Published: October 2003
ADR update

Itraconazole-Induced Congestive Heart Failure

Prescriber Update 24(2): 28–29
October 2003

Medsafe Editorial Team

Antifungal treatment with itraconazole has been associated with congestive heart failure.  Prescribers are reminded of this rare but serious adverse reaction, and the need to consider the risks and benefits of itraconazole therapy in individual patients.  Before starting itraconazole treatment, patients should be informed of the signs and symptoms of congestive heart failure.

Itraconazole indicated for treatment of local and systemic fungal infections

Itraconazole (Sporanox®) is a synthetic triazole derivative approved in New Zealand for the treatment of skin and nail fungal infections, vulvovaginal candidiasis, and systemic mycoses.1  Itraconazole has a broad antifungal spectrum and acts by inhibiting the synthesis of ergosterol, an essential component of fungal cell membranes.2, 3

New Zealand case report of CHF associated with itraconazole use

Itraconazole has been shown to have a negative inotropic effect, and has been associated with reports of congestive heart failure (CHF).4  The Centre for Adverse Reactions Monitoring (CARM) has received the following case report of CHF associated with itraconazole therapy.

A fit, 41-year-old man was prescribed three-month pulse treatment (one week per month) with itraconazole (400mg/day) for a fungal toenail infection.  During each week of pulse treatment, he experienced ankle swelling, weight fluctuations, shortness of breath on exertion, and puffiness around the face.  Four months later, the fungal toenail infection returned, and the patient was prescribed further pulse treatment with itraconazole (400mg/day) for six months.  Five months into the second treatment period, the patient presented to his GP with significant weight gain (6kg in one month), peripheral oedema and dull left-sided chest pain.  He was found to be hypertensive.  An echocardiogram was performed; the findings were within normal limits except for mild left ventricular hypertrophy, which may represent an athletic (fit) heart.  The patient, who had no other medical conditions and was on no other medicines at the time of the itraconazole therapy pulses, was admitted to hospital where he was assessed as being in heart failure.  Treatment with itraconazole was discontinued and the patient recovered without sequelae.

Consider itraconazole-induced CHF even in patients with no risk factors

The mechanism of itraconazole-induced CHF is presently undetermined, and neither is it known whether the heart damage is reversible.  There are insufficient data to provide a comparative likely incidence of CHF developing in patients with risk factors for CHF and those without.  Therefore, prescribers are reminded that itraconazole can cause CHF in any individual and that it should not be used in patients who have a history of CHF unless the benefit clearly outweighs the risk.  The risk-benefit assessment should consider the severity of the indication, and individual risk factors for CHF such as pre-existing cardiac or respiratory disease.  Patients with risk factors should be informed of the signs and symptoms of CHF before treatment begins.  In patients on itraconazole who present with oedema or shortness of breath, consider CHF as part of the differential diagnosis.  If CHF develops during itraconazole use, the risk-benefit profile of continued treatment should be reassessed against the availability of other systemic antifungal medicines.

Competing interests (authors): none declared.

  1. Janssen-Cilag Pty Ltd. Sporanox data sheet January 2002.
  2. Polak A. Antifungal therapy - state of the art at the beginning of the 21st century. Progress in Drug Research 2003;59:1-190.
  3. Leyden J. Pharmacokinetics and pharmacology of terbinafine and itraconazole. Journal of the American Academy of Dermatology 1998;38(5):S42-S47.
  4. Ahmad S, Singer S, Leissa B. Congestive heart failure associated with itraconazole. Lancet 2001;357:1766-1767.