Instruction for use: Dilaxa

Active substance Celecoxib

ÀÒÕ M01AH01 Celecoxib

Pharmacological group

Non-steroidal anti-inflammatory drug [NSAIDs - Coxiba]

Nosological classification (ICD-10)

M06.9 Other specified rheumatoid arthritis

Rheumatoid arthritis,Pain syndrome in rheumatic diseases, Pain in rheumatoid arthritis, Inflammation in rheumatoid arthritis, Degenerative forms of rheumatoid arthritis, Children's rheumatoid arthritis, Exacerbation of rheumatoid arthritis, Acute articular rheumatism, Rheumatic arthritis, Rheumatic polyarthritis, Rheumatoid arthritis, Rheumatic polyarthritis, Rheumatoid arthritis, Rheumatoid arthritis of active course, Rheumatoid arthritis, Rheumatoid polyarthritis, Acute rheumatoid arthritis, Acute rheumatism

M19.9 Arthrosis, unspecified

Change in brush with osteoarthritis, Osteoarthritis, Osteoarthrosis, Arthrosis of large joints, Pain syndrome in osteoarthritis, Pain syndrome in acute inflammatory diseases of the musculoskeletal system, Pain syndrome in chronic inflammatory diseases of the musculoskeletal system, Deforming arthrosis, Deforming osteoarthritis, Deforming osteoarthritis of joints, Osteoarthritis in the acute stage, Osteoarthritis of large joints, Acute pain syndrome with osteoarthritis, Post-traumatic osteoarthritis, Rheumatic osteoarthritis, Spondylarthrosis, Chronic osteoarthritis

M45 Ankylosing spondylitis

Ankylosing spondylarthrosis, Marie-Strumpel disease, Ankylosing spondylitis, Pain syndrome in acute inflammatory diseases of the musculoskeletal system, Pain syndrome in chronic inflammatory diseases of the musculoskeletal system, Bechterew's disease, Ankylosing spondylitis, Diseases of the spinal column, Rheumatic spondylitis, Bechterew-Marie-Strumpel disease

M54.9 Dorsalgia, unspecified

Pain syndrome with radiculitis, Pain syndrome in the back,Pain with radiculitis, Degenerative changes in the spine, Degenerative and dystrophic disease of the spine and joints, Degenerative disease of the spine, Osteoarthrosis of the spine, Painful lesions of the spine

N94.4 Primary dysmenorrhea

Primary functional dysmenorrhea, Pain in primary dysmenorrhea, Primary algodismenorea, Menstrual cramps

R52.9 Unspecified Pain

Pain after cholecystectomy, Pain shooting, Non-malignant pain, Obstetric and gynecological pain, Pain syndrome, Pain in the postoperative period, Pain in the postoperative period after orthopedic surgery, Pain of inflammatory genesis, Pain than cancer genesis, Pain syndrome after diagnostic procedures, Pain after surgery Diagnostic, Pain after surgery, Pain after orthopedic surgery, Pain after injuries, Pain after the removal of hemorrhoids, Pain at the non-rheumatic inflammation of nature, Pain in inflammatory lesions of the peripheral nervous system, Pain in diabetic neuropathy, Pain in acute inflammatory diseases of the musculoskeletal system, Pain when the tendon pathology, Pain smooth muscle spasm, Pain spasm of smooth muscles (renal and biliary colic, intestinal spasms, dysmenorrhea), Pain spasm of smooth muscles of internal organs, Pain spasm of smooth muscles of internal organs (kidney and biliary colic, intestinal spasms, dysmenorrhea), Pain in trauma syndrome, Pain with injuries and after surgical interventions, Pain in chronic inflammatory diseases of the musculoskeletal system, Pain with duodenal ulcer, Pain syndrome in gastric ulcer, Pain syndrome in gastric ulcer and duodenal ulcer, pain, Pain during menstruation, pain syndromes, painful condition, Painful foot fatigue, Sore gums when wearing dentures, Soreness of the cranial nerves exit points, Painful menstrual irregularities, Painful dressings, Painful muscle spasm, Painful teeth growth, Melosalgia, Pain in the area of the surgical wound, Pain in the postoperative period, Pain in the body, Pain after diagnostic procedures, Pain after orthopedic surgery, Pain after surgery, The pains of the flu, Pain in diabetic polyneuropathy, Pain for burns, Pain during sexual intercourse, Pain during diagnostic procedures, Pain during therapeutic procedures, for colds Pain, Pain in sinusitis, Pain in trauma, Pain traumatic, The pain in the postoperative period, Pain after diagnostic procedures, The pain after sclerotherapy, Pain after surgery, postoperative Pain, Pain postoperative and posttraumatic, posttraumatic pain, Pain when swallowing, Pain in infectious and inflammatory diseases of the upper respiratory tract, The pain of burns, The pain in traumatic muscle injury, Pain in trauma, The pain of tooth extraction, The pain of traumatic origin, Pain caused by spasm of smooth muscles, Expressed pain syndrome, Expressed pain syndrome, traumatic origin, Postoperative pain, Post-traumatic pain, Post-traumatic pain syndrome, Torpid pain, Traumatic pain, Traumatic pain, Mild pain, Moderately severe pain, Moderate pain, Polyarthralgia with polymyositis

