Celebrex Capsules 200mg N10
Condition: New product
1000 Items
Rating:
Be the first to write a review!
More info
Active ingredients
Celecoxib
Release form
Capsules
Composition
Active ingredient: Celecoxib Concentration of active ingredient (mg): 200 mg
Pharmacological effect
Celecoxib has anti-inflammatory, analgesic and antipyretic effects by blocking the formation of inflammatory prostaglandins (pg) mainly due to inhibition of cyclooxygenase-2 (cog-2). induction of cog-2 occurs in response to inflammation and leads to the synthesis and accumulation of prostaglandins, especially prostaglandin e2, with an increase in the manifestations of inflammation (swelling and pain). In therapeutic doses in humans, celecoxib does not significantly inhibit cyclooxygenase-1 (cog-1) and does not affect prostaglandins synthesized as a result of cog-1 activation, and also does not affect the normal physiological processes associated with cog-1 and occurring in tissues, and especially in the tissues of the stomach, intestines and platelets. The effect on the function of kidney-celecoxib reduces urinary excretion of pge2 and 6-keto-pgf1 (prostacyclin metabolite), but does not affect serum thromboxane b2 and urinary excretion of 11-dehydro-thromboxane in 2 , metabolite and thromboxane (both are products of cog-1). Celecoxib does not cause a decrease in glomerular filtration rate (SCF) in elderly patients and those with chronic renal insufficiency, it transiently reduces sodium excretion. in patients with arthritis, the observed incidence of peripheral edema, hypertension and heart failure is comparable to that in patients receiving non-selective cog inhibitors, which have inhibitory activity against cog-1 and cog-2. This effect was most pronounced in patients receiving diuretic therapy. However, there was no increase in the incidence of hell and heart failure, and peripheral edema was mild and self-inflicted.
Pharmacokinetics
When taken on an empty stomach, celecoxib is well absorbed, reaching Cmax in the blood plasma in about 2-3 hours. Cmax in plasma after administration of 200 mg - 705 ng / ml. The absolute bioavailability of the drug has not been studied. Cmax and AUC are approximately proportional to the dose taken in the dose range up to 200 mg 2 times a day; when using celecoxib in higher doses, the degree of increase in Cmax and AUC occurs lessproportional. Effect of ingestionTselecoxib intake with fatty foods increases the time to reach Cmax by about 4 hours and increases total absorption by about 20%. Celecoxib penetrates the blood-brain barrier. Metabolism Celecoxib is metabolized in the liver by hydroxylation, oxidation and partially glucuronidation. Metabolism mainly occurs with the participation of cytochrome P450 CYP2C9 (see the section Interaction with other drugs). Metabolites found in blood are not pharmacologically active against COX-1 and COX-2. Cytochrome P450 CYP2C9 activity is reduced in individuals with a genetic polymorphism, such as a polymorphism that is homozygous for CYP2C9 * 3, which leads to a decrease in the effectiveness of enzymes. less than 1% of the dose taken - unchanged. With repeated use T1 / 2 is 8-12 hours, and clearance is about 500 ml / min. With repeated use, equilibrium plasma concentrations are reached by day 5. The variability of the main pharmacokinetic parameters (AUC, Cmax, T1 / 2) is about 30%. The average distribution in equilibrium is approximately 500 l / 70 kg in young healthy adult patients, which indicates a wide distribution of celecoxib in the tissue. Specific patient groups Elderly patients In patients over 65, there is an increase of 1.5-2 times the average Cmax, AUC celecoxib, which is largely due to a change in body weight, rather than age (older patients, as a rule, have a lower average body weight than younger people, as a result of which, all other things being equal, Higher celecoxib concentrations are achieved. For the same reason, older women usually have a higher concentration of the drug in the blood plasma than older men. These pharmacokinetic features, as a rule, do not require dose adjustment. However, in elderly patients with a body weight below 50 kg, treatment should be started with the lowest recommended dose. Rasa representatives of the Negroid race AUC celecoxib are approximately 40% higher than in Europeans.The causes and clinical significance of this fact are not known, so their treatment is recommended to start with the minimum recommended dose. Liver function impairment Celecoxib concentration in plasma in patients with mild hepatic insufficiency (class A according to Child-Pugh classification) changes slightly. In patients with moderately severe liver failure (class B according to Child-Pugh classification), plasma concentration of celecoxib can be almost doubled. Impaired renal function in elderly patients with decreased GFR> 65 ml / min / 1.73 m2 related to age changes, and in patients with GFR of 35-60 ml / min / 1.73 m2, the pharmacokinetics of cepecoxib does not change. There is no significant relationship between serum creatinine content (or creatinine clearance) and celecoxib clearance. It is assumed that the presence of severe renal failure does not affect the clearance of celecoxib, since the main route of its elimination is the transformation in the liver into inactive metabolites.
