Espacox 200mg medicine reduces symptoms in the treatment of osteoarthritis, rheumatoid arthritis (3 blisters x 10 tablets)

Cycloxygenase is responsible for the synthesis of prostaglandin. The two COX-1 and Cox-2 substances have been determined. Cox-2 is an enzyme that is induced by inflammatory stimulation and is thought to be the main responsibility for the synthesis of prostanoid intermediaries that cause pain, inflammation and fever. Cox-2 also participates in the process of ovulation, nesting and arteriosclerosis, regulating kidney function and central nervous system (causing fever, receiving pain and cognitive function).

COX-2 can also play a role in healing ulcers. COX-2 has been identified in tissue around the stomach ulcer in people with the relationship between this enzyme and the healing of the ulcer has not been proven.

Differences in platelet resistant activity between some NSAID inhibits COX-1 and selective inhibitors can be clinically significant in patients with thrombosis.

Selective Cox-2 inhibitors reduce the synthesis of systemic prostacyclin (and therefore can reduce endothelial prostacyclin) without affecting thrombocyte thromboxan.

Celecoxib is a Diaryl Pyrazol derivative with chemical structure similar to other sulfonamids without other aromatic amino groups (such as thiazids, furosemids) but unlike sulfonamids with aromatic amino groups (such as sulfamethoxizol and other sulfonamid antibiotics).

The effect has been recorded depending on the dose on the formation of TB2 when using high doses of Celecoxib. However, in healthy people, in small -scale studies using multi -dose 600 mg, twice a day (3 times higher than the maximum proposal), Celecoxib does not affect platelet aggregation and bleeding time compared to placebo.

A number of clinical studies have confirmed the effectiveness and safety of the drug in the case of osteoarthritis, rheumatoid arthritis and joint spondylitis. Celecoxib has been evaluated in the treatment of inflammation and pain caused by osteoarthritis and hip joints on about 4,200 patients in trials with placebo and active ingredients for 12 weeks.

The drug has also been evaluated in the treatment of rheumatitis and rheumatoid arthritis on about 2,100 patients in trials with placebo and active ingredients for 24 weeks. Celecoxib with daily dose from 200 mg - 400 mg has an analgesic effect within 24 hours after use.

Celecoxib has been assessed in the treatment of joints of the joints on 896 patients in clinical tests with fake control and active ingredients for 12 weeks. Celecoxib at a dose of 100 mg, 2 times a day; 200 mg daily; 200 mg, 2 times a day and 400 mg once a day in these studies shows the possibility of pain in the pain symptoms, the degree of activity of the disease and the whole function in the joint piemontashing.

5 controlled, random, double -group studies, which perform the above gastrointestinal endoscopy according to the scheduled schedule on about 4,500 patients without
chemical ulcers at the beginning (Celecoxib dose from 50 mg - 400 mg, 2 times a day).

Through 12 -week studies that have been tested by gastrointestinal endoscopy, the risk of gastrointestinal ulcers of Celecoxib (dose of 100 - 800 mg/day) is significantly lower than Naproxen (1,000 mg/day) and ibuprofen (2,400 mg/day). This data is not true when compared to Diclofenac (150 mg/day). In 2 studies lasting 12 weeks, the proportion of patients with gastric and duodenal ulcer defined by laparoscopy has no significant differences between the placebo group and the group using Celecoxib 200 mg, twice a day and 400 mg, 2 times a day.

In a study of long -term safety (6 to 15 months, studying Class), 5,800 patients with osteoarthritis and 2,200 patients with rheumatoid arthritis have been used for 400 mg Celecoxib, 2 times a day (4 times higher and 2 times proposed to treat osteoarthritis and rheumatoid arthritis), Ibuprofen 800 mg, 3 times a day, or 2 times a day. treatment). 22% of patients participating in this study simultaneously use low -dose acetylsalicylic acetylsalicylic acid (≤ 325 mg/day), mainly to prevent cardiovascular events. With the main research criteria of ulcerative complication (defined as bleeding, perforation or gastrointestinal obstruction), Celecoxib has no significant difference compared to each ibutrofen or diclofenac drug.

