Roukoksib-Routek - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 43.15 mg, croscarmellose sodium 3.00 mg, sodium lauryl sulfate 8.10 mg, povidone K-30 6.75 mg, magnesium stearate 9.00 mg.

Capsule shell composition:

Housing: gelatin 81.400%, methyl parahydroxybenzoate 0.800%, propyl parahydroxybenzoate 0.200%, sodium lauryl sulfate 0.100%, water 14.500%, titanium dioxide 3,000%.

Cap: gelatin 82.237%, methyl parahydroxybenzoate 0.800%, propyl parahydroxybenzoate 0.200%, sodium lauryl sulfate 0.100%, water 14.500%, titanium dioxide 1.200%, dye azorubin 0.428%, dye Ponso 4R 0,535%.

Description:

Hard gelatin capsules number 2, the body is white, the lid is dark red.

The contents of capsules are white or almost white powder.

Pharmacotherapeutic group:NSAIDs

ATX: & nbsp

M.01.A.H.01 Celecoxib

Pharmacodynamics:

Celecoxib has an anti-inflammatory, analgesic and antipyretic effect, blocking the formation of inflammatory prostaglandins (Pg) mainly due to the 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 E₂, while there is an increase in manifestations of inflammation (edema 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.

Influence on kidney function. Celecoxib reduces excretion in the urine 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 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 to that of non-selective COX inhibitors, which have inhibitory activity against COX-1 and COX-2.

Pharmacokinetics:

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

Effect of food intake. Taking celecoxib along with fatty foods increases the time to reach the Stach by about 4 hours and increases the overall absorption by about 20%.

Distribution. The connection with plasma proteins does not depend on the concentration and is about 97%, celecoxib does not bind to red blood cells. The drug penetrates the blood-brain barrier.

Metabolism. Celecoxib It is metabolized in the liver by hydroxylation, oxidation and partially glucuronidation. Metabolism mainly occurs with the participation of cytochrome P450 CYP2C9. (see "Interaction with other drugs"). Metabolites found in the blood are not pharmacologically active against COX-1 and COX-2. The activity of cytochrome P450 CYP2C9 is reduced in persons with genetic polymorphism, such as homozygous for CYP2C9 * 3 polymorphism, which leads to a decrease in the effectiveness of enzymes.

Excretion. Celecoxib metabolized in the liver, excreted in feces and urine in the form of metabolites (57% and 27%, respectively), less than 1% of the dose - unchanged. At repeated application the half-life period is 8-12 hours, and the clearance is about 500 ml / min. With repeated application, equilibrium concentrations in the plasma are reached by day 5. The variability of the main pharmacokinetic parameters (AUC, FROM_mOh, half-life) is about 30%. The average volume of distribution in the equilibrium state is approximately 4,500 l / 70 kg in young healthy adult patients, indicating a wide distribution of celecoxib in the tissue.

Special Groups

Elderly patients. In patients older than 65 years there is an increase in 1,5-2 times the average values of C_mOh, 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 plasma concentration of the drug than older men. These features of pharmacokinetics, as a rule, do not require dose adjustment. Nevertheless, in elderly patients with a body weight below 50 kg, treatment with the lowest recommended dose should be started.

Race. In a representative Negroid race AUC celecoxib is about 40% higher than that of Europeans. The causes and the clinical significance of this fact are not known, therefore it is recommended to start their treatment with the minimum recommended dose.

Violation of the function of the liver. Concentrations of celecoxib in plasma in patients with mild degree of hepatic insufficiency (class A according to the Child-Pugh classification) vary slightly. In patients with moderate hepatic impairment (Child-Pugh class B), the concentration of celecoxib in plasma can almost double.

Impaired renal function. In patients with chronic renal failure with a glomerular filtration rate (GFR)> 65 ml / min / 1.73 m² 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 association between serum creatinine (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.

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;

- increased hypersensitivity to sulfonamides;

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

- condition after aorto-coronary bypass surgery;

- erosive and ulcerative changes in the mucous membrane of the stomach or duodenum, active gastrointestinal bleeding; cerebrovascular-vascular or other bleeding;

- hemophilia and other bleeding disorders;

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

- heart failure, decompensation stage (functional class II-IV by classification NYHA);

- clinically confirmed ischemic heart disease, peripheral arterial disease and cerebrovascular disease in the severe stage;

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

- severe hepatic insufficiency (no experience of use);

- severe renal failure (QC 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 (the preparation contains lactose).

Carefully:

Celecoxib should be taken with caution under the following conditions: gastrointestinal tract (peptic ulcer disease, history of bleeding), infection Helicobacter pylori, shared use with anticoagulants (warfarin), antiplatelet agents (acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (prednisolone), selective serotonin reuptake inhibitors (citalopram, fluoxetine, paroxetine, sertraline); fluid retention and swelling; violations of the liver function of moderate severity (see "Special instructions"); diseases of the cardiovascular system (see "Special instructions"); cerebrovascular diseases; dyslipidemia / hyperlipidemia; diabetes; diseases of peripheral arteries; simultaneous use with inhibitors СУР2С9; long-term use of NSAIDs; severe physical illness; ulcerative disease of the stomach and duodenum, ulcerative colitis, Crohn's disease, liver disease in history, hepatic porphyria, chronic renal failure (KK 30-60 ml / min), a significant decrease in the volume of circulating blood (including after surgery), elderly patients (including those receiving diuretics, weakened patients and with low body weight), smoking, prolonged use of NSAIDs, tuberculosis, alcoholism.

