Celebrex
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Celebrex - NSAIDs, not narcotic analgetic, anaesthetising; a specific inhibitor of cyclooxygenase of 2nd type (COX-2). Does not interfere with normal physiological processes in a stomach, an intestine, thrombocytes. It is applied to an expected treatment of an inflammation and pains: an osteoarthritis (an osteoarthrosis, an arthrosis), a pseudorheumatism, a reactive synovitis.
CELEBREX.
Structure and the release form:
Celebrex capsules for peroral application on 10 or 30 pieces in packing.
1 capsule Celebrex contains: Celecoxib 100 or 200 mg.
Active-operating substance:
Celecoxib.
Properties / Action:
Celebrex - a nonsteroid antiinflammatory preparation, not narcotic analgetic, anaesthetising. Celebrex - a specific inhibitor of cyclooxygenase of 2nd type (COX-2).
Celebrex (Celecoxib) is the agent of the new class which mechanism of action consists in inhibition of synthesis of Prostaglandinums, first of all, at the expense of inhibition of cyclooxygenase of 2nd type (COX-2). In therapeutic concentration at person Celebrex (Celecoxib) does not inhibit (COX-1).
COX-2 it is induced in reply to inflammatory stimulus. It leads to synthesis and accumulation inflammatory prostanoids, in particular, Prostaglandinum E2 that causes an inflammation, edemas and a pain. Celecoxib operates as an antiinflammatory preparation at the expense of blocking of production inflammatory prostanoids by means of inhibition of cyclooxygenase of 2nd type.
Researches in vivo and ex vivo show that Celebrex (Celecoxib) possesses very low affinity constitutively to expressed enzyme to cyclooxygenase of 1st type. Hence, in therapeutic doses Celebrex (Celecoxib) does not render influence on prostanoids, synthesised at the expense of activation COX-1, and thanks to it does not interfere with the normal physiological processes bound with COX-1 in tissues, especially in a stomach, an intestine, thrombocytes.
In controllable clinical tests it has been shown that frequency of serious complications (cankers of a stomach and a duodenum, bleedings, perforations, obstruction pyloric apertures) against reception Celebrex authentically does not differ from placebo and almost in 8 times more low, than at application of nonspecific inhibitors COX (indometacin, diclofenac, Ibufrofenum, Naproxenum, aspirin, etc.).
Frequency ulceration at treatment Celebrex authentically did not differ from placebo, did not show dependence on a dose in a range of doses from 50 to 400 mg 2 times/sut and constantly was in 3-4 times more low, than at application of nonspecific inhibitors COX.
Celebrex in comparison with placebo did not render influence on aggregation of thrombocytes and a bleeding time at application in therapeutic doses and doses, sixfold exceeding therapeutic.
Pharmacokinetics:
At reception Celebrex on an empty stomach Celecoxib it is well soaked up, and approximately in 2-3 hours the peak of its concentration in plasma is reached. Biological availability Celebrex - 99 %. Reception Celebrex with nutrition (especially rich with fats) slows down absorption with augmentation of time of achievement of peak of concentration on 4 h. Linkage Celecoxib with fibers of plasma which does not depend on dose Celebrex, makes about 97 %. Celecoxib it is metabolized in a liver by hydroxylation, oxidations and some glucuronide. Researches in vitro and in vivo show that metabolism Celecoxib is carried out mainly by cytochrome P450 CYP2C9. The basic metabolites which are found out in a blood, do not possess appreciable inhibiting action on COX-1 and COX-2. Deducing Celecoxib is carried out mainly by a liver; less than 1 % of a dose is excreted with urine in not changed kind. After multiple dose Celebrex semideducing time makes 8-12 hours, a clearance - about 500 ml/minutes At a multiple dose equilibrium concentration Celecoxib in plasma is reached by 5 day. Celecoxib it is in regular intervals distributed in tissues, it is capable to get through a hematoencephalic barrier.
At elderly patients with mass of a body below average (50 kg) it is necessary to begin treatment with the minimum recommended dose Celebrex.
