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 • What is Etoricoxib?

 • Dosing:

 • Uses:

 • The mechanism of action

 • Pharmacodynamics and pharmacokinetics

 • Side effects:

 • Special instructions:

 • Interaction:

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What is Etoricoxib?

Etoricoxib is a so-called non-steroidal anti-inflammatory drug (NSAID). Specifically: It belongs to a special group of anti-inflammatory drugs, cyclooxygenase inhibitors (COX inhibitors). They inhibit the enzyme cyclooxygenase, which occurs in the body in (at least) two sub-forms, COX-1 and called COX-2. Etoricoxib is a COX-2 inhibitor, that blocks the cyclooxygenase-2, which is formed in tissue injuries and inflammation. The enzyme is responsible for the synthesis of prostaglandins. Those are growth hormones that enhance inflammatory responses or maintained and also the occurrence of pain and involved. By inhibiting cyclooxygenase-2 Etoricoxib may thus pain, fever and inflammation counteract. But on COX-1, the active ingredient has no influence. This enzyme form is also used in healthy tissue before and is, inter alia, for the functioning of various organs, such as the blood flow to the kidney or to protect the gastric mucosa against the aggressive gastric acid, responsible.

Composition:

The form of the preparation is round tablets, covered with an outer shell. Their active ingredient is Etoricoxib. In addition, the composition of the drug includes the following substances: carmellose, cellulose, magnesium stearate and calcium hydrogen phosphate. They promote better absorption of the drug. The drug is available in a dosage of 60 mg, 90 mg and 120 mg.

Dosage form:

film coated tablets

Contraindications:
Hypersensitivity to components Etoricoxib, bronchial asthma, recurrent polyposis of the nasal mucosa or paranasal sinuses, intolerance to ASA and other NSAIDs (including in the anamnesis), erosive and ulcerous changes in the mucous membrane of the stomach or duodenum, active bleeding in the digestive tract , cerebrovascular or other bleeding, inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in the phase of exacerbation, hemophilia and other disorders of blood clotting, CHF (II-IV according to the NYHA classification), severe hepatic impairment (more than 9 on the Child-Piuga scale) or active liver disease expressed by CRF (KC less than 30 ml / min), progressive kidney disease, hyperkalemia, post-coronary artery bypass grafting, peripheral arterial disease, cerebrovascular disease, clinically expressed CAD, AD more than 140/90 mm Hg. Art. with uncontrolled arterial hypertension, pregnancy, lactation period, children’s age (under 16 years).
For LF containing lactose (in addition): deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Dosing:

Inside, regardless of meals, squeezed a small amount of water.
With osteoarthritis – 60 mg Etoricoxib once a day; with rheumatoid arthritis and ankylosing spondylitis – 90 mg once a day; with acute gouty arthritis – 120 mg once a day (no more than 8 days).
A minimum effective dose should be used with the minimum possible short course.
The average therapeutic dose of Etoricoxib with pain syndrome is 60 mg / day.

Uses:

The medicine is used mainly to alleviate the pain syndrome in osteochondrosis, arthrosis and other diseases of the bone system. The following indications for the use of etoricoxib can be singled out:

Pain in the joints

degenerative changes in cartilage of joints (osteoarthritis);
joint pain associated with autoimmune pathologies (eg, in rheumatoid arthritis and systemic lupus erythematosus);
inflammation of the joints, caused by gout;
toothache

The mechanism of action

The mechanism of action of this agent is related to the ability of Etoricoxib to selectively inhibit the activity of the enzyme cyclooxygenase-2. This, in turn, leads to a decrease in the production of prostaglandins – substances that contribute to the development of the inflammatory process. In contrast to the old-generation NSAIDs, Etoricoxib is a more gentle remedy and does not aggressively attack the gastric mucosa. And also the new drug does not dilute the blood.

The pharmacological properties of Etoricoxib are also related to its ability to improve blood supply in small vessels and to reduce the synthesis of kinins and leukotrienes. This also helps to relieve inflammation. In addition, the drug suppresses the production of bradykinin, as a result of which the pain is attacked and the body temperature decreases. Such properties make it possible to use this remedy for the pathology of the joints.

The description of the drug says that the drug is well absorbed. 1 hour after the patient took the pill, the concentration of Etoricoxib in the body reaches a peak. Anti-inflammatory agent is not recommended for eating, since this reduces its effectiveness and slows down absorption. Less than 1 day later, half the dose of the substance goes with urine and calves. If you use the drug constantly and regularly, then the uniform concentration of the drug in the body will be maintained.

The treatment of the drug is not affected by liver, kidney and advanced age. Pregnant women need to remember that this medication can penetrate the placenta.

Pharmacodynamics and pharmacokinetics

Etoricoxib inhibits the activity of COX-2 by the selective mechanism, prevents biosynthesis of mediators of inflammation of prostaglandins. There is a decrease in the severity of the symptoms of the inflammatory process. In this case, the substance does not affect the functional activity of platelets and does not damage the mucosa of the digestive tract. The degree of oppression of cyclooxygenase-2 is dose-dependent. The agent does not affect COX-1 (if the daily dosage does not exceed 150 mg).

This substance significantly reduces the degree of vascular permeability, improves blood microcirculation and the intensity of production of prostaglandins, kinins and leukotrienes. There is a blockage in the energy supply of the inflammatory process.

