CELEBREX CAPSULES 400MG + CAPS 200MG

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.

Adverse effects

Common (≥1% and <10%)

Are common: exacerbation of allergic diseases, gripe-like syndrome, accidental injuries.

Cardiovascular: peripheral edema.

From the digestive tract: abdominal pain, diarrhea, dyspepsia, flatulence, dental disease (postextraction hole alveolitis).

Nervous system: dizziness, increased muscle tone, insomnia.

On the part of the kidneys and urinary system: urinary tract infection.

Respiratory: bronchitis, cough, pharyngitis, rhinitis, sinusitis, upper respiratory tract infections.

From the skin: skin itch, skin rash.

Infrequently (≥0.1% and <1%)

From the blood: anemia, ecchymosis, thrombocytopenia.

Cardiovascular: aggravation of arterial hypertension, increased blood pressure, arrhythmia, hot flashes, palpitations, tachycardia.

Special senses: tinnitus, blurred vision.

From the digestive tract: vomiting.

Nervous system: anxiety, drowsiness.

From the skin: alopecia, urticaria.

Are common: swelling of the face.

Rarely (≥0.01% and <0.1%)

Cardiovascular: manifestation of congestive heart failure, ischemic stroke and myocardial infarction.

From the digestive tract: gastric and duodenal ulcer, esophageal ulceration, intestinal perforation, pancreatitis.

Immune system: angioedema, bullous eruption.

From the hepatobiliary system: increased liver enzymes.

Nervous system: confusion

Side effects identified in post-marketing observations:

Immune system: anaphylaxis.

Nervous system: loss of taste, loss of smell, aseptic meningitis, hallucinations.

Special senses: conjunctivitis.

From the side of the vessels: vasculitis, cerebral hemorrhage.

From the digestive tract: Gastrointestinal bleeding.

From the hepatobiliary system: hepatitis, liver failure, fulminant hepatitis, liver necrosis (see section "Specific instructions", subsection "Impact on liver function"), cholestasis, cholestatic hepatitis, jaundice.

On the part of the kidneys and urinary system: acute renal failure (see section "Special instructions", subsection "Impact on renal function"), interstitial nephritis, nephrotic syndrome, minimal impairment of renal function, hyponatremia.

From the skin: photosensitivity reactions, peeling of the skin (including erythema multiforme and Stevens-Johnson syndrome), toxic epidermal necrolysis, drug rash combined with eosinophilia and systemic symptoms (DRESS or hypersensitivity syndrome), acute generalized exanthematic pustules.

From the reproductive system: violation of the menstrual cycle, decrease in fertility in women (see the section "Use during pregnancy and during breastfeeding").

Respiratory, thoracic and mediastinal disorders: pulmonary embolism.

Systemic abnormalities: chest pain.

Contraindications

- hypersensitivity to celcoxibu 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;

- state after surgery of aorto-coronary shunting;

- peptic ulcer in the acute stage or gastrointestinal bleeding;

- inflammatory bowel disease;

- heart failure (NYHA II-IV);

- clinically confirmed coronary artery disease, peripheral artery disease and cerebrovascular diseases in the severe stage;

- pregnancy and lactation period (see the section "Use during pregnancy and during breastfeeding");

- severe hepatic and renal failure (no experience of use);

- age up to 18 years (no experience of use).

Celebrex should be taken carefully under the following conditions:

- Diseases of the gastrointestinal tract (peptic ulcer, bleeding in history), the presence of Helicobacter pylori infection;

- combined use with anticoagulants (warfarin), aptiagregantami (acetylsalicylic acid, clopidogrel), oral GCS (prednisolone), diuretics, selective serotonin reuptake inhibitors (citalopram, Fluoxetine, paroxetine, sertraline);

- fluid retention and edema;

- abnormal liver function of moderate severity;

- diseases of the cardiovascular system (see the section "Special Instructions");

- cerebrovascular disease;

- dyslipidemia / hyperlipidemia;

- diabetes;

- diseases of peripheral arteries;

- simultaneous ameneniya with inhibitors of an isoenzyme CYP2C9;

- patients who are slow metabolizers or are suspected of having such a condition;

- long-term use of NSAIDs;

- severe somatic diseases.

Use during pregnancy and lactation

There are insufficient data on the use of celecoxib in pregnant women. The potential risk of using the drug Celebrex during variability has not been established, but cannot be excluded.

In accordance with 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. For women who are planning a pregnancy or being screened for infertility, consideration should be given to discontinue NSAIDs, including celecoxib.

