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Celecoxib

Celecoxib. Amir Hooshang Vahedi MD - Physiatrist  . Celecoxib. Celecoxib was approved by the FDA rheumatoid arthritis osteoarthritis. ankylosing spondylitis . familial adenomatous polyposis (FAP). juvenile rheumatoid arthritis (JRA) in children 2 years of age and older. .

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Celecoxib

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  1. Celecoxib Amir HooshangVahedi MD - Physiatrist  

  2. Celecoxib

  3. Celecoxib was approved by the FDA • rheumatoid arthritis • osteoarthritis. • ankylosingspondylitis. • familial adenomatouspolyposis (FAP). • juvenile rheumatoid arthritis (JRA) in children 2 years of age and older.

  4. Pharmacokinetics: • Peak plasma concentrations of celecoxib occur 3 hours after an oral dose. • mean effective half-life is 11.2 hours under fasted conditions. • hepatic metabolism (> 97%) with little unchanged drug recovered in the urine and feces.

  5. Pharmacokinetics: peak plasma concentrations (Cmax) Area under the curve (AUC)

  6. Special Populations: significant changes in the pharmacokinetics of celecoxib. • Renal Impairment • Hepatic impairment • Advanced age • Elderly subjects (over 65 years old) have a 40% higher Cmax and a 50% higher AUC compared to young subjects.

  7. Patients with hepatic impairment: • In mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment, steady-state celecoxib AUC is increased about 40% and 180%. Patients with severe hepatic insufficiency have not been studied. • The recommended daily dose of celecoxib should be reduced by approximately 50% in patients with moderate hepatic impairment (Child-Pugh Class B). Celecoxib is not recommended in patients with severe hepatic impairment (Child-Pugh Class C).

  8. Patients with renal impairment: chronic renal insufficiency (GFR 35—60 mL/min), celecoxib AUC is approximately 40% lower than in subjects with normal renal function . Patients with severe renal insufficiency have not been studied. No dosage adjustment needed; however, celecoxib has not been studied in patients with severe renal insufficiency. The use of celecoxib is not recommended in patients with advanced renal disease.

  9. Maximum Dosage Limits: • Adults: 800 mg/day PO. • Elderly: 400 mg/day PO. • Adolescents: 200 mg/day PO for juvenile rheumatoid arthritis. • Children >= 2 years and > 25 kg: 200 mg/day PO for juvenile rheumatoid arthritis • Children >= 2 years and 10—25 kg: 100 mg/day PO for juvenile rheumatoid arthritis. • Children < 2 years: Safe and effective use has not been established. The safety and efficacy of celecoxib in infants have not been evaluated. Safety and efficacy in children below the age of 18 years has not been evaluated for most indications. Celecoxib is approved for use in children 2 years of age and older for the treatment of juvenile rheumatoid arthritis (JRA).

  10. Indications...Dosage • osteoarthritis: 200 mg PO once daily or 100 mg PO twice daily (both regimens were equally effective). • Rheumatoid arthritis: 100 or 200 mg PO twice daily. • Juvenile rheumatoid arthritis (JRA)/juvenile idiopathic arthritis (JIA): Children >= 2 years and > 25 kg and Adolescents: 100 mg PO twice daily. Children >= 2 years and 10—25 kg: 50 mg PO twice daily. Children < 2 years: Safety and efficacy have not been established.

  11. ankylosingspondylitis: 200 mg PO once daily or 100 mg PO twice daily. (effect after 6 weeks, consider a 6-week trial of 400 mg PO daily. If no effect after 6 weeks, a response is unlikely; consider alternate treatment.) • acute moderate pain and dysmenorrhea: 400 mg PO initially, then followed by an additional 200 mg PO on the first day, if needed. • moderate-to-severe pain associated with orthopedic surgery: 400 mg/day PO (up to 200 mg PO three times daily allowed) for 2—5 days after outpatient orthopedic surgery.

  12. Absolute contraindications • coronary artery bypass graft surgery (CABG) (Celecoxib is contraindicated for the treatment of peri-operative pain in the setting of (CABG). • NSAID hypersensitivity • salicylate hypersensitivity • sulfonamide hypersensitivity (celecoxib contains a sulfonamide side chain)

  13. contraindications • GI bleeding • GI disease • GI perforation • peptic ulcer disease • hepatic disease • renal disease • renal failure • renal impairment • edema • peripheral edema • Hypovolemia • dehydration • hypertension • acute bronchospasm • asthma • myocardial infarction • peripheral vascular disease • stroke • thrombophlebitis • heart failure • angina • cardiac disease • Cerebrovascular disease • alcoholism • anemia • anticoagulant therapy • bone marrow suppression • Immunosuppression • corticosteroid therapy • pregnancy • breast-feeding

  14. Celecoxib: • classified as FDA pregnancy category risk C. • avoided during the third trimester. • delay closure of the ductusarteriosis.