T88.9 Complication of surgical and medical care, unspecified

Pain in the postoperative period, Pain in the postoperative period after orthopedic surgery, Pain syndrome after diagnostic procedures, Pain after surgery Diagnostic, Pain after surgery, Pain after orthopedic surgery, Pain after the removal of hemorrhoids, Pain in the application of excimer laser, Pain with injuries and after surgical interventions, Pain syndromes in the dental practice, Painful diagnostic intervention, Painful diagnostic manipulations, Painful instrumental diagnostic procedures, Painful instrumental manipulation, Painful treatments, Painful manipulations, Painful dressings, Painful therapeutic interventions, Pain in the area of the surgical wound, Pain in the postoperative period, Pain after diagnostic procedures, Pain after orthopedic surgery, Pain during diagnostic procedures, Pain during therapeutic procedures, Pain in orthopedics, The pain in the postoperative period, Pain after diagnostic procedures, The pain after sclerotherapy, The pain after dental surgery, postoperative Pain, Pain postoperative and posttraumatic, The pain of tooth extraction, Inflammation after surgery or injury, Inflammation after orthopedic surgery, Inflammation after surgery, The inflammatory syndrome after surgery, Festering postoperative fistula, Operating wound, Complications after tooth extraction

Composition

Capsules 1 caps.

When produced at OOO KRKA-RUS, Russia

active substance:

celecoxib substance-granules 132.975 mg

(active ingredient of substance-granules - celecoxib - 100 mg)

auxiliary substances of the substance-granules: lactose monohydrate - 24,875 mg; sodium lauryl sulfate - 4.05 mg; Povidone K30 - 3,375 mg; croscarmellose sodium - 0.675 mg

auxiliary substances: croscarmellose sodium - 0,675 mg; magnesium stearate - 1.35 mg

hard gelatin capsules ¹3

body: titanium dioxide (E171) - 2%; gelatin - up to 100%

lid: titanium dioxide (E171) - 2%; gelatin - up to 100%

Capsules 1 caps.

When produced at OOO KRKA-RUS, Russia

active substance:

celecoxib substance-granules 265.95 mg

(active ingredient of substance-granules - celecoxib - 200 mg)

auxiliary substances of the substance-granules: lactose monohydrate - 49.75 mg; sodium lauryl sulfate - 8.1 mg; Povidone K30 - 6.75 mg; Croscarmellose sodium - 1.35 mg

auxiliary substances: croscarmellose sodium - 1.35 mg; magnesium stearate 2.7 mg

hard gelatin capsules ¹1

body: titanium dioxide (E171) - 1%; ferric iron oxide yellow (E172) - 1%; gelatin - up to 100%

lid: titanium dioxide (E171) - 1%; ferric iron oxide yellow (E172) - 1%; gelatin - up to 100%

Capsules 1 caps.

