Dilaxa capsules 200 mg, 30 pcs.

Composition

1 capsule of 100 mg / 200 mg contains:

Active ingredient:

Celecoxib 100.00 mg/200.00 mg

Excipients: lactose monohydrate, sodium lauryl sulfate, povidone-K 30, croscarmellose sodium, magnesium stearate

Solid gelatin capsules No.3

Body: Titanium dioxide (E171), gelatin

Cap: titanium dioxide (E171), gelatin

Solid gelatin capsules # 1

Body: Titanium dioxide (E171), iron oxide yellow dye (E172), gelatin

Cap: titanium dioxide (E171), iron oxide yellow dye (E172), gelatin

Pharmacological action

nonsteroidal anti-inflammatory drug (NSAID)

Clinical pharmacology

Pharmacodynamics

Celecoxib has anti-inflammatory, analgesic and antipyretic effects, blocking the formation of inflammatory prostaglandins (Pg) mainly due to the inhibition of cyclooxygenase-2 (COX-2). COX-2 induction occurs in response to inflammation and leads to the synthesis and accumulation of Pg, primarily PGE2, which causes increased manifestations of inflammation (swelling and pain). At therapeutic doses in humans, celecoxib does not significantly inhibit cyclooxygenase-1 (COX-1) and does not affect Pg concentrations that are synthesized as a result of COX-1 activation, as well as normal physiological processes associated with COX-1 and occurring in tissues, primarily in the stomach, intestines and platelets.

Effect on renal function

Celecoxib reduces renal excretion_of PGE2 and 6-keto-pgf1 (a prostacyclin metabolite), but does not affect serum thromboxane_B2 (TCB2) and renal excretion of 11-dehydro-tcb2_{, a}metabolite of thromboxane (both COX – 1 products).

Celecoxib does not cause a decrease in glomerular filtration rate (GFR) in elderly patients and patients with chronic renal failure (CRF), and transitorily reduces sodium excretion. In patients with arthritis, the incidence of peripheral edema, hypertension, and heart failure was comparable to that of nonselective COX inhibitors, which have inhibitory activity against COX-1 and COX-2. This effect was most pronounced 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 resolved independently.

Pharmacokinetics

Suction

When taken on an empty stomach, celecoxib is well absorbed, reaching its maximum concentration (cmax) in blood plasma after approximately 2-3 hours. _Cmax in blood plasma after taking 200 mg of celecoxib is 705 ng / ml. The absolute bioavailability of celecoxib has not been studied. _Cmax and the area under the concentration-time curve (AUC) are approximately proportional to the dose taken in the therapeutic dose range up to 200 mg 2 times a day, with celecoxib used in higher doses, the degree of increase in_cmax and AUC occurs less proportionally.

Effect of food intake

Taking celecoxib concomitantly with fatty foods increases the time to reach_cmax by about 4 hours and increases absorption by about 20%.

Distribution

The degree of binding to plasma proteins does not depend on the concentration of celecoxib in blood plasma and is about 97%. Celecoxib does not bind to red blood cells. Celecoxib penetrates the blood-brain barrier.

Celecoxib is primarily metabolized by the cytochrome P450 (CYP) isoenzyme CYP2C9 in the liver via hydroxylation, oxidation, and partial glucuronidation (see section “Interactions with other drugs”). The resulting metabolites are pharmacologically inactive against COX-1 and COX-2.

The activity of the CYP2C9 isoenzyme is reduced in patients with a genetic polymorphism, such as homozygous for the CYP2C9*3 polymorphism, which leads to a decrease in the efficiency of the enzymes.

Elimination

Celecoxib is excreted via the intestine and kidneys as metabolites (57% and 27%, respectively), less than 1% of the dose taken is unchanged. With repeated use, the half-life (T_1/2) is 8-12 hours, and the clearance is about 500 ml / min. With repeated use, equilibrium plasma concentrations are reached by the 5th day of administration. The variability of the main pharmacokinetic parameters (AUC, _cmax, T_1/2) is about 30%. The average volume of distribution at steady state is approximately 500 l / 70 kg in young healthy patients, which indicates a broad distribution of celecoxib in tissues.

