Endocrine Abstracts

Tolvaptan (a selective V2 receptor antagonist) is licensed for the inpatient management of SIADH induced hyponatraemia, a common complication in patients with malignancy. Licensed daily doses start at 15 mg but there is evidence that some patients have a rise in serum sodium (Na) of >12 mmol/l per 24 h in response to this. Lower initial doses (7.5 mg) may therefore be appropriate^1,2.

Methods: A retrospective case note audit was performed. Thirty-four oncology inpatients (mean (±S.D.) age 67±9 years, 15 males) were treated with tolvaptan (Nov 2009–Sept 2013). Twenty-six patients had small cell lung cancer (remaining diagnoses: renal cell carcinoma, oesophageal cancer, myeloma, testicular teratoma, cholangiocarcinoma and adrenal liposarcoma).

Results: Thirty-one patients had a trial of demeclocycline and fluid restriction prior to tolvaptan; 29 received endocrine team review. Nineteen met full biochemical criteria for SIADH (plasma osmolality <280 mOsm/kg, urine osmolality >100 mOsm/kg, urinary sodium >20 mmol/l). Three patients died. No incidents of central pontine myelinosis were recorded. Mean (±S.D.) (Na) pre-tolvaptan was 117±5 mmol/l. In the 28 patients receiving 7.5 mg, the initial increase (Na)/24 h was 7.4±5 mmol/l (27/28 showed a rise in (Na)); 4/28 patients had a rise in (Na)/24 h≥12 mmol/l. To achieve (Na) >130 mmol/l, three patients required escalation to a 15 mg dose. Twelve patients achieved a (Na) >130 mmol/l within 48 h with eight requiring tolvaptan on discharge. Mean (±S.D.) (Na) was 131±6 mmol/l on discharge. The six patients receiving an initial dose of 15 mg showed a mean (±S.D.) rise in (Na)/24 h of 13.8±4 mmol/l (5/6 were ≥12 mmol/l).

Conclusion: Tolvaptan 7.5 mg safely and effectively increased (Na) to >130 mmol/l in this group of patients. Higher doses of tolvaptan were more likely to cause a 24 h rise in (Na) outside of recommended limits. Further work is required to improve investigation and monitoring of hyponatremia in oncology patients.