Tolvaptan for the management of syndrome of inappropriate antidiuretic hormone secretion: lessons learned in titration of dose.

OBJECTIVE: To report a patient with idiopathic syndrome of inappropriate antidiuretic hormone secretion (SIADH) who developed profound aquaresis with symptomatic extracellular fluid depletion after initiation of therapy with tolvaptan who was later successfully treated with smaller doses of compounded tolvaptan to prevent rapid correction of serum sodium.
METHODS: Case report and review of the literature.
RESULTS: A 51-year-old woman was diagnosed with SIADH during admission for elective surgery resulting in multiple complications. The patient failed multiple therapies including fluid restriction, salt tablets, and demeclocycline. She was admitted to the hospital for initiation of tolvaptan therapy. After a 15-mg dose of tolvaptan, the patient had rapid increase in urine output and symptomatic hypotension. Sodium levels corrected rapidly overnight from 126 mEq/L to 139 mEq/L. A lower dose of tolvaptan resulted in similar symptoms and sodium correction. Due to continuing symptoms of hyponatremia including headaches, nausea, vomiting, and paresthesias after reinitiation of fluid restriction and salt tablets, tolvaptan was compounded to continue to titrate at lower doses. The patient was then admitted and tolvaptan was initiated at a dose of 1.5 mg with no significant improvement in sodium levels. Tolvaptan was titrated to 3 mg, which resulted in correction of sodium to 129 mEq/L with no associated symptoms of hypovolemia.
CONCLUSIONS: Tolvaptan should be initiated in an inpatient setting with close monitoring of serum sodium levels. In patients who are not able to tolerate recommended dosages, consideration should be given to using a compounded formulation to further titrate to lower doses.