Similarly, with the group using NSAID combined, there is no difference with statistical significance of ulcerative complications (the risk of relative is 0.77; 95% reliability is 0.41 - 1.46 based on assessment of the entire research time). With the combined research criteria of symptomatic ulcerative complications, this ratio in the group using Celecoxib is significantly lower than that of NSAID groups, the risk is relatively 0.66; 95% confidence interval is 0.45 - 0.97 but there is no difference between Celecoxib and Diclofenac. Patients who use Celecoxib and simultaneously take low -dose acetylsalicylic acetylsalicylic acid with an ulcerative ratio of ulcerative complications is 4 times higher than in the single Celecoxib group. The hemoglobin reduction rate has clinical significance (> 2 g/dl), which is confirmed through the blood test, in the group of patients treated with Celecoxib is significantly lower than in the NSAID group (the relative risk is 0.29; 95% confidence is 0.17 - 0.48). The incident rate is noticeably lower in the group using Celecoxib, whether or not using acetylsalicylic acid.

In a 24 -week random rescue study, the safety of 260 -year -old patients or a history of stomach - duodenal ulcer (patients using Asa are eliminated from the study), the proportion of patients with hemoglobin reduction (2 g/dl) and/or hematocrit (≥ 10%) identified or are thought to be caused by digestive tract in the daily dose of colicicbibs, 2 mg daily dose, 2 mg daily dose, 2 mg daily (N = 2.238) Lower than patients using Diclofenac, the release of the release tablet lasts at a dose of 75 mg, twice a day with Omeprazol 20 mg, once a day (n = 2.246) (0.2% compared to 1.1% for the cause from the identified digestive tract P = 0.004; 0.4% compared to 2.4% with the causes of gastrointestinal tract, P = 0.0001). The rate of digestive complications with clinical manifestations such as perforation, obstruction or bleeding is very low and there is no difference between treatment groups (4 to 5 shifts per group).

pharmacokinetic

absorption

Celecoxib is well absorbed, reaching the peak concentration in plasma after about 2-3 hours. Use in meals (rich in fat) slowly absorbing about 1 hour.

distribution

Celecoxib has pharmacokinetic depends on the dose and time in the treatment period. The ratio of plasma proteins is about 97% with the levels of treatment in plasma and non -priority drugs attached to red blood cells. The sale time is 8-12 hours. The concentration of drugs in a stable state in plasma is achieved within 5 days of treatment. Pharmacological activity is the original drug. The main metabolites found during the circulation are not active on COX-1 or COX-2.

transformation

Celecoxib metabolism is mainly done through cytochrom P450 2C9.

Three metabolites that have no active inhibitors inhibit the COX-1 or COX-2 have been determined in human plasma including a main alcohol, corresponding carboxylic acid and glucuronid combinative form.

The activity of cytochrom P450 2C9 decreases in a genetic polymorphic patient reducing enzyme activity, such as patients with a polymorphic contract of CYP2C9*3.

In a pharmacokinetics study, using Celecoxib 200 mg once a day on a healthy volunteer with CYP2C9*1/*1, 1, CYP2C9*1/*3 or CYP2C9*3/*3,/Value Cmax and AUC0-24 of the average Celecoxib on the 7th day in patients with CYP2C9 genotype*3/*3 times higher than 4 times and 7 times in turn 4 times Other genotypes.

In three separate studies using single dose, including a total of 5 patients with CYP2C9*3/*3, AUC-24 genotype when using a single dose increased by 3 times compared to those with normal metabolic levels. The frequency of genotypes *3/ *3 Deaths is estimated at 0.3 - 1.0% in different ethnic groups.

Patients who have been known or suspected to have weak metabolic CYP2C9 based on a history/experience with other substrates of CYP2C9 should be cautious when using Celecoxib.

Do not detect clinical differences in the pharmacokinetics parameters of Celecoxib between black and elderly white people.

Celecoxib concentration in plasma increased by about 100% in elderly women (> 65 years).