When manufacturing at JSC "Krka, dd, Novo mesto", Slovenia

active substance:

celecoxib 100/200 mg

auxiliary substances: lactose monohydrate 24,875 / 49,75 mg; sodium lauryl sulfate 4.05 (8.1 mg; Povidone K30 3.375 / 6.75 mg; croscarmellose sodium 1.35 / 2.7 mg; magnesium stearate 1.35 / 2.7 mg

hard gelatin capsules ¹3 / 1

body: titanium dioxide (E171) - 2/1%; iron dye oxide yellow (E172) - - / 1%; gelatin - up to 100/100%

lid: titanium dioxide (E171) - 2/1%; iron dye oxide yellow (E172) - - / 1%; gelatin - up to 100/100%

Description of dosage form

Capsules, 100 mg: hard gelatin capsules ¹3 white (body and lid).

Capsules, 200 mg: hard gelatin capsules No. 1 brownish-yellow (body and lid).

The contents of the capsules are a granular powder of white or almost white color.

pharmachologic effect

Pharmacological action - anti-inflammatory, antipyretic, analgesic.

Pharmacodynamics

Celecoxib has an anti-inflammatory, analgesic and antipyretic effect, blocking the formation of inflammatory PH mainly due to the inhibition of COX-2.

Induction of COX-2 occurs in response to inflammation and leads to the synthesis and accumulation of PG, especially PGE2, which causes an increase in inflammation (swelling and pain). At therapeutic doses in humans, celecoxib significantly does not inhibit COX-1 and does not affect the concentrations of PG that are synthesized as a result of activation of COX-1, as well as normal physiological processes associated with COX-1 and proceeding in tissues, primarily the stomach, intestines, and thrombocytes.

Effect on kidney function

Celecoxib reduces the excretion of PGE2 and 6-keto-PGF1 (metabolite prostacyclin) by the kidneys, but does not affect the serum concentration of thromboxane B2 (TxB2) and the excretion of 11-dehydro-TxB2 by the kidneys, and the metabolite of thromboxane (both products of COX-1).

Celecoxib does not cause a decrease in the glomerular filtration rate in elderly patients and patients with chronic renal failure, transiently reduces excretion of sodium. In patients with arthritis, the incidence of peripheral edema, arterial hypertension, and heart failure was comparable to that of non-selective COX inhibitors that had inhibitory activity against COX-1 and -2. The most pronounced effect was in patients receiving diuretic therapy. Nevertheless, there was no increase in the incidence of increased blood pressure and heart failure, and peripheral edema was mild and passed independently.

Pharmacokinetics

Suction. When taken on an empty stomach, celecoxib is well absorbed, reaching Cmax in the blood plasma after about 2-3 hours. Cmax in the blood plasma after taking 200 mg of celecoxib is 705 ng / ml. Absolute bioavailability of celecoxib has not been studied. Cmax and AUC are approximately proportional to the dose taken in the therapeutic dose range to 200 mg twice daily, with celecoxib administered at higher doses, the increase in Cmax and AUC is less proportional.

Influence of food intake. Taking celecoxib concomitantly with fatty foods increases the time to reach Cmax by about 4 hours and increases the absorption by about 20%.

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

Metabolism. Celecoxib is metabolized mainly with the involvement of the cytochrome P450 (CYP) CYP2C9 isoenzyme in the liver by hydroxylation, oxidation and partial glucuronation (see "Interaction").

The resulting metabolites are pharmacologically inactive with respect to COX-1 and -2.

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

Excretion. Celecoxib is excreted through the intestine and kidneys in the form of metabolites (57 and 27%, respectively), less than 1% of the dose taken in unchanged form. With repeated use of T1 / 2 is 8-12 hours, and the clearance is about 500 ml / min. At repeated application Css in a blood plasma are reached or achieved to 5th day of reception. The variability of the main pharmacokinetic parameters (AUC, Cmax, T1 / 2) is about 30%. The average Vss is approximately 500 l / 70 kg in young healthy patients, indicating a wide distribution of celecoxib in tissues.

Individual patient groups

Patients of advanced age. In patients older than 65 years, there is an increase in 1.5-2 times the average values of Cmax and AUC, which is more due to changes in body weight, rather than age (in elderly patients, as a rule, a lower average body weight than in persons of a younger age, so that they, with other conditions being equal, achieve higher concentrations of celecoxib). For the same reason, older women usually have a higher concentration of celecoxib in the blood plasma than older men. These features of pharmacokinetics, as a rule, do not require dose adjustment. However, in elderly patients with a body weight of less than 50 kg, treatment should be started with the minimum recommended dose.