Pharmacokinetics in selected groups of patients

Elderly patients

In patients over 65 years the increase 1.5-2 times the average values of C_max and AUC, which is largely due to changes in body weight, but not age (elderly patients, tend to have a lower average body weight than in those of younger age, because of what they have, ceteris paribus achieved higher concentrations celecoxib). For the same reason, older women usually have a higher plasma concentration of celecoxib than older men. These features of pharmacokinetics, as a rule, do not require dose adjustment. However, elderly patients with a body weight of less than 50 kg should start treatment with the minimum recommended dose.

Race

The AUC of celecoxib is approximately 40% higher in the Black race than in the Caucasian race. The causes and clinical significance of this fact are unknown, so treatment of black people is recommended to start with the minimum recommended dose.

Impaired liver function

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

Impaired renal function

The pharmacokinetics of celecoxib did not change in elderly patients with age-related GFR > 65 ml/min/1.73 m2 and in patients with GFR equal to 35-60 ml/min/1.73 m2. There is no significant correlation between serum creatinine concentration (or creatinine clearance (CC)) and celecoxib clearance. It is assumed that the presence of severe renal insufficiency does not affect the clearance of celecoxib, since its main route of elimination is conversion to inactive metabolites in the liver.

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.

Use during pregnancy and lactation

Pregnancy

Animal studies (rats and rabbits) have shown the presence of reproductive toxicity, including malformations. The use of Pg synthesis inhibitors may negatively affect pregnancy. Data from epidemiological studies suggest an increased risk of miscarriage after the use of Pg synthesis inhibitors in early pregnancy. There are insufficient data on the use of celecoxib in pregnant women, but the potential risk of use cannot be excluded. Celecoxib, like other drugs that inhibit Pg synthesis, can cause weakness of labor and premature closure of the ductus arteriosus in the third trimester of pregnancy.

When used in the second and third trimesters of pregnancy, NSAIDs, including celecoxib, can cause impaired renal function in the fetus, which can lead to a decrease in the volume of amniotic fluid or in severe cases to lack of water. These effects may develop soon after starting treatment and are usually reversible.

The use of Dilaxa® is contraindicated during pregnancy and in women planning pregnancy. If pregnancy occurs during treatment, celecoxib should be discontinued.

During breastfeeding

, Celecoxib is excreted in milk in lactating rats at concentrations similar to those in blood plasma. Studies have shown that celecoxib is excreted in the breast milk of women in very low concentrations. Breast-feeding should be discontinued when Dilaxa is used.

Fertility

In accordance with the mechanism of action, when using NSAIDs, including celecoxib, in the ovaries, there may be a delay in the maturation of the follicle or the absence of rupture of the follicle wall, which may be associated with reversible infertility.

Contraindications

• Hypersensitivity to celecoxib or any other component of the drug.

• Known hypersensitivity to sulfonamides.
• Complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis, and intolerance to acetylsalicylic acid or other NSAIDs, including other COX-2 inhibitors (including in the anamnesis).
• The period after coronary artery bypass grafting surgery.

• Active erosive and ulcerative lesions of the gastric or duodenal mucosa, peptic ulcer of the stomach and duodenum in the acute stage, or gastrointestinal bleeding.
• Inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute phase.
• Chronic heart failure (NYHA functional class II-IV).
• Clinically confirmed coronary heart disease, peripheral arterial diseases, and advanced cerebrovascular diseases.
• Hemorrhagic stroke.
• Subarachnoid hemorrhage.

• Pregnancy and lactation (see the section “Use during pregnancy and lactation”).

• Severe hepatic insufficiency (Child-Pugh class C) (no previous experience).

• Severe renal insufficiency (creatinine clearance less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia (no experience with use).
• Age up to 18 years (no experience in using it).

• Lactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome (Dilaxa contains lactose).

Side effects

Adverse reactions (HP) are presented by organ system classes and frequency of occurrence in accordance with the data obtained:

