Endocrine Abstracts (2012) 29 P1149

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. Montañez, P. Martin, C. Marcuello, P. de Miguel, A. Calle & I. Runkle


Hospital Clinico San Carlos, Madrid, Spain.


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 (Nap) ranging from 111 to 126 mmol/l, Nau 39–92 mmol/l, Osmolalityp 224–257 mOsmol/kg, Osmolalityu 152–462 mOsmol/kg. Patients were euvolemic, with normal adrenal, thyroid, and renal function. 5 patients with initial Nap < 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: Nap increments are all calculated from baseline. Day 1: Median baseline Nap: 126 mmol/l (121–133). After 6 hours median Nap variation was 2 mmol/l (0–4), with median Nap 128 mmol/l (122–135). Day 2: median Nap increase was 5 mmol/l (1–10), median Nap 134 mmol/l (125–136). Day 3: patients 2–7: Median Nap rise was 7 mmol/l (5–12), Median Nap 134 mmol/l (128–138). Patient 1’s Nap had risen 6 mmol/l on day 3 and 13 mmol/l on day 4. 12 h Nap 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 Nap 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
PatientNadir Nap mmol/l Baseline (Day 1) Nap mmol/l 6-hour Nap (increase from baseline) mmol/l Day 2 Nap (increase from baseline) mmol/l Day 3 Nap (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.

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