Race. In representatives of the Negroid race AUC, celecoxib is approximately 40% higher than in the representatives of the Caucasoid race. The causes and clinical significance of this fact are unknown, therefore, it is recommended to start treatment of people of the Negroid race with the minimum recommended dose.

Violation of the function of the liver. Concentrations of celecoxib in blood plasma in patients with mild liver failure (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 GFR> 65 mL / min / 1.73 m2 associated with age-related changes and in patients with GFR of 35-60 mL / min / 1.73 m2, the pharmacokinetics of celecoxib do not change. There is no significant correlation between serum creatinine concentration (or creatinine clearance) and celecoxib clearance. It is assumed that the presence of severe renal failure does not affect the clearance of celecoxib, since the main way of its elimination is conversion into the liver into inactive metabolites.

Indication

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;

hypersensitivity to other sulfonamide derivatives;

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

period after the operation of aortocoronary shunting;

active erosive and ulcerative lesions of the mucous membrane of the stomach or duodenum, peptic ulcer of the stomach and duodenum in the acute stage or gastrointestinal bleeding;

inflammatory bowel disease (Crohn's disease, ulcerative colitis) in the phase of exacerbation;

Heart failure (NYHA class II-IV functional class);

clinically confirmed coronary heart disease, peripheral arterial disease and cerebrovascular disease in a pronounced stage;

hemorrhagic stroke;

subarachnoid hemorrhage;

pregnancy;

the period of breastfeeding (see "Application during pregnancy and lactation");

severe hepatic insufficiency (class C according to Child-Pugh classification) (no experience of application);

severe renal failure (Cl creatinine less than 30 ml / min), progressive kidney disease, confirmed hyperkalemia (no experience of use);

age to 18 years (no experience of application);

lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome (the Dilaxa® preparation contains lactose).

With caution: gastrointestinal diseases (peptic ulcer or duodenal ulcer, ulcerative colitis, Crohn's disease, history of bleeding), presence of Helicobacter pylori infection, concomitant use with digoxin, anticoagulants (eg warfarin), antiplatelet agents (eg acetylsalicylic acid, clopidogrel), GCS for oral administration (eg prednisolone), diuretics, SSRIs (eg citalopram, fluoxetine, paroxetine, sertraline), inhibitors of the isoenzyme CYP2C9, in patients who are slow metabolizers or are available suspicion of such a condition, fluid retention and swelling, poor liver function of moderate severity (see "Special instructions"), liver disease in history, hepatic porphyria, impaired renal function (Cl creatinine 30-60 ml / min), a significant decrease in BCC (including after surgery), SSS diseases, arterial hypertension (see "Special instructions"), cerebrovascular diseases, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, prolonged use of NSAIDs, severe somatic diseases Ania, elderly patients (including 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 Dilaxa® during pregnancy is not established, however, it can not 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 lead to complications during pregnancy or impairment of fertility. Women who plan pregnancy or undergo infertility examinations should consider abolishing NSAIDs, including celecoxib.

Celecoxib, belonging to the group of inhibitors of the synthesis of PG, during admission 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 GHG synthesis in early pregnancy can adversely affect the course of pregnancy.

There are limited data on the excretion of celecoxib with breast milk. Studies have shown that celecoxib is excreted in breast milk at 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 evaluated, given the importance of taking Dilaxa® for the mother.

Side effects

Classification of the incidence of adverse events WHO: very often - ≥1 / 10; often from ≥1 / 100 to <1/10; infrequently - from ≥1 / 1000 to <1/100; rarely - from ≥ 1/10000 to <1/1000; very rarely - from <1/10000.

From the CCC: often - peripheral edema, increased blood pressure, including weighting the course of arterial hypertension; infrequent - tidal, palpitations; rarely - CHF, arrhythmia, tachycardia, ischemic stroke and myocardial infarction.

