Coxileb 200 glomed hard capsules for treating rheumatoid arthritis (3 blisters x 10 tablets)

ATC code: M01AH01.

The mechanism of action of Celecoxib is the initial prostaglandin synthesis through inhibition of Cycloxygenase-2 enzyme (COX-2). At celecoxib treatment concentration does not inhibit cyclooxygenase-1 enzyme (COX-1). COX-2 is created to respond to inflammatory agents.

This leads to the synthesis and accumulation of inflamed prostanoids, especially prostaglandin E2, causing inflammation, edema and pain. Celecoxib has the same effect as anti-inflammatory, analgesic and cooling agents on animals due to the prevention of the production process of inflammatory prostanoids through COX-2 inhibitors. In the colon tumor in animals, Celecoxib reduces the new incidence and multiplication of tumors.

In Vivo and EX Vivo studies show that Celecoxib has a very low affinity with Cox-1 enzyme. Therefore, in the treatment dose, Celecoxib does not work on prostanoids synthesized by activating COX-1 in tissues, especially with the stomach, intestines and platelets.

Clinical research

osteoarthritis (OA): Celecoxib has shown that it has the ability to reduce joint pain significantly compared to placebo. Celecoxib is evaluated in the treatment of signs and symptoms of knee and pink osteoarthritis on about 4200 patients in clinical trials with a placeborned control and other active ingredients for a maximum of 12 weeks. In osteoarthritis patients, celecoxib treatment 100 mg 2 times daily or 200 mg once a day helps to improve the womac degenerative index (Western ontario and McMaster Universities), which is the synthesis of measurement quantities of pain, stiffness and degenerative function. In 3 studies lasting 12 weeks of pain with osteoarthritis, Celecoxib used a dose of 100 mg twice a day or 200 mg 2 times/day to significantly reduce the pain within 24 - 48 hours after the starting dose.

In the dose of 100 mg 2 times/day or 200 mg 2 times/day, the effect of Celecoxib is similar to the effectiveness of Naproxen 500 mg 2 times daily. Dosage 200 mg twice daily does not bring any more benefits compared to the dose of 100 mg twice a day. The daily dosage of 200 mg has shown the same effect, whether used 100 mg 2 times daily or 200 mg once a day.

Rheumatoid arthritis (output): Celecoxib has been shown to have the ability to significantly reduce pain/joint pain and joint swelling compared to placebo. Celecoxib is evaluated to treat signs and symptoms of rheumatoid arthritis (RA) on about 2100 patients in clinical trials that are controlled with placebo and other active ingredients for a maximum of 24 weeks. Celecoxib shows that the effect is superior to the placebo in these studies, using the ACR20 response index (American rheumatism 20), which is a summary index of clinical measurement quantities, tests, and functions in rheumatoid arthritis. Celecoxib dose 100 mg twice daily and 200 mg twice daily is similarly effective and both are equivalent to Naproxen 500 mg twice daily.

Although Celecoxib 100mg twice daily and 200mg twice daily for the same overall efficiency, some patients have gained higher benefits when taking 200mg twice a day. The dose of 400mg twice daily does not bring any more benefits compared to the dose of 100mg or 200mg twice daily.

Age arthritis (JIA): In comparative research is not inferior, multi -central, parallel group, with a control of active, double, random blindness, for 12 weeks including 242 patients from 2 to 17 years old with teenage arthritis in low arthritis, low arthritis or multi -joints (with positive or negative rheumatism) and teenage arthritis, full -body arthritis) Treatment with one of the following regimen: Celecoxib 3 mg/kg twice a day (maximum 150 mg/day); Celecoxib 6 mg/kg twice a day (maximum 300 mg/day); Naproxen 7.5 mg/kg 2 times (maximum 500 mg/day). The response ratio is based on the criteria of 30 ACR pediatrics, which is the criterion of synthesizing the measurement of clinical factors, tests and functions of teen spontaneous arthritis (JIA). The ratio of 30 ACR pediatric response at 12 weeks is 69%, 80% and 67%, respectively for Celecoxib treatment groups 3 mg/kg, Celecoxib 6 mg/kg and Naproxen 7.5 mg/kg, proving both doses are not inferior to Naproxen. The stability of the treatment effect is observed during the 12 weeks of the open label research after conducting the double -lasting blind research on the above -mentioned 12 weeks, of which 202 patients receive Celecoxib 6mg/kg to a maximum of 200mg twice daily.

pharmacokinetic

absorption

Distribution

The ratio of cohesion to plasma proteins (this ratio does not depend on concentrations) is about 97% at the concentration of treatment in plasma and Celecoxib is not prioritized to erythrocytes.

