Composition:For 1 capsule:
Active substance: celecoxib-200 mg.
Excipients: lactose monohydrate 43.15 mg, sodium croscarmellose 3.00 mg, sodium lauryl sulfate 8.10 mg, povidone K-30 6.75 mg, magnesium stearate 9.00 mg.
The composition of the capsule shell:
Case: gelatin 81,400%, methyl parahydroxybenzoate 0,800%, parahydroxybenzoate 0,200%, sodium lauryl 0,100%, water 14,500%, titanium dioxide 3,000%.
Cap: gelatin 82,237%, methylparahydroxybenzoate 0,800%, propylparahydroxybenzoate 0,200%, sodium lauryl sulfate 0,100%, water 14,500%, titanium dioxide 1,200%, dye azorubin 0,428%, dye Ponso 4R 0,535%.
Solid gelatine capsules No. 2, white housing, cap is dark red in color.
The contents of capsules-white or almost white powder.
Celecoxib has anti-inflammatory, analgesic and antipyretic action by blocking the formation of inflammatory prostaglandins (Pg) mainly due to the inhibition of cyclooxygenase-2 (COX-2). Induction of COX – 2 occurs in response to inflammation and leads to the synthesis and accumulation of prostaglandins, especially prostaglandin E2, while there is an increase in the manifestations of inflammation (swelling and pain). At therapeutic doses in humans celecoxibonline not inhibit cyclooxygenase-1 (COX-1) and has no effect on prostaglandins that are synthesized by activation of COX-1 and has no effect on the normal physiological processes associated with COX-1 and flowing in the tissues, primarily in tissues of the stomach, intestines and platelets.
The impact on renal function. Celecoxib reduces the urinary excretion of PgE2 and 6-keto-PgF1 (a prostacyclin metabolite), but no effect on serum thromboxane B2 and the urinary excretion of 11-dehydro-thromboxane B2, a thromboxane metabolite (both products of COX-1). Celecoxib does not cause a reduction of glomerular filtration rate in elderly patients and individuals with chronic renal failure, and transiently reduces the excretion of sodium. Patients with arthritis of the observed incidence of peripheral edema, hypertension, and heart failure is comparable to that in patients receiving non-selective COX inhibitors, which have inhibitory activity against COX-1 and COX-2.
Suction. When taking on an empty stomach, celecoxib is well absorbed, reaching a maximum concentration (Cmax) in plasma after about 2-3 hours. Cmax in plasma after taking 200 mg-705 ng / ml. The absolute bioavailability of the drug has not been investigated. Cmax, and the area under the pharmacokinetic curve “concentration-time ” (AUC) is approximately proportional to the dose taken in the dose range up to 200 mg 2 times a day; when the drug is used in higher doses, the degree of increase in Cmax and AUC is less proportional.
The impact of eating. Welcome celecoxib together with fatty foods increases the time to reach Cmax by about 4 hours and increases full absorption by about 20%.
Distribution. Communication with plasma proteins does not depend on the concentration and is about 97%, celecoxib does not bind to red blood cells. The drug penetrates the blood-brain barrier.
Metabolism. Celecoxib is metabolized in the liver by gidrauxilirovania, oxidation and part of glukuronirovania. Metabolism occurs mainly by cytochrome P450 CYP2C9. (see “Interaction with other medicinal products”). Metabolites found in the blood are not pharmacologically active against COX-1 and COX-2. The activity of cytochrome P450 CYP2C9 is reduced in individuals with genetic polymorphisms such as homozygous for the CYP2C9*3 polymorphism, which leads to a decrease in the efficiency of the enzymes.
Breeding. Celecoxib is metabolized in the liver, excreted in the feces and urine as metabolites (57% and 27%, respectively), less than 1% of the dose – unchanged. If you re-use the half-life is 8-12 hours and clearance is about 500 ml/min. With repeated use the equilibrium concentrations in plasma are reached 5 days. The variability of the main pharmacokinetic parameters (AUC, Cmax, half-life) is about 30%. The average volume of distribution in the equilibrium state is approximately 4500 l / 70 kg in young healthy adult patients, indicating a wide distribution of celecoxib in the tissue.
Elderly patient. In patients older than 65 years, there is an increase in 1.5-2 times the average Cmax, AUC celecoxib, which is largely due to changes in body weight, rather than age (in elderly patients, as a rule, there is a lower average body weight than in younger people, which is why, under other equal conditions, higher concentrations of celecoxib are achieved). For the same reason, older women usually have a higher concentration of the drug in plasma than older men. These features of pharmacokinetics, as a rule, do not require dose adjustment. However, in elderly patients weighing less than 50 kg should begin treatment with the lowest recommended dose.