Elimination

Celecoxib is excreted mainly through metabolic. Under 1% of the dose is excreted in the form of unchanged urine. The oscillation of Celecoxib concentration between individuals is about 10 times.

liver failure

Compared to people with normal liver function, patients with mild liver failure with cmax values ​​of Celecoxib on average increased by 53% and AUC increased by 26%. The increase in the corresponding values ​​in patients with the average level of liver failure is 41% and 146% respectively. The ability to metabolize in patients with mild to moderate liver failure has the most closest correlation with albumin value.

It is recommended to start treating at half the recommended dose in patients with average liver failure (serum albumin concentration from 25 to 35 g/l). Patients with severe liver failure (serum albumin

kidney failure

Experience using Celecoxib for patients with kidney failure is still small. Celecoxib's pharmacokinetics have not been studied in patients with renal failure but is less likely to change in these patients. Therefore, it is necessary to treat patients with renal failure. Celecoxib in case of severe renal failure.

Caution when using

The signs of the digestive tract on [perforation, ulcer or hemorrhage (PUB)] have appeared in patients treated with Celecoxib, some of which lead to death. Caution should be careful when treating patients at high risk of developing complications in the digestive tract due to NSAID; Elderly, patients use any other NSAIDs or acetylsalicylic acid or patients with a history of gastrointestinal diseases such as ulcers or gastrointestinal bleeding.

The risk of adverse effects on the gastrointestinal tract (ulcers or other complications on the gastrointestinal tract) increases when Celecoxib is used simultaneously with acetylsalicylic acid
(even at low doses).

The clear difference in the safety of the gastrointestinal tract when using the selective inhibitors of COX - 2 + Acetylsalicylic acid compared to NSAID + Acetylsalicylic acid has not been shown in prolonged clinical trials.

Need to avoid simultaneous use of Celecoxib and a NSAID non -aspirin.

Increasing the number of serious cardiovascular events, mainly myocardial infarction has been recorded in a place where a place where a placeborn is regarded in patients with several Celecoxib treatments at a dose of 200 mg, 2 times and 400 mg, 2 times a day compared to the placebo group.

Due to the Celecoxib's cardiovascular risk may increase according to the dose and time of use, the drug should be used in the shortest possible time and with the lowest daily dose effectively effective. It is necessary to re -evaluate the need to reduce the symptoms of patients as well as respond to drugs, especially in osteoarthritis patients.

Patients with significant risk factors for cardiovascular events (such as hypertension, hyperlipidemia, diabetes, smoking) should only be treated with Celecoxib after careful consideration.

Selective inhibitors of COX-2 do not replace acetylsalicylic acid in the blood tolerance prevention due to thrombocytopenia. Therefore, should not stop using anti -platelets.

Similar to other drugs that have been known to inhibit the synthesis of prostaglandin, fluid and edema have been recorded in patients using Celecoxib. Because prostaglandin inhibitors can worsen renal function and fluid retention, should be cautious when using Celecoxib for patients with a history of heart failure, left ventricular dysfunction or hypertension as well as in patients with edema regardless of the cause. It is also necessary to be cautious when taking medication for patients being treated with diuretics or patients at risk of reducing blood volume.

Similar to all NSAIDs, Celecoxibs can cause new hypertension or worsen available hypertension before, both cases can increase the frequency of cardiovascular events. Therefore, it is necessary to closely monitor blood pressure when starting with Celecoxib and during treatment.

Damage to kidney or liver function and especially heart dysfunction is often more likely to occur in elderly patients and therefore, it is necessary to maintain appropriate medical monitoring in these patients.

NSAIDs like Celecoxib may cause kidney toxicity. Clinical trials with Celecoxib show the effect of the drug on the kidneys similar to the comparison of NSAIDs. Patients with the highest risk of kidney toxicity are those with kidney failure, heart failure, liver dysfunction, patients who are taking diuretics, angiotensin transfer inhibitors, Angiotensin II receptor antagonists and the elderly (see item

interact with other drugs and other types of interactions). These patients need to be carefully monitored during Celecoxib treatment.