Anesthesia is carried out by reducing the intensity of inflammation, reducing the amount of bradykinin produced during the process. Due to the ability of the drug to reduce the excitability of the center of heat regulation in the diencephalon, it has antipyretic effect.

After oral administration of the agent, the substance is quickly absorbed in the digestive tract and penetrates into the blood. The drug has almost 100% bioavailability. After taking 120 mg of Etoricoxib, the maximum concentration in the blood is observed after 60 minutes. The intake of food reduces the maximum concentration by 35%, and the time it takes to reach 2 hours.

The degree of binding to plasma proteins is 92%. The drug overcomes blood-brain and placental barriers. Metabolism occurs with the participation of microsomal enzymes of the liver, forms inactive metabolites: 6-hydroxymethyl-Etoricoxib, 6-carboxy-acetyl-Etoricoxib and others.

Daily intake of the drug at a dosage of 120 mg leads to the establishment of an equilibrium concentration during the week. The half-life is about 22 hours. The drug is withdrawn with the help of kidneys and with fecal masses, in the form of metabolites and in unchanged form (less than 2%).

It was established that the age, renal and hepatic insufficiency slightly change the pharmacokinetic parameters of the substance. Studies have not been conducted in patients younger than 12 years of age and with severe hepatic impairment.

Side effects:

Frequency: very often – more than 10%, often – 1-10%, infrequently – 0.1-1%, rarely – 0.01-0.1%, very rarely – less than 0.01%, including individual cases.
On the part of the digestive system: often – epigastric pain, nausea, diarrhea, dyspepsia, flatulence; infrequent abdominal distention, eructation, increased peristalsis of the gastrointestinal tract, constipation, dryness of the oral mucosa, gastritis, stomach ulcer or duodenal ulcer, irritable bowel syndrome, esophagitis, ulcers of the oral cavity, vomiting, gastroenteritis; very rarely – other gastrointestinal ulcers (with bleeding or perforation), hepatitis.
From the nervous system: often – headache, dizziness, weakness; infrequent – a taste disorder, drowsiness, sleep disturbances, impaired sensitivity (including paresthesia / hyperesthesia), anxiety, depression, impaired concentration; very rarely – hallucinations, confusion.
From the sense organs: infrequently – indistinctness of visual perception, conjunctivitis, tinnitus, vertigo.
From the urinary system: infrequently – proteinuria, urinary tract infection; very rarely – renal failure (reversible with the cancellation of Etoricoxib).
Allergic reactions to the components of Etoricoxib: very rarely – anaphylactic / anaphylactoid reactions, (including a marked decrease in blood pressure, shock).
From the CCC: often – palpitations, increased blood pressure; infrequently – , cerebrovascular accident, atrial fibrillation, development of heart failure, ECG changes, myocardial infarction; very rarely – hypertensive crisis.
On the part of the respiratory system: infrequently – cough, shortness of breath, epistaxis, upper respiratory tract infections; very rarely – bronchospasm.
From the skin: often – ecchymosis; infrequently – edema of the face, itching, rash; very rarely – hives, Stevens-Johnson syndrome, Lyell’s syndrome.
From the musculoskeletal system: infrequently – muscle cramps, arthralgia, myalgia.
Other: often – flu-like syndrome, swelling, fluid retention; infrequently – pain in the chest, changes in appetite, weight gain.
Laboratory indicators: often – increased activity of transaminases; infrequently – increased urea nitrogen in blood and urine, increased activity of CKK, decreased hematocrit, decreased Hb, hyperkalemia, leukopenia, thrombocytopenia, hypercreatininaemia, hyperuricemia; rarely – hypernatremia.

Special instructions:

Admission Etoricoxib requires careful monitoring of blood pressure during the first 2 weeks of treatment and periodically thereafter.
It is necessary to regularly monitor the indicators of liver and kidney function.
If the activity of transaminases is increased 3 times or more, Etoricoxib must be canceled.
It should be periodically assessed the need to continue taking the drug and the possibility of reducing its dose.
Do not use simultaneously with other NSAIDs.
The use of the drug may adversely affect female fertility; It is not recommended for women planning a pregnancy.
During the treatment with Etoricoxib tablets, it is necessary to refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Interaction:

With the simultaneous use of tablets Etoricoxib (120 mg per day) with warfarin, there was an increase in INR by 13%. It is necessary to monitor this indicator at the beginning of treatment or when changing the dose (especially in the first few days).
May attenuate the hypotensive effect of ACE inhibitors. If renal function is impaired (with dehydration or in old age) a combination with ACE inhibitors can aggravate functional kidney failure.
It can increase the concentration of Li + in the plasma.
Simultaneous reception with low doses of ASA can lead to an increased incidence of ulcerative gastrointestinal lesions and other complications.
At achievement Css (at reception of 120 mg once a day) does not render influence on antiaggregant activity ASK in low doses (81 mg / sut). The drug does not replace the antiplatelet effect of ASA.
Cyclosporine and tacrolimus increase the risk of developing nephrotoxicity.
With the simultaneous administration of Etoricoxib (more than 90 mg per day) and methotrexate, there may be an increase in the side effects of the latter.
Receiving Etoricoxib in a dose of 120 mg with combined oral contraceptives increases the AUC of ethinyl estradiol by 50-60% – the risk of developing thromboembolic complications.
Increases Cmax of digoxin by 33%, which can lead to digitalis intoxication.
Simultaneous reception with rifampicin leads to a decrease in AUC Etoricoxib by 65%.

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