Celebrex - instructions for use, dose, side effects, contraindications

lactose monohydrate 149.7 mg / 49.8 mg, sodium lauryl sulfate 8.1 mg / 8.1 mg, povidone K30 6.8 mg / 6.7 mg. croscarmellose sodium 2.7 mg / 2.7 mg, magnesium stearate 2.7 mg / 2.7 mg; shell: titanium dioxide about 1.7 mg, gelatin about 58.3 mg. Ink for capsules 100 mg (blue ink SB-6018) contain: Shellac 22-27%. ethanol 33-38%, isopropanol 0.5-4%, butanol 4-8%, propylene glycol 3-6%, ammonia water 1-2%, lacquer aluminum blue FD&C Blue # 2 on the basis of the dye indigotine (HI32-28%. Ink for capsules 200 mg (yellow ink SB-3002) contain shellac 22-27%, ethanol 33-38%, isopropanol 3-7%, butanol 4-9%, polyethylene glycol 3-6%, ammonia water 1-2%, iron dye oxide yellow (B 172) 18-22 %.

Capsules 400 mg

lactose monohydrate 99.6 mg, sodium lauryl sulfate 16.2 mg, povidone K30 13.4 mg, croscarmellose sodium 5.4 mg, magnesium stearate 5.4 mg; shell: titanium dioxide 2.79 mg, gelatin 79.69 mg. Ink (ink green SB-4027) contain: shellac 22-28%, ethanol 35-41%.isopropanol 1-6%, butanol 4-9%, propylene glycol 0.5-4.5%, ammonia water 0.5-3%. dye iron oxide yellow (12172) 13-17%, aluminum blue lacquer based on indigocarmine 4-9%.

Description:Capsule 100 mg: opaque white or almost white, hard gelatin capsule with white markings on blue strips: "100" - on one part and "7767" on the other part of the capsule.

Capsule 200 mg: opaque white or almost white, hard gelatin capsule with markings white on yellow strips: "200" - on one part and "7767" on the other part of the capsule.

Contents of the capsules: white or almost white granules.

Capsule 400 mg: An opaque white or almost white, hard gelatin capsule with a size of 0 with the inscription white on green strips: "400" on the capsule case and "7767" on the cap of the capsule.

Contents of capsules: granules of white or almost white color.

Pharmacotherapeutic group:NSAIDs (non-steroidal anti-inflammatory drug).

ATX: & nbsp

M.01.A.H.01 Celecoxib

Pharmacodynamics:

Celecoxib has anti-inflammatory, analgesic and antipyretic effects, blocking the formation of inflammatory prostaglandins (Pg) mainly due to inhibition of cyclooxygenase-2 (COX-2).Induction of COX-2 occurs in response to inflammation and leads to the synthesis and accumulation of prostaglandins, in particular prostaglandin Bt. thus there is an intensification of manifestations of inflammation (swelling and pain). In therapeutic doses in humans celecoxib does not significantly inhibit cyclooxygenase-1 (COX-1) and does not affect prostaglandins synthesized by activation of COX-1, nor does it affect normal physiological processes associated with COX-1 and that occur in tissues, stomach tissues, intestines and platelets.

Effect on kidney functionTselskoksib reduces urinary excretion PgE₂ and 6-keto-PgF₁ (metabolite prostacyclin), but does not affect serum thromboxane B₂ and urinary excretion of 11-dehydro-thromboxane B₂, a metabolite of thromboxane (both products of COX-1). Celecoxib does not cause a decrease in glomerular filtration rate (GFR) in elderly patients and people with chronic renal failure, transiently reduces excretion of sodium. In patients with arthritis, the observed incidence of peripheral edema, arterial hypertension and heart failure is comparable with that of non-selective COX inhibitors, which have inhibitory activity against COX-1 and 11, OG-2.The most pronounced effect was in patients receiving diuretic therapy. However, there was no increase in the incidence of high blood pressure and heart failure, and peripheral edema was mild and passed independently.