At patients with moderate hepatic insufficiency of concentration Celecoxib in plasma approximately twice above, than at corresponding control group. For patients with easy disturbance of function of a liver of selection of dose Celebrex it is not required. Treatment Celebrex of patients with moderate hepatic insufficiency should be begun with the minimum recommended dose.
at elderly volunteers with age depression of rate glomerular filtrations (GFR) (average GFR> 65 ml/minutes/1 of 73 m 2 ) and at patients with chronic stable renal insufficiency (GFR 35-60 ml/minutes/1 of 73 m 2 ) compared Pharmacokinetics Celecoxib to pharmacokinetics Celebrex at patients with normal function of kidneys. Authentic communication between Serum creatinine (or a creatinine clearance) and clearance Celecoxib it was revealed not. Serious renal insufficiency should not influence clearance Celecoxib.
Indications:
Celebrex it is applied to an expected treatment of an inflammation and pains:
Way of application and a dose:
Application Celebrex for adults:
the Osteoarthritis : usual recommended daily dose Celebrex makes 200 mg and is accepted once a day or is parted on two doses. If necessary it is possible to apply a dose of 200 mg on two times a day (400 mg/sut).
the Pseudorheumatism : recommended daily dose Celebrex makes 200-400 mg and is parted on two doses.
Application Celebrex for the elderly: selection of dosage Celebrex usually it is not required. However at elderly patients with mass of a body below average (50 kg) treatment is recommended to begin with the lowest recommended dose.
Application Celebrex at disturbance of function of a liver: for patients with easy disturbances of function of a liver of selection of dosage Celebrex it is not required. Treatment Celebrex of patients with moderate disturbances of function of a liver begin with is minimum recommended dose. Clinical experience of treatment Celebrex of patients with serious disturbances of function of a liver is not available.
Application Celebrex at disturbance of function of kidneys: for patients with easy and moderate disturbances of function of kidneys of selection of dosage Celebrex it is not required. Clinical experience of treatment Celebrex of patients with serious disturbances of function of kidneys is not available.
Application Celebrex for children:
Application Celebrex for persons is younger than 18 years was not studied.
Overdosage:
Clinical experience on overdosages Celebrex is not available. Healthy volunteers accepted unitary dose Celebrex to 1200 mg and repeatedly to 1200 mg on two times a day without clinically significant adverse effects. In case of suspicion on overdosage Celebrex it is necessary to provide corresponding supporting treatment. The dialysis, most likely, is not an effective method of deducing Celebrex.
Contraindications:
Celebrex apply with care: allergic reactions to others NSAIDs (for example, an urticaria), serious disturbances of function of a liver and kidneys, a heart failure, a stomach and duodenum peptic ulcer in an exacerbation phase, pregnancy, age till 18 years and advanced age.
Application at pregnancy and feeding:
the Clinical data on application Celebrex at pregnancy is not available. Researches on animals have found out toxic action on a foetus in development. The possible risk for the person is not known. Celebrex it is not necessary to apply at pregnancy without obvious necessity. As on the person it was not spent researches for an estimation of influence Celebrex on closing a duct, it is necessary to avoid its appointment in the third trimester of pregnancy. Application Celebrex in I and II trimesters of pregnancy is possible only in that case when the prospective advantage for mother exceeds potential risk for a foetus.
Researches on rats show that Celecoxib is allocated in milk in the concentration close to those in plasma. As researches on the person it was not spent, Celebrex it is not necessary to prescribe in thoracal feeding. In need of application Celebrex in a lactemia it is necessary to solve a question on the termination of thoracal feeding.
Side effect:
In clinical tests Celebrex with active or platsebo-control frequency of cancellation of the treatment caused by the adverse phenomena, made 7,1 % for the patients receiving Celebrex, and 6,1 % for the patients receiving placebo. Frequency of the adverse phenomena on which it was informed in controllable clinical tests, was following:
often meeting (> 1 %) :
From the alimentary system: an abdominal pain, a diarrhoeia, a dyspepsia, a meteorism, a nausea.
From a CNS and peripheric nervous system: a headache, giddiness, a sleeplessness.
From respiratory system: a pharyngitis, a rhinitis, a sinusitis, infections of the top respiratory tracts.
Dermatological reactions: an itch, an eruption.
Other: peripheric edemas.
seldom meeting (1 %-0.1 %) :
From hemopoiesis system: an anaemia.
From cardiovascular system: a hypertensia, palpitation.