Indications
Symptomatic treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Pain syndrome (back pain, musculoskeletal, postoperative and other types of pain). Treatment of primary dysmenorrhea.
Contraindications
Hypersensitivity to celecoxib or any other component of the drug. Known hypersensitivity to sulfonamides. Bronchial asthma, urticaria, or allergic reactions after taking acetylsalicylic acid or other NSAIDs, including other COX-2 inhibitors. Condition after coronary artery bypass surgery. Peptic ulcer in the acute stage or gastrointestinal bleeding. Inflammatory bowel disease. Heart failure (NYHA II-IV). Clinically proven ischemic heart disease, peripheral arterial disease and cerebrovascular disease in the severe stage. Pregnancy and lactation period (see. "Use during pregnancy and lactation"). Severe hepatic and renal failure (no experience of use). Age up to 18 years (no experience of use).
Precautionary measures
In a dry place at a temperature of 15 ° to 30 ° C. Keep out of the reach of children.
Use during pregnancy and lactation
Absorption When taken on an empty stomach, celecoxib is well absorbed, reaching Cmax in the blood plasma in about 2-3 hours. Cmax in plasma after administration of 200 mg - 705 ng / ml. The absolute bioavailability of the drug has not been studied. Cmax and AUC are approximately proportional to the dose taken in the dose range up to 200 mg 2 times a day; when using celecoxib in higher doses, the degree of increase in Cmax and AUC occurs less proportionally. is about 97%, celecoxib does not bind to red blood cells. Celecoxib penetrates the blood-brain barrier. Metabolism Celecoxib is metabolized in the liver by hydroxylation, oxidation and partially glucuronidation. Metabolism mainly occurs with the participation of cytochrome P450 CYP2C9 (see the section Interaction with other drugs). Metabolites found in blood are not pharmacologically active against COX-1 and COX-2. Cytochrome P450 CYP2C9 activity is reduced in individuals with a genetic polymorphism, such as a polymorphism that is homozygous for CYP2C9 * 3, which leads to a decrease in the effectiveness of enzymes. less than 1% of the dose taken - unchanged. With repeated use T1 / 2 is 8-12 hours, and clearance is about 500 ml / min. With repeated use, equilibrium plasma concentrations are reached by day 5. The variability of the main pharmacokinetic parameters (AUC, Cmax, T1 / 2) is about 30%. The average distribution in equilibrium is approximately 500 l / 70 kg in young healthy adult patients, which indicates a wide distribution of celecoxib in the tissue. Specific patient groups Elderly patients In patients over 65, there is an increase of 1.5-2 times the average Cmax, AUC celecoxib, which is largely due to a change in body weight, rather than age (older patients, as a rule, have a lower average body weight than younger people, as a result of which, all other things being equal, Higher celecoxib concentrations are achieved. For the same reason, older women usually have a higher concentration of the drug in the blood plasma than older men.These pharmacokinetic features, as a rule, do not require dose adjustment. However, in elderly patients with a body weight below 50 kg, treatment should be started with the lowest recommended dose. Rasa representatives of the Negroid race AUC celecoxib are approximately 40% higher than in Europeans. The causes and clinical significance of this fact are not known, so their treatment is recommended to start with the minimum recommended dose. Liver function impairment Celecoxib concentration in plasma in patients with mild hepatic insufficiency (class A according to Child-Pugh classification) changes slightly. In patients with moderately severe liver failure (class B according to Child-Pugh classification), plasma concentration of celecoxib can be almost doubled. Impaired renal function in elderly patients with decreased GFR> 65 ml / min / 1.73 m2 related to age changes, and in patients with GFR of 35-60 ml / min / 1.73 m2, the pharmacokinetics of cepecoxib does not change. There is no significant relationship between serum creatinine content (or creatinine clearance) and celecoxib clearance. It is assumed that the presence of severe renal failure does not affect the clearance of celecoxib, since the main route of its elimination is the transformation in the liver into inactive metabolites.
