An initial dose of 7.5 mg Tolvaptan is safe and effective in the treatment of hyponatremia caused by SIADH

M. Cuesta; E. Gomez-Hoyos; C. Montanez; P. Martin; C. Marcuello; Miguel P. de; A. Calle; I. Runkle

Tolvaptan (TV), an ADH V2-receptor blocker, is useful in treating SIADH-induced hyponatremia. Maximum aquaresis following 15 mg TV occurs on day 1, when excess body water is greatest. This can cause a sharp rise in natremia, and poses a risk of overcorrection. Our aim was to evaluate an initial dose of 7.5 mg.

Methods: We studied 7 hospitalized patients with SIADH (4 females), median age 80 (57–95), with nadir natremias (Na_p) ranging from 111 to 126 mmol/l, Na_u 39–92 mmol/l, Osmolality_p 224–257 mOsmol/kg, Osmolality_u 152–462 mOsmol/kg. Patients were euvolemic, with normal adrenal, thyroid, and renal function. 5 patients with initial Na_p < 120 mmol/l were first treated with 3% hypertonic saline and/or furosemide and oral salt. All 7 had presented an inadequate response to water restriction, or a Furst formula predicting non-response. TV dose was 7.5 mg (day 1), and was increased to 15 mg on day 2 (patients 2-7) or on day 3 (patient 1).

Results: Na_p increments are all calculated from baseline. Day 1: Median baseline Na_p: 126 mmol/l (121–133). After 6 hours median Na_p variation was 2 mmol/l (0–4), with median Na_p 128 mmol/l (122–135). Day 2: median Na_p increase was 5 mmol/l (1–10), median Na_p 134 mmol/l (125–136). Day 3: patients 2–7: Median Na_p rise was 7 mmol/l (5–12), Median Na_p 134 mmol/l (128–138). Patient 1’s Na_p had risen 6 mmol/l on day 3 and 13 mmol/l on day 4. 12 h Na_p was determined in the first 3 patients, descending 1 mmol in 2/3 and rising 2 mmol in a 3rd vs 6-h natremia. Maximum 24-h and 48-h Na_p increments were 10 and 12 mmol/l respectively. Side Effects: one woman experienced intense thirst.

Conclusion: In our patients, starting tolvaptan at a dose of 7.5 mg was both safe and effective. Evolution of natremia following initiation of tolvaptan therapy

**Table 1**
Patient	Nadir Na_p mmol/l	Baseline (Day 1) Na_p mmol/l	6-hour Na_p (increase from baseline) mmol/l	Day 2 Na_p (increase from baseline) mmol/l	Day 3 Na_p (increase from baseline) mmol/l
1 age 84 female	118	122	122 (0)	127 (5)	128 (6)
2 age 66 female	126	126	130 (4)	130 (4)	133 (7)
3 age 94 male	119	124	125 (1)	134 (10)	136 (12)
4 age 75 male	122	128	128 (0)	134 (6)	135 (7)
5 age 80 female	118	127	130 (3)	136 (9)	132 (5)
6 age 52 female	111	133	135 (2)	134 (1)	138 (5)
7 age 85 male	116	121	123 (2)	125 (4)	128 (7)

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Endocrine Abstracts

P1149