Pharmacokinetics:

Suction

When taken on an empty stomach celecoxib well absorbed, reaching maximum concentration (C_max) in the blood plasma after about 2-3 hours. FROM_max in the blood plasma after taking 200 mg - 705 ng / ml. Absolute bioavailability of the drug has not been studied. FROM_maxand the area under the pharmacokinetic curve "concentration-time" (AUC) approximately proportional to the dose taken in the dose range up to 200 mg twice a day; when using celecoxib in higher doses, the degree of increase in C_max and AUC occurs less proportionately.

Distribution

The connection with plasma proteins does not depend on the concentration and 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 section "Interaction with other drugs"). Metabolites found in the blood are not pharmacologically active against COX-1 and COX-2. The activity of cytochrome 1450 CYP2C9 decreased in persons with genetic polymorphism, such as homozygous for CYP2C9*3 polymorphism, which leads to a decrease in the effectiveness of enzymes.

Excretion

Celecoxib is metabolized in the liver, excreted through the intestines and kidneys in the form of metabolites (57% and 27%, respectively), less than 1% of the dose taken - unchanged. At repeated application the half-life period is 8-12 hours, and the clearance is about 500 ml / min. With repeated application, the equilibrium concentrations in the blood plasma are reached by day 5. The variability of the main pharmacokinetic

parameters (AUC, FROM_max, half-life) is about 30%. The average volume of distribution in the equilibrium state is approximately 500 l / 70 kg in young healthy adult patients, indicating a wide distribution of celecoxib in tissues.

Effect of food intake

Taking celecoxib along with fatty foods increases the time to reach C_max for about 4 hours and increases the total absorption by about 20%.

Special patient groups

Elderly patients

In patients older than 65 years, an increase of 1.5-2 times the average values C_max, AUC celecoxib, which is largely due to changes in body weight, rather than age (in elderly patients, as a rule, a lower average body weight is observed than in younger people, so that, with other conditions being equal, higher concentrations are achieved celecoxib). For the same reason, older women usually have a higher concentration of the drug in the blood plasma than in older men. These features of pharmacokinetics, 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 minimum recommended dose.

Race

Representatives of the Negroid race AUC celecoxib is about 40% higher than that of Europeans. The causes and clinical significance of this fact are not known.

Impaired liver function

Concentrations of celecoxib in blood plasma in patients with mild degree of hepatic insufficiency (class A according to the Child-Pugh classification) vary slightly.In patients with moderate hepatic insufficiency (class B according to the Child-Pugh classification), the concentration of celecoxib in the blood plasma can increase almost 2-fold.

Impaired renal function

In elderly patients with a decrease in GFR> 65 mL / min / 1.73 m²associated with age

and in patients with GFR. equal to 35-60 ml / min / 1.73 m², the pharmacokinetics of celecoxib do not change. There is no significant relationship between the serum creatinine content (or creatinine clearance (CC)) and the clearance of celecoxib. It is assumed that the presence of a severe degree of renal failure does not affect the clearance of celecoxib, since the main way of its elimination is to convert 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.

A complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses, and intolerance to acetylsalicylic acid or other NNRV, including other inhibitors of C0G-2 (including in the anamnesis).

The period after the operation of aortocoronary shunting.

Active erosive-ulcerative lesions of the mucous membrane of the stomach or duodenum, or peptic ulcer of the stomach and duodenal ulcer in the acute stage or gastrointestinal bleeding.

Inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the phase of exacerbation.

Chronic heart failure (II-IV functional class according to NYIIA).

Clinically confirmed ischemic heart disease, peripheral arterial disease and cerebrovascular disease in a pronounced stage.

Hemorrhagic stroke.

Subarachnoid hemorrhage.

Pregnancy and lactation period (see section "Application during pregnancy and during breast-feeding").

Severe hepatic insufficiency (no experience of use).

Severe renal insufficiency (QC less than 30 ml / min), progressive kidney disease,confirmed hyperkalemia (no experience of use).

Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption.

Age under 18 years (no experience of application).