Metabolism

Celecoxib is metabolized mainly through Cytocrom P450 2C9. Three metabolic products do not have the effect of inhibiting COX-1 or COX-2 identified in human plasma is the most alcohol, the corresponding carboxylic acid and the form associated with its glucuronid.

The activity of Cytocrom P450 2C9 decreases in people with polymorphism and this leads to a decrease in enzyme activity, for example, a contractor for polymorphism CYP2P9*3.

In the pharmacokinetic study of Celecoxib 200 mg used 1 time/day in healthy volunteers, with the CYP2C9*1/*1, 1 1, CYP2C9*1/*3 or CYP2C9*3/*3, the average CMAX and the AUC of Celecoxib on the 7 times, approximately 4 times and 7 times, in people with CYP2C9*3/*3/3/*3/3/3 genotypes. In 3 separate doses studies, a total of 5 objects with the CYP2C9*3/*3 genotype, AUC single dose, single dose increased by 3 times compared to normal metabolic people. Estimated frequency of genotypes *3/ *3 is 0.3% to 1.0% between different racial groups.

Be careful when using Celecoxib in patients who know or suspect that there is a poor metabolism of CYP2C9 based on a history/experience with other substrates of CYP2C9. It is advisable to consider starting treatment with half of the lowest recommended dose.

Elimination

Eliminating Celecoxib is mainly due to the metabolism through the liver with less than 1% of the dosage excreted in the urine. After multi -dose use, the sale time is 8 - 12 hours and the clearance rate is about 500 ml/min. With multi -dose, stable plasma concentration is achieved before the 5th day. Variations among objects of the main pharmacokinetics parameters (AUC, (CMAX The semi -discharged time) is about 30%. The distribution of the average stable state is about 500L/70 kg in healthy adults showing the wide distribution of Celecoxib into the tissue.

Effect of food

Use drugs with food (rich in fat) that slows down the absorption shown through t ... achieved after about 4 hours and bioavailability increases 20%.

In healthy volunteers, the body absorption (AUC) of Celecoxib is equivalent to the form of a capsule or dissolved in apple smoothie. There is no significant change in C. T, or T, after taking whole pills or dissolved into apple smoothie.

Coles 200 has a capsule form, the content of Celecoxib 200ng is not suitable for the dose of 50mg 100 mg at a time.

liver failure

No dose adjustments for patients with mild liver failure (group A). Use Celecoxib at the recommended dose for patients with arthritis or suffer from medium liver failure (group B).

There are no studies in patients with severe liver failure (group C).

kidney failure

No dose adjustment for patients with medium and mild renal impairment. There are no clinical studies in patients with severe renal impairment.

Used in combination with fluconazole: Celecoxib should be used with half recommended dose in patients being treated with fluconazole, a CYP2C9 inhibitor. Caution should be used when using a form combining Celecoxib with CYP2C9 inhibitors.

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 using overdose? Use a single dose of up to 1200 mg or multiple doses (2 times/day) with a total dose of 1200 mg in healthy people does not show any unwanted effects of clinical significance. In case of an overdose suspected, appropriate medical support measures should be taken. The fertilizer is not an effective measure to eliminate drugs because the drug is strongly connected to the protein.

What to do when forgetting 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 dose to compensate for missed dose.

Precautions when using

Effects on the heart

Cardiovascular thrombosis: Celecoxib can increase the risk of serious cardiovascular thrombosis, myocardial infarction, and stroke, which can be fatal. All NSAIDs may have this risk. This risk may increase according to the dose, time of use and cardiovascular risk factors. Patients with a history of cardiovascular disease may be at higher risk. To minimize the risk of unwantedness on the heart in patients treated with Celecoxib, the lowest dose should be used as effective and in the shortest possible time. Doctors and patients need to be alert to the progression of these events, even without the previous cardiovascular symptoms.

Patients need to be notified of signs and symptoms of serious toxicity on cardiovascular and steps when they occur.

Two major clinical trials, controlled shows that there is an increase in the rate of myocardial infarction and stroke when using another NSAID selective effect on COX-2 to treat pain in the first 10-14 days after artificial coronary artery transplant surgery (CABG).

Celecoxib is not an alternative to acetylsalicylic acid in preventing blockages - cardiovascular thrombosis due to lack of platelet function. Because Celecoxib does not inhibit platelet aggression, platelet resistance should not be stopped (for example, acetylsalicylic acid) while using Celecoxib.

Hypertension: Like all other NSAIDs, Celecoxib may start the hypertension or worsen the inherent hypertension, both of which can increase the risk of cardiovascular events. Be careful when using NSAIDs, including Celecoxib, on hypertension patients. Need to monitor blood pressure closely when starting treatment with Celecoxib as well as during treatment.

