Pharmacotherapeutic group Celecoxib 200 mg:
Celebrex – a specific inhibitor of cyclooxygenase type-2 (COX-2, COX-2).
Celecoxib is a new class of agent, mechanism of action consists in inhibiting prostaglandin synthesis, primarily through inhibition of cyclooxygenase type-2 (COX-2, COX-2). At therapeutic concentrations in humans celecoxib does not inhibit COX-1 (COX-1). COX-2 is induced in response to inflammatory stimuli. This leads to the synthesis and accumulation of inflammatory prostanoids, particularly prostaglandin E2, which causes inflammation, swelling and pain. Celecoxib acts as an anti-inflammatory drug by blocking the production of inflammatory prostanoids by inhibition of cyclooxygenase type-2 (COX-2).
Studies in vivo and ex vivo show that celecoxib has a very low affinity for the expressed constitutively the enzyme cyclooxygenase type 1. Therefore, celecoxib at therapeutic doses has no effect on prostanoids synthesized by activation of COX-1 (COX-1), and thus does not prevent the normal physiological processes associated with COX-1 (COX-1) in the tissues, especially in the stomach , intestines, blood platelets.
Pharmacokinetics Celecoxib 200 mg:
In the fasting celecoxib is well absorbed, and after about 2-3 hours it reached a peak concentration in plasma. Bioavailability of 99%.
Plasma protein binding, which does not depend on the dose, at therapeutic concentrations of drug in plasma is about 97%.
In elderly patients with a body weight below average (50 kg) treatment should begin with a minimum recommended dose.
Celecoxib is metabolized in the liver by hydroxylation, oxidation and some glyukuronidirovaniya. Studies in vitro and in vivo studies indicate that the metabolism is mainly by cytochrome P450 CYP2C9. The main metabolites found in blood, do not have a noticeable inhibitory effect on COX-1 or COX-2.
Excretion of celecoxib is mainly the liver, less than 1% of the dose excreted in the urine in unchanged form. After receiving multiple half-life is 8-12 hours, a clearance – about 500 ml / min. Repeated reception of the equilibrium concentration of drug in plasma is achieved by the 5th day.
The drug can penetrate the blood-brain barrier.
In patients with moderate hepatic insufficiency celecoxib concentrations in plasma approximately two times higher than in the corresponding control group. For patients with mild hepatic impairment dose adjustment is required. Celebrex treatment of patients with moderate hepatic impairment should begin with a minimum recommended dose.
Pharmacokinetics of celecoxib in the elderly volunteers with age-related decrease in the rate klubochkovoi filtration rate (GFR) (mean GFR> 65 mL/min/1.73 m2) and in patients with chronic stable renal insufficiency (GFR 35-60 mL/min/1.73 m2) compared with the pharmacokinetics of drug in patients with normal renal function. Severe renal insufficiency should not affect the clearance of celecoxib.
Uses Celecoxib 200 mg:
Symptomatic treatment of inflammation and pain associated with osteoarthritis and rheumatoid arthritis.
Dosage and administration Celecoxib 200 mg:
Adults:
Osteoarthritis: the usual recommended daily dose is 200 mg taken once daily or divided into two doses. If necessary, apply a dose of 200 mg twice a day.
Rheumatoid arthritis: the recommended daily dose is 200-400 mg and is divided into two doses.
Older: choosing the dosage is usually not required. However, in elderly patients with a body weight below average (50 kg) is recommended to start treatment with the lowest recommended dose.
Abnormal liver function: For patients with mild hepatic impairment the dosage selection is not required. Celebrex therapy in patients with moderate hepatic impairment start with the lowest recommended dose. Clinical experience in treating patients with severely impaired liver function is not available.
Renal impairment: in patients with mild to moderate renal impairment the dosage selection is not required. Clinical experience in treating patients with severely impaired renal function is not available.
Children:
The use of Celebrex in patients younger than 18 years has not been studied.
Overdose Celecoxib 200 mg:
Clinical experience of overdose are not available. Healthy volunteers received a single dose of 1200 mg and repeated up to 1200 mg twice a day with no clinically significant adverse effects. In cases of suspected overdose should provide appropriate supportive care. Dialysis is probably not an effective method for removing drugs.
Incompatibility is unknown.
Contraindications Celecoxib 200 mg:
Hypersensitivity to any ingredient of the product, known hypersensitivity to sulfonamides.
Patients who after taking aspirin or NSAIDs occurred asthma, urticaria and allergic reaction type.