Race. Have a representative of the Negroid race celecoxib AUC is about 40% higher than that of Europeans. The causes and clinical significance of this fact are not known, so their treatment is recommended to start with the minimum recommended dose.
Impaired liver function. Celecoxib concentration in plasma in patients with mild hepatic insufficiency (class And on the classification of child-Pugh) change slightly. In patients with hepatic insufficiency of moderate severity (class according To the classification of child-Pugh) celecoxib concentration in plasma may increase by almost 2 times.
The impairment of renal function. In patients with chronic renal failure at glomerular filtration rate (GFR) > 65 ml/min/1.73 m2 and in patients with GFR equal to 35-60 ml/min/1.73 m2, the pharmacokinetics of celecoxib does not change. Not found significant relationships between serum creatinine (or creatinine clearance), and clearance celecoxib. It is assumed that the presence of severe renal insufficiency does not affect the clearance of celecoxib, since the main way of its removal is the transformation of the liver into inactive metabolites.
Celecoxib should be taken with caution under the following conditions: diseases of the gastrointestinal tract (peptic ulcer, bleeding history), infection with Helicobacter pylori,the joint use of anticoagulants (warfarin), antiplatelet agents (acetylsalicylic acid, clopidogrel) oral corticosteroids (prednisone), selective inhibitors of serotonin reuptake (citalopram, fluoxetine, paroxetine, sertraline); fluid retention and edema; the liver of moderate severity (see “Special instructions”); cardiovascular disease (see “Special instructions”); cerebrovascular disease; dyslipidemia / hyperlipidemia; diabetes mellitus; peripheral artery disease; simultaneous administration of inhibitors of CYP2C9; long-term use of NSAIDs; severe somatic diseases; ulcers disease stomach and duodenal ulcers, ulcerative colitis, Crohn’s disease, liver disease, a history of hepatic porphyria, chronic renal insufficiency (QC 30-60 ml/min), a significant decrease of circulating blood volume (including after surgery), elderly patients (including receiving diuretics, the weakened patients with low body mass), Smoking, prolonged use of NSAIDs, tuberculosis, alcoholism.
Pregnancy and lactation:
There is a lack of sufficient data on the use of celecoxib in pregnant women. The potential risk of using celecoxib during pregnancy is not established, but can not be excluded. Celecoxib, belonging to the group of prostaglandin synthesis inhibitors, when taken during pregnancy, especially in the III trimester, can cause weakness of uterine contractions and premature closure of the arterial duct.
There is limited evidence that celecoxib is excreted in breast milk. Taking into account the potential for adverse effects in a child, should assess the appropriateness of continued breastfeeding, given the importance of the reception celecoxib mother.
The use of the drug may adversely affect female fertility and is not recommended for women planning pregnancy. In patients with infertility (including undergoing examination) it is recommended to cancel the drug.
Method of application and doses:
Inside, not liquid, squeezed water, regardless of meals.
Because the risk of cardiovascular complications may increase with increasing dose and duration of taking the drug Roboxin-Rotek should take the minimum effective dose minimum possible course. The maximum recommended daily dose for long-term administration is 400 mg.
Symptomatic treatment of osteoarthritis: the recommended dose is 200 mg per day.
Symptomatic treatment of rheumatoid arthritis: the recommended dose is 200 mg 1-2 times a day.
Symptomatic treatment of ankylosing spondylitis: the recommended dose is 200 mg 1-2 times a day.
Treatment of pain and primary dysmenorrhea: the recommended starting dose is 400 mg, followed if necessary by further doses of 200 mg on the first day. In the following days, the recommended dose is 200 mg 2 times a day, if necessary.
Elderly patients: generally, dose adjustment is not required. However, in patients weighing less than 50 kg treatment is better to start with the lowest recommended dose.
The impaired liver function: in patients with mild hepatic insufficiency (class And on the classification of child-Pugh) dose adjustment is not required in the case of liver failure of moderate severity (class according To the classification of child-Pugh) treatment should begin with the minimum recommended dose. The drug Celecoxib should not take patients with severe hepatic impairment (see “Contraindications”.).
The violation of the kidney: insufficiency dose adjustment is not required. Experience in the use of the drug in patients with severe renal insufficiency is not (see section “Special instructions”).
Concurrent use of fluconazole: patients receiving fluconazole (inhibitor of CYP2C9), drug Rocksim-Rotek should assign the minimum recommended dose.
The frequency of side effects listed below was determined accordingly (world health organization classification): very often (more than 10%), often (more than 1% and less than 10%), infrequently (more than 0.1% and less than 1%), rarely (more than 0.01% and less than 0.1%), very rarely (less than 0.01%), including individual messages; the frequency is unknown (can not be estimated using available data).