Surveying and edema: Like drugs that inhibit prostaglandin synthesis, edema and fluids have been observed on some patients using Celecoxib. Therefore, it is necessary to closely monitor patients with congestive heart failure or hypertension. Caution should be careful when using Celecoxib in patients who have damaged heart, edema or other conditions may be more serious due to fluid and edema, including patients taking diuretics or risk of blood volume.

Effects on gastrointestinal tract

Perforation, ulcers or gastrointestinal bleeding on the upper and lower gastrointestinals occurred with patients using Celecoxib. Patients who are at risk of this gastrointestinal complication when taking NSAID drugs are mostly elderly people, patients with cardiovascular diseases, patients who are taking aspirin, glucocorticoids, or other NSAIDs, patients using alcohol, or patients with a history or patients who are suffering from progressive gastrointestinal diseases such as ulcers, bleeding or gastrointestinal inflammation. Most random reports on death -related deaths related to Celecoxib occur in the elderly or patients with weakness.

Effects on the kidneys

NSAIDs including Celecoxib can be toxic to the kidneys. Clinical trials have shown that Celecoxib has the effects on the kidneys similar to other NSAIDs. Patients with the highest risk of kidney toxicity are those who impaired renal function, heart failure, liver failure and the elderly. Careful monitoring for these patients when treated with Celecoxib.

Be careful when starting to treat patients dehydration. First need to rehydrate the patient before treating with Celecoxib.

Progressive kidney disease

Need to closely monitor kidney function in patients with renal disease progressive treatment with Celecoxib.

Anaphylactic reaction

As well as NSAID drugs in general, anaphylactic reactions occur in patients using Celecoxib.

Serious skin reactions

Serious skin reactions, some may lead to death, including flaking dermatitis, Stevens-Johnson syndrome and poisoned epidermal necrosis, have been reported but very rare in using Celecoxib. Patients are often at high risk for these events in the early stages of the treatment process, most of these cases occur mainly in the first month of treatment. Celecoxib should be stopped as soon as skin redness appears, mucosal damage or any hypersensitivity signs.

Effects on the liver

There is no study in patients with severe liver failure (group C). Do not use Celecoxib in patients with severe liver failure. Caution should be used when using Celecoxib in medium-medium liver failure patients (group B) and should start at a dose equal to half the recommended dose.

Patients with symptoms and/or signs of liver failure or people with abnormal liver function tests need to be closely monitored on serious signs of progression of liver reactions during treatment with Celecoxib.

Use with oral anticoagulants

Teenagic spontaneous arthritis on the body

Be cautious when taking NSAID drugs including Celecoxib in patients with self -arthritis of teenagers on the body, due to the risk of pervasive intravascular coagulation. Patients with spontaneous arthritis of the teens onset when using Celecoxib must be monitored to see if the development of abnormal blood clotting tests.

Overview

With anti -inflammatory effects, Celecoxib can fade diagnostic signs, such as fever symptoms in infection diagnosis.

Need to avoid simultaneous use of Celecoxib with NSAID drugs not Aspirin.

CYP2D6 inhibition

Celecoxib is a medium level CYP2D6 inhibitor. For drugs metabolized through CYP2D6, it is necessary to reduce the dose of these drugs when starting to use with Celecoxib or increase the dose of these drugs when stopping using Celecoxib.

The effect of drugs on driving and operating machinery

There is no study on the effects of Celecoxib on the ability to drive and operate machinery, but based on the characteristics of learning and general description of the drug safety, can be considered as non -influential drugs.

Using drugs for women during pregnancy and lactation

Using drugs for pregnant women: There is no study in pregnant women. Some animal studies have shown toxicity on reproduction. There are no equivalent data on humans.

Celecoxib as well as other prostaglandin synthetic inhibitors, which can cause helplessness and early aortic muscle, should avoid using Celecoxib in the third quarter of pregnancy.

Should only use Celecoxib during pregnancy if the potential benefits to the mother outperform the potential risk to the fetus.

Prostaglandin synthesis inhibitors can cause disadvantages for pregnant women. Data from epidemiological studies shows increased risk of spontaneous miscarriage after taking prostaglandin synthetic inhibitors in the early stages of pregnancy. In animals, the use of synthetic inhibitors prostaglandin increases the risk of miscarriage before and after the embryo nest.

Use drugs for nursing women: Rat research shows that Celecoxib is excreted in milk with concentrations equivalent to plasma concentrations. In breastfeeding women using Celecoxib, very few Celecoxibs are transferred into milk. Because of the potential effects of Celecoxib in breastfeeding children, depending on the desired benefits of the drug for the mother, should consider stopping the drug or stop breastfeeding.

Drug interaction

Celecoxib mainly transformed through Cytocrom P450 (CYP) 2C9 in the liver. Caution should be used when using Celecoxib in patients who have or suspected poor metabolism through CYP2C9 based on a history with other substrates of CYP2C9 because these patients may have Celecoxib concentration in plasma abnormally high due to reduced metabolic clearance. Should start treatment with the dose equal to the lowest recommended dose.

