Low-Dose Cyclophosphamide Associated With Hyponatremia and Hepatotoxicity

Abstract

Cyclophosphamide (CY) is an alkylating agent often used as a chemotherapeutic agent, with increasing use as an immunosuppressant. Cyclophosphamide has many established adverse effects, including hyponatremia and limited reports of hepatotoxicity, particularly in high-dose treatment. A case of simultaneous hyponatremia and acute liver injury associated with the initiation of cyclophosphamide two weeks prior is discussed here. A 73-year-old male with acquired hemophilia A/factor VIII deficiency presented to the emergency department (ED) with four days of hip pain and was found to have jaundice and confusion. Laboratory evaluation demonstrated hyponatremia and an acute liver injury associated with his recent cyclophosphamide use. With the discontinuation of the offending agent and sodium correction, he made a full recovery. Cyclophosphamide-induced hyponatremia is likely secondary to the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) and is most often associated with high-dose regimens. While the mechanism of hepatotoxicity requires further study, it is likely dose-dependent and related to excess levels of 4-hydroxycyclophosphamide (HCY). The management of cyclophosphamide-induced water toxicity and hepatotoxicity is centered around the discontinuation of medication, the correction of electrolyte abnormalities, and supportive treatment.

Keywords: acute liver injury; case report; cyclophosphamide; drug toxicity; hepatotoxicity; hyponatremia.

Figure 1. Metabolism of cyclophosphamide with the estimated breakdown quantification of administered dose.