Celecoxib, belonging to a 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 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 being fed, the feasibility of canceling either breastfeeding or taking celecoxib should be evaluated, given the importance of taking Celebrex® for mother.

Application for violations of the liver

In patients with mild liver failure (class A according to the Child-Pugh classification), dose adjustment is not required. In the case of moderate liver failure (Child-Pugh class A), treatment should begin with the minimum recommended dose. Experience with the use of the drug in patients with severe liver failure (class C according to the classification of Child-Pugh) is not (see "Contraindications").

Application for violations of kidney function

In patients with mild and moderate renal insufficiency, dose adjustment is not required. Experience in the use of the drug in patients with severe renal insufficiency is not (see sections "Special instructions", "Contraindications").

Use in children

Contraindicated in children under 18 years old

Use in elderly patients

Elderly patients usually do not need dose adjustment. However, in patients with a body weight below 50 kg, it is better to begin treatment with the lowest recommended dose.

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, can 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, patients taking 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.

With the use of NSAIDs (selective COX-2 inhibitors) in patients after surgery for coronary artery bypass surgery for the treatment of pain in the first 10-14 days, it is possible to 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 for the prevention of thromboembolism. Also in this regard, antiplatelet therapy (eg, acetylsalicylic acid) should not be canceled in patients at risk of developing thromboembolic complications.

Like all NSAIDs, celecoxib can lead to an increase in blood pressure, which can also be a cause of complications of the cardiovascular system. All NSAIDs, including celecoxib, in patients with arterial hypertension should be used with caution. Blood pressure monitoring should be performed at the start of celecoxib therapy, as well as during the course of treatment.

Effect on the digestive tract

Celecoxib patients had extremely rare cases of perforation, ulceration and bleeding from the gastrointestinal tract. 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 anticoagulants

It was reported about serious (some of them fatal) bleeding in patients who received concomitant treatment with warfarin or similar means. Since an increase in prothrombin time was reported, after the start of treatment with Celebrex® or changes in its dose should be controlled anti-coagulant activity.

Fluid retention and edema

As with the use of other drugs that inhibit the synthesis of prostaglandins in a number of patients taking Celebrex®, fluid retention and edema can occur, so care should be taken when using this drug in patients with conditions that predispose or worsen due to fluid retention. Patients with a history of heart failure or arterial hypertension should be closely monitored.

Impact 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, impaired liver function and in elderly patients. Renal function in these patients should be carefully monitored.

Caution must be exercised when using the drug Celebrex.® in patients with dehydration. In such cases, it is advisable to first rehydrate, and then begin therapy with Celebrex.®.

Impact on liver function

Celebrex® should not be used in patients with severe liver function abnormalities (class C according to the Child-Pyo classification). Celebrex® should be used with caution in the treatment of patients with moderately severe liver failure and should be prescribed at the lowest recommended dose.

In some cases, severe reactions of the liver were observed, including fulminant hepatitis (sometimes fatal), liver necrosis, liver failure (sometimes fatal or the need for liver transplantation). 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 detected by laboratory methods, should be carefully monitored for the development of more severe liver reactions during treatment with Celebrex®.

Anaphylactic reactions

When taking the drug Celebrex®Anaphylactic reactions have been reported.

Serious skin reactions

It has been extremely rare for celecoxib to have severe skin reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, some of which 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. You should stop taking the drug Celebrex® with the appearance of skin rash, changes in the mucous membranes or other signs of hypersensitivity.

Glucocorticosteroid Therapy

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

Influence on the ability to drive a car and control mechanisms

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 the overall safety profile, it seems unlikely that Celebrex® has such an effect.

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 administered in 2 doses per day.

If overdose is suspected, appropriate supportive care 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.

Drug interaction

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 interactions in vivo with drugs whose metabolism is associated with CYP2D6 isofermeitis.

Warfarin and other anticoagulants: with simultaneous admission may increase prothrombin time.

Fluconazole, Ketoconazole : with the simultaneous use of 200 mg of Fluconazole once a day there is a 2-fold increase in plasma celecoxib concentration. 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 the 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 can 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 blood pressure.

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 renal function, including possible acute renal failure. Usually these effects are reversible.

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: No clinically significant effect on the pharmacokinetics of the contraceptive combination was noted (1 mg norethisterone / 35 μg ethinyl estradiol).

Lithium: There was an increase in plasma lithium concentration 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: there were 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.

Terms and conditions of storage

In a dry place at a temperature of 15 ° to 30 ° C.

Keep out of the reach of children.