Dosage and administration
Inside, without chewing, drinking water, regardless of the meal. Since the risk of possible cardiovascular complications may increase with an increase in the dose and duration of Celebrex, it should be prescribed in the shortest possible courses and in the lowest recommended doses. The maximum recommended daily dose for prolonged use is 400 mg. Symptomatic treatment of osteoarthritis: The recommended dose is 200 mg per day for 1 or 2 doses. The safety of taking doses up to 400 mg 2 times a day is noted. Symptomatic treatment of rheumatoid arthritis: The recommended dose is 100 or 200 mg 2 times a day. Marked safety doses up to 400 mg 2 times a day. Symptomatic treatment of ankylosing spondylitis: The recommended dose is 200 mg per day for 1 or 2 doses. 11At the prescription, the dose may be increased to 400 mg per day. Treatment of pain and primary dysmenorrhea: The recommended initial dose is 400 mg, followed, if necessary, by taking an additional dose of 200 mg on the first day. In the following days, the recommended dose is 200 mg 2 times a day, as needed.Elderly patients: Usually, dose adjustment is not required. However, in patients with a body weight below 50 kg, it is better to begin treatment with the lowest recommended dose. Liver dysfunction: Patients with a mild degree of liver failure (class A according to Child-Pugh classification) do not need dose adjustment, in case of moderate liver failure (class A according to Child-Pugh classification), treatment should be started with the minimum recommended dose. . Impaired renal function: In patients with mild to moderate renal insufficiency, dose adjustment is not required. Experience in the use of the drug in patients with severe renal insufficiency is not (see. "Special instructions"). Simultaneous use with fluconazole: Patients taking fluconazole (CYP2C9 inhibitor), Celebrex should be prescribed in the minimum recommended dose.
Side effects
Often found (> 1% and <10%) General: exacerbation of allergic diseases, flu-like syndrome, accidental injuries. From the side of the cardiovascular system: peripheral edema. On the part of the gastrointestinal tract: abdominal pain, diarrhea, dyspepsia, flatulence, diseases of the teeth (postextraction hole alveolitis). On the part of the nervous system: dizziness, increased muscle tone, insomnia. On the part of the kidneys and urinary system: urinary tract infection. On the part of the respiratory system: bronchitis, cough, pharyngitis, rhinitis, sinusitis, infections of the upper respiratory tract. On the part of the skin: itching, skin rash. Infrequently (> 0.1% and <1%) On the blood side: anemia, ecchymosis, thrombocytopenia. From the side of the cardiovascular system: weighting of the course of arterial hypertension, increase in arterial pressure, arrhythmia, “flushes”, palpitations, tachycardia. From the senses: tinnitus, blurred vision. From the gastrointestinal tract: vomiting. Mental status: anxiety, drowsiness. For the skin: alopecia, urticaria. Rarely (> 0.01% and <0.1%) From the side of the cardiovascular system: manifestation of congestive heart failure, ischemic stroke and myocardial infarction. On the part of the gastrointestinal tract: gastric ulcer and duodenal ulcer, esophageal ulceration, intestinal perforation, pancreatitis.On the part of the immune system: angioedema, bullous eruptions. On the part of the hepatobiliary system: increased activity of liver enzymes. Mental status: confusion. Side effects identified in post-marketing observations: From the immune system: anaphylaxis. Mental status: hallucinations. The nervous system: loss of taste, loss of smell, aseptic meningitis. On the part of the vessels: vasculitis. On the part of the gastrointestinal tract: gastrointestinal bleeding. On the part of the hepatobiliary system: hepatitis, liver failure (see section "Special instructions", "effect on the function of the liver"). On the part of the kidneys and urinary system: acute renal failure (see section "Special instructions", "impact on the function of the kidneys"), interstitial nephritis. On the part of the skin: photosensitivity reactions, peeling of the skin (including erythema multiforme and Stevens-Johnson syndrome), toxic epidermal necrolysis, acute generalized exantmatous pustus. Reproductive system: menstrual disorders.
Overdose
The clinical experience of overdose is limited. Without clinically significant side effects, single doses of up to 1,200 mg and multiple doses of up to 1,200 mg were taken in 2 doses per day. If overdose is suspected, appropriate supportive therapy should be provided. Presumably dialysis is not an effective method of removing the drug from the blood, due to the high degree of drug binding to plasma proteins.
Interaction with other drugs
In vitro studies have shown that celecoxib, although not a substrate of the CYP2D6 isoenzyme, inhibits its activity. Therefore, there is the likelihood of drug interaction in vivo with drugs whose metabolism is associated with CYP2D6 isofermeitis. Warfarin and other anticoagulants: an increase in prothrombin time is possible with simultaneous administration. blood 2 times. This effect is associated with inhibition of celecoxib metabolism by fluconazole via the CYP2C9 isoenzyme.Patients taking flucoiazole (an inhibitor of the CYP2C9 isoenzyme) celecoxib should be used at the lowest recommended dose (see section Dosage and administration). Ketoconazole (an inhibitor of the CYP3A4 isoenzyme) has no clinically significant effect on celecoxib metabolism. ACE inhibitors / angiotensin II antagonists: Inhibition of prostaglandin synthesis may reduce the antihypertensive effect of ACE inhibitors and / or angiotensin II antagonists. This interaction should be taken into account when using celecoxib in conjunction with ACE inhibitors and / or angiotensin II antagonists. However, there was no significant pharmacodynamic interaction with lisinopril regarding the effect on BP. In elderly patients who are dehydrated (including patients receiving diuretic therapy) or in patients with impaired renal function, the simultaneous use of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors can lead to a deterioration in kidney function, including possible acute renal failure. These effects are usually reversible. Diuretics: previously known NSAIDs in some patients may reduce the natriuretic effect of furosemide and thiazides by reducing renal prostaglandin synthesis, this should be borne in mind when using celecoxib. Oral contraceptives: there was no clinically significant effect on the pharmacokinetics of the contraceptive combination (1 mg norethisterone / 35 µg ethinyl estradiol). Lithium: There was an increase in plasma lithium levels by about 17% when co-taking lithium and celecoxib. Patients receiving lithium therapy should be closely monitored when taking or canceling celecoxib. Other NSAIDs: the simultaneous use of celecoxib and other NSAIDs (not containing acetylsalicylic acid) should be avoided. Other drugs: no clinically significant interactions between celecoxib and antacids (aluminum and magnesium-containing drugs), omeprazole, methotrexate, glibenclamide, phenytoin or tolbutamide have been observed. Celecoxib does not affect the antiplatelet effect of acetylsalicylic acid, taken in low doses. Celecoxib has a weak effect on platelet function, so it cannot be considered as a substitute for acetylsalicylic acid used in the prevention of cardiovascular diseases.
