Celecoxib

When ATH:
M01AH01

Celecoxib – Characteristic.

NSAIDs. Selective COX-2 inhibitor.

Pale yellow solid. Molecular weight 381,38.

Celecoxib – Pharmacological action

Anti-inflammatory, analgesic, pyretic.

Celecoxib – Application

Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriaticheskiy arthritis.

Celecoxib – Contraindications

Hypersensitivity, incl. to other NSAIDs, allergic reactions to sulfonamide drugs, "Aspirinovaâ" triad (a combination of asthma, recurrent nasal polyposis, and paranasal sinuses and intolerance of aspirin and other NSAIDs, incl. COX-2 inhibitors), peptic ulcer in the acute stage, or bleeding from the gastrointestinal tract, colitis, congestive heart failure (II-IV centuries. po NYHA), coronary artery bypass surgery, CHD (clinically confirmed), peripheral artery disease and cerebrovascular disease denominated, severe hepatic / renal failure, pregnancy (III Plus), lactation.

Celecoxib – Restrictions apply

Peptic ulcer and duodenal (incl. history), gastrointestinal bleeding history, concomitant use of warfarin and other anticoagulants, CYP2C9 inhibitors, swelling, fluid retention, hepatic insufficiency of moderate severity, Age to 18 years.

Celecoxib – Pregnancy and breast-feeding

Teratogenic effects. At oral doses ≥150 mg / kg / day (about 2 Exposure times longer in humans at a dose 200 mg twice a day, as assessed by AUC_0–24) rabbits, receiving celecoxib during organogenesis, celecoxib caused an increase in the frequency of defects of the heart septum (a rare complication) and fetal deformation ribs, breastbone. At oral doses of ≥30 mg / kg / day (about 6 Exposure times longer in humans at a dose 200 mg twice a day, as assessed by AUC_0–24) rats, receiving celecoxib during organogenesis, there was a dose-dependent increase in the incidence of diaphragmatic hernia.

There are no adequate and well-controlled studies in pregnant women have not held. When pregnancy is possible, if the effect of therapy outweighs the potential risk to the fetus.

Nonteratogenic effects. Celecoxib induced transformation- and post-implantation losses and reduced embryo / fetal survival in rats at oral doses ≥50 mg / kg / day (about 6 times the exposure, assessed by AUC_0–24 at a dose 200 mg 2 once a day). These changes are related, apparently, with inhibition of PG synthesis, and are not the result of permanent changes in the female reproductive function.

Research, dedicated to assessing the impact of celecoxib on the closure of the ductus arteriosus in humans, not carried out. The use of celecoxib in the III trimester of pregnancy should be excluded.

Effects of celecoxib on labor and delivery in humans is unknown.

Category actions on the fetus by the FDA — with. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

Celecoxib is excreted in the milk of lactating rats, The concentrations in milk similar to those in plasma. Unknown, whether celecoxib gets into breast milk of women, so you should stop breast-feeding during treatment or avoid its use during breastfeeding.

Celecoxib – Side effects

Side effects, observed in controlled clinical trials (results 12 research), celecoxib at doses of 100-200 mg daily in patients with osteoarthritis or rheumatoid arthritis (regardless of causal relationship to drug intake) are presented in Table.

Table

Adverse Reactions, marked with a frequency ≥2% premarketingovyh cases in controlled trials in patients with arthritis, poluchavshih celecoxib, compared to placebo

The following side effects were observed at a frequency of less than 2% (regardless of causal relationship to drug intake):

From the digestive tract: 0,1-1.9% - constipation, diverticulitis, dysphagia, belching, esophagitis, gastritis, gastroenteritis, hastroэzofahealnыy reflux, hemorrhoids, hiatal hernia, ground, anorexia, increased appetite, dry mouth, stomatitis, tenesmus, dental disease, vomiting, abnormal liver function, increase in AST and / or ALT; <0,1% - cholelithiasis.

Cardio-vascular system and blood (hematopoiesis, hemostasis): 0,1-1.9% - the aggravation of hypertension, heartbeat, tachycardia, angina, coronary artery disease, myocardial infarction, thrombocythemia, anemia; <0,1% - syncope, congestive heart failure, Atrial fibrillation, stroke, perifericheskaя gangrene, tromboflebit, thrombocytopenia.

From the nervous system and sensory organs: asthenia, weakness, leg cramps, increased muscle tone, gipesteziya, migraine, neuralgia, neuropathy, paraesthesia, vertigo, anxiety, depression, nervousness, drowsiness, hearing disorder, deafness, ear pain, tynnyt, change in taste, blurred vision, Cataract, conjunctivitis, sore eyes, glaucoma; <0,1% -ataxia, suicide.

On the part of the musculoskeletal system: arthralgia, bone diseases, Random fracture, myalgia, Tendinitis, stiff muscles.

With the genitourinary system: dysmenorrhoea, vaginal bleeding, vaginitis, prostate disease, albuminuria, cystitis, dizurija, hematuria, increased frequency of urination, kidney stones, urinary incontinence, urinary tract infection; <0,1% - Acute renal failure.

From the respiratory system: 0,1-1.9% - otitis media, bronchitis, bronchospasm / worsening bronchospasm, cough, dyspnoea, laringit, pneumonia; <0,1% - pulmonary embolism.

