Flexidron 90 Abbott reduces symptoms of osteoarthritis, rheumatoid arthritis (3 blisters x 10 tablets)

Pharmacology

Pharmacological group: Anti -inflammatory and rheumatoid drugs, non -steroids, Coxib groups.

ATC code: M01AH05.

Mechanism of action

Etoricoxib is a strong, very selective, very selective, very selective, very selective, very selective, very selective, very selective when taken in clinical dosage.

In all clinical studies, Etoricoxib has the effect of inhibiting COX-2 depending on the dose of use without inhibiting COX-1 when using the dose up to 150 mg daily. Etoricoxib does not inhibit prostaglandin synthesis in the stomach and does not affect platelet function.

Cycloxygenase is responsible for creating prostaglandin. 2 isomers have been identified, COX-1 and COX-2 have been identified. Cox-2 is the isomer of the enzyme that has been shown to be created by inflammatory stimuli and is mainly responsible for the synthesis of the intermediate substances of the prostanoid causing pain, inflammation and fever. Cox-2 also participates in the process of ovulation, transplant and arteriosclerosis, regulating kidney function and central nervous system function (fever, pain awareness and cognitive function). It can also play a role in healing ulcers. Cox-2 has been determined in tissue around the stomach ulcers in humans but has not identified its association with healing ulcers.

Dynamic pharmacokinetics

absorption

Etoricoxib is well absorbed by oral. The oral average is nearly 100%oral. After taking the dose of 120 mg once a day until it reaches a stable state, the peak concentration in plasma (average cmax nucleus = 3.6 mcg/ml) is recorded nearly 1 hour (TMAX) after the adult object takes the medication when hungry. The average AUC 0 - 24 hours is 37.8 mcg. Mobile pharmacokinetics of linear Etoricoxib with clinical dose range.

Food (high -fat meal) does not affect the absorption level after taking the Etoricoxib 120 mg. The absorption rate is affected, resulting in a reduction of 36% CMAX and an additional 2 -hour increase. These data are not considered clinical significance. In clinical trials, Etoricoxib is used not related to food.

distribution

About 92% of the dose of Etoricoxib attached to protein in human plasma when used within the concentration of 0.05 - 5 mcg/ml. The distribution voltage is about 120 liters in sustainable state (VDSS). Etoricoxib passes through the placenta in rats and rabbits, and goes through the blood-flabby barrier in the rat.

transformation

Etoricoxib is strongly metabolized with

Elimination

After an intravenous injection of a single -dose of 25 mg Etoricoxib has radioactive attachment to healthy objects, 70% of radioactive active ingredients are found in urine and 20% in feces, mostly in the form of metabolites. Under 2% of radioactive active ingredients found in non -metabolic drugs.

Most Etoricoxib is excreted mainly through metabolism, then through the excretion in the kidneys. Etoricoxib's concentration in a sustainable state is achieved within 7 days of treatment when taking a dose of 120 mg once a day, with an accumulated ratio of nearly 2, corresponding to the accumulated waste time of about 22 hours. It is estimated that the removal of drugs in plasma after venous doses of 25 mg is approximately 50 ml/min.

The characteristics of patients (Special population)

Elderly: Pharmacokinetics in the elderly (≥65 years old) are similar to young people.

Sex: Etoricoxib's pharmacokinetics in men and women are the same.

Hepatic failure:

In patients with mild liver failure (Child-Pugh 5-6 score), Etoricoxib dose 60 mg once a day with an average AUC higher than 16% higher than healthy objects used in the same dose mode. Patients with average liver failure (Child-Pugh 7-9 score) using Etoricoxib dose 60 mg once a day, the average AUC is similar to that in healthy objects using Etoricoxib 60 mg once a day; The dose of Etoricoxib 30 mg once a day has not been studied in this population. There is no clinical document or pharmacokinetics when taking drugs in patients with severe liver failure (Child-Pugh score ≥ 10).

kidney failure:

Child patients:

In a dynamic study (n = 16) conducted on teenagers (12-17 years old), pharmacokinetic pharmacokinetics among teenagers weighing 40 - 60 kg using Etoricoxib 60 mg once a day and in adolescents weighing> 60 kg of Etoricoxib 90 mg once a day, it is like pharmacokinetics in adults using Etoricoxib 90 mg once daily. Etoricoxib's safety and effectiveness has not been established in children's patients.

Elderly

No dose adjustment in the elderly. Should be cautious when used in the elderly.