• NR with a frequency of more than 0.01% and more often than in the placebo group was observed when celecoxib was used at doses of 100-800 mg / day in patients with osteoarthritis and rheumatoid arthritis lasting up to 12 weeks in 12 placebo – and/or controlled clinical trials with the active drug. In additional studies using non-selective NSAIDs (reference drug), about 7,400 patients with arthritis received celecoxib at doses up to 800 mg / day, including about 2,300 patients treated for at least 1 year or more; HP corresponded to those in patients with osteoarthritis and rheumatoid arthritis;
• HP with a higher frequency than in the placebo group was observed in patients receiving celecoxib at a dose of 400 mg / day in long-term studies (up to 3 years) to study the prevention of intestinal polyps (Adenoma Prevention with Celecoxib (APC) and Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP); to study the effect of the drug on cardiovascular safety in patients with sporadic adenomatous polyps);
• HP in the post-marketing period based on spontaneous reports during celecoxib therapy in more than 70 million patients (at different doses, with different duration, and according to different indications for use). Despite the fact that HP was observed in the post-marketing period, data from clinical studies were used to assess the frequency of HP. The incidence of HP was calculated on the basis of a consolidated meta-analysis that combined many studies in which 38,102 patients received the drug.

HP is grouped according to MedDRA terminology and frequency of occurrence: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥1/1000 to < 1/100); rare (≥1/10,000 to < 1/1000); very rare (

Adverse drug reactions reported in celecoxib clinical trials and follow-up experience (MedDRA terminology)1,2

Infectious and parasitic diseases:

common: sinusitis, upper respiratory tract infections, pharyngitis, urinary tract infections.

Disorders of the blood and lymphatic system:

infrequently: anemia;

rarely: leukopenia, thrombocytopenia;

very rarely: pancytopenia 4.

Immune system disorders:

common: hypersensitivity;

very rare: anaphylactic shock 4, anaphylactic reactions 4.

Metabolic and nutritional disorders:

infrequently: hyperkalemia.

Mental disorders:

often: insomnia;

infrequently: anxiety, depression, fatigue;

rarely: confusion, hallucinations 4.

Nervous system disorders:

common: dizziness, hypertension, headache 4;

infrequent: cerebral infarction 1, paresthesia, drowsiness;

rare: ataxia, dysgeusia;

very rare: intracranial hemorrhage (including fatal outcome)4, aseptic meningitis 4, epilepsy (including exacerbation of epilepsy)4, ageusia 4, anosmia 4.

Visual disturbances:

infrequently: blurred vision, conjunctivitis 4;

rarely: intraocular hemorrhage 4;

very rarely: retinal artery occlusion 4, retinal vein occlusion 4.

Hearing disorders and labyrinth disorders:

infrequently: tinnitus, hearing loss 1.

Cardiac disorders:

often: myocardial infarction 1;

infrequently: heart failure, palpitation, tachycardia;

rarely: arrhythmia 4.

Vascular disorders:

very common: arterial hypertension 1 (including worsening of the course of arterial hypertension);

rare: pulmonary embolism 4, hot flashes 4;

very rare: vasculitis 4.

Respiratory, thoracic and mediastinal disorders:

common: rhinitis, cough, dyspnea 1;

uncommon: bronchospasm 4;

rare: pneumonitis 4.

Disorders of the gastrointestinal tract:

common: nausea 4, abdominal pain, diarrhea, dyspepsia, flatulence, vomiting 1, dysphagia 1;

uncommon: constipation, gastritis, stomatitis, inflammation of the gastrointestinal tract (GI) tract (including the reinforcement of the existing inflammation), eructation;

rare: gastrointestinal bleeding 4 ulcer 12 duodenal ulcer, gastric ulcer, an ulcer of the esophagus, ulcers of the intestine, large intestinal ulcer, intestinal perforation, esophagitis, melena, pancreatitis, colitis 4.

Liver and biliary tract disorders:

uncommon: abnormal liver function, increased activity of “liver” enzymes (including alanine aminotransferase and aspartate aminotransferase);

rare: hepatitis 4;

very rare: hepatic failure 4 (sometimes with a fatal outcome or need for liver transplantation), fulminant hepatitis 4 (sometimes fatal), liver necrosis 4,4 cholestasis, cholestatic hepatitis 4, jaundice 4.

Skin and subcutaneous tissue disorders:

common: skin rash, itching (including generalized);

uncommon: urticaria, ecchymosis 4;

rare: angioedema 4, alopecia, photosensitivity;

very rare: exfoliative dermatitis 4,4 erythema multiforme, Stevens-Johnson 4, toxic epidermal necrolysis 4, drug reaction with eosinophilia and systemic symptoms (DRESS, or hypersensitivity syndrome)4, acute generalized exanthematous pustulosis (OGEP)4, bullous dermatitis 4.

Musculoskeletal and connective tissue disorders:

common: arthralgia 4;

uncommon: muscle spasms (calf muscle spasms);

very rare: myositis 4.