Carefully:Celebrex should be taken with caution under the following conditions: gastrointestinal tract diseases (peptic ulcer of stomach and duodenum, ulcerative colitis, Crohn's disease, history of bleeding), presence of Helicobacter pylori infection; combined use with anticoagulants and (warfarin), antiplatelet agents (acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (prednisolone). diuretics, selective serotonin reuptake inhibitors (citalopram, fluoxetine, paroxetine, sertraline), digoxin; fluid retention and swelling; violations of the liver of moderate severity (see section "Special instructions"), liver disease in history, hepatic porphyria; chronic renal failure (CK 30-60 ml / min); a significant decrease in the volume of circulating blood (including after surgery); diseases of the cardiovascular system, arterial hypertension (see Fig.section "Special instructions"); cerebrovascular diseases; dyslipidemia / hyperlipidemia; diabetes; diseases of peripheral arteries; simultaneous application with inhibitors of the isoenzyme CYP2C9; in patients who are slow metabolizers or are suspected of such a condition; long-term use of NSAIDs; severe physical illness; elderly patients (including those receiving diuretics, weakened patients with low body weight); smoking; tuberculosis; alcoholism.

Pregnancy and lactation:

There is insufficient data on the use of celecoxib in pregnant women. The potential risk of using Celebrex® during pregnancy is not established, it can not be ruled out.

In accordance with the mechanism of action, when using NSAIDs, including celecoxib, some women may develop changes in the ovaries, which can lead to complications during pregnancy or impaired fertility. Women who plan pregnancy or undergo infertility examinations should consider abolishing NPHP, including celecoxib.

Celecoxib, which belongs to the group of prostaglandin synthesis inhibitors, when taken during pregnancy, especially in the third trimester, can cause weakness of uterine contractions and premature closure of the ductus arteriosus. The use of inhibitors of prostaglandin synthesis in the early stages of pregnancy can adversely affect the course of pregnancy.

There is limited evidence that celecoxib excreted in breast milk. In studies it was shown that celecoxib is excreted in breast milk in very low concentrations. Nevertheless, taking into account the potential for the development of side effects from celecoxib in the infant fed, the feasibility of abolishing either breastfeeding or taking celecoxib should be assessed, given the importance of taking Celebrex® for the mother.

Dosing and Administration:

Inside, not liquid, squeezed water, regardless of food intake. Since the risk of possible complications from the cardiovascular system may increase with increasing dose and duration of Celebrex®, it should be applied with the minimum possible short course at the lowest effective dosepreparation. The maximum recommended daily dose for long-term admission is 400 mg.

Symptomatic treatment of osteoarthritis: the recommended dose is 200 mg per day for 1 or 2 doses.

Symptomatic treatment of rheumatoid arthritis: the recommended dose of celecoxib is 100 or 200 mg twice a day.

Symptomatic treatment of ankylosing spondylitis: The recommended dose of celecoxib is 200 mg per day for 1 or 2 doses. Some patients noted the effectiveness of 400 mg per day.

Treatment of pain syndrome: the recommended initial dose of celecoxib is 400 mg, followed, if necessary, by an additional dose of 200 mg, on the first day. In the following days, the recommended dose is 200 mg twice a day, as needed.

Treatment of primary dysmenorrhea: the recommended initial dose of celecoxib is 400 mg, followed, if necessary, by an additional dose of 200 mg on the first day. In the following days, the recommended dose is 200 mg twice a day, as needed.

Elderly patients: usually no dose adjustment is required. However, in patients with a body weight below 50 kg, treatment should be started with a minimum recommended dose.

Onhepatic impairment: in patients with mild liver failure (class A according to Child-Pugh classification) dose adjustment is not required. In patients with moderate hepatic insufficiency (class A according to Child-Pugh classification), the initial recommended dose of the drug should be reduced by half. Experiments with the use of the drug in patients with severe hepatic insufficiency (class C according to the Child-Pugh classification) are not available (see section "Contraindications").

Impaired renal function: in patients with mild and moderate renal failure, dose adjustment is not required. Experiments with the use of the drug in patients with severe renal failure are not available (see sections "Special instructions", "Contraindications").

Simultaneous use with fluconazole: with simultaneous application of fluconazole (inhibitor of isoenzyme CYP2C9) and the preparation Celebrex®, the initial recommended dose of the drug should be reduced by half. Caution should be exercised when used simultaneously with other isoenzyme inhibitors CYP2C9. Celebrex® should be used with caution in patients who are slow metabolizers or suspected of such a condition, as 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 half.

Side effects:

Criteria for frequency estimation: very often > 10 %; often - >1% and <10%; infrequently - > 0.1% and <1%; rarely -> 0.01% and <0.1%. very rarely - <0.01%.