Hepatic failure

In patients with mild liver failure (Child-Pugh 5-6 score), the dose should not exceed 60 mg once a day. In patients with average liver failure (Child-Pugh 7-9 score), do not exceed the dose of 30 mg once a day.

Be careful when using special use in average liver failure because clinical experience is limited. There is no clinical document when taking drugs in patients with severe liver failure (Child-Pugh≥ 10), so contraindicated in these patients.

kidney failure

No dose adjustment in patients with renal impairment with creatinine clearance coefficient ≥ 30 ml/min. Contraindicated to use Etoricoxib in patients with creatinine clearance ratio

Children

contraindicated Etoricoxib in children and teenagers under 16 years old.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

What to do when overdose?

symptoms:

There is no significant toxicity occurs when using single -dose Etoricoxib and several times to 150 mg/day, 21 days in clinical trials. There have been reports on the use of acute Etoricoxib, but there is no report on adverse effects that occur in most cases of overdose. The most common adverse effects recorded in accordance with the safety characteristics of Etoricoxib (such as the effects on the gastrointestinal tract, on the kidney blood vessels).

Management:

In case of overdose, reasonable is that it is advisable to apply commonly used support measures, such as removing substances that have not been absorbed from the digestive tract, clinical monitoring and supportive treatment, if necessary.

cannot eliminate Etoricoxib by hemolysis; It is not known whether it is possible to use peritoneal fertilizer to remove Etoricoxib.

In case of emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double doses to compensate for missed dose.

Be cautious when using

need to be very careful when taking the drug for patients in the following cases:

Effects on gastrointestinal

Patients treated with Etoricoxib have appeared complications of gastrointestinal ulcers on [perforation, ulcer or bleeding], some can lead to death.

Be cautious when treating with patients at risk of developing the highest gastrointestinal complications with NSAID; Elderly, patients use simultaneously with any NSAID or other acetylsalicylic acid or patients with a history of gastrointestinal disease, such as ulcers and gastrointestinal bleeding.

Increased risk of side effects on the gastrointestinal tract (ulcers or other gastrointestinal complications) when used simultaneously Etoricoxib with acetylsalicylic acid (even at low doses). The relative difference in stomach safety - The intestines between the diaphragm of the selective inhibitors of COX -2 + Acetylsalicylic acid compared to NSAIDS + Acetylsalicylic Acetylsalicy acid has not been fully evaluated in long -term clinical trials.

Heart effect

Heart thrombosis

Non -steroid anti -inflammatory drugs (NSAIDs), non -aspirin, use systemic sugar, may increase the risk of cardiovascular thrombosis, including myocardial infarction and stroke, which can lead to death. This risk can appear early in the first few weeks of taking the drug and can increase over time. The risk of cardiovascular thrombosis is recorded mainly at high doses.

Doctors need to periodically evaluate the appearance of cardiovascular events, even if the patient has no previous cardiovascular symptoms.

Patients need to be warned about the symptoms of serious cardiovascular events and need to see a doctor as soon as these symptoms appear.

To minimize the risk of adverse events, Flexidron 90 is needed at the lowest daily daily doses in the shortest possible time.

should only use Etoricoxib after careful consideration in patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipidemia, diabetes, smoking).

Cox-2 selective inhibitors are not acetylsalicylic acid replacement substances in cardiovascular disease because it does not work on platelets.

Therefore, do not stop platelets.

Effects on the kidneys

Prostaglandin produced in the kidneys may have a role in compensating for the maintenance of kidney perfusion. Therefore, under the conditions of reducing kidney perfusion, the use of Etoricoxib can reduce the establishment of prostaglandin and reduce blood flow to secondary kidneys and thus reduce kidney function. Patients with the highest risk of this reaction are those who have reduced kidney function, people with loss of heart failure, or people with cirrhosis significantly. Should consider monitoring kidney function in such patients.

Keeping water, edema and hypertension

As other drugs have the effect of inhibiting prostaglandin synthesis, water retention, edema and hypertension are also recorded in several patients using Etoricoxib. All nonsteroidal anti -inflammatory drugs (NSAIDs) including Etoricoxib may be related to a new onset or recurrence of congestive heart failure (see "unwanted effect"). Precautions should be used in patients with a history of heart failure, left ventricular dysfunction, or hypertension, and patients who have had the situation of edema due to any previous cause. Appropriate measures should be taken, including stopping using Etoricoxib if there is clinical evidence of the deterioration of the disease gradually in these patients.