Some cases of serious reactions in the liver, including hepatitis outbreak (some cases lead to death), liver necrosis and liver failure (some cases leading to death or liver transplant) have been recorded when using Celecoxib. Among the cases that reported the time, most of the serious adverse events in the liver progressed within 1 month after the start of Celecoxib (see the unwanted effect section).

If during the treatment process, the function of any system of the patient worsens as described above, it is necessary to apply appropriate treatment measures and should consider stopping treatment with Celecoxib.

Celecoxib inhibits CYP2D6. Although Celecoxib is not a strong enzyme inhibitor, the reduction of the dose may be necessary for drugs metabolized by CYP2D6 to detect doses for each patient.

Be careful when treating patients who have been determined to have weak metabolic CYP2C9.

Serious reactions on the skin, some fatal, including flaking dermatitis, Stevens - Johnson syndrome and poisoned epidermal necrosis were recorded with very rare frequency due to the use of Celecoxib. Patients are at the highest risk of these reactions in the early stage of the treatment process: the time of the reaction in most cases is within 1 month of treatment. Serious hypersensitivity reactions (including anaphylaxis, angioedema and rash due to drugs accompanied by eosinophilia and systemic symptoms (dress or hypersensitivity syndrome) have been recorded in patients using Celecoxib. Patients with a history of allergies to sulfonamid or any drug allergies may be at risk of serious skin reactions and higher hypersensitivity reactions (see -to -off). When the first rash appears, mucosal damage or any other hypersensitivity signs.

Celecoxib can cover fever and other inflammatory signs.

In patients treated simultaneously with warfarin, serious hemorrhage events have been recorded. Caution should be used when using Celecoxib combination with warfarin and other oral anticoagulants.

Warning about excipients:

The drug contains lactose. Patients with rare genetic diseases are galatose intolerance, lactase laptop deficiency or glucose-galactose absorption should not be taken.

Risk of cardiovascular thrombosis:

Non -steroid anti -inflammatory drugs (NSAIDs), non -aspirin, using systemic sugar, may increase the risk of cardiovascular thrombosis, including myocardial and stroke infarction, which can lead to death. This risk can appear early in the first few weeks of taking the drug and can be given 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 does not have 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, Espacox is needed at the lowest daily daily doses in the shortest possible time.

Use drugs for women during pregnancy and lactation

Pregnant women

There is no clinical data on pregnant women exposed to Celecoxib. Animal studies (rats and rabbits) show that toxicity to reproduction, including deformities.

It is unclear potential risk in pregnant women, but cannot exclude this risk. Similar to other prostaglandin synthesis drugs, Celecoxib can cause inert uterus and early closing arterioscleria for the last 3 months of pregnancy. Celecoxib contraindicated for pregnant women and women suspected pregnancy. If a woman is pregnant during treatment, it is necessary to stop using Celecoxib

breastfeeding women

Celecoxib is secreted into mouse milk with the same concentration as in plasma. Using Celecoxib for a limited number of breastfeeding women shows a very small amount of Celecoxib secreted in milk. Women who are using Celecoxib should not breastfeed.

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

Patients with dizziness, dizziness or sleep while using Celecoxib to avoid driving or operating machinery.

Drug interaction

Pharmacological interaction

Need to monitor anticoagulant activity, especially in the first few days after the start of treatment or change of Celecoxib doses in patients using warfarin or other anticoagulants because these patients are increased at risk of hemorrhage complications. Therefore, patients are using oral anticoagulants should be closely monitored in prothrombin Inr, especially in the first few days after starting treatment or changing Celecoxib doses (see sections of special and cautious warnings when used). Prothrombin bleeding events have been recorded, mainly in the elderly, patients use Celecoxib simultaneously with Warfarin, some deaths.