Kidney and urinary tract disorders:

infrequently: increased plasma creatinine and urea concentrations;

rare: acute renal failure 4, hyponatremia 4;

very rare: tubulointerstitial nephritis 4, nephrotic syndrome 4, disease of minimal changes 4.

Genital and breast disorders:

rare: menstrual cycle disorder 4;

frequency unknown: infertility in women (reduced fertility in women)3.

General disorders and disorders at the injection site:

common: flu-like condition, peripheral edema/fluid retention;

uncommon: facial edema, chest pain 4.

Injuries, intoxications, and manipulation complications:

often: injuries (accidental injuries).

1 HP developed in 2 clinical trials for the prevention of polyp formation (APC and PreSAP lasting up to 3 years), when using celecoxib at a dose of 400 mg / day. Only HP that was previously reported in the post-marketing period or developed with a higher frequency than in studies of the drug in the population of patients with arthritis are listed above.

2 Previously unknown HP that developed in 2 clinical trials for the prevention of polyp formation (APC and PreSAP lasting up to 3 years), when celecoxib was used at a dose of 400 mg / day:

often: angina pectoris, irritable bowel syndrome, nephrolithiasis, increased plasma creatinine, benign prostatic hyperplasia, weight gain;

infrequently: Helicobacter pylori infection, herpes zoster, erysipelas, pneumonia, labyrinthitis, an infection of the gums, lipoma, floating opacities in the vitreous hemorrhage in the conjunctiva, deep vein thrombosis, dysphonia, hemorrhoidal hemorrhage, frequent defecation, ulcerative stomatitis, allergic dermatitis’s a ganglion, nocturia, vaginal bleeding, breast tenderness, fracture of the lower limb, the increase in the content of sodium in the blood plasma.

3 Accessing the database to find out the frequency was not informative, since women planning pregnancy were excluded from all studies.

4 Frequency values are based on data from a meta-analysis of studies in which 38,102 patients took the drug.

In the final (confirmed) data obtained from the APC and PreSAP studies (combined data from both studies), in patients treated with celecoxib 400 mg/day for up to 3 years, the increase in the frequency of myocardial infarction relative to placebo was 7.6 cases per 1000 patients (infrequently). There was no increase in the incidence of stroke (without differentiation by type) relative to placebo.

Interaction

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

Warfarin and other anticoagulants: when used concomitantly, prothrombin time may be prolonged.

Fluconazole, ketoconazole: with simultaneous use of 200 mg of fluconazole 1 time a day, there is a 2-fold increase in the concentration of celecoxib in blood plasma. This effect is associated with inhibition of celecoxib metabolism by fluconazole via the CYP2C9 isoenzyme. Patients taking fluconazole (an inhibitor of the CYP2C9 isoenzyme) should reduce the recommended dose of celecoxib by half (see section “Dosage and administration”). Ketoconazole (an inhibitor of the CYP3A4 isoenzyme) does not have a clinically significant effect on celecoxib metabolism.

Dextromethorphan and metoprolol: concomitant administration of celecoxib at a dose of 200 mg per day was found to increase the concentrations of dextromethorphan and metoprolol (substrates of the CYP2D6 isoenzyme) by 2.6 and 1.5 times, respectively. This increase in concentrations is due to the inhibition of the metabolism of substrates of the CYP2D6 isoenzyme by celecoxib by inhibiting the activity of the CYP2D6 isoenzyme itself.

Methotrexate: No clinically significant pharmacokinetic interactions were observed between celecoxib and methotrexate.

Antihypertensive drugs, including angiotensin converting enzyme (ACE)inhibitors/angiotensin II receptor antagonists (ARA II), diuretics and beta-blockers: inhibition of Pg synthesis may reduce the effect of antihypertensive drugs, including ACE and/or ARA II inhibitors, diuretics and beta-blockers. This interaction should be taken into account when celecoxib is co-administered with ACE and/or ARA II inhibitors, diuretics, and beta-blockers. However, there was no significant pharmacodynamic interaction with lisinopril regarding the effect on blood pressure.