Etoricoxib can combine with more frequent and worse hypertension, compared to some NSAIDs and other COX-2 selective inhibitors, especially when taking high doses. Therefore, hypertension should be checked before treatment with Etoricoxib and pay special attention to blood pressure examination during treatment with Etoricoxib. Blood pressure should be monitored within two weeks after the beginning of treatment and periodically. If blood pressure increases significantly, other treatments must be considered.

Hepatic failure

About 1% of patients in clinical trials using Etoricoxib 30, 60, and 90 mg daily lasting up to 1 year have increased alanin aminotransferase (ALT) and/or Aspartat Aminotransferase (AST) (approximately ≥ 3 times the maximum normal level).

Need to monitor any patient with symptoms and/or signs of suggesting liver dysfunction, or in people who have abnormal liver function tests. Etoricoxib must be discontinued if the signs of liver failure appear, or if the liver function tests continuously (3 times the maximum maximum level).

General

If patients have worse disease progression at treatment, they must take appropriate measures, including therapeutic stops. The appropriate medical monitoring should be maintained when using Etoricoxib in the elderly and in patients with renal, liver or heart dysfunction.

Be careful when starting Etoricoxib therapy in patients with dehydration. Water compensation should be rehydrated before starting to use Etoricoxib.

In after-sales monitoring, it is very rare for serious skin reactions, which some reactions can be fatal, including flaky dermatitis, Stevens-Johnson syndrome and poisoned epidermal necrosis when using NSAIDs and some COX-2 inhibitors. It seems that the patient has the highest risk of these reactions early during treatment: Most cases have a reaction on the first month of treatment. There have been reports of severe sensitive reactions (such as anaphylactic reactions) in patients using Etoricoxib. A few selective inhibitors of COX-2 are often in combination with increased risk of skin reactions in patients with a history of allergies. Etoricoxib therapy should be discontinued at the beginning of the skin rash, mucosal lesions or any other signs of hypersensitivity reactions.

Etoricoxib can cover the symptoms of fever, which is a sign of infection.

Should be cautious when using Etoricoxib simultaneously with warfarin or oral anticoagulant.

It is not recommended to use Etoricoxib with any drug known to inhibit the synthesis of cyclooxygenase/prostaglandin in women who are trying to conceive.

The effect of the drug on the ability to drive and operate machinery

Patients who have been dizzy, nausea or drowsiness while using Etoricoxib should avoid driving or operating the machine.

Use drugs for women during pregnancy and lactation

using drugs for pregnant women: There is no clinical data on pregnant women. Animal studies have shown toxicity on fertility. The risk is unknown. As other drugs have the effect of inhibiting prostaglandin, Etoricoxib can cause a lower muscle contraction and early closing of the ductus arteriosus in the last months of pregnancy. Contraindicated Etoricoxib with pregnant women. Etoricoxib must be stopped if pregnant during treatment.

Using medication for nursing women: It is unclear whether Etoricoxib will excrete in human milk or not. Etoricoxib is excreted in mother mouse milk. Do not breastfeed if using Etoricoxib.

Drug interaction

Pharmacological interaction

Oral anticoagulants

In stable objects with chronic warfarin therapy, the Etoricoxib regimen 120 mg per day is usually associated with an increase of about 13% of the international standard chemical ratio in prothrombin (INR) time. Should closely monitor the values ​​of Inr Prothrombin, especially in the first few days in patients taking oral anticoagulants or dose changes with Etoricoxib.

Diuretics, Angiotensin (ACE) and Angiotensin II antagonistic medications

NSAIDS can reduce the effectiveness of diuretics and other hypertension drugs. In some patients with reduced renal function (such as patients with loss of circulatory fluid or elderly patients with impaired renal function) The simultaneous use of ACE inhibitors or Angiotensin II antagonists can make the kidney function worse, including severe acute renal failure, these effects can often recover. This interaction should be paid to using Etoricoxib at the same time as these drugs. Therefore, be careful when combining drugs, especially in the elderly. Patients should be fully rehydrated and pay attention to renal function after starting treatment simultaneously, and periodically later.

acetylsalicylic acid

In a healthy person's study, in a sustainable state, Etoricoxib 120 mg once a day does not affect the platelet resistance of acetylsalicylic acidic acid (81 mg once a day). Etoricoxib can be used at the same time as low -dose acetylsalicylic acid to prevent cardiovascular disease. However, using low -dose acetylsalicylic acids simultaneously with Etoricoxib increases the rate of gastrointestinal ulcer or other complications compared to the use of monon therapy Etoricoxib.

