Our evaluation is primarily based on an independent scientific review of the evidence on the effectiveness, safety, and adverse effects of NSAIDs, along with periodic review of research updates. A team of physicians and researchers at the Oregon Health & Science University Evidence-Based Practice Center conducted the analysis as part of the Drug Effectiveness Review Project, or DERP. DERP is a first-of-its-kind multi-state initiative to evaluate the comparative effectiveness and safety of hundreds of prescription drugs. A synopsis of DERP’s analysis of the NSAIDs forms the basis for this report. A consultant to Consumer Reports Best Buy Drugs is also a member of the Oregon-based research team, which has no financial interest in any pharmaceutical company or product.
Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Celebrex, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including Celebrex, in women who have difficulties conceiving or who are undergoing investigation of infertility.
The mechanisms responsible for the increased cardiovascular risk associated with coxibs and tNSAIDs are not well understood and are likely to be multifactorial. It seems likely that relative levels of nitric oxide, prostacyclin (PGI 2 ) and thromboxane A2 (TxA 2 ) will play an important role in endothelial homeostasis. Prostaglandins and TxA 2 are derived from arachidonic acid (Figure 1). PGH 2 is generated by the activity of cyclooxygenases from arachidonic acid via PGG 2 . PGH 2 acts as the substrate for specific synthases, the products of which are TxA 2 , PGI 2 , PGD 2 , PGE 2 and PGF 2α (Figure 1).