Pregnancy and lactation:

There is insufficient data on the use of celecoxib in pregnant women.The potential risk of celecoxib during pregnancy is not established, but can not be ruled out. CelecoxibBelonging to the group of prostaglandin synthesis inhibitors, when taking during pregnancy, particularly in the III trimester, can cause weakness uterine contractions and premature closure of the ductus arteriosus.

There is limited evidence that celecoxib excreted in breast milk. Taking into account the potential for the development of side effects in the child, the advisability of continuing breastfeeding should be evaluated, given the importance of taking celecoxib for the mother.

The use of the drug may adversely affect female fertility and is not recommended for women planning pregnancy. In patients with infertility (including undergoing examination) it is recommended to cancel the drug.

Dosing and Administration:

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

Since the risk of cardiovascular complications may increase with an increase in the dose and duration of administration of the drug Roquoxib-Rootec, the minimum effective dose of the drug should be taken as the minimum possible course.The maximum recommended daily intake for long-term admission is 400 mg.

Symptomatic treatment osteoarthritis: the recommended dose is 200 mg per day.

Symptomatic treatment rheumatoid arthritis: the recommended dose is 200 mg 1-2 times a day.

Symptomatic treatment ankylosing spondylitis: the recommended dose is 200 mg 1-2 times a day.

Treatment 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.

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

Impaired liver function: y patients with mild degree of hepatic insufficiency (class A according to Child-Pugh classification) dose adjustment is not required, in the case of moderate-degree liver failure (class B according to Child-Pugh classification) treatment should begin with the minimum recommended dose. A drug Celecoxib, should not be taken in patients with severe hepatic impairment (see "Contraindications.").

Impaired renal function: Dose correction is not required. The experience of using the drug in patients with severe renal failure is not (see section "Special instructions").

Simultaneous use with fluconazole: patients receiving fluconazole (inhibitor CYP2C9), The preparation of roukoxib-routek should be prescribed in the minimum recommended dose.

Side effects:

The incidence of side effects listed below was determined according to the following (classification of the World Health Organization): very often (more than 10%), often (more than 1% and less than 10%), infrequently (more than 0.1% and less than 1%), rarely (more than 0.01% and less than 0.1%), very rarely (less than 0.01%), including individual reports; the frequency is unknown (can not be estimated with the help of available data).

From the side of the cardiovascular system: hasto: peripheral edema, increased blood pressure, weighting the course of arterial hypertension; infrequently: "hot flashes", a feeling of heartbeat; rarely: tachycardia, manifestation of congestive heart failure, ischemic stroke and myocardial infarction; rarely - Vasculitis.

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

From the nervous system: often - dizziness, insomnia; infrequently - anxiety, increased muscle tone, drowsiness; rarely - confusion (psychosis), hallucinations; rarely - hemorrhage in the brain, aseptic minngitis, loss of taste, loss of smell.

From the kidneys and urinary system: often - urinary tract infection; rarely acute renal failure, hyponatremia; rarely - interstitial nephritis, nephrotic syndrome, impaired renal function.

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

From the skin: often - skin itching, skin rash; infrequently - urticaria, ecchymosis; rarely - alopecia, photosensitization; rarely - erythema multiforme, Stevens-Johnson syndrome, 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 blood: infrequently - anemia, ecchymosis, rarely - Thrombocytopenia.

From the immune system: rarely - angioedema; rarely - bullous eruptions; rarely anaphylactic reaction.

From the hepatobiliary system: infrequently - increased activity "Hepatic" enzymes; rarely - Hepatitis; rarely - hepatic insufficiency, fulminant hepatitis, liver necrosis, cholestasis, cholestatic hepatitis, jaundice.

From the sense organs: infrequently - sensation of "noise" in the ears, "indistinctness" of visual perception, conjunctivitis.

From the side of the reproductive system: rarely - violation of the menstrual cycle; frequency unknown - decreased fertility in women.

Are common: infrequently - exacerbation of allergic diseases, flu-like syndrome, facial edema, chest pain.

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 because of the high degree of binding of the drug to the protein.

Interaction:

Research "in vitro"Showed that celecoxib although it is not a substrate CYP2D6, but inhibits its activity. Therefore, there is a possibility of drug interaction "in vivo"With drugs whose metabolism is associated with cytochrome CYP2D6.

Warfarin and other anticoagulants (for example, coumarin preparations, sulfonamides): with simultaneous admission, an increase in prothrombin time is possible.

Fluconazole, ketoconazole: patients receiving fluconazole (inhibitor of CYP2C9) celecoxib should be given at the lowest recommended dose (see "Dosage and route of administration"). Ketoconazole (inhibitor CYP3 A4) does not have a clinically significant effect on the metabolism of celecoxib.