  15. Cardiovascular Effects: • Celecoxib inhibit the production of PGI2 but not of thromboxane A2, which is produced by COX-1. • PGI2 inhibits: • platelet aggregation. • vascular smooth muscle contraction and proliferation. • imbalance favoring a pro-thrombotic state. • sodium and water retention.

  16. Celecoxib may exacerbate hypertension and congestive heart failure and may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. • ACC/AHA guidelines state NSAIDs should not be administered to patients presenting with and hospitalized for ST-elevation myocardial infarction (STEMI) due to increased risk of mortality, reinfarction, hypertension, heart failure, and myocardial rupture associated with their use.

  17. Renal Effects: • Activity of COX-2 in the renal cortex appears to be inhibited by angiotensin II and stimulated by intravascular volume depletion and low sodium intake. • (ADH) production and sodium reabsorption are increased, which leads to a reduction in glomerular filtration rate, reduced urinary sodium excretion, and the potential for increased blood pressure.

  18. Patients at greatest risk of this reaction are those with renal impairment, renal failure, heart failure, liver dysfunction, hypovolemia (dehydration), those taking diuretics and ACE inhibitors, angiotensin II receptor antagonists, or older patients. • Patients should be rehydrated before starting therapy with celecoxib. Close monitoring of renal function and blood pressure throughout the duration of celecoxib use is advisable.

  19. Monitoring Parameters • CBC • LFTs • serum creatinine/BUN • stool guaiac • BP

  20. Fever, syncope , arthralgia, back pain , anorexia , hypertension , headache ,confusion , Cough , cyanosis, dyspnea , peripheral edema • abdominal pain , nausea/vomiting, diarrhea and constipation • GI bleeding ,GI obstruction,GI perforation ,hemorrhoids ,melena, • esophageal ulceration, esophagitis ,peptic ulcer , gastroesophageal reflux and gastritis, dyspepsia , dysphagia • cholelithiasis ,cholestasis , pancreatitis • elevated hepatic enzymes ,hepatic failure • aseptic meningitis ,intracranial bleeding , ataxia , tinnitus , hearing loss , stroke • chest pain (unspecified) , Angina ,myocardial infarction , ventricular fibrillation ,heart failure; pulmonary embolism ;phlebitis. • renal failure (unspecified) , azotemia , renal papillary necrosis , interstitial nephritis , hyponatremia, hematuria,proteinuria • Stevens-Johnson syndrome , toxic epidermal necrolysis, exfoliative dermatitis , angioedema , pruritus , erythemamultiforme , erythema • thrombocytopenia ,leukopenia ,pancytopenia, aplastic anemia, bleeding ,anemia

  21. Interactions • Celecoxib is a substrate of the cytochrome P450 (CYP) 2C9 isoenzyme, and CYP2C9 inhibitors may significantly increase plasma concentrations of celecoxib.

  22. Interactions • Alendronate • Pamidronate • NSAIDs • Salicylates • Corticosteroids • Amiodarone • Anticoagulants • Platelet Inhibitors • Radiopaque Contrast Agents • Rifampin • Vancomycin • Selective serotonin reuptake inhibitors (SSRIs) • Serotonin norepinephrine reuptake inhibitors(SNRIS) • Ofloxacin;norfloxacin;ciprofloxacin • Immunosuppressives • Methotrexate • Cyclosporine • Lithium • Photosensitizing Agents • Voriconazole • Ketoconazole • Fluconazole • Zafirlukast • Desmopressin • Dextromethorphan • Drospirenone; EthinylEstradiol • Ethanol • Galantamine • Ganciclovir • AmphotericinB • Antihypertensive Agents

  23. Single dose oral celecoxib for acute postoperative pain in adults • Single dose oral celecoxib is an effective means of postoperative pain relief. • Celecoxib at its recommended dosage of 400 mg for acute pain, is an effective analgesic, equivalent to ibuprofen 400 mg, but providing a longer duration of pain relief than many traditional NSAIDs.

  24. Celecoxib for rheumatoid arthritis • For an individual with RA the potential benefits of celecoxib need to be balanced against the uncertainty that the short-term reduced incidence of upper GI complications are maintained in the long-term and its increased cost in comparison to traditional NSAIDs.

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