NSAID can reduce the effects of diuretics and anti -hypertension drugs. Similar to NSAIDs, the risk of acute renal failure, often recovery can increase in some patients with kidney function damage (such as patients with dehydration, patients who are taking diuretics or elderly patients) when angiotensin transferring enzymes inhibitors or Angiotensin II antagonistic drugs are used in combination with NSAID as Celecoxib. Therefore, it is necessary to be careful when using these drugs, especially in the elderly. Patients need to be adequate water and need to consider monitoring the kidney function after starting to use the medication at the same time.

In a 28 -day clinical study in patients with stage I and II hypertension, which was controlled by Lisinopril, using Celecoxib 200 mg, twice a day without clinical significance of systolic blood pressure and diastolic blood pressure daily compared to placebo, determined by monitoring dynamic blood pressure 24 hours. Among patients treated with Celecoxib 200 mg, twice a day, 48% of patients are considered not responding to Lisinopril at the last visitor (defined as diastolic blood pressure> 90 mmHg or diastolic blood pressure increased by> 10% compared to the original) compared to 27% of patients in the placebo group; This difference is statistically significant.

Simultaneous use of NSAID with Ciclosporin or Tacrolimus increases the toxic effect on the kidneys of Ciclosporin and Tacrolimus. Need to monitor kidney function when using Celecoxib simultaneously with any of these drugs.

can use Celecoxib along with low -dose acetylsalicylic acids but Celecoxib does not replace acetylsalicylic acid in cardiovascular disease. In published studies, similar to other NSAIDs, increased risk of digestive ulcers or other digestive complications has been recorded when using Celecoxib simultaneously with low -dose acetylsalicylic acid compared to solitary Celecoxib.

pharmacokinetic interaction

The effect of Celecoxib on other drugs:

Celecoxib is a CYP2D6 inhibitor. During Celecoxib treatment, the substrate concentration of CYP2D6 is dextromethorphan in plasma increased by 136%. The concentration of the drug is the substance of this enzyme in plasma may increase when Celecoxib is used simultaneously. Examples of drugs metabolized by CYP2D6 are antidepressants (three rounds and SSRIs), sedatives, anti -arrhythmic drugs ... When starting with Celecoxib treatment, may need to reduce and detect the doses of substrates of CYP2D6, for each patient or increase the dose of these substrates when stopping using Celecoxib.

In vitro studies show that Celecoxib inhibits catalytic metabolism by CYP2C19. The clinical significance of this Vitro interaction is unknown. Examples of drugs metabolized by CYP2C19 are diazepam, citalopram and imipramin.

In an interactive study, Celecoxib does not cause clinical significance to the pharmacokinetics of oral contraceptives used by oral (1 mg of norethistherone /35 ng thinyylestradiol).

Celecoxib does not affect the pharmacokinetics of tolbutamid (substrate of CYP2C9) or Glibenclamid at clinical significance.

In patients with rheumatoid arthritis, Celecoxib does not affect statistically significant to pharmacokinetics (plasma clearance or renal discharge) of methotrexate (with low doses of rheumatoid arthritis). However, it is necessary to consider comprehensive toxic monitoring caused by methotrexate when combining these two drugs.

In healthy people, simultaneously using Celecoxib 200 mg, twice a day with 450 mg of lithium, 2 times a day increasing the average cmax of lithium by 16% and an increase of 18%. Therefore, closely monitor patients being treated with lithium at the beginning or stop using Celecoxib.

The effect of other drugs on Celecoxib

In people with weak metabolic CYP2C9 and the body's celecoxib concentration increases, simultaneously using CYP2C9 inhibitors can increase the concentration of Celecoxib. It is necessary to avoid combining these drugs in people with weak metabolic CYP2C9.

Because Celecoxib is mainly metabolized by CYP2C9, the dose is half -dose in patients using fluconazole. Simultaneous use of 200 mg of Celecoxib, the only dose along with 200 mg of fluconazole, a strong CYP2C9 inhibitor, once a day increases the average CMAX of Celecoxib by 60% and an increase of 130%. Concentrated use of CYP2C9 induction drugs such as rifampicin, carbamazepin and barbiturates may reduce the concentration of plasma crycoxibs.

ketoconazole or antacids have not been recorded as an impact on the pharmacokinetics of Celecoxib.