Ceozime 200mg Theragen Etex treatment of osteoarthritis, rheumatoid arthritis (3 blisters x 10 tablets)

Pharmacological effects: Non -steroid anti -inflammatory drugs

ATC code: M01AH01

Celecoxib is a nonsteroidal anti-inflammatory drug, selective inhibition of cyclooxygenase-2 (COX-2), has anti-inflammatory, analgesic, fever-reducing effects.

The mechanism of action of Celecoxib is due to inhibition of prostaglandin synthesis, mainly through inhibiting the isoenzyme cyclooxygenase-2 (COX-2), resulting in reducing the formation of prostaglandin precursors. Unlike most nonsteroidal anti-inflammatory drugs before, Celecoxib does not inhibit isenzyme cyclo-oxygenase-T (COX-1) with human treatment concentrations.

COX-I is a structural enzyme found in almost all large and platelet leukocytes. Cox-1 participates in thrombosis (such as thrombocytopenia to stop training) to maintain the protective mucosa fence of the stomach and kidney function (such as maintaining kidney perfusion).

Due to not inhibiting COX-1, Celecoxib is less likely to cause side effects (for example, for platelets of the gastric mucosa), but can cause kidney side effects similar to non-selective non-steroid anti-inflammatory drugs.

Pharmacokinetics

absorption

Celecoxib is quickly absorbed through the gastrointestinal tract.

Take Celecoxib with high -fat food that slows down the time to reach the peak plasma concentration compared to drinking at an hunger about 1 to 2 hours and increases 10-20% of the area under the curve (AUC). Celecoxib can be used simultaneously with food without paying attention to the time of meals. The plasma concentration of the drug is usually at 3 hours after taking a single dose of 200 mg at hunger, and the average is 705 ng/ml.

The drug concentration in a stable state in plasma is achieved within 5 days, there is no accumulation. In the elderly over 65 years old, the peak concentration in plasma and AUC increased by 40 and 50%, respectively, compared to young people; AUC of Celecoxib in a stable state increases 40 or 180% of mild or medium, corresponding liver failure people, and 40% decrease in chronic kidney failure (glomerular filtration speed 35 - 60 ml/min) compared to normal people.

Distribution

The distribution volt At plasma treatment concentration, 97% Celecoxib is attached to plasma proteins.

Metabolism

Celecoxib is metabolized in the liver into non -active metabolites by isenzyme CYP4502C9.

Elimination

Half of the lifetime eliminates plasma of Celecoxib after drinking is 11 hours, and the clearance coefficient in plasma is about 500 ml/minute. The half -life of the drug lasts for people with kidney failure or liver failure.

Celecoxib eliminates about 27% in urine and 57% in feces, less than 3% of the doses are eliminated unchanged.

Caution when using

Heart effects

cardiovascular 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 should be warned of symptoms of serious cardiovascular events and need to visit the doctor as soon as they appear.

To minimize the risk of adverse events, Celecoxib is needed in the lowest daily daily doses in the shortest possible time, two large clinical trials, controlled by a selective NSAID effect on another COX-2 in the first 10-14 days of painful treatment after artificial coronary artery transplant surgery (CABG), there is an increase in the rate of heart attack and stroke. Celecoxib is not an alternative to acetylsalicylic acid in preventing cardiovascular disease blockage due to lack of platelet function. Because Celecoxib does not inhibit platelet aggregation, platelet resistance should not be stopped (such as acetylsalicylic acid).

Hypertension: Like all NSAIDs, Celecoxib can start the hypertension or make hypertension worse, both of these factors can increase cardiovascular events. Should be cautious when using NSAIDs, including Celecoxib in 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 the synthesis of prostaglandin, edema and fluids are recorded in a part of the patient using Celecoxib. Therefore, it is necessary to closely monitor patients with congestive heart failure or hypertension. Celecoxib should be used to be cautious for patients who have been damaged by heart, edema or conditions that are more likely to become more serious due to fluid stasis and edema including those who use diuretics, or have a risk of reducing blood volume.

Effects on the gastrointestinal tract: The upper and lower gastrointestinal tract, ulcers or bleeding occurs with patients using Celecoxib. Patients with the highest risk of gastrointestinal complications of this type when taking NSAIDs include: Elderly, patients with cardiovascular diseases, patients taking aspirin, glucocorticoids or other NSAIDs, patients using alcoholic beverages or patients with a history of or suffering from progressive gastrointestinal diseases such as ulcers, bleeding or gastrointestinal inflammation.

