Reactions 1704, p214 - 2 Jun 2018 Itraconazole/posaconazole/ voriconazole Various toxicities: case report A woman in her late 60s [age not clearly stated] developed hives during treatment with itraconazole, alopecia during treatment with voriconazole and pseudo-hyperalsosteronism during treatment with posaconazole. Additionally, she also developed bilateral pitting pedal oedema secondary to itraconazole and posaconazole therapy [routes not stated; not all dosages and duration of treatments to reaction onsets stated]. The woman, who had a history of diabetes mellitus and multiple sclerosis, was diagnosed with disseminated histoplasmosis. For the treatment, she started receiving itraconazole, but she developed hives. Thereafter, her therapy was switched to voriconazole, which resulted in alopecia. She requested a change in therapy. Therefore, she started receiving posaconazole 300mg once daily extended release tablet formulation. After four months of starting posaconazole therapy, she developed bilateral pitting pedal oedema, orthopnoea and shortness of breath on exertion. A CT scan showed new large bilateral pleural effusion. A transthoracic echocardiogram (TTE) showed grade II diastolic dysfunction with normal ejection fraction, dilation of right ventricle and atrium along with severe functional mitral regurgitation. Additionally, her corrected QT interval was prolonged to 520ms. The woman’s posaconazole therapy was withheld. Considering the presentation of congestive heart failure, she was treated with furosemide. On initial examination, she was noted to be hypertensive. The laboratory tests showed hypokalaemia and mild alkalosis. The newly developed hypokalaemia and systemic hypertension were difficult to manage. Therefore, her treatment was started with four antihypertensives and strong potassium supplementation. Considering the pattern of hypokalaemia and hypertension, morning renin and aldosterone levels were checked. Morning cortisol level was 11.3 µg/dL, morning renin level was <3.0 and aldosterone level was <0.2. Considering the investigations, a diagnosis of pseudo-hyperaldosteronism was made. Over the subsequent 6 weeks, oedema of the lower extremity was resolved. Her treatment with diuretics and most of the antihypertensives were stopped, within 4 weeks of hospital admission. A repeat TTE after six weeks of hospitalisation showed normal right atrium and ventricle. Only mild to moderate mitral regurgitation was observed. Subsequently, a complete resolution of hypokalaemia and hypertension were also observed. Author comment: "This syndrome of pseudohyperaldosteronism is similar to that seen in the patient described in this report." "Resolution of newly developed systemic hypertension, hypokalemia, and edema after withholding posaconazole suggests that posaconazole was the cause of these problems." "Itraconazole, its metabolite hydroxyitraconazole, and posaconazole. . .may contribute to the peripheral edema and hypokalemia". Kuriakose K, et al. Posaconazole-induced pseudohyperaldosteronism. Antimicrobial Agents and Chemotherapy 62: e02130-17, No. 5, May 2018. Available from: URL: http://doi.org/10.1128/AAC.02130-17 - USA 803323503 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704
Reactions Weekly – Springer Journals
Published: Jun 2, 2018
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