Proton Pump Inhibitors May Increase the Risk of Delayed Bleeding Complications after Open Heart Surgery if Used Concomitantly with Warfarin

Hata, Mitsumasa; Hayasaka, Moriaki; Sezai, Akira; Niino, Tetsuya; Yoda, Masataka; Unosawa, Satoshi; Taoka, Makoto; Osaka, Sadako; Furukawa, Nobuyuki; Kimura, Haruka; Minami, Kazutomo

doi:10.1055/s-2008-1038378

Cited by 14 publications

(9 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The drug interactions that were noted from our patient data appear to be different than previously reported in both pediatric and adult outpatients 1, 13. Lansoprazole, which is widely used in pediatric patients to treat symptoms of gastrointestinal reflux, was identified as a risk factor for an elevated INR, as well as corticosteroid therapy, another medication widely used in the pediatric patients 14, 15. However, amiodarone was not identified as a significant drug interaction in our dataset 16.…”

Section: Discussioncontrasting

confidence: 66%

Risk factors for elevated INR values during warfarin therapy in hospitalized pediatric patients

Moffett

Ung

Bomgaars

2011

Pediatric Blood & Cancer

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 66%

Risk factors for elevated INR values during warfarin therapy in hospitalized pediatric patients

Moffett

Ung

Bomgaars

2011

Pediatric Blood & Cancer

View full text Add to dashboard Cite

show abstract

“…Lansoprazole and omeprazole are metabolized mainly by CYP2C19 and partly by CYP3A4 [8]- [10], whereas rabeprazole is metabolized partly by CYP2C19 but non-enzymatically in most part [6]. Because R-warfarin (active stereoisomer of warfarin) is metabolized by CYP2C19 among others [9] [10], concomitant use of warfarin and PPI, especially lansoprazole and omeprazole, could result in the competitive inhibition of metabolism and in turn the effect of the agents become intensified. In this scenario, clinically relevant concern is the increased anti-coagulation activity, i.e., the bleeding tendency.…”

Section: Discussionmentioning

confidence: 99%

“…For example, R-warfarin inhibits CYP2C19 [7] [8], which metabolizes most of lansoprazole [9] and omeprazole [10]. It also metabolizes a part of rabeprazole [6].…”

Section: Introductionmentioning

confidence: 99%

Interaction between Warfarin and Proton Pump Inhibitors

Shirayama¹,

Shiraishi²,

Kuroyanagi³

et al. 2014

IJCM

View full text Add to dashboard Cite

Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin was prescribed from November 1, 2010 to October 30, 2011 were extracted from electronic health records. In retrospective analysis for 1 year, PPI were prescribed to 404 patients. Among them, 108 patients were taking warfarin for more than 6 weeks before and after PPI. The profile of these patients was analyzed: 63 patients took lansoprazole; 15 patients took omeprazole; 30 patients took rabeprazole. No statistical difference was observed among 3 groups in age, body weight, concomitant use of other drugs, and comorbidity. Warfarin dose and INR did not change after PPI. Multivariate stepwise logistic regression analysis revealed that upper quartile of increment of INR was associated with the presence of atrial fibrillation (OR 3.77, 95% CI 1.16 -12.27). The patients who had warfarin for shorter periods before PPI, or those who had PPI first (n = 141) had similar dose of warfarin and INR. In all patients analyzed (n = 404), including patients whose follow-up periods were shorter than 6 weeks (n = 155), a patient had cerebral bleeding, and 2 patients had cerebral infarction. Conclusions: Unfavorable interaction between warfarin and PPI was negligible in clinical use. Relatively higher INR was achieved after PPI in the presence of atrial fibrillation.

show abstract

“…Two case reports described an INR increase in users of phenprocoumon after initiation of omeprazole, which returned to normal after its cessation (Enderle et al , 2001). In one study of co‐medication with lansoprazole or rabeprazole in patients after open heart surgery (Hata et al , 2008), lansoprazole enhanced the anticoagulation effects of warfarin whereas rabeprazole could be used concomitantly without increasing the risk of overanticoagulation. We are not aware of a clinical study on the effect of esomeprazole on coumarins to support our findings.…”

Section: Discussionmentioning

confidence: 99%

Proton pump inhibitors and the risk of overanticoagulation during acenocoumarol maintenance treatment

et al. 2011

View full text Add to dashboard Cite

Summary In the Netherlands, several reports have described a potentiation of acenocoumarol‐induced anticoagulation by co‐medication of omeprazole or esomeprazole and competitive inhibition of CYP2C19 has been suggested as a possible mechanism for this interaction. We conducted an observational cohort study to investigate the effects of various proton pump inhibitors (PPIs) on acenocoumarol effectiveness. All 2755 subjects from the Rotterdam Study who received acenocoumarol maintenance treatment between April 1st, 1991 and September 9th, 2009 were followed for events of an international normalized ratio (INR) ≥ 6, until death, end of treatment, or end of the study period. The Andersen–Gill extension of the Cox proportional hazards model was used to calculate risks for repeated events of overanticoagulation in relation to concomitant PPI use. The risk for overanticoagulation was most pronounced for esomeprazole (HR 1·99, 95% CI 1·55–2·55) and lansoprazole (HR 1·49, 95% CI 1·05–2·10). There was also a lower and non‐significant risk increase for the other PPIs. We did not detect a modification of these results by CYP2C19*2 genotype. Caution should be paid to co‐medication with esomeprazole and lansoprazole during acenocoumarol treatment and possibly also with other PPIs.

show abstract

Proton Pump Inhibitors May Increase the Risk of Delayed Bleeding Complications after Open Heart Surgery if Used Concomitantly with Warfarin

Abstract: These results suggest that lansoprazole emphasizes the effects of warfarin. Rabeprazole could be safely used concomitantly with warfarin.

Cited by 14 publications

References 13 publications

Risk factors for elevated INR values during warfarin therapy in hospitalized pediatric patients

Risk factors for elevated INR values during warfarin therapy in hospitalized pediatric patients

Interaction between Warfarin and Proton Pump Inhibitors

Proton pump inhibitors and the risk of overanticoagulation during acenocoumarol maintenance treatment

Contact Info

Product

Resources

About