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Celecoxib

Classification: C

Drug products: Celebra®, Celebrex, Celecoxib 2care4, Celecoxib Ebb, Celecoxib Krka, Celecoxib Orion, Celecoxib Sandoz, Celecoxib STADA

ATC code: M01AH01

Substances: celecoxib

Summary

Comparable effect of celecoxib has been shown in arthrosis in men and women. Pharmacokinetic studies have shown that older women reach a higher plasma concentration given the same dose celecoxib as men. This may be explained by the generally lower body weight of women and needs to be considered when dosing the substance. To patients with a body weight below 50 kg, the lowest recommended dose should be used when starting treatment.

Celecoxib is contraindicated for use during pregnancy.

Additional information

Pharmacokinetics and dosing

A randomized bioequivalence trial in healthy volunteers (12 men, 12 women) receiving a single 200 mg dose celecoxib found higher AUC and Cmax in women. However, when adjusting for body weight, the differences disappeared [4]. According to the original manufacturer, a meta-analysis has revealed that women had 13% lower Cmax and longer terminal half-life (13.9 vs. 11.4 h) than men after a single dose of celecoxib. However, after multiple dosing, there was no significant difference in Cmax between men and women. Elderly women had higher Cmax and AUC than elderly men, but these differences were attributed to lower average body weight in the women [5, 6].Dose adjustment based on the differences in pharmacokinetics of celecoxib in elderly men and women is not recommended by the manufacturer [6]. However, for patients with a body weight less than 50 kg, the lowest recommended dose should be used regardless of sex when initiating therapy with celecoxib.

Effects

Predictors of response to etoricoxib 30 mg/day and celecoxib 200 mg/day in patients with osteoarthritis was analyzed with pooled data from two randomized, double-blind, placebo-controlled trials (404 men, 803 women). Data showed that sex did not predict the response to etoricoxib, celecoxib or placebo [7]. In a randomized study of a single dose celecoxib 400 mg in adults (27 men, 30 women) no difference in effect on postsurgical dental pain was observed between men and women [8].

Adverse effects

COX-2 inhibitors have an increased risk of cardiovascular adverse events due to the prothrombotic effect caused by the decrease in vasodilatation and antiaggregatory prostacyclin production. Data on sex differences in this risk is lacking [9, 10].A randomized double-blind trial (1256 men, 2731 women receiving celecoxib) analyzing the association between celecoxib and lower incidence of upper gastrointestinal effects reported no sex differences in adverse events [11].

Reproductive health issues

COX-2 is active in the ovaries during follicular development. COX-2 inhibitors can delay the follicular rupture, which have been associated with transient infertility in some women [1]. The expression of COX is influenced by the change in level of estrogen and progesterone during pregnancy [2]. Celecoxib and etoricoxib are contraindicated for use in all stages of pregnancy and in women of childbearing age. If a woman becomes pregnant during treatment, the COX-2 inhibitor should be discontinued [2,3].Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

The effect of COX-2 inhibition in young patients with type 1 diabetes mellitus has been analyzed in a small study (12 men, 9 women). Patients received celecoxib. COX-2 inhibition (200 mg/day for 14 days) increased filtration fraction and decrease in effective renal plasma flow and renal blood flow in women compared with men. Before COX-2 inhibition, women exhibited a decline in GFR in response to angiotensin II. COX-2 inhibition abolished this effect, while the response was not altered in men [12].A prospective population-based trial (2004 men, 2776 women) showed that daily use of COX-2 inhibitors was associated with a lower BMD (bone mineral density) in men at all sites (-3.1% for total hip) and a higher BMD in postmenopausal women not using estrogen replacement therapy in most sites (+3.0% at total hip). The effect on BMD was dose-dependent [13].

Updated: 2017-03-27

Date of litterature search: 2015-02-25

References

  1. Stone S, Khamashta MA, Nelson-Piercy C. Nonsteroidal anti-inflammatory drugs and reversible female infertility: is there a link?. Drug Saf. 2002;25:545-51. PubMed
  2. Chan VS. A mechanistic perspective on the specificity and extent of COX-2 inhibition in pregnancy. Drug Saf. 2004;27:421-6. PubMed
  3. ONENSAL (celecoxib). Summary of Product Characteristics. European Medicines Agency (EMA); 2011.
  4. Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - CELEBREX (celecoxib). Food and Drug Administration [www]. [updated 1999-12-23, cited 2015-02-25]. länk
  5. Davies NM, McLachlan AJ, Day RO, Williams KM. Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet . 2000;38:225-42. PubMed
  6. Prieto-Pérez R, Ochoa D, Cabaleiro T, Román M, Sánchez-Rojas SD, Talegón M et al. Evaluation of the relationship between polymorphisms in CYP2C8 and CYP2C9 and the pharmacokinetics of celecoxib. J Clin Pharmacol. 2013;53:1261-7. PubMed
  7. Bingham CO, Smugar SS, Wang H, Peloso PM, Gammaitoni A. Predictors of response to cyclo-oxygenase-2 inhibitors in osteoarthritis: pooled results from two identical trials comparing etoricoxib, celecoxib, and placebo. Pain Med. 2011;12:352-61. PubMed
  8. Cheung R, Krishnaswami S, Kowalski K. Analgesic efficacy of celecoxib in postoperative oral surgery pain: a single-dose, two-center, randomized, double-blind, active- and placebo-controlled study. Clin Ther. 2007;29 Suppl:2498-510. PubMed
  9. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001;286:954-9. PubMed
  10. Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J, Merhi A, Abramson S, Arber N et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769-79. PubMed
  11. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial Celecoxib Long-term Arthritis Safety Study. JAMA. 2000;284:1247-55. PubMed
  12. Cherney DZ, Scholey JW, Nasrallah R, Dekker MG, Slorach C, Bradley TJ et al. Renal hemodynamic effect of cyclooxygenase 2 inhibition in young men and women with uncomplicated type 1 diabetes mellitus. Am J Physiol Renal Physiol. 2008;294:F1336-41. PubMed
  13. Richards JB, Joseph L, Schwartzman K, Kreiger N, Tenenhouse A, Goltzman D et al. The effect of cyclooxygenase-2 inhibitors on bone mineral density: results from the Canadian Multicentre Osteoporosis Study. Osteoporos Int. 2006;17:1410-9. PubMed
  14. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Authors: Linnéa Karlsson Lind, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson