Effect of Oral Corticosteroids on Chronic Warfarin Therapy

Kathleen A. Hazlewood; Susan E. Fugate, PharmD BCPS CACP; Donald L. Harrison, PhD

Disclosures

The Annals of Pharmacotherapy. 2006;40(12):2101-2106. 

In This Article

Abstract and Introduction

Abstract

Background: A potential drug interaction exists between oral corticosteroids and warfarin, but there is limited documentation.
Objective: To evaluate the potential drug interaction between oral corticosteroids and long-term warfarin therapy.
Methods: A retrospective review was conducted of 387 medical records for active patients within an anticoagulation clinic. Inclusion criteria were stable anticoagulation therapy, short-term oral corticosteroid therapy, international normalized ratio (INR) recorded within 30 days prior to corticosteroid initiation (pre-INR), and INR recorded during corticosteroid therapy or within 14 days of discontinuation (post-INR). Patients were excluded if they had been started on any antibiotic or other drug with a probable interaction with warfarin at the same time as corticosteroid initiation. Thirty-two patient encounters met the predetermined inclusion and exclusion criteria. The primary outcome assessed was the difference between pre- and post-INR values. Secondary endpoints included bleeding events, emergency department (ED) visits, hospitalizations, and warfarin dose modifications.
Results: The mean difference between pre- and post-INR values was 1.24 (95% CI 0.86 to 1.62). Ninety-seven percent of the 32 patient encounters resulted in a change in their post-INR value, and 62.5% of patients had supratherapeutic INR values at the post-corticosteroid assessment. The majority of patients assessed had an elevation of their INR following concomitant use of warfarin and corticosteroids. The INR change was observed at a mean ± SD of 6.7 ± 3.3 days following the first dose of corticosteroid. Overall, 16 patients (50%) required a modification of their anticoagulation therapy during or following corticosteroid therapy. Only one adverse event of minor epistaxis was reported, and no ED visits or hospitalizations occurred as a consequence of the drug combination.
Conclusions: Use of oral corticosteroids in patients on long-term warfarin therapy may result in a clinically significant interaction, which requires close INR monitoring and possible warfarin dose reduction.

Introduction

Warfarin is the only oral anticoagulant currently available in the US and is indicated for the treatment and prevention of multiple thromboembolic conditions. Over 17 million warfarin prescriptions were dispensed in 2005.[1] Many factors can influence warfarin's anticoagulant effect, which may necessitate dose adjustments during a patient's therapy. The use of interacting drugs is one such factor that can be problematic, since warfarin has an extensive drug interaction profile.[2] Most of the interactions have been identified, but poorly investigated and reported. One particular interaction with very little published documentation is between warfarin and oral corticosteroids. The warfarin sodium product package insert provides limited information on this potential interaction, stating that the combination of corticosteroids and warfarin may result in an increase or decrease in prothrombin time (PT) and international normalized ratio (INR) results.[3] A proposed mechanism of this interaction is altered liver metabolism of warfarin by corticosteroids.

Two small studies and 3 case reports have described the interaction between oral anticoagulants and corticosteroids. Two case reports and 1 prospective observational study determined that the response to oral anticoagulation was enhanced after corticosteroid administration, whereas the other study and case report observed diminished anticoagulant activity with this drug combination.[4,5,6,7] However, little information has currently been published in the medical literature concerning the effect of oral corticosteroids on the INR in patients on stable warfarin therapy.

Oral methylprednisolone, prednisone, and warfarin were among the top 300 prescribed drugs in 2005. Consequently, oral corticosteroids and warfarin may commonly be prescribed together.[1] This combination is often difficult to avoid, as this interaction has been reported with multiple corticosteroids.[4,5,6,7] In addition, a logical therapeutic alternative for corticosteroid therapy often does not exist. For this reason, it is imperative that pharmacists and other healthcare providers are informed of the interaction so that anticoagulation can be managed properly during concomitant therapy.

The purpose of this observational study was to evaluate the potential drug interaction between long-term warfarin and oral corticosteroids. The specific aim of this study was to examine the frequency and significance of this drug interaction, and to supplement existing literature enabling healthcare providers to make more informed decisions regarding the management of anticoagulation during concomitant use of corticosteroids.

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