxib and methotrexate, appropriate monitoring should be carried out regarding the toxicity of methotrexate.

Oral contraceptives. Etoricoxib at a dose of 60 mg, when used simultaneously with oral contraceptives containing 35 μg of ethinylestradiol and 0.5-1 mg of norethindrone, for 21 days led to an increase in ethinyl estradiol AUC0-24 by 37%. Etoricoxib at a dose of 120 mg when used with the above-mentioned oral contraceptives simultaneously or with an interval of 12 hours increased the AUC0-24 value of ethinyl estradiol in equilibrium by 50-60%. This increase in ethinyl estradiol concentration should be kept in mind when choosing an oral contraceptive to be used concomitantly with etoricoxib. Increased exposure to ethinyl estradiol may increase the incidence of adverse reactions associated with the use of oral contraceptives (for example, venous thromboembolism in women at risk).

Hormone replacement therapy. Taking 120 mg of etoricoxib with hormone replacement drugs, including conjugated estrogens (Premarin ™ 0.625 mg), for 28 days increases the average AUC0-24 in the equilibrium state of unconjugated estrone (by 41%), equilin (by 76%) and 17-β- estradiol (by 22%). The effect of doses of etoricoxib recommended for long-term use (30, 60 and 90 mg) has not been studied.

Etoricoxib at a dose of 120 mg reduced the exposure (AUC0-24) of the estrogenic components of Premarin by less than half as compared with Premarin alone; the dose of the latter was increased from 0.625 to 1.25 mg. The clinical significance of these increases is unknown, and higher doses of Premarin in combination with etoricoxib have not been studied. Such increases in estrogen concentration should be taken into account when choosing a hormonal drug for use in the postmenopausal period with the simultaneous use of etoricoxib, since an increase in estrogen exposure may increase the risk of adverse reactions during hormone replacement therapy.

Prednisone / prednisolone. In drug interaction studies, etoricoxib did not have a clinically significant effect on the pharmacokinetics of prednisone / prednisolone.

Digoxin. When using etoricoxib at a dose of 120 mg 1 time per day for 10 days by healthy volunteers, there was no effect on the AUC0-24 index in equilibrium and on the excretion of digoxin by the kidneys. There was an increase in the Cmax of digoxin (approximately 33%). This increase is usually not significant for most patients. However, patients at high risk for the toxicity of digoxin should be monitored for concomitant use of etoricoxib and digoxin.

The effect of etoricoxib on drugs metabolized by sulfotransferases.

Etoricoxib is an inhibitor of human sulfotransferase activity, in particular SULT1E1, and can also increase serum ethinyl estradiol concentrations. Поскольку в настоящее время мало данных о влиянии различных сульфотрансфераз, а клиническая значимость для применения многих препаратов еще изучается, целесообразно с осторожностью назначать эторикоксиб одновременно с другими препаратами, которые метаболизируются, главным образом, человеческими сульфотрансферазами (например, пероральный сальбутамол и миноксидил).

The effect of etoricoxib on drugs metabolized by isoenzymes of the CYP system.

Based on data from in vitro studies, inhibition of cytochromes P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 is not expected by etoricoxib. In a study in healthy volunteers, daily administration of 120 mg etoricoxib had no effect on hepatic CYP3A4 activity as determined by the erythromycin breath test.

Effects of other drugs on the pharmacokinetics of Etoricoxib

The main metabolic pathway of Etoricoxib depends on enzymes of the CYP system. CYP3A4 promotes the metabolism of etoricoxib in vivo. In vitro studies indicate that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 can also catalyze the main metabolic pathway, but their quantitative characteristics have not been studied in vivo.

Ketoconazole. Ketoconazole is a potent CYP3A4 inhibitor. When used by healthy volunteers at doses of 400 mg 1 time per day for 11 days, ketoconazole did not have a clinically significant effect on the pharmacokinetics of a single dose of etoricoxib 60 mg (increase in AUC by 43%).

Rifampicin. The simultaneous use of etoricoxib and rifampicin (a powerful inducer of CYP enzymes) led to a decrease in plasma concentrations of etoricoxib by 65%. This interaction can be accompanied by a relapse of symptoms if etoricoxib is used concomitantly with rifampicin. While these data may indicate the need for dose escalation, it is not recommended to use Etoricoxib in doses that exceed those indicated for each indication, since the combination of rifampicin and Etoricoxib at such doses has not been studied.

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


Side effects 

Thesafety of etoricoxib has been evaluated in clinical trials involving 9295 participants, including 5774 patients with OA, RA and chronic low back pain (approximately 600 patients with OA or RA received treatment for a year or longer).

In clinical studies, the profile of adverse reactions was the same in patients with OA or RA who used etoricoxib for 1 year or longer.