Concomitance Celecoxib with CYP2C9 inhibitors increases the concentration of celecoxib in plasma. Therefore, Celecoxib should be reduced when used simultaneously with CYP2C9 inhibitors.

Concomitance Celecoxib with CYP2C9 induction substances such as Rifampicin, Carbamazepin and Barbiturate reduces the concentration of celecoxib in plasma. Therefore, it is necessary to increase the dose of Celecoxib when used simultaneously with CYP2C9 induction.

Clinical pharmacokinetics research and In vitro studies show that although Celecoxib is not a substrate, CYP2D6 inhibitors. Therefore, there may be In Vivo interaction with drugs metabolized by CYP2D6.

with specific drugs

Interaction between Celecoxib and Warfarin or similar drugs.

Lithium: In healthy objects, plasma lithium concentrations increase by about 17% when used simultaneously lithium and Celecoxib. Closely monitoring patients are being treated with lithium and Celecoxib. Need to closely monitor patients being treated with lithium when starting or stopping use simultaneously with Celecoxib.

Aspirin: Celecoxib does not affect the anti -platelet effect of low -dose aspirin. Because there is no platelet effect, Celecoxib is not an alternative to aspirin in the treatment of cardiovascular disease.

Anticboo -pressure drugs include Angiotensin (ACEI) and Angiotensin II antagonists (known as Angiotensin, ARB) receptor inhibitors, diuretics and beta receptor blockers: Prostaglandin inhibitors can reduce the anti -hypertension effect of Angiotensin (ACEI) and//anti -anti -anti -Angiotensin drugs Diuretics and beta receptor blockers. It should be noted that these interactions when using Celecoxib and enzyme inhibitors Angiotensin (Acei) and/or Angiotensin II antagonistic drugs, diuretics and beta receptor blockers.

In elderly patients, people who have fluid reduced (including diuretics are taking) or kidney damage, simultaneous use of NSAIDs, including COX-2 inhibitors, with angiotensin (ACEI), Angiotensin II antagonists or diuretic drugs that can lead to kidney function damage including acute renal failure. These effects are often recovered. Therefore, be careful when using Celecoxib simultaneously with these drugs. Patients need to be compensated enough and monitor kidney function when they start a combination and periodic use regimen.

Results from Lisinopril research: In a 28 -day clinical study in stage I and II patients with Lisinopril's control, the use of Celecoxib 200 mg twice a day does not increase the systolic and diastolic hypertension when compared to the placebo -use groups during blood pressure control process 24 hours. In the group of patients using simultaneously with Celecoxib 200 mg twice a day, 48% of patients do not respond to Lisinopril during the last visitor (meaning diastolic blood pressure greater than 90 mmHg or diastolic hypertension increased by more than 10% compared to the original time), for the placebo group this number is 27%. This difference is statistically significant.

Cyclosporin: Because NSAIDs work on kidney prostaglandin, these drugs may increase the risk of cyclosporin kidney poisoning.

fluconazole and ketoconazole: simultaneously use Fluconazole at a dose of 200 mg, 1 time/day double the plasma celecoxib concentration due to fluconazole has the effect of inhibiting enzyme metabolism of Celecoxib CYP P450 2C9. Celecoxib should be started at half the recommended dose in patients who are taking drugs that inhibit CYP2C9 as fluconazole. Ketoconazole, a CYP3A4 inhibitor, has no significant celecoxib metabolism inhibitors.

Dextromethorphan and Metoprolol: The simultaneous use of Celecoxib 200 mg twice a day increases 2.6 times and 1.5 times the concentration of dextromethorphan and metoprolol in plasma (substrates of CYP2D6). This is because Celecoxib inhibits metabolism of substrates of CYP2D6. Therefore, it is necessary to reduce the dose of medications as substrate of CYP2D6 when starting to use Celecoxib simultaneously and need to increase the dose of these drugs when stopping using Celecoxib.

Diuretics: Clinical studies show that in some patients, NSAIDs can reduce the effect of increasing the sub -sodium sodium of Furosemid and Thiazid by inhibiting prostaglandin synthesis in the kidneys.

Methotrexate: There are no important clinical and pharmacokinetic interactions between Celecoxib and Methotrexate in clinical research between these two drugs.

Oral contraceptives: In an interactive study, Celecoxib does not have a clinical clear effect with pharmacokinetics of oral contraceptive pills (1 Mgnorethindron/0.035 mg of ethinylestradiol).

Other drugs: No clinical interactive reports between Celecoxib and antacids (aluminum and magnesium), Omeprazol, Glibenclamid (Glybid), Phenytoin or Tolbutamid.