From the cardiovascular system: often - peripheral edema, increased blood pressure, including weighting the course of arterial hypertension; infrequently - "hot flashes", a feeling of heartbeat: rarely - manifestations of chronic heart failure, arrhythmia, tachycardia, ischemic stroke and myocardial infarction.

From the gastrointestinal tract: often - abdominal pain, diarrhea, dyspepsia, flatulence, vomiting; infrequently - Diseases of the teeth (postextraction lunechke alveolitis); rarely - ulcer of the stomach and duodenum, ulceration of the esophagus; rarely - intestinal perforation, pancreatitis.

From the nervous system: often - dizziness, insomnia; infrequently - anxiety, increased muscle tone, snotty; rarely - confusion of consciousness (psychosis).

From the side of the kidneys and urinary system: often - urinary tract infection.

From the respiratory system: often - bronchitis, cough, sinusitis, infections of the upper respiratory tract; infrequently - pharyngitis, rhinitis.

From the skin: often - skin itch (including generalized), skin rash; infrequently - urticaria, ecchymosis: rarely - alopecia.

From the side of the blood: infrequently - anemia, ecchymosis; rarely - thrombocytopenia.

From the immune system: rarely - angioedema; rarely - bullous eruptions (bullous dermatitis).

From the senses: infrequently - noise in the ears, blurred vision.

From the hepatobiliary system: infrequently - an increase in the activity of "hepatic" enzymes (including alanine aminotransferase and aspartate aminotransferase).

From the side of the blood: infrequently - anemia; rarely - thrombocytopenia.

General: infrequently - hypersensitivity, flu-like syndrome, accidental trauma, facial edema.

Side effects revealed in post-marketing observations:

Despite the fact that these reactions were identified during post-marketing observations, they were distributed in frequency as follows: very often > 10 %; often - >1 % and <10%; infrequently - > 0.1% and <1%; rarely -> 0.01% and <0.1%, very rarely - <0.01%, the frequency is unknown - it is impossible to estimate the frequency based on the available data

From the immune system: very rarely - anaphylactic reactions.

From the nervous system: rarely - hallucinations; rarely - hemorrhages in

brain, aseptic meningitis, loss of taste, loss of smell.

From the side of the organ of vision: infrequently - conjunctivitis.

From the side of the vessels: very rarely - vasculitis.

From the respiratory system: rarely - thromboembolism of the pulmonary artery, pneumonitis.

From the gastrointestinal tract: rarely - gastrointestinal bleeding.

From the hepatobiliary system: rarely - hepatitis; rarely - hepatic insufficiency, fulminant hepatitis, liver necrosis (see section "Special instructions", subsection "Influence on liver function"), cholestasis, cholestatic hepatitis, jaundice. From the skin and subcutaneous tissue: rarely - photosensitivity reaction; rarely - Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, drug rash in combination with eosinophilia and systemic symptoms (DRESS or hypersensitivity syndrome), acute generalized exanthematous pustulosis, exfoliative dermatitis.

From the side of the kidneys and urinary system: rarely - acute renal failure (seesection "Special instructions", subsection "Influence on kidney function"), hyponatremia; rarely - tubulointerstitial nephritis, nephrotic syndrome, the disease of minimal changes.

From the side of the reproductive system: rarely - violation of the menstrual cycle; frequency unknown - decrease in fertility in women (see section "Application during pregnancy and during breast-feeding").

Systemic disorders: infrequently chest pain.

Women planning pregnancy were excluded from the study, so they were not taken into account when calculating the frequency of the reaction.

Overdose:Clinical experience of overdose is limited. Without clinically significant side effects, single-dose up to 1200 mg and multiple doses up to 1200 mg in 2 divided doses were used. If suspected overdose, appropriate maintenance therapy should be provided. Presumably dialysis is not an effective method of removing the drug from the blood, due to the high degree of binding of the drug to plasma proteins.

Interaction:

Simultaneous use of celecoxib with isozyme inhibitors CYP2D6 can lead to an increase in its concentration in the blood plasma. In such cases, a dose reduction of celecoxib may be necessary.