In elderly patients, dehydrated patients (including patients receiving diuretic therapy), or patients with impaired renal function, concomitant use of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, ARA II inhibitors, and diuretics may lead to deterioration of renal function, including possible acute renal failure. These effects are usually reversible. In this regard, caution should be exercised when using these drugs simultaneously. In such cases, it is advisable to first perform rehydration, and then start therapy with Dilaxa®. In addition, monitoring of renal function should be considered at the beginning of therapy and periodically during concomitant use of drugs.

Cyclosporine: Given that NSAIDs affect the renal synthesis of Pg, they may increase the risk of nephrotoxicity when used concomitantly with cyclosporine.

Diuretics: NSAIDs in some patients may reduce the natriuretic effect of furosemide and thiazides by reducing renal Pg synthesis. This should be taken into account when using celecoxib.

Oral contraceptives: celecoxib does not have a clinically significant effect on the pharmacokinetics of the combined contraceptive drug (1 mg norethisterone / 35 mcg ethinyl estradiol).

Lithium: with the simultaneous use of lithium salts at a dose of 450 mg 2 times a day and celecoxib at a dose of 200 mg 2 times a day, an increase in the concentration of lithium in blood plasma by approximately 17% was noted. Patients taking lithium medications should be closely monitored when using or discontinuing celecoxib. Other NSAIDs: concomitant use of celecoxib and other NSAIDs (not containing acetylsalicylic acid) should be avoided (the risk of side effects increases).

Other medications: There were no clinically significant interactions between celecoxib and antacids (magnesium/aluminum hydroxide), omeprazole, glibenclamide, phenytoin, or tolbutamide.

Celecoxib does not affect the antiplatelet effect of acetylsalicylic acid in low doses. Celecoxib does not have an antiplatelet effect on platelets, so they should not be replaced with acetylsalicylic acid in order to prevent cardiovascular diseases.

In healthy volunteers, NSAIDs do not affect the pharmacokinetics of digoxin. However, with the simultaneous use of digoxin and Indometacin, ibuprofen in patients, an increase in the concentration of digoxin in blood plasma was noted. This should be taken into account when used concomitantly with other drugs that increase the concentration of digoxin in blood plasma. There is no information about the interaction of celecoxib and digoxin. Given celecoxib’s other cardiovascular effects, caution should be exercised when taking it concomitantly with digoxin. In this case, it is recommended to carefully monitor adverse reactions. Celecoxib is primarily metabolized in the liver by the CYP2C9 isoenzyme. Since barbiturates are inducers of the CYP2C9 isoenzyme, when co-administered with celecoxib, a decrease in the concentration of the latter in blood plasma may occur.

Children: Interaction assessment studies were conducted only with adult patients.

How to take, course of administration and dosage

Inside, without chewing, with water, regardless of food intake.

Since the risk of cardiovascular complications may increase with increasing dose and duration of Dilaxa® administration, the minimum effective dose of the drug should be taken in the shortest possible course. The maximum recommended daily dose for long-term use is 400 mg.

Symptomatic treatment of osteoarthritis: The recommended dose is 200 mg per day in 1 or 2 divided doses.

Symptomatic treatment of rheumatoid arthritis: the recommended dose is 100 mg or 200 mg 2 times a day.

Symptomatic treatment of ankylosing spondylitis: The recommended dose is 200 mg per day in 1 or 2 divided doses. In some patients, the effectiveness of using 400 mg per day was noted.

Treatment of pain syndrome and primary dysmenorrhea: The recommended starting dose 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 2 times a day, if necessary.

Elderly patients: usually, no dose adjustment is required. However, in patients with a body weight of less than 50 kg, it is best to start treatment with the minimum recommended dose.

Hepatic impairment: No dose adjustment is required in patients with mild hepatic insufficiency (Child-Pugh Class A). In patients with moderate hepatic insufficiency (Child-Pugh class B), the initial recommended dose should be reduced by half. There is no experience of using Dilaxa® in patients with severe hepatic insufficiency (Child-Pugh class C) (see section “Contraindications”).

Impaired renal function: No dose adjustment is required in patients with mild to moderate renal insufficiency. There is no experience of using Dilaxa® in patients with severe renal insufficiency (see sections “Special instructions”, “Contraindications”).

Concomitant use with fluconazole: Concomitant administration of fluconazole (a CYP2C9 inhibitor) and Dilaxa should reduce the initial recommended dose by half. Caution should be exercised when used concomitantly with other inhibitors of the CYP2C9 isoenzyme.