Most random reports on deaths caused by the gastrointestinal tract are related to Celecoxib are in weak physical patients or the elderly.

The impact on the kidneys: NSAIDs including Celecoxib may be toxic to the kidneys. Clinical trials with Celecoxib have shown the same effects as with other NSAIDs compared. Patients with the highest risk of kidney toxicity are those who impaired renal function, heart failure, liver failure and the elderly. Need to carefully monitor these patients when treated with Celecoxib.

Be careful when starting to treat patients with dehydration. First should rehydrate patients and then start treatment with Celecoxib.

Progressive renal disease: Need to closely monitor kidney function in patients with renal disease progressive using Celecoxib.

Anaphylactic reaction: Like NSAIDs in general, anaphylactic reactions occurred with patients using Celecoxib.

Serious skin reactions: serious skin reactions, some leading to death, including flaking dermatitis, Steven-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, which occur mainly in the first month of taking the drug. Celecoxib should be stopped as soon as skin redness appears, mucosal damage, or any hypersensitivity signs.

The effects on the liver: There is no study in patients with severe hepatic impairment (C-Pough C). Do not use Celecoxib in patients with severe liver failure. Celecoxib should be used cautiously in medium-sized liver failure patients (B-Pul degree), and should start at half the recommended dose.

Unwanted unwanted effects rare in the liver, including hepatitis (some deaths), liver necrosis and liver failure (some deaths or liver transplantation) have been reported to Celecoxib.

Patients with symptoms and/or signs of liver failure or people with abnormal liver function tests need to be closely monitored on signs of more severe liver reaction development during treatment with Celecoxib.

Concentrated with oral anticoagulants: simultaneous use of NSAIDs with oral anticoagulants increases the risk of bleeding and should be used cautiously. Oral anticoagulants include Warfarin/Coumarin and new generation oral anticoagulants (such as Apixaban, Dabigatran and Rivaroxaban).

There have been reports on serious bleeding cases in patients using simultaneously with warfarin or similar substances, including some deaths. Due to a report on increasing prothrombin (INR) time, anticoagulant/INR effects should be monitored in patients with Warfarin/Coumarin anticoagulants or dose after starting celecoxib treatment (see the interaction of the drug).

Overview: With the effect of reducing inflammation, Celecoxib can fade diagnostic signs, such as fever symptoms in infection diagnosis.

Need to avoid simultaneous use of Celecoxib with an NSAIDs non -aspirin.

CYP 2D6 inhibitors: Celecoxib shows the ability to inhibit CYP2D6 at an average level. For drugs metabolized by CYP2D6, it may be necessary to reduce the dose during the starting period of Celecoxib or increase the dose when stopped with Celecoxib.

Poor metabolism via CYP2C9:

Patients who have known or suspected poor metabolism via CYP2C9 based on a history/experience with other substrates of CYP2C9 should be cautious when using Celecoxib.

The drug contains lactose. Patients with rare genetic problems such as galactose tolerance, lactase deficiency or malposive glucose-galactose should not take this drug.

The ability to drive and operate machinery

The drug can cause adverse reactions such as insomnia, dizziness, headache, so it should be cautious when participating in driving and operating machinery.

Pregnant and lactating women

pregnancy

There is no research on pregnant women. Some animal studies have shown toxicity on reproduction. There are no equivalent data on humans.

Celecoxib, as well as other prostaglandin synthesis inhibitors, can cause powerless uterine muscle and early aortic ductus, should not use Celecoxib in the last 3 months of pregnancy.

Should only use Celecoxib during pregnancy if the benefit may have to the mother outstanding potential risk to the fetus.

Prostaglandin synthesis inhibitors can cause disadvantages for pregnant women. Data from epidemic studies shows increased risk of spontaneous miscarriage after using prostaglandin synthesis inhibitors in the early stages of pregnancy. The use of prostaglandin synthesis drugs on animals shows the risk of miscarriage increases in the stage before and after the embryo nest.

Breastfeeding period

Mouse research shows that Celecoxib is excreted in milk with concentrations equivalent to plasma concentrations. In nursing women using Celecoxib, very few Celecoxib appear in milk. Because it may have the unwanted effect of Celecoxib on breastfeeding children, depending on the benefits of the drug with the mother, should consider stopping the drug or stop breastfeeding.

Effects on fertility

Based on the mechanism of operation, the use of NSAIDs, including Celecoxib, can delay or prevent ovulation, related to infertility can recover in some women.

Women who are difficult to conceive or are treating infertility, need to consider stopping nsaids, including Celecoxib.