Simultaneous use of celecoxib with isoenzyme inducers CYP2C9, such as rifampicin, carbamazepine and barbiturates, can lead to a decrease in its concentration in the blood plasma. In such cases, an increase in the dose of celecoxib may be necessary.

In clinical studies of pharmacokinetics and research in vitro it was shown that celecoxib although it is not a substrate of isoenzyme CYP2D6, but inhibits its activity. Therefore, there is a possibility of drug interaction in vivo with drugs whose metabolism is associated with the isoenzyme CYP2D6.

Warfarin and other anticoagulants: with simultaneous admission, an increase in prothrombin time is possible.

Fluconazole, ketoconazole: with the simultaneous use of 200 mg of fluconazole, an increase in the concentration of celecoxib in the blood plasma is observed twice a day. This effect is associated with inhibition of celecoxib metabolism by fluconazole via isoenzyme CYP2C9. Patients receiving fluconazole (inhibitor of isoenzyme CYP2C9), the recommended dose of celecoxib should be reduced by half (see the section "Dosing and Administration"). Ketocoiazole (inhibitor of isoenzyme CYP3A4) does not have a clinically significant effect on the metabolism of celecoxib.

Dextromethorphan and metoprolol: it was found that with simultaneous use of celecoxib at a dose of 200 mg per day, led to an increase in the concentrations of dextromethorphan and metoprolol (isoenzyme substrates CYP2D6) in 2.6 and 1.5 times respectively. Such an increase in concentrations is due to inhibition of the metabolism of isoenzyme substrates CYP2D6 celecoxib by inhibiting the activity of the isoenzyme itself CYP2D6. In this regard, during the initiation of therapy with celecoxib, the dose of preparations that are substrates of the isoenzyme CYP2D6, and after the end of treatment with celecoxib, the dose of these drugs should be increased.

Methotrexate: there were no pharmacokinetic clinically significant interactions between celecoxib and methotrexate.

Antihypertensive drugs, including angiotensin converting enzyme (angiotensin converting enzyme) / angiotensin II antagonists (or angiotensin receptor blockers), diuretics and beta adrenoblockers: inhibition of prostaglandin synthesis can reduce the effect of antihypertensive drugs, including ACE inhibitors and / or angiotensin receptor blockers, diuretics and beta-blockers. This interaction should be taken into account when using celecoxib in conjunction with ACE inhibitors and / or angiotensin receptor blockers, diuretics and beta-blockers. In elderly patients, dehydrated (including patients receiving diuretic therapy) or in patients with impaired renal function, concurrent use of NSAIDs, including selective inhibitors of COX-2, with inhibitors of PSL. antagonists of aigiotensin 11 and diuretics, can lead to impaired renal function, including possible acute renal failure. Usually, these effects are reversible. In this regard, care should be taken when using these drugs at the same time. In such cases, it is advisable to first rehydrate, and then begin therapy with Celebrex®. In addition, the possibility of monitoring the function of the kidneys at the beginning of therapy and periodically during simultaneous application of the drugs should be considered.

Cyclosporine: Considering that NSAIDs affect the renal synthesis of prostaglandins, they can increase the risk of developing nephrotoxicity while being used with cyclosporine.

Diuretics: previously known NSAIDs in some patients may reduce the natriuretic effect of furosemide and thiazides by reducing renal synthesis of prostaglandins, 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: an increase in the concentration of lithium in blood plasma by about 17% was observed with the combined use of lithium and celecoxib. Patients receiving lithium therapy should be carefully monitored when taking or withdrawing celecoxib.

Other NSAIDs: simultaneous use of celecoxib and other NSAIDs (not containing acetylsalicylic acid) should be avoided.

The results of the study of lisinopril: in a 28-week study of patients with arterial hypertension of 1 and 2 degrees receiving on this occasion lisinopril it was found,that concomitant use of celecoxib 200 mg twice daily did not result in a clinically significant increase in mean systolic or diastolic pressure (based on 24-hour blood pressure monitoring), compared with placebo. Among patients receiving celecoxib in a dose of 200 mg twice a day, 48% of them had no response to lisinopril therapy (the criteria for the response were indicators of a diastolic blood pressure more than 90 mmHg or an increase in diastolic pressure by 10% compared to the baseline level), compared with patients receiving placebo (27% of patients did not respond in this group).