Slow metabolism of CYP 2C9 isoenzyme substrates: Dilaxa should be used with caution in patients who are slow metabolizers or who have a suspected such condition, as this may lead to accumulation of celecoxib in high concentrations in blood plasma. In such patients, the initial recommended dose should be reduced by half.

Overdose

Clinical data on overdose are limited. A single dose of up to 1200 mg and repeated use at a dose of up to 1200 mg 2 times a day were not accompanied by clinically significant side effects. If an overdose is suspected, maintenance therapy should be given. Dialysis is presumably ineffective, since the binding of celecoxib to plasma proteins is high (97%).

Description

Capsules of 100 mg. Solid gelatin capsules No.3 in white color (body and lid). The contents of the capsules are white or almost white granulated powder.

200 mg capsules. Solid gelatin capsules No.1 are brownish-yellow in color (body and lid). The contents of the capsules are white or almost white granulated powder.

Special instructions

Diseases of the gastrointestinal tract (peptic ulcer of the stomach and duodenum, ulcerative colitis, Crohn’s disease, history of bleeding), the presence of Helicobacter pylori infectionconcomitant use with digoxin, anticoagulants (e. g., warfarin), antiplatelet agents (e. g., acetylsalicylic acid, clopidogrel), corticosteroids (corticosteroids) for oral administration (e. g., prednisone), diuretics, selective serotonin reuptake inhibitors (e. g., citalopram, fluoxetine, paroxetine, sertraline), inhibitors of the CYP2C9 isoenzyme, in patients who are slow metabolizers or have a suspected condition, fluid retention and edema, moderate hepatic impairment (see section “Special instructions”), a history of liver disease, hepatic porphyria, impaired renal function (creatinine clearance 30-60 ml/min), significant decrease in circulating blood volume (including after surgery), cardiovascular diseases, arterial hypertension (see section “Special Instructions”), cerebrovascular diseases, dyslipidemia/hyperlipidemia diabetes mellitus, peripheral arterial diseases, long-term use of NSAIDs, severe somatic diseases, in elderly patients (including those receiving diuretics, debilitated patients with low body weight), smoking, tuberculosis, alcoholism.

Contraindicated in persons under 18 years of age.

Elderly patients: usually, no dose adjustment is required. However, in patients with a body weight of less than 50 kg, it is best to start treatment with the minimum recommended dose.

Hepatic impairment: No dose adjustment is required in patients with mild hepatic insufficiency (Child-Pugh Class A). In patients with moderate hepatic insufficiency (Child-Pugh class B), the initial recommended dose should be reduced by half. There is no experience of using Dilaxa® in patients with severe hepatic insufficiency (Child-Pugh class C).

Impaired renal function: No dose adjustment is required in patients with mild to moderate renal insufficiency. There is no experience of using Dilaxa in patients with severe renal insufficiency.

The drug Dilaxa®, which has an antipyretic effect, can reduce the diagnostic value of fever, which makes it difficult to diagnose infection.

Effects on

the cardiovascular system Celecoxib, like all coxibs, can increase the risk of serious cardiovascular complications, such as blood clots, myocardial infarction, and stroke, which can lead to death. The risk of developing these reactions increases with increasing dose, duration of use of the drug, as well as in patients with diseases of the cardiovascular system or with risk factors for developing cardiovascular diseases. In order to reduce the risk of developing these reactions, Dilaxa should be used in the minimum effective doses and the shortest possible course (at the discretion of the attending physician). The attending physician and patient should consider the possibility of developing such complications even in the absence of previously known symptoms of impaired cardiovascular function. Patients should be informed about the symptoms of serious adverse effects from the cardiovascular system and about the measures that should be taken if they occur.

When using NSAIDs (selective COX-2 inhibitors) in patients after coronary artery bypass grafting to treat pain in the first 10-14 days, it is possible to increase the frequency of myocardial infarction and cerebral circulatory disorders.

Celecoxib does not have an antiplatelet effect on platelets, so they should not be replaced with acetylsalicylic acid in order to prevent thromboembolism. Also, 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 lead to complications from the cardiovascular system. Like other NSAIDs, celecoxib should be used with caution in patients with hypertension. Blood pressure should be monitored at the beginning and during celecoxib therapy.

