Clinical experience of the efficacy and safety of low dose tolvaptan therapy in a UK tertiary oncology setting
Authors
Chatzimavridou-Grigoriadou, ViktoriaAl-Othman, Sami
Brabant, Georg E
Kyriacou, Angelos
King, Jennifer
Blackhall, Fiona H
Trainer, Peter J
Higham, Claire E
Affiliation
Department of Endocrinology, Christie Hospital NHS Foundation Trust, ManchesteIssue Date
2021
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Background: In patients with cancer, hyponatraemia is associated with increased morbidity and mortality and can delay systemic therapy. Methods: The safety and efficacy of low-dose tolvaptan (7.5 mg) for hospitalized, adult patients with hyponatraemia due to Syndrome of Inappropriate Antidiuresis (SIAD), and co-existing malignancy were retrospectively evaluated in a tertiary cancer centre. Results: Fifty-five patients with mean baseline serum sodium (sNa) 117.9±4.6 mmol/L were included. 90.9% had severe hyponatraemia (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 one 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 seventeen (30.9%) patients experienced sNa rise of ≥8 and ≥12 mmol/L/24hrs, 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=0.036). Moreover, in the over-rapid correction cohort (≥12 mmol/L/24hrs) demeclocycline was appropriately discontinued only in 60% compared to 91.7% of the remaining participants (P=0.047). Lower creatinine was predictive of higher sNa correction rate within 24 hours (p=0.01). Conclusion: In the largest series to date, although low-dose tolvaptan was demonstrated to be effective in correcting hyponatraemia 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. Background: In patients with cancer, hyponatraemia is associated with increased morbidity and mortality and can delay systemic therapy. Methods: The safety and efficacy of low-dose tolvaptan (7.5 mg) for hospitalized, adult patients with hyponatraemia due to Syndrome of Inappropriate Antidiuresis (SIAD), and co-existing malignancy were retrospectively evaluated in a tertiary cancer centre. Results: Fifty-five patients with mean baseline serum sodium (sNa) 117.9±4.6 mmol/L were included. 90.9% had severe hyponatraemia (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 one 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 seventeen (30.9%) patients experienced sNa rise of ≥8 and ≥12 mmol/L/24hrs, 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=0.036). Moreover, in the over-rapid correction cohort (≥12 mmol/L/24hrs) demeclocycline was appropriately discontinued only in 60% compared to 91.7% of the remaining participants (P=0.047). Lower creatinine was predictive of higher sNa correction rate within 24 hours (p=0.01). Conclusion: In the largest series to date, although low-dose tolvaptan was demonstrated to be effective in correcting hyponatraemia 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.Citation
Chatzimavridou-Grigoriadou V, Al-Othman S, Brabant G, Kyriacou A, King J, Blackhall F, et al. Clinical experience of the efficacy and safety of low dose tolvaptan therapy in a UK tertiary oncology setting. J Clin Endocrinol Metab. 2021.Journal
Journal of Clinical Endocrinology and MetabolsimDOI
10.1210/clinem/dgab131PubMed ID
33693944Additional Links
https://dx.doi.org/10.1210/clinem/dgab131Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1210/clinem/dgab131
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