Syndrome of inappropriate antidiuretic hormone secretion induced by a single dose of oral cyclophosphamide

Ann Pharmacother. 2012 Sep;46(9):e23. doi: 10.1345/aph.1R296. Epub 2012 Aug 21.


Objective: To report a case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by a single oral dose of cyclophosphamide.

Case summary: A 69-year-old woman was treated with oral CTD (cyclophosphamide/thalidomide/dexamethasone) chemotherapy for multiple myeloma. Two days after the first dose (including cyclophosphamide 500 mg), the patient developed vomiting, drowsiness, and headache. Medication history included sertraline, started in 2005. On admission, laboratory values were serum sodium 113 mEq/L, serum osmolality 240 mOsm/kg, urinary osmolality 701 mOsm/kg, urinary sodium 91 mEq/L, and serum creatinine 0.71 mg/dL. Thyroid and adrenal function were normal. SIADH was diagnosed. Cyclophosphamide and sertraline were stopped and fluid restriction was commenced. The patient was discharged on day 9 following chemotherapy with serum sodium 132 mEq/L. Sertraline was restarted. Four days later she developed vomiting with serum sodium 119 mEq/L. Fluid restriction, which the woman had not performed, was reinstituted and she was discharged on day 17. Two further cycles of chemotherapy were subsequently given without cyclophosphamide and serum sodium remained within normal limits.

Discussion: Cyclophosphamide-induced severe hyponatremia and SIADH have been documented in patients receiving treatment for a wide range of malignant and autoimmune disorders. All cases have involved intravenous therapy, with doses ranging from single pulse doses of 500 mg to 3000 mg/m(2). Selective serotonin reuptake inhibitors are a common cause of SIADH. Because sertraline was instituted in 2005 and reinstituted without incident, it was eliminated as a contributing factor. Malignancy, tumor lysis syndrome, other medications, hydration to prevent hemorrhagic cystitis, and renal impairment were also ruled out. The Naranjo probability scale indicated a probable association between SIADH and cyclophosphamide administration.

Conclusions: To our knowledge, our report represents the first case of SIADH due to a single oral dose of cyclophosphamide. Clinicians should be aware of this rare adverse event, as it can have life-threatening consequences.

Publication types

  • Case Reports

MeSH terms

  • Administration, Oral
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Female
  • Humans
  • Inappropriate ADH Syndrome / chemically induced*
  • Multiple Myeloma / drug therapy


  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide