Hospital Pharmacy - July/August 2017 - 455

717621
research-article2017

HPXXXX10.1177/0018578717717621Hospital PharmacyMancano

ISMP Adverse Drug Reactions
Hospital Pharmacy
2017, Vol. 52(7) 455-458
© The Author(s) 2017
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https://doi.org/10.1177/0018578717717621
DOI: 10.1177/0018578717717621
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ISMP Adverse Drug Reactions:
Allergic Angina Caused by Fluconazole
Rhabdomyolysis Caused by Risperidone
High Incidence of Hyponatremia With High-Dose
Trimethoprim-Sulfamethoxazole
Lithium Carbonate-Induced Hypersalivation
Persistent Hemorrhage After Idarucizumab Administration
Michael A. Mancano1,2

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of
prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA) MedWatch program (800FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with
our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936;
e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is
provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and
Temple University School of Pharmacy. ISMP is an FDA MedWatch partner.

Allergic Angina Caused by Fluconazole
A 42-year-old female initiated therapy with fluconazole
(Diflucan) for a superinfection she contracted after an
eczematous flare. Other than a history of eczema, the patient
was in good health with no concomitant diseases or cardiac
history. The patient administered her first dose of fluconazole, and within 30 minutes, she experienced palpitations
and became lightheaded. The patient was taken to her local
emergency room, and she was diaphoretic, short of breath,
tachycardiac with a pulse rate of 118 beats per minute (bpm),
and hypotensive with systolic blood pressure of 90 mm Hg.
She began to experience nonpleuritic, nonradiating, retrosternal chest pressure, and an electrocardiogram revealed an ST
segment elevation suggestive of an acute inferior wall myocardial infarction. The patient was emergently sent to the
catheterization lab and had an urgent coronary angiography.
Her angiography did not reveal obstructive disease, and her
ejection fraction was >60%. Based on these findings, she did
not require percutaneous cardiac intervention.
The patient was admitted to the Coronary Care Unit for
observation, and at this time, the results of her initial lab tests
were available. Labs tests indicated an elevated troponin and
a mild peripheral eosinophilia. The patient's hypotension
responded well to normal saline administration, and the
patient was stable and discharged to home the next day.
Based on this patient's presentation, she was diagnosed with
fluconazole-induced Kounis syndrome type 1.
Kounis syndrome is also synonymous with hypersensitivity coronary syndrome or allergic angina. This condition is

associated with mast cell activation and has 3 distinct types.
Type I Kounis syndrome occurs in patients with no obvious
cardiac risk factors and nonobstructive coronary anatomy. In
these patients, an acute allergic insult is thought to trigger a
vasospasm leading to an acute coronary event. Type 2 Kounis
syndrome is seen in patients with preexisting arthrosclerotic
coronary disease in which an acute allergic insult triggers
plaque destabilization and rupture which in turn leads to a
myocardial infarction. Patients with type 3 Kounis syndrome
experience an allergic insult and have an in-stent thrombosis.
These patients have a history of atopy and baseline elevations in IgE.
Mahal1 states that drugs that have been associated with
causing Kounis syndrome are common antibiotics, corticosteroids, nonsteroidal antiinflammatory drugs, antidepressants,
analgesics, and contrast media. The proposed mechanism of
Kounis syndrome is that an allergen triggers IgE and mast cell
activation and degranulation which releases histamine. The
effects of histamine on cardiac function are mediated through
H1 and H2 receptors situated on cardiac chambers and
coronary arteries. This histamine release causes a coronary
1

Temple University School of Pharmacy, Philadelphia, PA, USA
Institute for Safe Medication Practices, Horsham, PA, USA

Corresponding Author:
Michael A. Mancano, Chair and Clinical Professor, Department of
Pharmacy Practice, Temple University School of Pharmacy, Philadelphia,
PA 19140, USA.
Email: michael.mancano@temple.edu

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