special instructions
Celebrex, given the antipyretic effect, can reduce the diagnostic significance of a symptom such as fever and affect the diagnosis of infection. Effect on the cardiovascular system Celecoxib, like all coxibs, may increase the risk of serious complications of the cardiovascular system, such as thrombus formation, myocardial infarction and stroke, which can be fatal. The risk of these reactions may increase with the dose, the duration of the drug, as well as in patients with diseases of the cardiovascular system and risk factors for such diseases. To reduce the risk of these reactions in patients receiving Celebrex, it should be used in the smallest effective doses and as short as possible (at the discretion of the attending physician). The attending physician and patient should keep in mind the possibility of such complications even in the absence of previously known symptoms of impaired function of the cardiovascular system. Patients should be informed about the signs and symptoms of a negative effect on the cardiovascular system and on measures to be taken if they occur. When using NSAIDs (selective COX-2 inhibitors) in patients after coronary bypass surgery for the treatment of pain in the first 10-14 days may increase the incidence of myocardial infarction and cerebral circulation disorders. Due to the weak effect of celecoxib on platelet function, it cannot be a substitute for acetylsalicylic acid You for the prevention of thromboembolism. Also in this regard, antiplatelet therapy (for example, acetylsalicylic acid) should not be discontinued in patients at risk of developing thromboembolic complications. Like all NSAIDs, celecoxib can lead to increased blood pressure, which can also cause cardiovascular complications. All NSAIDs, including celecoxib, in patients with arterial hypertension should be used with caution. Blood pressure monitoring should be carried out at the beginning of celecoxib therapy, as well as during the course of treatment. Influence on patients with celecoxib on the gastrointestinal tract, extremely rare cases of perforation, ulceration and bleeding from the gastrointestinal tract were observed.The risk of these complications in the treatment of NSAIDs is highest in the elderly, patients with cardiovascular diseases, patients simultaneously receiving acetylsalicylic acid, and patients with such diseases of the gastrointestinal tract as ulcers, bleeding, inflammation in the acute stage and in history. Other risk factors for the development of bleeding from the gastrointestinal tract are simultaneous use with oral GCS and anticoagulants, a long period of NSAID therapy, smoking, and alcohol consumption. Most of the spontaneous reports of serious side effects on the gastrointestinal tract were for elderly and debilitated patients. Combined use with warfarin and other anticoagulantsSome serious (some of them were fatal) bleeding in patients who received concomitant treatment with warfarin or similar drugs were reported. Since an increase in prothrombin time has been reported, anti-coagulant activity should be monitored after initiating treatment with Celebrex or changing its dose. Fluid retention and edema As with other drugs that inhibit prostaglandin synthesis, a number of patients taking Celebrex may experience fluid retention and swelling therefore, care should be taken when using this drug in patients with conditions predisposing or worsening due to fluid retention. . Patients with a history of heart failure or arterial hypertension should be closely monitored. Effects on renal function of PNVP, including celecoxib, can have a toxic effect on renal function. It was found that celecoxib is not more toxic than other NSAIDs. Celebrex should be used with caution in patients with impaired renal function, heart failure, impaired liver function, and in elderly patients. The function of the kidneys in such patients should be carefully monitored. Care should be taken when using the drug Celebrex in patients with dehydration. In such cases, it is advisable to first rehydrate, and then begin therapy with Celebrex. Effects on the function of the liver Celebrex should not be used in patients with severe hepatic impairment (class C according to the Child-Pyo classification).Celebrex should be used with caution when treating patients with moderately severe liver failure and given at the lowest recommended dose. In some cases, severe reactions were observed from the liver, including fulminant hepatitis (sometimes fatal), hepatic necrosis, hepatic failure (sometimes fatal or the need for a liver transplant). Most of these reactions developed 1 month after starting celecoxib. Patients with symptoms and / or signs of abnormal liver function, or those patients who have abnormal liver function using laboratory methods, should be carefully monitored for more severe reactions. liver during treatment with the drug Celebrex. Anaphylactic reactions When taking the drug Celebrex, cases of anaphylactic reactions have been reported. Serious reactions of the skin when receiving celecoxib to serious reactions were observed from the side of the skin, such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, some of them were fatal. The risk of such reactions is higher in patients at the beginning of therapy; in most cases noted, such reactions began in the first month of therapy. Celebrex should be discontinued when a skin rash, mucosal changes or other signs of hypersensitivity occur. was investigated. However, based on the pharmacodynamic properties and overall safety profile, it seems unlikely that Celebrex has such an effect.