Celebrex, capsules 200 mg, 30 pcs.

Composition

1 capsule. contains celecoxib 200 mg

. Pharmacological action

Pharmaceutical group:

NSAIDs.

Pharmaceutical action:

Celebrex is an NSAID. 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 prostaglandins, especially prostaglandin E2, while increasing the manifestations of inflammation (swelling and pain).

In therapeutic doses in humans, celecoxib significantly does not inhibit cyclooxygenase-1 (COX-1) and does not affect prostaglandins synthesized as a result of COX-1 activation, and also does not affect normal physiological processes associated with COX-1 and occurring in tissues, and primarily in the tissues of the stomach, intestines and platelets.

Effect on kidney function. Celecoxib reduces urinary excretion of PgE2 and 6-keto-PgF1 (a prostacyclin metabolite), but does not affect serum thromboxane B2 and urinary excretion of 11-dehydro-thromboxane B2, a metabolite of thromboxane (both COX – 1 products).

Celecoxib does not cause a decrease in glomerular filtration rate in elderly patients and people with chronic renal failure, and transitorily reduces sodium excretion. In patients with arthritis, the observed incidence of peripheral edema, hypertension, and heart failure is comparable to that of nonselective COX inhibitors, which have inhibitory activity against COX-1 and COX-2.

Pharmacokinetics: Absorption. When taken on an empty stomach, celecoxib is well absorbed, reaching its maximum plasma concentration (Cmax) after approximately 2-3 hours. Cmax in plasma after administration of 200 mg – 705 ng / ml. Absolute bioavailability of the drug has not been studied. Cmax 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 2 times a day; when using the drug in higher doses, the degree of increase in Cmax and AUC occurs less proportionally. Effect of food intake. Taking celecoxib together with fatty foods increases the time to reach Cmax by about 1 to 2 hours and increases total absorption by about 20%.

Distribution. Binding to plasma proteins is independent of concentration and is about 97%, celecoxib does not bind to red blood cells. The drug penetrates the blood-brain barrier.

Metabolism. Celecoxib is metabolized in the liver by hydroxylation, oxidation, and partial glucuronidation. Metabolism mainly occurs with the participation of cytochrome P450 CYP2C9. (see “Interaction with other drugs”). The metabolites found in the blood are pharmacologically inactive against COX-1 and COX-2.

Cytochrome P 450 CYP2C9 activity is reduced in individuals with a genetic polymorphism, such as the CYP2C9*3 homozygous polymorphism, which leads to a decrease in the efficiency of enzymes.

Output. Celecoxib is metabolized in the liver, excreted in the faeces and urine as metabolites (57% and 27%, respectively), less than 3% of the dose taken is unchanged. With repeated use, the half-life is 8-12 hours, and the clearance is about 500 ml / min. With repeated use, steady-state plasma concentrations are reached by day 5. The variability of the main pharmacokinetic parameters (AUC, Cmax, half-life) is about 30%. The average volume of distribution at steady state is approximately 400 liters.

Special groups

Elderly patients.

In patients over 65 years of age, there is a 1.5-2-fold increase in the average values of Cmax, AUC of celecoxib, which is more due to changes in body weight, and not age (elderly patients, as a rule, have a lower average body weight than younger people, which is why, all other things being equal, they achieve higher concentrations of 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. However, elderly patients with a body weight below 50 kg should start treatment with the lowest recommended dose.

Race.

The representative black race has an AUC of celecoxib approximately 40% higher than that of Europeans. The causes and clinical significance of this fact are not known, so their treatment 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) do not change significantly. In patients with moderate hepatic insufficiency (Child-Pugh class B), the plasma concentration of celecoxib may increase almost 2-fold.

Impaired renal function.

In patients with chronic renal failure with 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 did 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 insufficiency does not affect the clearance of celecoxib, since its main route of elimination is conversion to inactive metabolites in the liver.

Indications

-osteoarthritis; – rheumatoid arthritis – – pain syndrome of various etiologies (including postoperative, toothache, menstrual, bone and muscle pain).

Use during pregnancy and lactation

The use of Celebrex during pregnancy (especially in the third trimester) is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to use Celebrex during lactation, the question of stopping breastfeeding should be decided.

Contraindications

-a history of allergic reactions (urticaria, bronchospasm) associated with taking acetylsalicylic acid or other NSAIDs; – severe renal impairment; – severe liver function disorders – – third trimester of pregnancy – – lactation (breastfeeding); – known hypersensitivity to sulfonamides – – hypersensitivity to the components of the drug.

Side effects

From the digestive system: often-abdominal pain, diarrhea, dyspepsia; rarely-nausea, vomiting, heartburn, anorexia; with prolonged use in high doses – ulceration of the gastrointestinal mucosa, bleeding, NSAIDs-gastropathy, constipation, flatulence, increased AST and ALT activity.