Other drugs: there were no clinically significant interactions between celecoxib and antacids (aluminum and magnesium-containing drugs), omeprazole, glibenclamide, phenytoin, or tolbutamide.

Celecoxib does not affect the antiplatelet effect of acetylsalicylic acid, taken in low doses. Celecoxib has a weak effect on the function of platelets, so it can not be regarded as a substitute for acetylsalicylic acid,used for the prevention of cardiovascular diseases.

In healthy volunteers, NSAIDs have no effect on the pharmacokinetics of digoxin. However, with the simultaneous use of digoxin and indomethacin and ibuprofen in patients, there was an increase in the concentration of digoxin in the blood plasma. This must be taken into account when used simultaneously with other drugs that increase the concentration of digoxin in the blood plasma. The meta-information about the interaction of celecoxib and digoxin. Given the other effects of celecoxib on the cardiovascular system, caution should be taken simultaneously with digoxin. In this case, it is recommended to carefully monitor adverse reactions. Celecoxib predominantly metabolized in the liver by isoenzyme CYP2C9. Since barbiturates are inducers of isoenzyme CYP2C9, when they are used simultaneously with celecoxib, there may be a decrease in the concentration of the latter in the blood plasma.

Special instructions:

SPECIAL INSTRUCTIONS

Celebrex®, considering the antipyretic effect, may reduce the diagnostic significance of such a symptom as fever, and affect the diagnosis of infection.

Influence on the cardiovascular system

Celecoxib, like all coxibs, can increase the risk of serious complications from the cardiovascular system, such as thrombosis, myocardial infarction and stroke, which can lead to death. 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 the risk factors for such diseases. To reduce the risk of these reactions, in patients taking Celebrex®, it should be used in the lowest effective doses and the minimum possible short course (at the discretion of the treating physician). The attending physician and the patient should keep in mind the possibility of such complications, even in the absence of previously known symptoms of cardiovascular dysfunction. Patients should be informed of the signs and symptoms of adverse effects on the cardiovascular system and the measures to be taken if they occur.

In the application of NSAIDs (selective inhibitors of COX-2) in patients after aorto-coronary bypass surgery for the treatment of pain in the first10-14 days may increase the incidence of myocardial infarction and cerebral circulation disorders.

Due to the weak effect of celecoxib on the function of platelets, it can not be a substitute for acetylsalicylic acid for the prevention of thromboembolism. Also, therefore, antiplatelet therapy (eg, acetylsalicylic acid) should not be discontinued in patients at risk of developing thromboembolic complications.

Like all NSAIDs, celecoxib can lead to an increase in blood pressure, which can also cause complications from the cardiovascular system. All NSAIDs, including celecoxib, in patients with hypertension should be used with caution. Monitoring of blood pressure should be performed at the beginning of therapy with celecoxib, and during the course of treatment.

Effect on the gastrointestinal tract

In patients who took celecoxib, extremely rare cases of perforation, ulceration and bleeding from the gastrointestinal tract were observed. The risk of developing these

complications in the treatment of NSAIDs is highest in the elderly, patients with cardiovascular diseases, cardiovascular diseases, patients simultaneously receiving acetylsalicylic acid, and patients with such diseases of the gastrointestinal tract as an ulcer, bleeding, inflammatory processes in the acute stage and in an anamnesis. Other risk factors for bleeding from the gastrointestinal tract are simultaneous use with oral glucocorticosteroids and anti-coagulants and, for a long period of therapy, NSAIDs, smoking, and alcohol use. Most spontaneous reports of serious side effects on the gastrointestinal tract were related to elderly and debilitated patients.

Co-administration with oral anticoagulants

With the simultaneous use of NSAIDs with oral anticoagulants, the risk of bleeding increases. Care should be taken when using these drugs at the same time. Oral anticoagulants include warfarin, anti coagulant coumarin series and new oral anticoagulants (for example, apixaban, dabigatran and rivaroxaban). Serious (some of them fatal) bleeding was reported in patients who received concomitant treatment with warfarin or similar agents.As reported on the increase in prothrombin time (international prothrombin time (MNO)), then, after initiating treatment with Celebscox® or changing its dose, patients who are simultaneously receiving warfarin therapy or anticoagulants of the coumarin series should be monitored for anticoagulant activity and / or MBUT.

