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Life-Threatening Heart Failure Associated With Itraconazole
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Life-Threatening Heart Failure Associated With Itraconazole
June 01, 2008 | Infections In Medicine Journal [1]
By Craig B. Brown, DO [2], John S. Raniolo, DO [3], and Tim Kuberski, MD [4]
Life-threatening heart failure associated with itraconazole antifungal therapy developed in a patient
with disseminated Coccidioides immitis infection. This was documented by cardiac studies that
demonstrated a deterioration of cardiac function during therapy and an improvement after
itraconazole therapy was discontinued. Heart failure associated with itraconazole can be missed by
those unfamiliar with this complication. In any patient with a fungal infection who is being treated
with itraconazole, this serious complication can occur; however, it can be reversible with
discontinuation of the drug. [Infect Med. 2008;25:292-293]
Itraconazole is a widely used antifungal agent. Heart failure is a suspected complication of its use.1
We treated a patient with disseminated Coccidioides immitis infection with oral itraconazole;
however, life threatening heart failure developed after 4 months of therapy. The heart failure
improved after discontinuation of the antifungal.
Case report
In May 2002, a disseminated pulmonary infection attributed to C immitis was diagnosed in a
previously healthy 44-year-old man of African American descent. Diagnosis was confirmed by
isolation of the organism and positive serological test results. The patient was initially treated with
amphotericin B followed by oral fluconazole. The infection was complicated by dissemination to the
spine. In October 2002, the patient underwent spinal surgery to debulk infection and stabilize the
spine. The patient was treated postoperatively with intravenous liposomal amphotericin B, and a
clinical improvement was seen.
By November 2002, the C immitis infection was controlled. The patient was switched to oral
itraconazole, 100 mg bid. Four months later, in February 2003, the patient was hospitalized for heart
failure, which was treated with standard measures. The patient improved. Catheterization of the left
side of the heart was performed and showed normal coronary arteries and normal ventricular
contractility. An echocardiogram showed an ejection fraction of 26%. There was no evidence of
active C immitis infection, and when the patient was discharged, itraconazole was prescribed at the
same dosage that the patient already had been receiving (100 mg bid).
In March 2003, the patient was again admitted with signs and symptoms of heart failure. This time,
he required intubation and mechanical ventilation. Heart failure improved, and the patient was
extubated. He had no peripheral edema or gallop rhythm. Itraconazole therapy was considered a
potential cause of heart failure, and it was discontinued. The patient's medication was switched to
oral fluconazole 400 mg daily, and he was discharged.
The Figure shows changes in ejection fraction during 4 months of itraconazole use before the
development of heart failure. At the time of hospitalization for heart failure in February 2003, the
ejection fraction was 26%, which was established by a cardiac catheterization. Improvement in
ejection fraction to 47% was documented by an echocardiogram in November 2003, 8 months after
itraconazole therapy was discontinued. In addition to echocardiograms, outpatient bioimpedance
cardiac studies during follow-up also demonstrated a gradual improvement in ejection fraction.2
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Life-Threatening Heart Failure Associated With Itraconazole
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Figure - Relationship of ejection fraction, heart failure, and itraconazole.
Discussion
There are sparse data on the relationship between itraconazole and heart failure. One publication
reviewed 58 cases reported to the FDA.1 Twenty eight (48%) of these patients were hospitalized and
remarkably, 13 (22%) died. However, the causal relationship between itraconazole and heart failure
was not clearly established because most of the patients described in that report represented
complicated cases. The patients were very ill and were receiving a variety of medications in addition
to itraconazole. Our patient received itraconazole alone for 4 months before being hospitalized for
heart failure.
Itraconazole is thought to have better bone penetration than other antifungal azoles and was chosen
because our patient had multiple bone lesions attributed to C immitis infection. 3 The patient's
situation provided us with an observational study over time that documented a relationship between
heart failure and itraconazole therapy for management of a C immitis infection. The only medication
taken by this patient before his first episode of heart failure was itraconazole. He continued to take
itraconazole after his initial discharge because the possible association between this therapy and
heart failure had not yet been recognized. Our patient illustrates the importance of recognizing this
potential complication and of ascertaining that heart failure may be an adverse effect of itraconazole
therapy and not a preexisting condition or a complication of the underlying fungal infection.
There does not appear to be a similar association between heart failure and other azole antifungals.
The mechanisms through which itraconazole causes heart failure are unknown, but negative
inotropic effects are postulated.1 Itraconazole given to healthy volunteers caused a transient
asymptomatic decrease in left ventricular ejection fraction. 4 It should be noted that calcium channel
blockers also can have negative inotropic effects, and their use in management of
itraconazole-associated heart failure theoretically could be additive, potentially worsening the heart
failure.
Physicians should maintain a high index of suspicion for heart failure in patients taking itraconazole.
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Life-Threatening Heart Failure Associated With Itraconazole
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References:
1. Ahmad SR, Singer SJ, Leissa BG. Congestive heart failure associated with itraconazole.
Lancet. 2001;357:1766-1767.
2. Parrott CW, Burnham KM, Quale C, Lewis DL. Comparison of changes in ejection fraction to
changes in impedance cardiography cardiac index and systolic time ratio. Congest Heart Fail.
2004;10(2 suppl 2):11-13.
3. Galgiani JN, Catanzaro A, Cloud GA, et al. Comparison of oral fluconazole and itraconazole for
progressive nonmeningeal coccidioidomycosis: a randomized, double-blind trial. Mycoses
Study Group. Ann Intern Med. 2000;133:676-686.
4. Sporanox (itraconazole) [package insert]. Titusville, NJ: Janssen Pharmaceuticals; 2004.
Source URL:
http://www.patientcareonline.com/articles/life-threatening-heart-failure-associated-itraconazole
Links:
[1] http://www.patientcareonline.com/infections-medicine-journal
[2] http://www.patientcareonline.com/authors/craig-b-brown-do
[3] http://www.patientcareonline.com/authors/john-s-raniolo-do
[4] http://www.patientcareonline.com/authors/tim-kuberski-md
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