Inductors CYP 2С9: Simultaneous application of inducers CYP 2C9, such as rifampicin, chlorphenamine, promethacin, colestyramine, carbamazepine and barbiturates, can reduce plasma concentrations of celecoxib.

Angiotensin converting enzyme inhibitors / angiotensin II antagonists: inhibition of prostaglandin synthesis can reduce the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors / angiotensin II antagonists. This interaction should be taken into account in the appointment of celecoxib in conjunction with ACE inhibitors / angiotensin II antagonists. However, there was no significant pharmacodynamic interaction with lisinopril in terms of the effect on blood pressure.

Diuretics: previously known NSAIDs in some patients may reduce the natriuretic effect of furosemide and thiazides by reducing the renal synthesis of prostaglandins, this should be borne in mind when assigning 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 plasma lithium concentration of about 17% was noted with the combined use of lithium and celecoxib.Patients receiving lithium therapy should be closely monitored for the appointment or withdrawal of celecoxib.

Other NSAIDs: It should avoid the simultaneous use of celecoxib and other NSAIDs (not containing acetylsalicylic acid).

Digoxin: it is possible to increase the level of digoxin in blood plasma when combined with celecoxib.

Antidiabetic agents for oral administration: possibly increased hypoglycemic effect.

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

Co-administration with paracetamol increases nephrotoxicity, with methotrexate-hepato- and nephrotoxicity.

Simultaneous appointment of celecoxib and methotrexate is possible only with the use of low doses of the latter (monitoring the concentration of methotrexate in the blood plasma).

Probenecid reduces plasma clearance and volume distribution of celecoxib, increases its concentration in the blood plasma and increases the half-life.

When taking Mifepristone, celecoxib can be used 8-12 days after taking mifepristone, since NSAIDs reduce the effect of drugs in this group.

Celecoxib does not affect the antiplatelet effect of acetylsalicylic acid, therefore it can not be considered as a substitute for acetylsalicylic acid, which is prescribed for the prevention of cardiovascular diseases.

Special instructions:

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 duration of the drug, as well as in patients with diseases of the cardiovascular system. To reduce the risk of these reactions, in patients receiving Celecoxib, it should be administered at the lowest recommended doses and as short as possible (at the discretion of the treating physician). The attending physician and patient should keep in mind the possibility of such complications even in the absence of previously known cardiovascular symptoms.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.

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 taking celecoxib, extremely rare cases of perforation, ulceration and bleeding from the gastrointestinal tract were observed. The risk of these complications in the treatment of NSAIDs is highest in the elderly, patients with cardiovascular diseases, patients receiving acetylsalicylic acid concurrently, and patients with gastrointestinal tract diseases such as ulcers, bleeding in the acute stage and in the anamnesis. Most spontaneous reports of serious side effects on the gastrointestinal tract were related to elderly and debilitated patients.

Sharing with warfarin and other anticoagulants. Serious (some of them fatal) bleeding was reported in patients who received concomitant treatment with warfarin or similar agents. Since the prothrombin time has been reported, anticoagulant activity should be monitored after initiation of celecoxib treatment or a change in its dose.

Fluid retention and swelling. As with the use of other drugs that inhibit the synthesis of prostaglandins, in a number of patients taking celecoxib, fluid retention and swelling may occur, so caution should be exercised in prescribing this medication to 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. Celecoxib should be used with caution in patients with impaired renal function. The function of the kidney in such patients should be carefully monitored.

Caution should be exercised when prescribing celecoxib therapy for patients with dehydration.In such cases, it is advisable to first rehydrate, and then begin therapy with celecoxib.

Effects on liver function. Celecoxib should be used with caution in the treatment of patients with moderate hepatic impairment and prescribe at the lowest recommended dose.

In some cases severe liver reactions have been observed, including fulminant hepatitis (sometimes fatal), liver necrosis (sometimes fatal 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 liver dysfunction, or those patients who are diagnosed with liver dysfunction in laboratory settings, should be closely monitored for the development of more severe liver reactions during treatment with celecoxib.

Anaphylactic reactions. When receiving celecoxib, cases of anaphylactic reactions were reported.

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

Ceserious 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 in patients at the beginning of therapy is higher, in most noted cases such reactions began in the first month of therapy. Celecoxib should be discontinued when skin rashes, changes in mucous membranes, or other signs of hypersensitivity occur.

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 pharmacodynamic properties and general safety profile, it seems unlikely that celecoxib has such an impact.

Form release / dosage:

Capsules, 200 mg.

Packaging:

For 10 capsules in an aluminum / PVC / PVDC blister.

One blister with instructions for use is placed in a cardboard box.

Storage conditions:

At a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003486

Date of registration:03.03.2016

Expiration Date:03.03.2021

The owner of the registration certificate:ARS, LLC ARS, LLC Russia

Manufacturer: & nbsp

SCAN BIOTECH, Ltd. India

Representation: & nbspARS, LLCARS, LLC

Information update date: & nbsp10.08.2016

Illustrated instructions

Instructions

Roquoxib-Routeck (Roucoxib-Rowtech)