ciclosporin and tacrolimus

Although this interaction has not been studied with Etoricoxib, simultaneous use of ciclosporin or tacrolimus with any NSAID can increase the toxicity of the kidneys of Ciclosporin or Tacrolimus. Kidney function should be monitored when combining Etoricoxib with one of these drugs.

pharmacokinetic interaction

Etoricoxib's effect on the pharmacokinetics of other drugs as follows:

lithium

NSAIDS reduces lithium excretion through the kidneys and thus increases lithium concentration in plasma. If necessary, closely monitor the blood lithium concentration and adjust the lithium dose when used in combination or stop NSAIDs.

methotrexate

There are 2 research tests of Etoricoxib effects of 60, 90 or 120 mg once a day in 7 days in patients taking methotrexat dose of 7.5 - 20 mg once a week to treat rheumatoid arthritis. Etoricoxib dose 60 and 90 mg does not affect methotrexate concentration in plasma or medication clearance. In a trial, Etoricoxib 120 mg does not affect the concentration of methotrexate in plasma (evaluated through AUC) or the drug clearance through the kidneys, in the remaining test, Etoricoxib 120 mg increases methotrexate levels in plasma to 28% and reduces the clearance of methotrexate through the kidney by up to 13%. Methotrexate -related toxicity monitoring should be monitored when used simultaneously Etoricoxib and Methotrexate.

contraceptives

Etoricoxib 60 mg is used at the same time as a contraceptive pill containing 35 mcg ethinyl estradiol and 0.5 - 1 mg norethindrone in 21 days has increased the AUC0-24 hours of Ethinyl Estradiol in a sustainable state of up to 37%. The AUC0-24 hours of Ethinyl Estradiol in a sustainable state has increased by 50 - 60% when Etoricoxib 120 mg is used at the same time or 12 hours from this type of oral contraceptive. It is necessary to increase the increase in Ethinyl estradiol level when choosing a contraceptive tablet with Etoricoxib. Increasing exposure to Ethinyl estradiol may increase the proportion of adverse effects that are often associated with using contraceptives (such as venous thrombosis in risky women).

Hormone replacement therapy

Etoricoxib 120 mg is used with hormone replacement therapy containing conjugated estrogen (0.625 mg premarin ”) for 28 days, increasing the average AUC0-24 hours in the sustainable state of non-conjugate estrus (41%), Equilin (76%) and 17-B-Eestradiol (22%). Researched. The impact of Etoricoxib 120 mg on concentration (AUC0-24) of these estrogen components in premarin is half less than the observation effect when using a single premarin and when the dose increases from 0.625 to 1.25 mg. Estrogen when choosing to replace postmenopausal hormones to use with Etoricoxib, because increasing the level of estrogen may increase the risk of adverse effects when hormone replacement therapy.

Prednisone/Prednisolone

In interactive research, Etoricoxib does not have an important clinical impact on pharmacokinetics of Prednisone/Prednisolone.

digoxin

Use Etoricoxib 120 mg/day for 10 days in healthy volunteers do not change AUC 0 - 24 hours in sustainable state or eliminate digoxin through the kidneys. There is an increase in cmax of digoxin (about 33%). This increase is usually not important in most patients. However, patients should be highly toxic with digoxin when using Digoxin and Etoricoxib.

Effects of Etoricoxib on metabolic drugs by enzymes sulfotransferase

Etoricoxib is an active inhibitor sulfotransferase in humans, especially sult1e1, and has been shown to increase the concentration of ethinyl estradiol in serum. Although the existing data on the effects of many sulfotransferase is limited and clinical effects on many drugs are still being checked, it is necessary to be cautious when using Etoricoxib simultaneously with other drugs metabolized mainly by sulfotransferase in humans (for example: Salbutamol and oral Minoxidil).

ETORICOXIB's effect on drugs metabolized by isenzyme CYP

Based on In vitro, Etoricoxib studies do not show the inhibition of Cytochrom P450 (CYP) 1A2, 2C9, 2C19, 2D6, 2E1 or 3A4. In a study in healthy objects, the daily dose of Etoricoxib 120 mg does not change the activity of the liver's CYP3A4 when evaluated by Erythromycin breathing test.

Effect of other drugs on Etoricoxib's pharmacokinetics:

Etoricoxib's main metabolic path depends on the CYP enzyme. CYP3A4 can contribute to the metabolism of Etoricoxib in in Vivo. In vitro studies show that CYP2D6, CYP2C9, CYP1A2 and CYP2C19 can also catalyze the main metabolic path, but their quantitative role has not been studied in In Vivo.