On the part of the digestive system: often - abdominal pain, diarrhea, indigestion, flatulence, vomiting; infrequently - dental disease (postextraction lunechke alveolitis); rarely - gastric and duodenal ulcers, ulceration of the esophagus; very rarely - intestinal perforation, pancreatitis.

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

From the urinary system: often - infection of the urinary tract.

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

From the skin: often - skin itching (including generalized), skin rash; infrequently - hives, ecchymoses; rarely - alopecia.

On the part of the organs of hematopoiesis: infrequently anemia; rarely - thrombocytopenia.

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

Laboratory indicators: infrequently - increased activity of hepatic enzymes (including ALT and AST).

Allergic reactions: rarely - angioedema; very rarely - bullous eruptions (bullous dermatitis).

Other: infrequent - exacerbation of allergic diseases (hypersensitivity), flu-like syndrome, accidental trauma, facial edema.

According to post-marketing surveillance data

Allergic reactions: very rarely anaphylaxis (anaphylactic reactions).

From the nervous system: rarely - hallucinations; very rarely - hemorrhages in the brain, aseptic meningitis, loss of taste, loss of smell.

From the senses: infrequently - conjunctivitis.

From the CCC: rarely - PE; very rarely - vasculitis.

From the digestive system: rarely - gastrointestinal bleeding, hepatitis; very rarely - liver failure, fulminant hepatitis, necrosis of the liver (see "Special instructions", "Influence on the function of the liver"), cholestasis, cholestatic hepatitis, jaundice.

From the skin: rarely photosensitivity reactions; very 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 urinary system: rarely - acute renal failure (see "Special instructions", subsection "Influence on kidney function"), hyponatremia; very rarely - interstitial nephritis, nephrotic syndrome, minimal renal dysfunction.

From the side of the reproductive system: rarely - a violation of the menstrual cycle; frequency unknown - decreased fertility in women * (see "Application in pregnancy and lactation").

Other: infrequent - pain in the chest.

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

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 isoenzyme CYP2D6.

Warfarin and other anticoagulants: with the simultaneous use of an extension of the PV.

Fluconazole, ketoconazole: with simultaneous application of 200 mg fluconazole, an increase in the concentration of celecoxib in the blood plasma is observed twice a day, which is associated with inhibition of celecoxib metabolism by fluconazole through the isoenzyme CYP2C9. Patients taking fluconazole (inhibitor of the isoenzyme CYP2C9) should lower the recommended dose of celecoxib by half (see "Method of administration and dose"). Ketoconazole (an inhibitor of the isoenzyme CYP3A4) does not have a clinically significant effect on the metabolism of celecoxib.

Dextromethorphan and metoprolol: it was found that the simultaneous use of celecoxib at a dose of 200 mg per day led to an increase in the concentrations of dextromethorphan and metoprolol (substrates of the isoenzyme CYP2D6) by 2.6 and 1.5 times, respectively. Such an increase in concentrations is due to the inhibition of the metabolism of the CYP2D6 isoenzyme substrate by celecoxib by inhibiting the activity of the CYP2D6 isoenzyme itself. Methotrexate: There have been no pharmacokinetic clinically significant interactions between celecoxib and methotrexate.

Hypotensive drugs, including ACE inhibitors / antagonists of ARA II, diuretics and beta adrenoblockers: inhibition of PG synthesis can reduce the antihypertensive effect, incl. ACE inhibitors / ARA II, diuretics and beta-blockers. This interaction should be considered when concurrent use of celecoxib with ACE inhibitors / ARA II, diuretics and beta-blockers. However, no significant pharmacodynamic interaction with lisinopril was observed with respect to the effect on BP.

In elderly patients, in patients with dehydration (including patients receiving diuretic therapy) or in patients with impaired renal function, simultaneous use of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, APA II may lead to impairment kidney 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 Dilaxa®. In addition, the possibility of monitoring the function of the kidneys at the beginning of therapy and periodically during simultaneous use of the drugs should be considered.

Cyclosporin: Considering that NSAIDs have an effect on renal GHG synthesis, they may increase the risk of developing nephrotoxicity when used concomitantly with cyclosporine.

