Endocrine Abstracts

Introduction: Clinical trials indicate that Tolvaptan is safe and effective in the treatment of patients with sustained mild/moderate SIADH-induced euvolemic hyponatremia. Tolvaptan doses are often modified during chronic use. We present the weekly doses of a series of patients on chronic therapy, followed up in outpatient clinic.

Methods: Retrospective, cross-sectional. 114 patients receiving tolvaptan for chronic SIADH were followed up in a Hyponatremia outpatient clinic in a tertiary hospital, initiating therapy between 2011 and 2019. Therapeutic goal: euvolemia, and serum sodium (SNa) 138–140, inmmol/l. Patients were instructed to drink freely when thirsty, and during meals. Salt was freely added to diet. Tolvaptan doses were modified as follows: increased 7.5 – 15 mg/day if patients were euvolemic with SNa ≤ 136, without polydipsia. Doses were lowered 50% when SNa > 140 mmol/l, patients presented thirst, polyuria, or low central venous pressure (maximum height of the internal jugular vein pulse below the sternal angle).Classification according to etiology of SIADH/additional diagnosis, for comparison of weekly doses: medication--induced (interruption of medication not viable) (MED), idiopathic SIADH of the elderly (IDIO), non-oncological pulmonary disease (PULM),neurological/neurosurgical disease (NEURO), oncological ectopic SIADH (ONCO), patients with chronic SIADH of diverse etiologies and prior episodes of heart failure (HF), and OTHERS. Weekly doses, mg, compared among groups. [Interquartile range].

Results: 66 (57.9%) women. Median age: 76 [65–83.3]. Mean Pre-tolvaptan Nadir SNa: 121.1 (s.d.:5.86). MED: 22/114 (19.3%) patients, IDIO: 25/114 (22%), PULM: 17/114 (14.9%), NEURO: 9/114 (7.9%),ONCO: 13/114 (11.4%), HF: 6/114 (5.3%), others: 22/114 (19.3%). Median months therapy: 11[5.3–33.5], 45[20–61], 27[12.5–61] months, 7 [4.5–20.5], 10 [7–26.5], 46 [20.8–69.8], 21.5 [10.5–38] respectively.

Final median doses were significantly lower than at start in MED: 26.25 [22.5–52.5] vs 105 [52.5–105] (P < 0.001), IDIO 26.25[22.5–52.5] vs 105 [52.5–105] (P < 0.001), PULM 26.25 [26.3–105] vs 105 [78.8–131.3] (P = 0.019), NEURO 26.25 [0–65.62] vs 105 [52.5–105] (P = 0.002), OTHERS 52.5[26.25–105] vs 105 [52.5–210] (P = 0.006).

Final median doses were significantly higher in ONCO: 105 [52.5–262.5] than in MED: (P = 0.001), IDIO (P < 0.001), PULM (P = 0.043), NEURO (P = 0.012), OTHERS (P = 0.017).

There was no correlation between pre-tolvaptan nadir SNa and final doses.

Mean nadir SNa during tolvaptan therapy: 135.35 (s.d.:2.85). Mean maximum tolvaptan SNa: 141.04 (s.d.:1.8).

Side effects: No patient presented hypernatremia, nor liver-enzyme elevation. Thirst and/or polyuria were indications for lowering dose.

Conclusion: Chronic ambulatory tolvaptan therapy in SIADH is safe and effective. Doses can often be reduced, with the exception of oncology patients and SIADH patients with a history of heart failure. Eunatremia seems to be easier to maintain than to attain.