From the cardiovascular system: often: peripheral edema, increased blood pressure, weighting the flow of hypertension; infrequently: “tides”, a feeling of heartbeat; rarely: tachycardia, a manifestation of congestive heart failure, ischemic stroke and myocardial infarction; very rarely – vasculitis.
The gastro-intestinal tract: often – abdominal pain, diarrhea, dyspepsia, flatulence, vomiting; rare – diseases of the teeth (alveolus postextraction alveolitis); rarely gastric and duodenal ulcers, ulceration of the esophagus, gastrointestinal bleeding; very rarely – intestinal perforation, pancreatitis.
From the nervous system: often – dizziness, insomnia; rare – anxiety, increased muscle tone, drowsiness; rarely – confusion (psychosis), hallucinations; rarely – bleeding in the brain, aseptic meningitis, loss of taste sense, loss of sense of smell.
The kidneys and urinary system: often – urinary tract infection; rare – acute renal failure, hyponatremia; very rarely – interstitial nephritis, nephrotic syndrome, impaired renal function.
From the respiratory system: often-bronchitis, cough, sinusitis, upper respiratory tract infections; infrequently-pharyngitis, rhinitis; very rarely – pulmonary embolism.
With the skin: often – itching, skin rash; rarely, urticaria, ekhimozy; rare – alopecia, photosensitivity; very rarely – erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash in combination with eosinophilia and systemic symptoms (DRESS, or hypersensitivity syndrome), acute generalized absentmindly Pustules, exfoliative dermatitis.
From the blood: infrequently-anemia, ecchymosis, rarely-thrombocytopenia.
From the immune system: rarely – angioedema; very rarely – bullous rashes; very rarely – anaphylactic reaction.
From the hepatobiliary system: infrequently – increased activity of “hepatic” enzymes; rarely-hepatitis; very rarely – liver failure, fulminant hepatitis, liver necrosis, cholestasis, cholestatic hepatitis, jaundice.
From the sensory organs: rare – the feeling of “noise” in my ears, “blurred” vision, conjunctivitis.
On the part of the reproductive system: rarely – menstrual disorders; the frequency is unknown – reduced fertility in women.
General: infrequently-exacerbation of allergic diseases, flu-like syndrome, swelling of the face, chest pain.
Clinical experience of overdose is limited. Single doses up to 1200 mg and multiple doses up to 1200 mg in 2 doses per day were used without clinically significant side effects.
If you suspect an overdose it is necessary to provide appropriate supportive therapy. Presumably dialysis is not an effective method of removing the drug from the blood because of the high degree of binding of the drug with protein.
Studies in vitro have shown that although celecoxib is not a substrate of CYP2D6, but inhibits its activity. Therefore, there is a possibility of drug interaction “invivo” with drugs whose metabolism is associated with cytochrome CYP2D6.
Warfarin and other anticoagulants (for example, coumarin preparations, sulfonamides): while taking may increase prothrombin time.
Fluconazole, ketoconazole: patients taking fluconazole (CYP2C9 inhibitor) should be administered at the lowest recommended dose (see “Dosage and administration”). Ketoconazole (cyp3 A4 inhibitor) has no clinically significant effect on the metabolism of celecoxib.
CYP 2C9 inducers: concomitant use of CYP 2C9 inducers, such as rifampin, chlorpheniramine, promethazine, cholestyramine, carbamazepine and barbiturates may reduce plasma concentrations of celecoxib.
Angiotensin converting enzyme inhibitors / angiotensin II antagonists: inhibition of prostag andin synthesis can reduce the antihypertensive effect of angiotensin converting enzyme inhibitors (ACE) / angiotensin II antagonists. This interaction should be taken into account in appointing celecoxib in conjunction with ACE inhibitors / angiotensin II antagonists. However, there was no significant pharmacodynamic interaction with lisinopril in relation to the effect on blood pressure.
Diuretics: previously known NSAIDs in some patients can reduce the natriuretic effect of furosemide and thiazides by reducing renal prostaglandin synthesis, it should be borne in mind when assigning celecoxib.
Oral contraceptives: there was no clinically significant effect on the pharmacokinetics of contraceptive combination (1 mg of norethisterone /35 µg of ethinyl estradiol).
Lithium: there was an increase in the concentration of lithium in plasma by about 17% with co-administration of lithium and celecoxib. Patients receiving lithium therapy should be under careful surveillance when assigning or canceling celecoxib.
Other NSAIDs: simultaneous use of celecoxib and other NSAIDs (not containing acetylsalicylic acid) Should be avoided.
Digoxin: it is possible to increase the level of digoxin in blood plasma when combined with celecoxib.
Antidiabetic agents for oral use: may increase hypoglycemic effect.
Other drugs: there were no clinically significant interactions between celecoxib and antacids (aluminium – and magnesium-containing drugs), omeprazole, methotrexate, glibenclamide, phenytoin or tolbutamide.