For the skin: alopecia, dermatitis, contact dermatitis, nail disease, photosensitivity reaction, erythematous rash, maculopapular rash, skin diseases, xerosis, hypertrophy of the stratum corneum, increased sweating, cellulitis.

Allergic reactions: aggravation of allergies, itch, hives, generalized edema, swelling of the face.

Other: flu-like symptoms, pain syndrome, incl. chest pain; fever, tides, increase in AP, increasing the concentration of blood urea nitrogen, increase in non-protein nitrogen, increase in creatinine phosphokinase, giperkreatininemiя, diabetes, hypercholesterolemia, kaliopenia, weight gain, fibroadenoma of the breast, lump in the breast, pain in the breast, ecchymosis, nose bleed, Herpes simplex, Herpes zoster, fungal infection, candidiasis, incl. genital, soft tissue infection, viral infection; <0,1% - Sepsis, sudden death.

Side effects, It marked only in the post-marketing studies, a frequency <0,1% - vasculitis, deep vein thrombosis, agranulocytosis, aplasticheskaya anemia, pancytopenia, leukopenia, gipoglikemiâ, giponatriemiya, agevziya, anosmia, fatal intracranial hemorrhage, hepatitis, jaundice, hepatic failure, aseptic meningitis, interstitial nephritis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactoid reactions, angioedema.

Celecoxib – Cooperation

Established in vitro, that Celecoxib is an inhibitor of cytochrome P450 isoenzyme CYP2C9, so there is the possibility of drug interactions with other drugs, that Biotransformiroetsa involving this isozyme. In in vitro studies show, Celecoxib seems to be built, although it is not a substrate of CYP2D6 isoenzyme, inhibits its, so there is potential for interactions with drugs in vivo, metabolized by this isoenzyme.

NSAIDs may reduce the hypotensive effect of ACE inhibitors, which should be considered while applying celecoxib and ACE inhibitors. NSAIDs can reduce the natriuretic effect of furosemide and thiazides due to the decrease in renal PG synthesis. The simultaneous use of celecoxib and acetylsalicylic acid in low doses, However, it should be taken into account, that in such a combination increases the risk of GI ulceration or other complications of, compared with using one of celecoxib. In the absence of action on platelets celecoxib should not be considered a substitute for acetylsalicylic acid for prophylaxis of cardiovascular diseases.

Fluconazole (CYP2C9 inhibitor) increases the plasma concentration of celecoxib (Fluconazole inhibits the metabolism of celecoxib), so if you need such a combination should be administered celecoxib in the minimum recommended dose.

With simultaneous use of celecoxib (200 mg twice a day) and lithium preparations (450 mg twice a day) plasma levels of lithium at steady state increased by 17% as compared with that of patients, receiving only medication lithium. Patients, receiving the drug lithium, should closely monitor the concentration of Li⁺ in serum after initiation of therapy with celecoxib and after changing the dosing regime.

It does not have a significant effect on the pharmacokinetics of methotrexate.

You should carefully monitor the anticoagulant activity, especially in the first few days after the beginning of therapy with celecoxib or changes in patients, receiving warfarin or similar medicines (increased risk of bleeding).

Celecoxib – Overdose

None reported overdose of celecoxib in clinical trials. Doses up 2400 mg / day in the period up to 10 days, 12 patients resulted in severe toxicity. Symptoms of an acute overdose of NSAIDs: drowsiness, slackness, epigastric pain, nausea, vomiting, possible bleeding from the gastrointestinal tract, rarely - hypertension, acute renal failure, respiratory depression, coma, anaphylactoid reactions may occur.

Treatment: induction of vomiting and / or administration of activated charcoal (60100 g - adult, 1-2 G / kg - children) and / or osmotic laxatives can be displayed within 4 h after administration. Carrying out of the symptomatic and supportive therapy. The specific antidote is not found. Forced diuresis, alkalization of urine, hemodialysis or haemoperfusion not effective due to the high protein binding. No information about the removal of celecoxib from the body by hemodialysis, However, based on the, The binding protein of >97%, unlikely, that hemodialysis is effective.
Dosing and Administration.
Inside, 200 mg / day in 1-2 reception, if necessary daily dose increased to 400 mg.

Celecoxib – Precautions

The risk of gastrointestinal complications. NSAIDs, including as celecoxib, cause increased risk of serious side effects from the gastrointestinal tract, including bleeding, ulceration and perforation of the stomach or intestines. These complications can occur at any time without the use of NSAIDs heralding symptoms, possible fatal outcome. A higher risk of serious gastrointestinal complications are elderly patients, probability of occurrence of these complications increases as long-term use.

In elderly patients, in patients with reduced body weight, with symptoms (mild and moderate) heart failure, and in violation of liver function moderate severity - treatment should begin with minimal doses.

In some patients,, prinimavshih celecoxib, observed fluid retention and swelling, so it should be used with caution in patients with impaired cardiac function and other conditions, predisposing to fluid retention.

During treatment requires monitoring of peripheral blood and functional state of the liver and kidneys. If you want to determine the 17-ketosteroids treatment should be discontinued for 48 h before the test.

It should refrain from potentially hazardous activities, requiring attention, because it may be a violation of accommodation and the elongation of reaction time.