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

Contraceptives for oral administration: celecoxib does not have a clinically significant effect on the pharmacokinetics of a combined contraceptive (1 mg norethisterone / 35 μg ethinyl estradiol).

Lithium: with the simultaneous use of lithium salts in a dose of 450 mg twice a day and celecoxib at a dose of 200 mg twice a day, an increase in the concentration of lithium in the blood plasma by about 17% is noted. Patients taking lithium drugs should be carefully monitored when celecoxib is used or withdrawn.

Other NSAIDs: avoid concomitant use of celecoxib and other NSAIDs (not containing acetylsalicylic acid) (increased risk of side effects).

Other drugs: 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 has no antiaggregant effect on platelets, so they should not replace acetylsalicylic acid in order to prevent cardiovascular disease.

In healthy volunteers, NSAIDs do not affect 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. There is no information on the interaction of celecoxib and digoxin. Considering other effects of celecoxib on CCC, caution should be taken simultaneously with digoxin. In this case, it is recommended to carefully monitor adverse reactions. Celecoxib is predominantly metabolized in the liver by the CYP2C9 isoenzyme. Since barbiturates are inducers of the CYP2C9 isoenzyme, concomitant use with celecoxib may decrease the concentration of the latter in the blood plasma.

Dosing and Administration

Inside, not liquid, squeezed water, regardless of food intake.

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

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

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

Symptomatic treatment of ankylosing spondylitis. The recommended dose is 200 mg / day in 1 or 2 doses. Some patients noted the effectiveness of 400 mg twice a day.

Treatment of pain syndrome and primary dysmenorrhea. The recommended initial dose is 400 mg, followed, if necessary, by taking an additional dose of 200 mg on the first day. In the following days, the recommended dose is 200 mg 2 times a day, as needed.

Patients of advanced age. Usually dose adjustment is not required. However, in patients with a body weight of less than 50 kg, it is better to start treatment with the minimum recommended dose.

Violation of the function of the liver. In patients with mild liver failure (Class A Child-Pugh classification), dose adjustment is not required. In the case of a moderate degree of hepatic insufficiency (class B according to the Child-Pugh classification), the initial recommended dose of the drug should be reduced by half. The experience of using Dilaxa® in patients with severe hepatic insufficiency (class C according to the Child-Pugh classification) is not available (see Contraindications).

Impaired renal function. In patients with mild and moderate severity of renal failure, dose adjustment is not required. The experience of using Dilaxa ® in patients with severe renal failure is not present (see "Special instructions", "Contraindications").

Simultaneous use with fluconazole. With the simultaneous use of fluconazole (inhibitor of the isoenzyme CYP2C9) and Dilaxa®, the initial recommended dose should be reduced by half. Caution should be exercised when used simultaneously with other inhibitors of the isoenzyme CYP2C9.

Slow metabolism of the substrates of the isoenzyme CYP2C9. In patients who are slow metabolizers or suspected of such a condition, Dilaxa® preparation should be used with caution. this can lead to the accumulation of celecoxib in high concentrations in the blood plasma. In such patients, the initial recommended dose should be reduced by a factor of 2.

Overdose

Clinical data on overdose are limited. A single dose in a dose of up to 1200 mg and repeated application in a dose of up to 1200 mg twice a day was not accompanied by clinically significant side effects.

Treatment: if you suspect an overdose, supportive therapy should be given. Dialysis is presumably not effective, because the association of celecoxib with plasma proteins is high (97%).

special instructions

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

Influence on CAS. Celecoxib, like all coxibs, can increase the risk of serious complications from CVS, such as thrombosis, myocardial infarction and stroke, which can lead to death. The risk of these reactions increases with increasing dose, duration of drug intake, as well as in patients with diseases or risk factors for the development of CAS. In order to reduce the risk of these reactions, the Dilaxa® preparation should be used in minimum effective doses and with the minimum possible short course (at the discretion of the treating physician). The attending physician and the patient should consider the possibility of developing such complications, even in the absence of previously known symptoms of a disturbance of the function of the CAS. Patients should be informed of the symptoms of serious adverse effects from CAS and the measures to be taken if they occur.