Fluid retention and swelling

As with other drugs that inhibit the synthesis of prostaglandins, a number of patients taking Celebrex® may experience fluid retention and swelling, so caution should be exercised when using this medication in patients with conditions predisposing or worsening due to fluid retention. Patients with a history of heart failure or hypertension should be closely monitored.

Effect on kidney function

NSAIDs, including celecoxib, can have a toxic effect on kidney 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,a violation of liver function and in elderly patients. The function of the kidney in such patients should be carefully monitored (see section "Method of administration and dose"). Caution should be exercised when using Celebrex® in patients with dehydration. In such cases, it is advisable to first rehydrate, and then begin therapy with Celebrex®.

Effects on liver function

Celebrose® should not be used in patients with severe liver failure (class C according to Child-Pugh classification). Celebrex® should be used with caution in the treatment of patients with moderate hepatic impairment and reduce the initial recommended dose of the drug by half (see the section "Method of administration and dose").

In some cases severe liver reactions have been observed, including fulminant hepatitis (sometimes fatal), liver necrosis, liver failure (sometimes with a legal outcome or the need for liver transplantation). Most of these reactions developed 1 month after the initiation of celecoxib.

Patients with symptoms and / or signs of impaired liver function, or those patients,who have been diagnosed as having liver function abnormalities by laboratory methods, should be carefully monitored for the development of more severe liver reactions during treatment with Celebrex®.

Anaphylactic reactions

When taking Celebrex®, cases of anaphylactic reactions were reported (see "Contraindications").

Serious reactions from the skin

Very rarely, when taking celecoxib, serious skin reactions were observed, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, some of which were fatal. The risk of occurrence of such reactions is higher in patients at the beginning of therapy, in most noted cases such reactions began in the first month of therapy. Celebrex® should be discontinued if skin rashes, changes in mucous membranes or other signs of hypersensitivity occur.

Glucocorticosteroid therapy

Celebrex® can not replace glucocorticosteroids or be used as a therapy for glucocorticosteroid insufficiency.

Inhibition of the isoenzyme function CYP2D6

It was found that celecoxib is a moderate inhibitor of isoenzyme CYP2D6. During the initiation of celecoxib therapy, the dose of drugs metabolized by isoenzyme CYP2D6, and after treatment with celecoxib The dose of these drugs should be increased (see section "Interaction with other drugs").

Effect on the ability to drive transp. cf. and fur:

The effect of celecoxib on the ability to drive a car and control mechanisms has not been investigated. However, based on the pharmacodynamic properties and general safety profile, it seems unlikely that Celebrex® has such an effect.

Care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, as the drug may cause dizziness and other side effects that may affect these abilities.

Form release / dosage:

1) Capsules 100 and 200 mg

2) Combined packaging (400 mg + 200 mg)

Packaging:

1) Capsules 100 and 200 mg

10 capsules in a PVC / aluminum foil blister.

For 1, 2, 3, 4, 5 or 10 blisters with instructions for use in a cardboard pack with the control of the first opening.

2) Combined packaging (400 mg + 200 mg)

1 capsule 400 mg and 1 capsule 200 mg in a blister of PVC / aluminum foil;

1 capsule 400 mg and 5 capsules 200 mg and a blister of PBX / aluminum foil;

1 capsule 400 mg and 9 capsules 200 mg in a blister of PBX / aluminum foil;

1 400 mg capsule and 13 capsules 200 mg in a PVC / aluminum foil blister;

For 1 blister with instructions for use in a cardboard box with the control of the first autopsy.

Storage conditions:In a dry place at a temperature of 15 to 30 ° C. Keep out of the reach of children.

Shelf life:3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N015986 / 01

Date of registration:20.02.2009

The owner of the registration certificate: Pfizer Inc. Pfizer Inc. USA

Manufacturer: & nbsp

PFIZER PHARMACEUTICALS, LLC Puerto Rico

Representation: & nbspPfizer H. Si. Pi. CorporationPfizer H. Si. Pi. Corporation

Information update date: & nbsp09.10.2015

Illustrated instructions

Instructions

Celebrex® (Celebrex®)