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celecoxib (Celebrex)

Tradename: Celebrex. Molecular formula: C17H14F3N3O2S. 1st generic FDA-approved May 30, 2014 [14] Indications: 1) pain, including acute pain & inflammatory conditions 2) dysmenorrhea [5] 3) inhibition of colonic polyps - adjunctive therapy for familial adenomatous polyposis (FAP) Contraindications: - allergy to sulfonamides [7] - severe hepatic impairment or active liver disease (Canada) - avoid in patients with cardiovascular risk factors - hypertension, hyperlipidemia, renal failure ... [13,16] Dosage: 1) 100-200 mg BID or 200 mg QD 2) 100 mg TID (acute crystalline arthritis) Tabs: 100 & 200 mg. Pharmacokinetics: 1) plasma protein binding 97% 2) volume of distribution 400 L/kg 3) hepatic metabolism occurs via cyt P450 2C9 4) inhibits cyt P450 2D6 5) elimination 1/2life is 11.2 hours (fasting) 6) 57% eliminated in feces; 27% eliminated in urine Monitor: - liver function tests periodically [11] Adverse effects: 1) gastrointestinal a) abdominal pain b) diarrhea c) flatulence d) GI bleed, gastritis, peptic ulcer e) GI complications less frequent than with non-selective NSAIDs [6] 2) peripheral edema (less than rofecoxib (Vioxx) [8]) 3) pharyngitis 4) rhinitis 5) nephrotoxicity [3] - impaired renal physiologic responses similar to non-selective NSAIDs 6) sulfonamide derivative: may cause allergies in patients with sulfa allergies [3] 7) myocardial infarction (MI) a) no increased risk compared with ibuprofen, naproxen or diclofenac [6,15,17] b) 2.5 fold increased risk at 400-800 mg/day [9] c) no increased risk at 400 mg/day [9] d) increased risk at doses > 200 mg/day [10] e) see APC trial 8) risk of stroke comparable to ibuprofen & naproxen [15] 10) aseptic meningitis (within 2 weeks) [6]; recovery with stopping drug 11) ocular effects a) blurred vision, cataracts, conjunctivitis, conjunctival hemorrhage, eye pain, glaucoma, vitreous floaters b) adverse effects might be caused by alteration of retinal blood flow &/or inflammation resulting from secretion of the medication in tears c) stopping celecoxib should resolve most ocular side effects within 72 hours Drug interactions: 1) any drug which inhibits cyt P450 2C9 can increase celecoxib levels 2) any drug which induces cyt P450 2C9 can diminish celecoxib levels 3) may increase levels of drugs metabolized by cyt P450 2D6 Laboratory: - celecoxib in serum/plasma Mechanism of action: 1) selectively inhibits cyclo-oxygenase-2 (COX-2) 2) at therapeutic concentrations in humans, celcoxib does not inhibit COX-1 3) does NOT inhibit platelet aggregation

Interactions

drug interactions drug adverse effects (more general classes) monitor with non steroidal anti-inflammatory agents (NSIADs)

Related

cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)

General

cyclooxygenase-2 (COX-2) specific inhibitor indole sulfonamide

Properties

INHIBITS: cyclooxygenase-2 SIZE: MW = 381.4 G/M MISC-INFO: elimination route LIVER 1/2life 11-16 HOURS protein-binding 97%

Database Correlations

PUBCHEM cid=2662

References

  1. Searle-Pfizer package insert
  2. Prescriber's Letter 7(2):11, Feb. 2000
  3. Prescriber's Letter 7(10):55 2000
  4. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  5. Prescriber's Letter 8(11):61 2001
  6. Prescriber's Letter 9(5):26 2002
  7. Prescriber's Letter 11(7):42 2004 Detail-Document#: 200702 (subscription needed) http://www.prescribersletter.com
  8. Journal Watch 24(14):109, 2004 Mamdani M, Juurlink DN, Lee DS, Rochon PA, Kopp A, Naglie G, Austin PC, Laupacis A, Stukel TA. Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study. Lancet. 2004 May 29;363(9423):1751-6. PMID: 15172772
  9. Associated Press, Netscape 12/17/04 sites NCI study conducted for Pfizer
  10. Prescriber's Letter 13(10): 2006 Cardiovascular Risks of NSAIDs and COX-2 Inhibitors Detail-Document#: 221003 (subscription needed) http://www.prescribersletter.com
  11. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: 260704 (subscription needed) http://www.prescribersletter.com
  12. Cryer B et al. GI-REASONS: A novel 6-month, prospective, randomized, open-label, blinded endpoint (PROBE) trial. Am J Gastroenterol 2013 Mar; 108:392. PMID: 23399552
  13. Medical Knowledge Self Assessment Program (MKSAP) 16 American College of Physicians, Philadelphia 2012
  14. FDA News Release. May 30, 2014 FDA approves first generic versions of celecoxib. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm399428.htm
  15. Nissen SE, Yeomans ND, Solomon DH et al Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med. Nov 13, 2016 PMID: 27959716 http://www.nejm.org/doi/full/10.1056/NEJMoa1611593 - FitzGerald GA. ImPRECISION: Limitations to interpretation of a large randomized clinical trial. Circulation 2016 Nov 13; PMID: 27840335 http://circ.ahajournals.org/content/early/2016/11/11/CIRCULATIONAHA.116.026324
  16. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/
  17. Elia J, Sadoughi S, Saitz R. Celecoxib Gets Partial Exoneration from FDA Panels Physician's First Watch, April 26, 2018 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Stein R Celebrex As Safe As Ibuprofen And Naproxen, FDA Advisers Say. Health News from NPR. April 25, 2018 https://www.npr.org/sections/health-shots/2018/04/25/605226604/fda-panel-affirms-safety-of-painkiller-celebrex

Component-of

amlodipine/celecoxib (Consensi)