Hospital Pharmacy - February 2018 - 55

738079
research-article2017

HPXXXX10.1177/0018578717738079Hospital PharmacyRose et al

Article

Acute Hepatocellular Jaundice After
Dofetilide Initiation: A Case Report

Hospital Pharmacy
2018, Vol. 53(1) 55-58
© The Author(s) 2017
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https://doi.org/10.1177/0018578717738079
DOI: 10.1177/0018578717738079
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Patrick Gary Rose1, Robert Seabury1, and Gregory Cwikla1

Abstract
Dofetilide's hepatotoxicity is not well described. In this case report, we describe acute hepatocellular jaundice related to
dofetilide use in a 33-year-old male being treated for atrial fibrillation. Both viral and ischemic causes of hepatocellular damage
were ruled out as unlikely in this case. This case report outlines a rare yet probable report of idiosyncratic dofetilide-induced
liver injury.
Keywords
adverse drug reactions, adverse drug reactions reporting/monitoring, cardiac agents, cardiovascular, gastrointestinal disorders

Introduction
Dofetilide is a class III antiarrhythmic medication that
blocks the rapid delayed potassium rectifier current (IKr)
resulting in prolongation of the repolarization phase of the
cardiac myocyte.1 While adverse events of dofetilide such
as Torsades de Pointes (TdP) have been well described as an
intrinsic class effect of class III antiarrhythmics, druginduced liver injury (DILI) has not. The purpose of this case
report is to describe potential DILI with dofetilide as the
causative agent.
A MEDLINE search using the terms ("Drug-Induced
Liver Injury" AND "dofetilide") as well as ("dofetilide"
AND "Hepatitis") did not yield results to describe dofetilide's ability to cause DILI. Dofetilide has been described to
cause liver damage in ≤2% of its overall use and numerically
more frequent than placebo per manufacturer data.2

Patient Case Presentation
A 33-year-old, 60-kg Caucasian male coming from home
presents with a chief complaint of worsening shortness of
breath. For 4 months prior to admission (PTA), the patient
experienced dyspnea walking upstairs and lying flat. These
symptoms became exacerbated during the 2 weeks PTA.
The patient was subsequently admitted with a diagnosis of
acute hypoxic respiratory failure secondary to congestive
heart failure.
The patient's medical history was significant for congenital transposition of the great arteries status post right
and left aortopulmonary shunt placement in adolescence as
well as persistent atrial fibrillation for 7 months PTA.
Further details of this patient's clinical course are outlined

in Figure 2. Approximately 1 month PTA, the patient was
successfully cardioverted and initiated on dofetilide 500
µg every 12 hours. Dofetilide use continued until 4 days
PTA when the patient reported nausea and dofetilide was
discontinued. At the time of admission, the patient who is
an accurate historian self-assessed good medication adherence and stated he was taking furosemide 60 mg daily,
levothyroxine 50 µg daily before breakfast, loratadine 10
mg daily, and warfarin 6 mg daily. The patient's family and
social history are unremarkable and negative for alcohol or
illicit drug use.
Upon admission, a supratherapeutic INR likely secondary to warfarin, mildly elevated hepatic transaminases, and
elevated total bilirubin were noted, and these values continued to rise until hospital day 5 (Figure 1). Albumin and alkaline phosphatase values were within normal limits on and
throughout admission. The patient was subsequently diagnosed with acute liver failure. Dofetilide was restarted at
250 µg every 12 hours on hospital day 2 after morning labs
were taken and all anticoagulation was held throughout the
hospital stay. Other medications the patient received during
his hospital course were an oral acetylcysteine 72-hour protocol beginning on hospital day 4, albuterol, bumetanide,
furosemide, ipratropium-albuterol, levothyroxine, lorazepam, methylprednisolone, oxazepam, phytonadione, spironolactone, and thiamine.
1

State University of New York Upstate Medical University, Syracuse,
NY, USA
Corresponding Author:
Patrick Gary Rose, State University of New York Upstate Medical
University, 750 East Adams Street, Syracuse, NY 13210-2306, USA.
Email: rosep@upstate.edu

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