Severe hyponatraemia in two patients with breast cancer caused by low-dose cyclophosphamide and precipitated by aprepitant

BMJ Case Rep. 2022 Mar 22;15(3):e248408. doi: 10.1136/bcr-2021-248408.

Abstract

Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant - a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.

Keywords: Breast cancer; Chemotherapy; Drug interactions.

Publication types

  • Case Reports

MeSH terms

  • Aprepitant
  • Breast Neoplasms* / complications
  • Breast Neoplasms* / drug therapy
  • Cyclophosphamide / adverse effects
  • Female
  • Humans
  • Hyponatremia* / chemically induced
  • Hyponatremia* / complications
  • Hyponatremia* / diagnosis
  • Inappropriate ADH Syndrome* / complications

Substances

  • Aprepitant
  • Cyclophosphamide