Selective cyclooxygenase2 COX2 inhibitors

Experience

This group of drugs includes celecoxib, etoricoxib, lumiracoxib, parecoxib, rofecoxib, and valdecoxib. Their half-lives range from 8 to 17 hours.

Celecoxib is a lipophilic substance, of which 97% is bound to plasma protein, and it exhibits a high distribution volume. A peak concentration of 133ng/ml was measured in the milk 5 hours after the administration of 100 mg, which corresponds to 20 pg/kg per day to a breastfed infant, or a weight-adjusted dose of approximately 1% (Knoppert 2003). A more recent publication studied oral administration of celecoxib 200 mg to six lactating volunteers. The median M/P ratio was 0.18 (0.15-0.26). The median infant dose was 0.23% (0.17-0.30%) of the maternal dose, adjusted for weight (Gardiner 2006).

After the application of 25 mg rofecoxib, an M/P ratio of 0.25 was determined. A relative dose of 1.8-3.2% was calculated (Gardiner 2005). Becausc cardiotoxic side effects were suspected, rofecoxib was withdrawn from the market. Valdecoxib was also withdrawn because of dermatological side effccts. There is insufficient experience with the other COX-2-inhibitors during lactation.

Recommendation. Because of the lack of experience with these substances during breastfeeding, selective COX-2 inhibitors should be avoided. Single doses do not require cessation of breastfeeding.

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