Pregnancy and lactation Celecoxib 200 mg:
Clinical data on the use of Celebrex during pregnancy are not available. Animal studies have found toxic effects on the fetus during development. Possible risk to humans is unknown. Celebrex should not be used during pregnancy without any obvious need. Because the man has not been studies to assess the impact of the closure of Celebrex botallova duct, it is necessary to avoid its use in the third trimester of pregnancy.
Studies in rats indicate that celecoxib is released in milk in concentrations similar to those in plasma. Since human research has been conducted, Celebrex should not be used during breast-feeding.
Side effects Celecoxib 200 mg:
In clinical trials with active or placebo-controlled frequency of discontinuation due to adverse events was 7.1% for patients treated with Celebrex, and 6.1% for patients receiving placebo. The frequency of adverse events reported in controlled clinical trials were as follows:
Common (> 1%)
Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, flatulence, nausea
Nervous System: Headache, dizziness
Psychiatric: insomnia
Respiratory: Pharyngitis, rhinitis, sinusitis, upper respiratory tract infection
Skin: Itching, rash
Other: Peripheral edema
Rare (1% -0.1%)
Blood: Anemia
Cardiovascular: Hypertension, heart
Gastrointestinal: Constipation, burping, gastritis, stomatitis, vomiting
Liver: abnormal liver function, increased ACT and ALT
Metabolism: Abnormal renal function test results
Nervous System: blurred vision, hypertonia, paraesthesia
Psychiatric: Anxiety, depression
Respiratory: Cough, shortness of breath
Skin: Urticaria
Other: leg cramps, tinnitus, fatigue, urinary tract infection
It is extremely rare (Blood: Leukopenia, thrombocytopenia
Gastrointestinal: Gastric and duodenal ulcer, dysphagia, intestinal perforation, oesophagitis, melaena
Nervous system: Ataxia
Skin: Alopecia, photosensitivity
Other: Change in taste
Cautions and precautions Celecoxib 200 mg:
Before starting treatment Celebrex patients with active gastric ulcer or duodenal ulcer, a history check in the full healing of ulcers.
Some patients taking Celebrex, there was fluid retention and swelling. Therefore, in patients with impaired cardiac function and other conditions predisposing to fluid retention, Celebrex should be used with caution.
Patients with severe renal and hepatic failure Celebrex should be used only in exceptional circumstances.
Effects on ability to drive and operate machinery Celecoxib 200 mg:
Effect of Celebrex’s ability to drive and operate machinery has not been studied, but based on its pharmacodynamic properties and the overall safety profile, this effect seems unlikely.
Drug Interactions Celecoxib 200 mg:
Celebrex metabolism mediated by cytochrome P450 primarily 2C9 in the liver. In patients with proven or suspected decrease in the activity factor metabolizing CYP2C9 should be prescribed Celebrex with caution because of the reduced metabolic clearance, they may unduly raise the level of drug in plasma.
When studying the effect of Celebrex on the pharmacokinetics and / or pharmacodynamics of glyburide CYP2C9 substrate, phenytoin, tolbutamide and warfarin in vivo clinically significant interactions were found. Nevertheless, the appointment of Celebrex with warfarin should apply precaution as warfarin creates for these patients, an increased risk of bleeding complications.
Patients receiving CYP2C9 inhibitor fluconazole, Celebrex should be prescribed in the recommended minimum dose. When concomitant administration of Celebrex with other inhibitors of CYP2C9 should proceed with caution.
Effect of inducers of CYP2C9, such as rifampin, carbamazepine, and barbiturates, on the pharmacokinetics of celecoxib has not been studied.
In vitro studies indicate that celecoxib, although not a substrate of CYP2D6, inhibits it. Studies in vivo, performed with the use of CYP2D6 substrate and inhibitor paroxetine, showed no clinically significant interaction.
CYP2C19 enzyme may be involved in the metabolism of celecoxib, a very small extent (~ 1%). In a study of Celebrex in vivo did not affect the clearance of a single dose of CYP2C19 substrate phenytoin. The risk of interactions with substrates of CYP2C19 is negligible.
Ketoconazole (an inhibitor of CYP3A4) did not show any significant interaction with Celebrex.
Antacids (aluminum and magnesium) reduce the extent of absorption of celecoxib at 10%, which does not cause clinically significant effects.
In studying the effect on the pharmacokinetics of drugs Celebrex extracted through the kidneys, lithium and methotrexate in vivo clinically significant interactions were found.
Celebrex can be used with low-dose acetylsalicylic acid. Due to the lack of action on platelets Celebrex is not a substitute for aspirin prophylaxis of cardiovascular disorders.