In a clinical study, patients with acute gouty arthritis received etoricoxib 120 mg daily for 8 days. The adverse reaction profile in this study was broadly the same as in the pooled studies of OA, RA, and chronic low back pain.

In the cardiovascular safety program, which included data from 3 actively controlled studies, 17,412 patients with OA or RA were treated with etoricoxib (60 mg or 90 mg) for an average of 18 months.

In clinical studies of acute postoperative pain associated with dental surgery, in which 612 patients were treated with ARKOKSIA (90 mg or 120 mg), the profile of adverse reactions was generally similar to that in the combined studies of OA, RA and chronic low back pain. ...

The following adverse reactions have been reported with a greater frequency with the drug than with placebo in clinical trials in patients with OA, RA, chronic low back pain, or AS who used Etoricoxib at a dose of 30 mg, 60 mg, or 90 mg for 12 weeks , in studies of the MEDAL program, in short studies of acute pain, and during the post-marketing period.

Frequency is defined as: very often (? 1/10), often (? 1/100 to <1/10), infrequently (? 1/1000 to <1/100), rarely (? 1/10 000 up to <1/1000), very rarely (<1/10000), unknown (cannot be determined from the available data).

Infections and invasions: often - alveolar osteitis; infrequently - gastroenteritis, upper respiratory tract infections, urinary tract infections.

On the part of the blood and lymphatic system: infrequently - anemia (mainly as a result of gastrointestinal bleeding), leukopenia, thrombocytopenia.

From the side of the immune system: very rarely - hypersensitivity reactions, including angioedema, anaphylactic / anaphylactoid reactions, including shock.

From the side of metabolism and nutrition: often - edema / fluid retention; infrequently - decreased or increased appetite, increased body weight.

From the side of the psyche: infrequently - anxiety, depression, deterioration of mental activity; very rarely - confusion, hallucinations; unknown - anxiety.

From the nervous system: often - dizziness, headache; infrequently - dysgeusia, insomnia, paresthesia / hypesthesia, drowsiness.

From the side of the organs of vision: infrequently - blurred vision, conjunctivitis.

On the part of the hearing organs and the labyrinth: infrequently - ringing in the ears, vertigo.

From the side of the heart: often - palpitation; infrequently - atrial fibrillation, congestive heart failure, nonspecific ECG changes, angina pectoris, myocardial infarction *; unknown - tachycardia, arrhythmia.

From the vascular system: often - hypertension; infrequently - hot flushes, stroke *, transient ischemic disorders of cerebral circulation; very rarely - hypertensive crisis.

* Based on an analysis of long-term placebo- and actively-controlled clinical trials, there is an increased risk of serious arterial thrombosis, including myocardial infarction and stroke, with the use of selective COX-2 inhibitors. Based on the available data, it is unlikely that the absolute risk of such events exceeds 1% per year (infrequently).

From the respiratory tract, chest and mediastinal organs: infrequently - cough, dyspnea, epistaxis; very rarely - bronchospasm.

From the gastrointestinal tract: often - gastrointestinal disorders (such as abdominal pain, flatulence, heartburn), diarrhea, dyspepsia, a feeling of discomfort in the epigastric region, nausea; infrequently - bloating, acid reflux, changes in the nature of intestinal motility, constipation, dry mouth, gastroduodenal ulcers, irritable bowel syndrome, esophagitis, oral ulcer, vomiting, gastritis; very rarely - peptic ulcers, including gastrointestinal perforation and bleeding (more often in the elderly); unknown - pancreatitis.

From the side of the hepatobiliary tract: often - an increase in the level of ACT, an increase in the level of ALT; very rarely - hepatitis; unknown - jaundice.

On the part of the skin and subcutaneous tissue: often - ecchymosis; infrequently - facial swelling, itching, rash; rarely, erythema; very rarely - urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis; unknown - persistent drug erythema.

From the musculoskeletal system, connective tissue and bones: infrequently - muscle spasms / cramps, musculoskeletal pain / stiffness.

From the side of the kidneys and urinary tract: infrequently - proteinuria, increased serum creatinine; very rarely - impaired renal function, including renal failure.

General condition and disorders associated with the method of drug administration: often - asthenia / weakness, flu-like symptoms; infrequently - chest pain.

Surveys: infrequently - increased blood urea nitrogen, increased creatine phosphokinase, hyperkalemia, increased uric acid levels; rarely - a decrease in the level of sodium in the blood.

The following serious adverse reactions have been reported with the use of NSAIDs, therefore, the possibility of their occurrence with the use of etoricoxib cannot be ruled out: nephrotoxicity, including nephritis and nephrotic syndrome; hepatotoxicity, including liver failure.