title: Possible drug-drug interaction between high-dose esomeprazole and phenprocoumon.
abstract: OBJECTIVE
  It is established that omeprazole increases (R)+ warfarin levels with around 10 %. Whether (es)omeprazole also increase the plasma levels of acenocoumarol or phenprocoumon is still uncertain. We analyzed whether addition of (es)omeprazole to acenocoumarol or phenprocoumon increases the international normalized ratio (INR) levels and the risk of overanticoagulation.
  
  
  METHODS
  We analyzed all hospital admissions in four teaching hospitals. Patients who used coumarins and pantoprazole or (es)omeprazole simultaneously for at least four consecutive days were included in the study. We analyzed the highest INR level and whether patients had an INR level above six. We compared patients using omeprazole or esomeprazole with patients using pantoprazole, because for pantoprazole, no interaction has been reported.
  
  
  RESULTS
  We analyzed 5747 admissions with 4540 patients using one of the drug combinations. For acenocoumarol (4578 admissions), no significant differences were found between users of esomeprazole, omeprazole, and pantoprazole. For phenprocoumon (1169 admissions), the highest INR measured was significantly higher in users of esomeprazole than in users of pantoprazole (4.7 versus 4.3; p = 0.035). No significant difference was found with omeprazole versus pantoprazole (4.3 versus 4.3; p = 0.66). A non-significant association was found between the esomeprazole dose and the highest INR level (p = 0.055). The risk of an INR above six did not differ significantly between esomeprazole and pantoprazole (27.7 % versus 22.9 %; p = 0.34).
  
  
  CONCLUSIONS
  The use of esomeprazole simultaneously with phenprocoumon during hospital admissions might increase the anticoagulant effect. The clinical relevance seems to be limited, because no statistically significant increased risk of overanticoagulation was found.
authors.affiliation: Pharmacy Foundation of Haarlem Hospitals, Boerhaavelaan 24, 2035 RC, Haarlem, The Netherlands. mbecker@sahz.nl.
authors.forename: M L
authors.initials: ML
authors.lastname: Becker
authors.affiliation: ATAL-MEDIAL Diagnostics Centers, Hoofddorp, The Netherlands.
authors.forename: W P J
authors.initials: WP
authors.lastname: Franken
authors.affiliation: Sint Lucas Andreas Hospital, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Karapinar
authors.affiliation: Amphia Hospital, Breda, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Verzijl-Zeegers
authors.affiliation: Universiteit Utrecht, Utrecht, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Schalekamp
authors.affiliation: Pharmacy Foundation of Haarlem Hospitals, Boerhaavelaan 24, 2035 RC, Haarlem, The Netherlands.
authors.forename: R T M
authors.initials: RT
authors.lastname: van der Hoeven
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000009:adverse effects; D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects*; D000368:Aged; D000369:Aged, 80 and over; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000009:adverse effects; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006760:Hospitalization; D006784:Hospitals, Teaching; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects; D000077402:Pantoprazole; D010644:Phenprocoumon / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D000925:Anticoagulants; D000077402:Pantoprazole; D000074:Acenocoumarol; D009853:Omeprazole; D064098:Esomeprazole; D010644:Phenprocoumon
keywords: Coumarins; Cytochrome P450; Drug interactions; International normalized ratio; Proton-pump inhibitors