Interaction of rofecoxib and celecoxib with warfarin

Effect of impaired renal function on the maintenance dose of warfarin in Japanese patients

“…In addition to the differences presented in Table 1, the ratio of patients taking antibiotics [52][53][54], proton pump inhibitors [55], non-steroidal anti-inflammatory drugs [56], and other antiplatelet agents [57,58] -all of which are among the drugs previously suggested to modify dose-effect relationship of warfarin [59] -were not significantly different either (Supplementary Table 5). …”

Potential Underprediction of Warfarin Drug Interaction From Conventional Interaction Studies and Risk Mitigation: A Case Study With Epacadostat, an IDO1 Inhibitor

“…The study enrolled 18 healthy adult volunteers in a fixed sequence and had a 1-way crossover design with 2 periods. The subjects received a single dose of 25 mg warfarin (5 × 5-mg Coumadin tablets) on day 1 of period 1 (days 1-7) and again on day 14 of period 2 (days [8][9][10][11][12][13][14][15][16][17][18][19][20]. The subjects also received epacadostat 300 mg twice daily during days [8][9][10][11][12][13][14][15][16][17][18][19][20].…”

“…17 Similarly, dedicated DDI studies concluded no clinically significant impact on warfarin from concurrent levofloxacin, 7 tolterodine, 8 rofecoxib, 10 or meloxicam, 12 but subsequent postmarketing reports for these drugs indicated unsafe levels of anticoagulation in some patients on concurrent warfarin therapy. [18][19][20][21] The apparent disconnect between the conclusion of a dedicated DDI study conducted in a small number of subjects with a controlled setting and actual clinical practice in patients postmarketing may be confounded by intrinsic factors to affect warfarin pharmacokinetics (PK) and pharmacodynamics (PD), which are mainly the genetic polymorphisms influencing the expression of cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1), respectively. 13 Changes in extrinsic factors such as concurrent medication or dietary habits with respect to consuming vitamin K-rich food may also alter anticoagulation levels in patients already on a stable warfarin regimen.…”

Varfarina: Uma revisão baseada na evidência das interacções alimentares e medicamentosas

“…5,10 Em suma, outra forma de interacção com a varfarina ocorre pela potenciação ou inibição do citocromo P 450 CYP2C9 a nível hepático, mecanismo responsável pela interacção com diversos fármacos -Quadro I (nível de evidência B). 1,[5][6][7][9][10][11]13,14 Diminuição da síntese de vitamina K pela flora intestinal Outro mecanismo de acção responsável por interacções medicamentosas com a varfarina passa pela redução da síntese de vitamina K pela flora intestinal (da qual depende, em parte, o pool de vitamina K endógeno). Isto explica que alguns antibióticos que alteram a flora intestinal e que diminuem, deste modo, a quantidade de vitamina K disponível, potenciem o efeito da varfarina.…”