Denebol® [Rofecoxib]

Pharmacological properties

Denebol contains rofecoxib - an NSAID - a highly selective cog-2 inhibitor. It has analgesic, antipyretic, anti-inflammatory effect. the anti-inflammatory effect of rofecoxib is due to inhibition of prostaglandin synthesis by inhibition of cog-2. in therapeutic concentrations, the drug does not inhibit cog-1. thus, it does not affect prostaglandins, which are synthesized through the activation of cog-1, and therefore does not interfere with the normal physiological processes associated with cog-1 in tissues, especially in the stomach, intestines, and platelets.

Pharmacokinetics Suction. When used internally, it is well absorbed, the bioavailability of rofecoxib is on average 93%. With daily use of the drug 1 time per day at a dose of 25 mg C_max in adult blood plasma, it is determined after approximately 2 hours and amounts to 0.305 mcg / ml. Bioavailability after i / m administration - about 100%, time to reach C_max rofecoxib in plasma - 45 min. About 87% of rofecoxib binds to plasma proteins in the body at a concentration of 0.05–25 μg / ml. Distribution and main indicators are given in the table.

Rofecoxib penetrates through the placental and BBB, into the synovial fluid.

Metabolism. In the body, rofecoxib breaks down into cis-dihydro and trans-dihydro derivatives of rofecoxib; about 56% of these derivatives are excreted in the urine. An additional 88.8% of the drug is recovered in the form of derivatives of hydroxy-glucosamide, which is a product of oxygen metabolism. Major metabolites do not inhibit COX-2 or COX-1.

Rofecoxib is metabolized primarily in the liver and a small amount (1%) by the kidneys. 72% of the drug is excreted in the urine in the form of metabolites, 14% - with feces.

Pharmacokinetics in special clinical cases

The pharmacokinetics of rofecoxib is not dependent on gender. The pharmacokinetics of rofecoxib in elderly patients (65 years and older) does not differ from that in young patients. But therapy in elderly patients begins with the minimum recommended dose.

Patients with liver failure showed a tendency to a slight increase in the concentration of the drug. In this case, caution should be exercised when administering the maximum doses of rofecoxib. Renal failure does not affect the pharmacokinetics of rofecoxib, but its use in severe renal failure is not recommended.

Indications

Pain syndrome of various origins, acute and chronic osteoarthritis, rheumatoid arthritis, periarthritis, bursitis, tendonitis, thrombophlebitis; with injuries of the musculoskeletal system and soft tissues; osteochondrosis, neuritis, neuralgia, radicular syndrome, lumbago, myalgia, algodismenorea, toothache, in the postoperative period in maxillofacial surgery and dentistry, in ENT practice (for injuries and operations on ENT organs); for relief of pain and inflammation after surgical interventions.

Application

Denebol tablets

Applied inside in adults.

In the treatment of pain and primary dysmenorrhea, the recommended dose of Denebol is 50 mg once a day, subsequent doses are 25 or 50 mg once a day, if necessary.

The maximum daily dose is 50 mg. Treatment is carried out until the acute pain syndrome is eliminated, but not more than 2 weeks.

Osteoarthritis and rheumatoid arthritis: the recommended initial dose of rofecoxib is 12.5 mg once a day, which can be increased to 25 mg once a day, which is the maximum recommended daily dose. Assign courses of 4-6 weeks. Denebol is used regardless of food intake.

Contraindications

Hypersensitivity to rofecoxib and other NSAIDs, in the third trimester of pregnancy and lactation.

Rofecoxib should not be used in patients with asthma, especially caused by acetylsalicylic acid.

The drug is not used for the treatment of cancer patients and patients at increased risk from the cardiovascular system (heart attack, stroke, hypertension (stage III), progressive clinical form of atherosclerosis).

Side effects

From the cardiovascular system: ag, congestive heart failure, swelling of the lower extremities, impaired cerebral and coronary circulation, rarely - stroke, myocardial infarction, heart rhythm disturbance (bradycardia, the occurrence of premature ventricular complex, tachycardia), acute heart failure, sudden stop heart, pulmonary embolism, unstable angina pectoris.

Allergic reactions: angioedema, pulmonary edema, Stevens-Johnson syndrome, urticaria, erythematous rashes, skin itching, allergic rhinitis, atopic dermatitis, vasculitis.

From the digestive tract: heartburn, dyspepsia, discomfort in the epigastric region, nausea; rarely - aphthous stomatitis. In the department