When NSAIDs (selective COX-2 inhibitors) are used in patients after aortocoronary bypass surgery to treat the pain syndrome in the first 10-14 days, an increase in the incidence of myocardial infarction and cerebral circulation disorders is possible.

Celecoxib has no antiaggregant effect on platelets, so they should not replace acetylsalicylic acid in order to prevent thromboembolism. Also, in connection with this, antiplatelet therapy (eg acetylsalicylic acid) should not be abolished in patients at risk of developing thromboembolic complications.

Like all NSAIDs, celecoxib can lead to an increase in blood pressure, which can cause complications from the CAS. Like other NSAIDs, celecoxib should be used with caution in patients with hypertension. At the beginning and during therapy with celecoxib, BP should be monitored.

Influence on the digestive system. In patients taking celecoxib, very rare cases of perforation, ulceration and bleeding from the gastrointestinal tract were observed. The risk of these complications in the use of NSAIDs is highest in elderly patients, patients with cardiovascular diseases, in patients receiving acetylsalicylic acid simultaneously, and in patients with gastrointestinal diseases such as ulcers, bleeding, inflammatory processes in the acute stage and in the anamnesis. Other risk factors for bleeding from the gastrointestinal tract are simultaneous use of GCS for oral administration or anticoagulants, long-term therapy with NSAIDs, smoking, and taking ethanol. Most spontaneous reports of serious adverse reactions with a fatal outcome were observed in elderly patients and weakened patients.

Simultaneous use with warfarin and other 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, coumarin anticoagulants and oral direct-acting anticoagulants (eg apixaban, dabigatran and rivaroxaban). Serious (some of them fatal) bleeding has been reported in patients who have used warfarin or similar agents concomitantly with celecoxib. Given the presence of reports of lengthening of the IV, after the initiation of treatment with Dilaxa® or with a change in its dose, it is necessary to monitor the clotting parameters of the blood.

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

Influence on kidney function. NSAIDs, incl. and celecoxib, can have a toxic effect on kidney function. It has been found that celecoxib has no greater toxicity 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, APA II, and in elderly patients. It is necessary to closely monitor the kidney function in these patients. Also, care should be taken in patients with dehydration. In such cases, it is advisable to rehydrate, and then begin therapy with Dilaxa®.

Effect on liver function. Dilaxa® should not be used in patients with severe liver failure (class C according to Child-Pugh classification). Patients with moderate hepatic impairment (Child-Pugh class B) should be treated with caution and at the lowest effective dose. In rare cases severe liver function abnormalities, including fulminant hepatitis (sometimes fatal), liver necrosis and liver failure (sometimes with a fatal outcome or the need for liver transplantation) have been observed. Most of these reactions developed 1 month after the initiation of celecoxib.

Patients with symptoms and / or signs of liver dysfunction or those who have a liver function disorder in the laboratory should be closely monitored for the development of more severe liver reactions during treatment with Dilaxa®.

Anaphylactic reactions. When taking Dilaxa®, cases of anaphylactic reactions developed.

Serious reactions from the skin. Very rarely, when taking celecoxib, severe skin reactions were observed, such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, some of which were fatal. The risk of developing such reactions is higher at the beginning of therapy, in most of the reported cases they occurred in the first month of therapy. If skin rash, changes in mucous membranes or other signs of hypersensitivity occur, you should stop taking Dilaxa®.

SCS therapy. Do not replace GKS therapy with Dilaxa® in the treatment of GCS insufficiency.

Inhibition of the isoenzyme function of CYP2D6. It was found that celecoxib is a moderate inhibitor of the CYP2D6 isoenzyme. During the initiation of 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 "Interaction with Other Drugs").

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

Influence on ability of driving of the car and management of mechanisms. Care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions. Dilaxa® can cause dizziness and other side effects that may affect these abilities.

Form of issue

Capsules, 100 mg, 200 mg. For 10 caps. in a contour squeeze box (blister) of PVC and aluminum foil.

1, 2, 3, 4, 5, 6, 9 or 10 contour squares (blisters) are placed in a pack of cardboard.

Conditions of leave from pharmacies

On prescription.

storage Conditions

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life of Dilaxa®

2 years.

Do not use after the expiry date printed on the package.