Severe Hyponatraemia Secondary to Micafungin Therapy Wilson SW Cheng 1, 2, Wei J. Zhang 1, Christos Kosmidis 1, Eavan G. Muldoon 1, 2

1 National Aspergillosis Centre, South Manchester of University Hospital, Manchester, United Kingdom 2 The University of Manchester, United Kingdom

Introduction • Due to her drug intolerance, and her azole • CPA diagnosed in 2011. • Her hyponatraemia was symptomatic, with resistant A. fumigatus, the decision was made • CT thorax demonstrating fungal ball, nausea and weakness. • Micafungin is an echinocandin antifungal. It to commence on micafungin therapy. Aspergillus specific IgG >200mg/L and A. was first approved in 2005. fumigatus isolated from bronchoavleolar • On discontinuation of the drug and • She was started on 150mg once daily IV lavage sample. appropriate fluid restriction, her symptoms • Echinocandins are narrow spectrum micafungin therapy. Her pre-treatment sodium resolved and serum sodium normalised. antifungals used to treat Candida spp. and was 134mmol/L. • She did not tolerate itraconazole, voriconazole occasionally Aspergillus spp infection, such as or IV amphoteracin therapy. • After normalisation of the sodium, pregabalin 1 chronic pulmonary aspergillosis (CPA). • On day 2, her sodium level fell to 121mmol/L. was reintroduced without further incident.

Micafungin was stopped. • In 2013, a pan-azole resistant isolate of A. Discussion • The use of micafungin is increasing as the fumigatus was isolated from her sputum. • Both patients are women in their 60s who incidence of aspergillosis and candidiasis • She had a low serum osmolality (244 2 received micafungin as salvage therapy for increases. Therefore it is important to mOsm/kg), high urine osmolality (605 • In 2014, a new aspergilloma was found in the recognise its side effect profile. their CPA. mOsm/kg) and high urinary sodium (91 right lung apex (Figure 2). mmol/L), consistent with a syndrome of • We have identified two cases of severe • Both developed a SIADH shortly after inappropriate antidiuretic hormone production • Due to her drug intolerance, and her azole commencing micafungin therapy. Both were symptomatic hyponatraemia associated with (SIADH). resistant A. fumigatus, the decision was made the use of micafungin at the National symptomatic and both resolved on to commence on micafungin therapy. discontinuation of micafungin with Aspergillus Centre, University Hospital of South • Her hyponatraemia was symptomatic, with Manchester (UHSM) in the past year. appropriate fluid restriction. nausea, vomiting, dizziness and weakness. • She was started on 150mg once daily IV Methods micafungin therapy. She had an initial

• On discontinuation of the drug and appropriate hyponatraemia of 119mmol/L, thought to be due • Twenty patients with CPA have been treated fluid restriction, her symptoms resolved and to pregabalin. between 2013 to 2014 with micafungain. serum sodium normalised. • On day 4, her sodium fell to 112mmol/L, • Two patients developed severe symptomatic Case 2 micafungin was stopped. hyponatraemia with micafungin therapy. • 65-year-old woman.

• She had a low serum osmolality (222 • Clinical and laboratory characteristics of the • Past medical history: ulcerative colitis. mOsm/kg), high urine osmolality (397 patients are reviewed. mOsm/kg) and high urinary sodium (38 Case 1 mmol/L), consistent with SIADH.

• 61-year-old woman.

• Past medical history: allergic bronchopulmonary aspergillosis.

• CPA diagnosed in 1998. • CT thorax demonstrating an aspergilloma (Figure 1), Aspergillus fumigatus isolated in her sputum. Figure 1: Sodium level of Case 1 and 2 when IV micafungin was given during their hospital stay • She did not tolerate itraconazole, nebulised Conclusion amphoteracin or IV amphotericin therapy. • SIADH may be a side effect associated with • In 2012, a pan-azole resistant isolate of A. micafungin therapy. fumigatus isolated from her sputum. • Electrolytes should be monitored closely when patient is commenced on micafungin, Figure 1. CT image showing aspergilloma in the left lower lobe Figure 2. CT image showing new aspergilloma in the right lung apex especially during the early treatment phase.

1. Torre P., Reboli A. Micafungin: an evidence-based review of its place in therapy. Core Evidence.2014;9:27-39 2. Higashiyama, Y., Kohno, S. Micafungin: a therapeutic review. Expert Review of anti-infective therapy. 2004;2(3):345-355 Copyright © 2015 Wilson Cheng. National Aspergillosis Centre, Southmoor Road, Manchester, M23 9LT, email: [email protected]