Clinical Experience of the Efficacy and Safety of Low-dose Tolvaptan Therapy in a UK Tertiary Oncology Setting

Context: In patients with cancer, hyponatremia is associated with increased morbidity and mortality and can delay systemic therapy. Objective: To assess the safety and efficacy of low-dose tolvaptan (7.5 mg) for hospitalized, adult patients with hyponatremia due to syndrome of inappropriate antidiuresis (SIAD), and coexisting malignancy. Methods: Retrospective evaluation in a tertiary cancer center. Results: Fifty-five patients with mean baseline serum sodium (sNa) 117.94.6 mmol/L were included. In total, 90.9% had severe hyponatremia (sNa<125 mmol/L). Mean age was 65.1 +/- 9.3 years. Following an initial dose of tolvaptan 7.5 mg, median (range) increase in sNa observed at 24 hours was 9 (1-19) mmol/L. Within 1 week, 39 patients (70.9%) reached sNa >= 130 mmol/L and 48 (87.3%) had sNa rise of >= 5 mmol/L within 48 hours. No severe adverse events were reported. Thirty-three (60%) and 17 (30.9%) patients experienced sNa rise of >= 8 and >= 12 mmol/L/24 hours, respectively. The rate of sNa correction in the first 24 hours was significantly higher among participants that continued fluid restriction after tolvaptan administration (median [quantiles]: 14 [9-16] versus 8 [5-11] mmol/L, P=.036). Moreover, in the over-rapid correction cohort (>= 12 mmol/L/24 hours) demeclocycline was appropriately discontinued only in 60% compared with 91.7% of the remaining participants (P=.047). Lower creatinine was predictive of higher sNa correction rate within 24 hours (P=.01). Conclusion: In the largest series to date, although low-dose tolvaptan was demonstrated to be effective in correcting hyponatremia due to SIAD in cancer patients, a significant proportion experienced over-rapid correction. Concurrent administration of demeclocycline and/or fluid restriction must be avoided due to the increased risk of over-rapid correction.

Automated summary

In a retrospective evaluation, low-dose tolvaptan was shown to effectively correct hyponatremia due to SIAD in cancer patients, but a significant proportion experienced over-rapid correction, emphasizing the need to avoid the risk of over-rapid correction.