Heart failure induced by itraconazole.

Itraconazole is a broad-spectrum antifungal agent. It rarely leads to adverse the cardiovascular effects, especially heart failure. We present here a case of a 60-year-old female patient with itraconazole induced heart failure.

Introduction

Itraconazole is a broad-spectrum antifungal agent, used to treat onychomycosis, aspergillosis, blastomycosis and histoplasmosis. It rarely leads to adverse cardiovascular effects. We present here a case of a 60-year-old female patient with itraconazole induced heart failure.

Case Report

A 60-year-old female patient presented with the complaints of shortness of breath and swelling of the legs for 5 days. She was referred to cardiology clinic and was prescribed 2 × 200 mg/day of oral itraconazole; therapy was initiated 5 days ago by a dermatologist with the diagnosis of onychomycosis. On physical examination, blood pressure was: 130/80 mmHg, cardiac examination was normal, respiratory sounds decreased in basilar of both lungs. There was bilateral pretibial edema. Her electrocardiography and echocardiography were normal. Density in right lower zone and blunting of the right sinus in chest X-ray was observed. Patient was referred to pneumonology clinic. There was no infection or primary pulmonary disease. Patient had no cardiovascular disease or any other cardiac pathology before. The complaints appeared after initiation of itraconazole. According to Framingham study the patients had three minor criteria and major criteria as cause of complaints and findings that's why patients were accepted heart failure. As there was no other cause itraconazole[1] was considered to be the culprit drug. Oral itraconazole was discontinued and patient was treated with 1 × 40 mg/day furosemide. Patient recovered within a week. Control echocardiography was normal. Exercise stress test was performed to eliminate coronary artery disease, which is a reason for heart failure and the test was normal. Thus, the patient's clinical signs and symptoms were thought to be due to itraconazole and not to any ischemic event with a probable causality relationship as analyzed by World Health Organization — Uppsala Monitoring Center Criteria.

Discussion

Itraconazole, an azole antifungal agent, is used systemically and it causes dose dependent side effects such as nausea and vomiting. Other frequent side-effects, particularly at high doses (>400 mg/day) are hypokalemia, aspartate aminotransferase elevation, alanine aminotransferase elevation, gastrointestinal disturbances, diarrhea and skin rash.[23] It very rarely causes congestive heart failure.[4] The mechanism of heart failure by itraconazole is unknown; however reasons which can lead to heart failure such as hypertension, cardiomyopathy and other possible factors were not present in our patient. And the presence of coronary artery disease in patient was eliminated by a negative stress electrocardiogram test. When itraconazole was administered, the signs and symptoms of heart failure began. And when discontinued it, the signs and symptoms disappeared. That's why, it was thought these findings showed that itraconazole caused signs and symptoms of heart failure. Since 1992, the year that United States Food and Drugs Administration (FDA) approved itraconazole, 58 possible heart failure cases due to itraconazole cases were reported.[4] For this reason, FDA advise to physicians that the patients with impaired left ventricular function must not be treated by itraconazole, but heart failure can also occur in patients with normal left ventricular function as in our patient. The mechanism of congestive heart failure due to itraconazole is undetermined. Qu et al. showed that itraconazole decreased cardiac contractility, which indicated a direct negative inotropic effect upon the heart.[5] It is uncertain whether the heart damage is reversible. They also showed that itraconazole decreased heart rate and coronary flow and prolongation of PR and QRS intervals.

This case shows that itraconazole causes cardiovascular adverse-effects such as heart failure and clinicians must take care on this aspect during their treatment with itraconazole. In addition to this itraconazole should not be prescribed to patients with left ventricular systolic dysfunction and heart failure.