The combined use of acetaminophen increases nefrotoksicnosti, with methotrexate – gepato – and nefrotoksicnosti.
Simultaneous administration of celecoxib and methotrexate is possible only with the use of low doses of the latter (control of the concentration of methotrexate in blood plasma is required).
Probenecid reduces plasma clearance and the volume of distribution of celecoxib, increases its concentration in blood plasma and increases the half-life.
When taking Mifepristone, celecoxib can be used 8-12 days after taking mifepristone, as NSAIDs reduce the effect of drugs of this group.
Celecoxib does not affect the antiplatelet action of acetylsalicylic acid, so it can not be considered as a replacement of acetylsalicylic acid, prescribed for the prevention of cardiovascular disease.
Influence on the cardiovascular system. Celecoxib, like all coxibe, can increase the risk of serious complications in the cardiovascular system, such as thrombosis, myocardial infarction and stroke, which can lead to death. The risk of these reactions may increase with the duration of taking the drug, as well as in patients with diseases of the cardiovascular system. To reduce the risk of these reactions in patients taking Celecoxib, it should be prescribed in the lowest recommended doses and the shortest possible periods (at the discretion of the attending physician). The attending physician and patient should bear in mind the possibility of such complications even in the absence of previously known cardiovascular symptoms. Patients should be informed about the signs and symptoms of adverse effects on the cardiovascular system and the measures to be taken in case of their occurrence.
All NSAIDs, including celecoxib, in patients with arterial hypertension should be used with caution. Monitoring of blood pressure should be carried out at the beginning of therapy with celecoxib, as well as during the course of treatment.
Effect on the gastrointestinal tract. In patients taking celecoxib were observed very rare cases of perforation, ulceration and bleeding from the gastrointestinal tract. The risk of these complications in the treatment of NSAIDs is highest in older people with cardiovascular diseases, patients simultaneously receiving acetylsalicylic acid, and patients with diseases of the gastrointestinal tract such as ulcers, bleeding in the acute stage and history. Most spontaneous reports of serious side effects on the gastro-intestinal tract belonged to elderly or debilitated patients.
Sharing with warfarin and other anticoagulants. Serious (some of them fatal) bleeding was reported in patients receiving concomitant treatment with warfarin or similar agents. Since an increase in prothrombin time has been reported, anticoagulant activity should be monitored after starting treatment with celecoxib or changing its dose.
Fluid retention and swelling. As the use of other drugs inhibiting prostaglandin synthesis, a number of patients taking celecoxib may experience fluid retention and swelling, so care should be taken in appointing the drug to patients with conditions predisposing to or worsening because of fluid retention. Patients with a history of heart failure or hypertension should be under close supervision.
The impact on renal function. Celecoxib should be used with caution in patients with impaired renal function. Kidney function in such patients should be carefully monitored.
Caution should be exercised when prescribing therapy with celecoxib in patients with dehydration. In such cases, it is advisable to first carry out rehydration, and then start therapy with celecoxib.
Influence on liver function. Celecoxib should be used with caution in the treatment of patients with moderate hepatic insufficiency and administered at the lowest recommended dose.
In some cases we observed severe reactions in the liver, including fulminant hepatitis (sometimes fatal), liver necrosis (sometimes with a fatal outcome or need liver transplantation). Most of these reactions develop after 1 month after starting celecoxib.
Patients with symptoms and / or signs of impaired liver function, or those patients who have revealed impaired liver function by laboratory methods, should be under close supervision for the development of more severe reactions from the liver during the treatment with celecoxib.
Anaphylactic reaction. When you receive celecoxib have been reported cases of anaphylactic reactions.
Celecoxib, given antipyretic effect, can reduce the diagnostic significance of such symptoms as fever and affect the diagnosis of infection.
Serious reactions from the skin. Very rarely when taking celecoxib was marked by serious reactions of the skin such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, some of them were fatal. The higher the risk of such reactions in patients at the beginning of therapy, in most cases, such reactions began in the first month of therapy. Should stop taking celecoxib the appearance of skin rash, changes in mucous membranes or other signs of hypersensitivity.
Influence on the ability to drive transports. Ms. and fur.:
The influence of celecoxib on the ability to drive and control mechanisms has not been investigated. However, based on the pharmacodynamic properties and General safety profile, it seems unlikely that celecoxib has such an effect.
Capsules, 200 mg.
10 capsules in aluminium/PVC/PVDC blister.
1 blister with the instruction on application place in a cardboard box.
At a temperature not exceeding 30° C.
Keep out of reach of children.
Do not use after expiry date.
The terms of release from pharmacies:prescription
|The purpose of the medication||Coxibes|