From the central nervous system and peripheral nervous system: rarely – headache, dizziness, drowsiness or insomnia, blurred vision, depression, agitation, confusion, anxiety, hallucinations, hearing loss, tinnitus.

Respiratory system disorders: rarely – sore throat, cough, shortness of breath, bronchospasm.

From the urinary system: rarely-renal failure, edematous syndrome.

From the hematopoietic system: rarely – agranulocytosis, anemia, leukopenia, thrombocytopenia.

From the cardiovascular system: rarely – arterial hypertension, arrhythmia, hot flashes, palpitations, congestive heart failure, tachycardia.

Allergic reactions: bullous skin rash, angioedema, bronchospasm, anaphylaxis, vasculitis, erythema multiforme, Stevens-Johnson syndrome.

Other services: alopecia, increased sweating, nosebleeds. There are isolated reports of acute pancreatitis.

Interaction

When Celebrex is co-administered with the CYP2C9 inhibitor fluconazole, it is possible to increase the concentration of celecoxib in plasma (celecoxib should be used at the lowest recommended dose).

It has been established in vitro that celecoxib is an inhibitor of CYP2D6, so there is a possibility of drug interaction with other drugs that are biotransformed with the participation of this isoenzyme.

Antacids (aluminum and magnesium) reduce the absorption of celecoxib by 10%, which does not cause clinically significant effects. When studying the effect of Celebrex on the pharmacokinetics and / or pharmacodynamics of CYP2C9 substrates glyburide, glibenclamide, tolbutamide in vivo, no clinically significant interaction was found.

In vitro studies have shown that the CYP2C19 isoenzyme can participate in celecoxib metabolism only to a small extent. In an in vivo study, multiple doses of celecoxib (200 mg twice daily for 7 days) did not affect the clearance of a single dose of the CYP2C19 phenytoin substrate. The risk of clinically significant inhibition of CYP2C19 substrate metabolism by celecoxib is considered to be negligible.

 When Celebrex is co-administered with warfarin and similar medications, it is possible to increase prothrombin time and develop serious bleeding (it is necessary to monitor clotting parameters and apply precautionary measures). There was no clinically significant interaction of celecoxib with ketoconazole, lithium preparations, and methotrexate.

How to take it, course of administration and dosage

Adults with osteoarthritis are prescribed Celebrex in a daily dose of 200 mg in 1 or 2 doses. In clinical trials, doses up to 400 mg / day were used.

In rheumatoid arthritis, the drug is prescribed in a daily dose of 200-400 mg, divided into 2 doses.In clinical trials, doses up to 800 mg/day were used.

For pain syndrome, the recommended single dose is 100-200 mg. If necessary, it is possible to use the drug in the same dose with an interval between doses of at least 4-6 hours until the maximum daily dose of 400 mg is reached.

In acute pain and algodismenorrhea, the recommended initial dose is 400 mg, then, if necessary, another dose of 200 mg is possible; the maximum dose on the first day of treatment is 600 mg/day; in subsequent days, the daily dose of the drug can vary from 200 mg to 400 mg.

The use of Celebrex in patients under 18 years of age has not been studied.

Overdose

There is no clinical experience of overdose. Healthy volunteers received a single dose of up to 1200 mg and multiple doses of up to 1200 mg 2 times / day without clinically significant adverse effects.

Treatment: conduct symptomatic therapy. Hemodialysis is ineffective.

Special instructions

Celebrex should be used with caution in patients with peptic ulcer of the stomach or duodenum, ulcerative colitis, heart failure, edematous syndrome, arterial hypertension.

Celebrex can be used with low doses of acetylsalicylic acid. Due to the lack of action on platelets, Celebrex does not replace acetylsalicylic acid in the preventive treatment of cardiovascular disorders.

If the activity of CYP2C9 decreases, Celebrex should be prescribed with caution, since in this case the plasma level of celecoxib may increase excessively.

Monitoring of laboratory parameters

During the use of the drug, it is necessary to monitor the picture of peripheral blood and laboratory parameters of liver and kidney function. If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

Use in pediatrics

There are no clinical data on the efficacy and safety of Celebrex in children and adolescents under 18 years of age.

Influence on the ability to drive motor vehicles and manage mechanisms

The question of the possibility of engaging in potentially dangerous activities that require increased attention and speed of psychomotor reactions should be resolved only after evaluating the individual patient’s response to the drug.

Form of production

Capsules.

Storage conditions

In a dry place, at a temperature of 15-30 °C

Shelf life

3 years

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

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

Weight

Weight: 28 gr.