Celebrex capsules 100 mg 10 pcs
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Active ingredients
Celecoxib
Release form
Capsules
Composition
Active ingredient: Celecoxib (Celecoxibum) Active ingredient concentration (mg): 100
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
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 dosesIncreasing Cmax and AUC occurs less proportionally. Effect of eating Celecoxib intake along with fatty foods increases the time to reach Cmax by about 4 hours and increases total absorption by about 20%. with 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.
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
- 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 phase; - gastrointestinal bleeding; - intestinal inflammatory diseases; - cardiac failure (II-IV functional classes according to NYHA classification); - clinically confirmed coronary artery disease; - peripheral artery diseases and severe cerebrovascular diseases; - severe hepatic insufficiency awn (no experience); - severe renal insufficiency (no experience); - pregnancy; - lactation (breastfeeding); - children and adolescents under 18 (no experience); - hypersensitivity to the drug; - hypersensitivity to sulfonamides.
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
There are insufficient data on the use of celecoxib in pregnant women. The potential risk of using Celebrex during variability has not been established, but cannot be excluded. According to the mechanism of action, with the use of NSAIDs, including celecoxib, some women may develop changes in the ovaries, which can cause complications during pregnancy. Women who are planning a pregnancy or being screened for infertility should consider withdrawing NSAIDs, including celecoxib. Celecoxib, a group of prostaglandin synthesis inhibitors, when taken during pregnancy, especially in the third trimester, can cause weak uterine contractions and premature closure of the arterial duct. The use of prostaglandin synthesis inhibitors at an early stage of pregnancy can adversely affect the course of pregnancy. There is limited evidence that celecoxib is excreted in breast milk. Studies have shown that celecoxib is secreted into breast milk at very low concentrations. However, taking into account the potential for side effects of celecoxib in an infant to be fed, the feasibility of canceling either breastfeeding or taking celecoxib should be evaluated, given the importance of taking Celebrex for the mother.
Dosage and administration
The drug is taken orally, regardless of the meal, without chewing, drinking water. Since the risk of possible cardiovascular complications may increase with an increase in the dose and duration of Celebrex, it should be prescribed as short as possible and in the smallest effective doses. The maximum recommended daily dose for long-term use is 400 mg. For symptomatic treatment of osteoarthritis, the recommended dose is 200 mg / day for 1 or 2 doses. For symptomatic treatment of rheumatoid arthritis, the recommended dose is 100 mg or 200 mg 2 times / day. For symptomatic treatment of ankylosing Spondylitis The recommended dose is 200 mg / day in 1 or 2 doses. In some patients, the effectiveness of the use of the drug in a dose of 400 mg 2 times / day is noted. When treating pain syndrome and primary dysmenorrhea, the recommended initial dose is 400 mg followed by, if necessary, receiving an additional dose of 200 mg on day 1.In the following days, the recommended dose is 200 mg 2 times / day, if necessary. Patients of advanced age usually do not need dose adjustment. However, in patients with a body weight below 50 kg, it is better to start treatment with the lowest recommended dose. Patients with a mild degree of liver failure (class A on the Child-Pugh scale) do not need dose adjustment. In the case of moderate liver failure (class B on the Child-Pugh scale), treatment should begin with the minimum recommended dose. There is no experience of using the drug in patients with severe hepatic impairment (class C on the Child-Pugh scale). Patients with renal insufficiency of mild and moderate severity do not require dose adjustment. Patients taking fluconazole (CYP2C9 inhibitor), Celebrex should be prescribed at the minimum recommended dose. The drug should be used with caution at the same time as other inhibitors of the CYP2C9 isoenzyme. Celebrex should be used with caution in patients who are slow metabolizers or are suspected of such a condition, since this can lead to the accumulation of high concentrations of celecoxib in the blood plasma. In such patients, the initial recommended dose of the drug should be reduced by 2 times.
Side effects
Often (≥ 1% and <10%) General reactions: exacerbation of allergic diseases, flu-like syndrome, accidental injuries. From the cardiovascular system: peripheral edema. From the digestive system: abdominal pain, diarrhea, dyspepsia, flatulence, diseases of the teeth ( post-extraction lune alveolitis). From the nervous system: dizziness, increased muscle tone, insomnia. From the urinary system: infection of the urinary tract. From the respiratory system: bronchitis, cough, pharyngitis, rhinitis, sinusitis , upper respiratory tract infections. From the skin: itchy skin, skin rash. Often (≥ 0.1% and <1%) General reactions: swelling of the face. From the hematopoietic system: anemia, ecchymosis, thrombocytopenia. From the cardiovascular system : weighting of the course of arterial hypertension, increased blood pressure, arrhythmia, hot flashes, palpitations,tachycardia. From the sensory organs: tinnitus, blurred vision. From the digestive system: vomiting. From the nervous system: anxiety, drowsiness. From the skin: alopecia, urticaria.Redko (≥ 0.01% and <0.1%) side of the cardiovascular system: the manifestation of congestive heart failure, ischemic stroke and myocardial infarction. On the part of the digestive system: gastric ulcer and duodenal ulcer, ulceration of the esophagus, intestinal perforation, pancreatitis, increased activity of liver enzymes.Alle rgic reactions: angioedema, bullous eruptions. On the nervous system: confusion. Side reactions identified by post-marketing observationsAllergic reactions: anaphylaxis. On the nervous system: hallucinations, aseptic meningitis. On the part of the senses: loss of taste, loss of obesity Since the cardiovascular system: vasculitis, bleeding in the brain. From the digestive system: gastrointestinal bleeding, hepatitis, liver failure, fulmi -invariant hepatitis, liver necrosis, cholestasis, cholestatic hepatitis, zheltuha.So the urinary system: acute renal failure, interstitial nephritis, nephrotic syndrome, minimal disturbance of function pochek.So the skin: photosensitivity, skin peeling (including with erythema multiforme and Stevens-Johnson syndrome), toxic epidermal necrolysis, drug rash in combination with eosinophilia and systemic symptoms (DRESS or hypersensitivity syndrome), acute generalized exanthematous pustules. From the reproductive system: menstrual disorder, decreased fertility in women side of the respiratory system: pulmonary embolism. Others: hyponatremia, chest pain.
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. 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.