From the alimentary system: a constipation, an eructation, a gastritis, a stomatitis, vomiting, disturbance of function of a liver, rising ACT and ALT.
From a metabolism: deviations from norm of results of analyses of function of kidneys.
From a CNS and peripheric nervous system: a sight illegibility, a hypertonia, paresthesia, uneasiness, depression.
From respiratory system: tussis, a dyspnea.
From integuments: an urticaria.
Other: cramps in feet, a ring in ears, fatigability, an infection of urinary ways.
the Extremely rare (<0.1 %) :
From hemopoiesis system: a leukopenia, a thrombocytopenia.
From the alimentary system: a stomach ulcer and a duodenum, a dysphagia, intestine punching, an esophagitis, a melena.
From a CNS and peripheric nervous system: ataxia.
From integuments: an alopecia, a photosensitivity.
Other: taste change.
Special indicatings and safety measures:
Appointment Celebrex as the patient with a stomach or duodenum peptic ulcer in the anamnesis probably only in case of full remission of disease.
At some patients accepting Celebrex, the delay of a liquid and edemas was observed. Therefore at patients with the broken warm function and other conditions contributing to a delay of a liquid, Celebrex it is necessary to apply with care.
At elderly patients with a body underweight, at patients with moderate disturbances of function of a liver and with a heart failure treatment Celebrex is necessary for beginning with the minimum doses. At serious renal and hepatic insufficiency Celebrex it is necessary to apply only in exclusive circumstances.
Celebrex it is possible to apply with low doses of Acidum acetylsalicylicum. In connection with absence of action with thrombocytes Celebrex does not replace Acidum acetylsalicylicum at preventive treatment of cardiovascular disturbances.
Metabolism Celebrex is mediated mainly by cytochrome P450 CYP2C9 in a liver. At patients with the proved or prospective depression of activity of metabolizing factor CYP2C9 it is necessary to prescribe Celebrex with care as because of the lowered metabolic clearance at them level Celecoxib in plasma can excessively raise.
the Clinical data about efficiency and safety of application Celebrex at children and teenagers is elderly till 18 years is absent.
Influence on ability to drive the car and to work with technics:
Influence Celebrex on ability to drive the car and to work with technics it was not studied, but, proceeding from it pharmacodynamic properties and the general profile of safety, such effect is represented improbable.
Medicinal interaction:
At studying of influence Celebrex on pharmacokinetics and-or a pharmacodynamics of substrates CYP2C9 Glyburidum, Phenytoinum, Tolbutamidum and warfarin in vivo clinically significant interactions it was revealed not. Nevertheless, at appointment Celebrex with warfarin it is necessary to apply safety measures as warfarin frames for such patients the raised risk of complications in the form of bleedings.
to the Patients receiving inhibitor CYP2C9 fluconazole, Celebrex it is necessary to prescribe in the minimum recommended dose (probably rising of concentration Celecoxib in plasma). At simultaneous appointment Celebrex it is necessary to be careful with other inhibitors CYP2C9.
Influence of inductors CYP2C9, such as rifampicin, carbamazepine and barbiturates, on pharmacokinetics Celecoxib was not studied.
Researches in vitro show that celecoxib though is not substrate CYP2D6, inhibits it. Researches in vivo, spent with substrate and inhibitor CYP2D6 use paroxetine, have not taped clinically significant interaction.
Enzyme CYP2C19 can be involved in metabolism Celecoxib in very small degree (~1 %). In research in vivo Celebrex did not influence a clearance of a single dose of substrate CYP2C19 of Phenytoinum. The risk of interaction with substrates CYP2C19 negligibly is small.
Ketokonazol (inhibitor CYP3A4) did not show essential interaction with Celebrex.
Antacids (an aluminium and magnesium hydroxide) reduce degree of absorption Celecoxib on 10 % that does not cause clinically significant effects.
At studying of influence Celebrex on pharmacokinetics of the medicines deduced through kidneys, lithium (lithium a carbonate) and Methotrexatum in vivo clinically significant interactions it was revealed not.
Storage conditions:
B.Hranit's List at temperature 15-30°C in a dry place inaccessible to children.
the Period of storage 3 years. The medicine should not be applied after the validity expiry of the term.
Conditions of holiday from a drugstore - it is released under the prescription.