Interaction of drugs

Concentrated with oral anticoagulant drugs: simultaneous use of NSAIDs with oral anticoagulant drugs increases the risk of bleeding and should be used carefully.

Oral anticoagulants include Warfarin/Coumarin and new generation oral anticoagulants (such as Apixaban, Dabigatran and Rivaroxaban). There have been reports on serious bleeding in patients using simultaneously with warfarin or similar substances, including some deaths.

Due to a report on increasing prothrombin (INR) time, anticoagulant/INR effects should be monitored in patients with Warfarin/Coumarin anticoagulants or dose adjustment after starting celecoxib treatment.

Anticboo -pressure drugs include angiotensin transfer inhibitors (ACEI), Angiotensin II (ARB) receptor resistant, diuretics and beta blockers: Prostaglandin inhibitors can reduce the effects of anti -hypertension drugs including Acei and/or ARB, diuretics and beta blockers. It should be noted this interaction when using Celecoxib simultaneously with Acei and/or ARB, diuretics and beta blockers.

For the elderly, the circulatory volume is reduced (including patients who are taking diuretics) or kidney function damage, the combination of NSAIDs, including COX 2 inhibitors, with angiotensin transmission inhibitors, Angiotensin II antagonistic drugs or diuretics can cause damage to kidney function, including acute renal insufficiency.

This effect is usually recovered. Therefore, it is necessary to be cautious when using these medications at the same time. It is necessary for patients to drink adequate and clinical water, need to monitor and evaluate the kidney function when starting combined and periodic treatment later.

Cyclosporin and tacrolimus: Due to the effect on kidney prostaglandin, NSAIDs may increase the risk of kidney toxicity caused by cyclosporin and tacrolimus.

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

CYP2C9 inhibitors: Celecoxib mainly transformed through Cytocrom P450 (CYP) 29 in the liver. Caution should be used when using Celecoxib in patients who have known or suspected metabolic through poorly based on a history of history with other substrates of CYP2C9 because the concentration of drugs in plasma may be abnormal due to reduced metabolic clearance. Consider applying the lowest dose of the recommended %.

Use combinations of Celecoxib with CYP2C9 inhibitors can lead to an increase in celecoxib concentration in plasma. Therefore, it is possible to weigh the celecoxib doses when using Celecoxib simultaneously with CYP2C9 inhibitors. CYP2C9 induction: Use Celecoxib in combination with CYP2C9 induction substances such as rifampicin, carbamazepin and barbiturat can lead to a decrease in plasma cells in plasma. Therefore, it may be necessary to increase the celecoxib dose when using Celecoxib simultaneously with CYP2C9 induction substances.

CYP2D6 inhibitors: Dynamic pharmacokinetics and In vitro research shows that although Celecoxib is not a substrate, it has the effect of CYP2D6 inhibitor. Therefore, there may be In Vivo interaction between Celecoxib and drugs metabolized by CYP2D6.

Methotrexat: No observations of pharmacokinetic and clinical interactions are important in clinical research between Celecoxib and Methotrexate.

Lithium: In healthy objects, lithium concentration in plasma increased by about 17% when used at the same time lithium and Celecoxib. Closely monitoring patients being treated with lithium using Celecoxib or stopping using Celecoxib.

Oral contraceptives: In an interactive study, Celecoxib does not have a clear clinical impact on pharmacokinetics of oral contraceptive pills (1 mg norethindron/0.035 mg ethinyl estradiol).

Glibenclamid/Tobutamid: Celecoxib does not affect the pharmacokinetics of tolbutamid (substrate of CYP2C9), or clinically glibenclamid.

fluconazole: simultaneously use Fluconazole at a dose of 200 mg x 1 time/day to double the concentration of Celecoxib in plasma. This increase is due to inhibiting the metabolism of Celecoxib via CYP P450 209 by fluconazole. Celecoxib should be used at half the recommended dose in patients using fluconazol, a CYP2C9 inhibitor.

ketoconazole and antacids: ketoconazole or antacids does not affect the pharmacokinetics of Celecoxib.

Dextromethorphan and Metoprolol: simultaneously use Celecoxib 200 mg twice a day, resulting in increasing 2.6 times and 1.5 times the concentration of dextromethorphan and metoprolol in plasma (substrate of CYP2D6). This increase is due to the inhibition of Celecoxib on the metabolism of the substrate of CYP2D6 via CYP2D6. Therefore, it may be necessary to reduce the dose of the drugs that are the substrate of GP206 when starting with curved or increased money when horizontal treatment with Celecoxib.

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