Effects on the digestive system

Extremely rare cases of perforation, ulceration and bleeding from the gastrointestinal tract were observed in patients taking celecoxib. The risk of developing these complications with NSAIDs is highest in elderly patients, patients with cardiovascular diseases, in patients receiving acetylsalicylic acid at the same time, and in patients with gastrointestinal diseases such as ulcers, bleeding, and inflammatory processes in the acute stage and in the anamnesis. Other risk factors for gastrointestinal bleeding include concomitant use of oral corticosteroids or anticoagulants, long-term NSAID therapy, smoking, and ethanol intake. The majority of spontaneous reports of serious adverse reactions with a fatal outcome were observed in elderly and debilitated patients.

Concomitant use with warfarin and other anticoagulants

Concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding. Caution should be exercised when using these drugs simultaneously. Oral anticoagulants include warfarin, coumarin-type anticoagulants, and direct-acting oral anticoagulants (for example, apixaban, dabigatran, and rivaroxaban). Serious (some of them fatal) bleeding events have been reported in patients treated with celecoxib concomitantly with warfarin or similar agents. Given the reported prolongation of prothrombin time, blood clotting parameters should be monitored after starting treatment with Dilaxa® or when changing its dose.

Fluid retention and edema

As with other drugs that inhibit Pg synthesis, some patients taking Dilaxa® may experience fluid retention and edema, so caution should be exercised when using the drug in patients with conditions predisposing or worsening due to fluid retention. Patients with a history of heart failure or hypertension should be closely monitored.

Effects on renal function

NSAIDs, including celecoxib, may have toxic effects on renal function. Celecoxib was not found to be more toxic than other NSAIDs.

Dilaxa should be used with caution in patients with impaired renal function, heart failure, impaired liver function, in patients taking diuretics, ACE inhibitors, ARA II, and in elderly patients. Renal function should be carefully monitored in these patients. Caution should be exercised when using Dilaxa in patients with dehydration. In such cases, it is advisable to perform rehydration, and then start therapy with Dilaxa®.

Effects on liver function

Dilaxa should not be used in patients with severe hepatic impairment (Child-Pugh Class C). In patients with moderate hepatic insufficiency (Child-Pugh Class B), Dilaxa should be used with caution and at the lowest effective dose. In rare cases, severe hepatic impairment has been observed, including fulminant hepatitis (sometimes fatal), liver necrosis, and liver failure (sometimes fatal or requiring liver transplantation). Most of these reactions occurred 1 month after starting celecoxib.

Patients with symptoms and / or signs of hepatic impairment, or those who have been diagnosed with laboratory-based hepatic impairment, should be closely monitored for more severe hepatic reactions during treatment with Dilaxa.

Whatabout galactic reactions

Cases of anaphylactic reactions have been reported when taking Dilaxa.

Serious skin reactions

Very rarely, celecoxib has been associated with serious skin reactions, such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, some of which have been fatal. The risk of developing such reactions is higher at the beginning of therapy, in most cases they occurred in the first month of therapy. If skin rash, mucosal changes, or other signs of hypersensitivity occur, you should stop taking Dilaxa®.

Corticosteroid therapy

Dilaxa should not be substituted for corticosteroid therapy in the treatment of corticosteroid insufficiency.

Inhibition of the CYP2D6 isoenzyme function

Celecoxib has been shown to be a moderate inhibitor of the CYP2D6 isoenzyme. When starting celecoxib therapy, the dose of drugs metabolized by the CYP2D6 isoenzyme should be reduced, and after the end of celecoxib treatment, the dose of these drugs should be increased (see the section “Interaction with other drugs”).

Special information on excipients

Dilaxa® contains lactose, so the drug is contraindicated in patients with lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions, as Dilaxa® may cause dizziness and other side effects that may affect these abilities.

Form of production

Capsules,100 mg,200 mg.

10 capsules in a blister of PVC and aluminum foil.

1,2,3,4,5,6,9 or 10 blisters together with the instructions for use are placed in a cardboard pack.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use the drug after the expiration date.

Active ingredient

Celecoxib

Conditions of release from pharmacies

By prescription

Dosage form

of the capsule

Purpose

For adults as prescribed by a doctor, For pregnant women of the first and second trimester as prescribed by a doctor

Indications

Osteochondrosis, Rheumatoid Arthritis, Sciatica, Osteoarthritis, Arthritis, Sciatica, Osteoarthritis, Lumbago

Weight

Weight: 30 gr.