Celecoxib

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].