Transcript Specialty Residency Programs: Psychiatric Pharmacy

Duloxetine-Induced
Takotsubo
Cardiomyopathy
Richard Perry, Pharm.D.
Assistant Professor Of Pharmacy Practice
Arnold & Marie Schwartz College of
Pharmacy and Health Sciences
Long Island University
Brooklyn, New York
Takotsubo Cardiomyopathy
Overview
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Type of stress-induced cardiomyopathy
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Also known as transient left ventricular apical
ballooning, cardiac syndrome X and broken heart
syndrome
Japanese name meaning “octopus trap”
Under recognized disease state
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May mimic an acute myocardial infarction (AMI)
Found in ~1-2% of patients with suspected AMI
Clinical Presentation
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Most commonly seen in
postmenopausal women
Chest pain
Dyspnea
ECG changes
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ST-segment elevation
QT Prolongation
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ECHO findings
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Laboratory Findings
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Left ventricle: ballooning of
apical and midventricular
segments, hyperkinetic
basal segment
EF: Severely decreased
CKMB, troponin,
catecholamine levels
Normal coronary arteries
or absence of acute
plaque rupture
Cardiac Wall Abnormalities
Scott et al. Circulation. 2005 Feb 1;111(4):472-9.
Pathophysiologic Triggers
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Specific cause is unknown
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Possibly catecholamine mediated
Epicardial vessel spasm
Reduction in myocardial oxygen supply
Commonly preceded by acute emotional or
physical stress
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Vigorous excitation
Acute medical illness
Acute cocaine intoxication
Duloxetine (Cymbalta®)
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Serotonin and norepinephrine reuptake
inhibitor (SNRI)
FDA approved for:
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Major depressive disorder
Diabetic peripheral neuropathic pain (DPNP)
Generalized anxiety disorder
Initial dose for DPNP – 60 mg/daily
Metabolized through CYP450 1A2 and 2D6
Case Report
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60 y/o HF (Ht, 160 cm; Wt, 58.6 kg) admitted to
emergency department
CC: Chest pain, lightheadedness, nausea and
diaphoresis
PMH: Type 2 diabetes mellitus, DPNP,
hypertension, hypothyroidism, s/p UTI, multiple
hernia and uterine fibroid surgeries
Medications on admission: Duloxetine 60 mg
QAM, levothyroxine, insulin, lisinopril, aspirin,
metformin, repaglinide
Case Report
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cont`…
All: Iodine (Rash)
FH: Unknown
SH: H/O alcohol use, unemployed, living
alone
PTA: Completing course of ciprofloxacin
(CYP450 1A2 inhibitor) for UTI
Time Course of Reaction
Outpatient Hospital Event
Day
1
2
3
AM: Initiated duloxetine 60mg QAM
for DPNP
PM: Felt lightheaded and nauseous
AM: Worsening symptoms
accompanied by dizziness upon
standing
AM: Pt fell during an episode of
dizziness
5 hrs later: symptoms worsened and
pt went to hospital
Presentation at Hospital
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Developed left sided chest pain
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Diaphoretic, experiencing palpitations
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Denied SOB
Vital Signs
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Nonradiating, 7/10 intensity, “pushing quality”
BP, 155/105 mmHg; HR, 114 bpm; RR, 16
bpm; Temp, 98.4oF
Lungs CTA B/L
Presentation at Hospital
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cont`…
ECG: anterior and inferolateral ST elevations, T
wave inversions and prolonged QTc interval (536
msec)
Pertinent lab values on admission
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Troponin I, 3.343 ng/mL; ref. range: </=0.059 ng/mL
Norepinephrine, 3492 pg/mL; ref. range: 70-750 pg/mL
C-Reactive Protein, 6.4 mg/L; ref. range: 0.215-3 mg/L
Creatine kinase, 72 U/L; ref. range: 35-155 U/L
Presentation at Hospital
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Believed to have AMI
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cont`…
Given aspirin, nitroglycerin, heparin,
metoprolol and clopidogrel
Rapid symptomatic improvement seen
Pt admitted to hospital
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Duloxetine continued
Scheduled for cardiac catheterization and
ECHO
Cardiac Study Findings
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Cardiac Catheterization
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ECHO:
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Normal coronary arteries
Akinesis of LV apex
Hyperdynamic motion of LV basal segments
EF of ~30%
Diagnosis of Takotsubo cardiomyopathy made
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Heparin continued due to stasis of left ventricle, to
prevent thrombus formation
Hospital Time Course
Inpatient Hospital
Event
Day
1-6
7
8
9
10
Resolution of presenting symptoms,
episodes of orthostatic hypotension,
BP meds d/c, resulting hypertension
Duloxetine d/c, APAP or APAP-codeine
for DPNP, BP meds restarted
EF
to ~35%
Resolution of orthostatic hypotension
Discharged, warfarin prescribed to
prevent thrombus formation in LV,
pregabalin prescribed for DPNP
Patient Case Follow-Up
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39 days post-discharge
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EF ~70%
LV wall segments contract normally
Slight impaired relaxation of LV
Warfarin therapy continued
Discussion
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Severe cardiovascular side effects uncommon
with duloxetine
Possible inhibition of duloxetine metabolism by
ciprofloxacin
Reaction likely due to norepinephrine surge
Temporal and causal association found between
duloxetine initiation and onset of Takotsubo
cardiomyopathy
Naranjo’s nomogram score 6: probable case of
duloxetine-induced Takotsubo cardiomyopathy
Conclusions
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Takotsubo cardiomyopathy is generally
transient and reversible but may mimic
AMI
Clinicians must be cognizant that
duloxetine may cause Takotsubo
cardiomyopathy
Avoid concurrent use of CYP 450 1A2 and
2D6 inhibitors with duloxetine
McCollough. Crit Care Nurse. 2007 Dec;27(6):20-7