The Potential Inhibitory Effect of Revaprazan, an Acid Pump Antagonist, on Anticoagulation with Warfarin

Abstract

Revaprazan is the first acid pump antagonist with a function similar to that of proton pump inhibitors (PPIs). It has a dual action, active suppression of gastric acid secretion and gastric mucosa protection. While PPIs are known to enhance the prolongation of prothrombin time by warfarin, no research has been done on the drug interaction between revaprazan and warfarin. This study was conducted in order to verify the potential drug interaction between revaprazan and warfarin. Omeprazole, a representative PPI, was used as the control for revaprazan. We searched for patients who were given either revaprazan or omeprazole along with warfarin using the medical record database of Seoul National University Hospital between July 2007 and June 2010. Among the 15 patients who took revaprazan and warfarin together, 73.3% (11/15) showed more than 30% reduction of anticoagulation effect by warfarin after revaprazan was added. The revaprazan group showed a significant shortening of prothrombin time during revaprazan administration compared to pre-and post-revaprazan medication (P < 0.05) while the omeprazole group did not show such difference. Revaprazan seems to have cumulative dose-dependent anti-warfarin or anti-coagulation effect, as judged from the fact that the longer medication with revaprazan showed correlation with the shortening of prothrombin time (R = −0.632, P < 0.05). This study shows a possible interaction between revaprazan and warfarin and suggests that revaprazan can cause shortening of prothrombin time. Therefore, when revaprazan is prescribed to patients on warfarin therapy, prothrombin time should be frequently monitored.

Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy

“…Proton pump inhibitors have been shown to reduce warfarin metabolism and clearance leading to increased prothrombin time prolongation induced by warfarin. 31,32 In studies of rats, a neutral or basic gastric pH was associated with faster warfarin absorption from the stomach into the plasma pool compared with an acidic pH, whereas low pH was associated with warfarin precipitation on the gastric wall mucosa and with slower plasma absorption. 33 Proton pump inhibitors may thus accelerate warfarin absorption.…”

New pharmacological treatments for gastroesophageal reflux: Potassium-competitive acid blockers and bile acid sequestrants

“…On the other hand, according to Jung et al 13 , there is a possible interaction between revaprazan and warfarin, suggesting that revaprazan can cause the shortening of prothrombin time (PT). Therefore, in cases where revaprazan is prescribed to patients on warfarin therapy, PT should be frequently monitored.…”