Secondary resistance to tolvaptan in two patients with SIAD due to small cell lung cancer

Garrahy, Aoife; Hannon, Anne Marie; Zia-Ul-Hussnain, Hafiz Muhammad; Williams, David; Thompson, Chris

doi:10.1007/s00228-017-2363-7

Cited by 7 publications

(8 citation statements)

References 3 publications

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“…Finally, acquired resistance to tolvaptan has rarely been described and has been attributed to escalating plasma AVP concentrations in the setting of progression of malignant disease, competing with tolvaptan at AVP kidney receptors. 32 In summary, several real-world studies have reported a substantial risk of overly rapid hyponatraemia correction, estimated at around 25% for individuals with a starting serum sodium of 120 mmol/litre. 25,28,30 This significantly greater magnitude of sodium rise in real-life data compared with RCTs, as summarised in Table 1, is most likely explained by real-life tolvaptan use in individuals with much lower baseline serum sodium levels.…”

Section: Real-world Data On the Effectiveness And Safety Of Tolvaptan...mentioning

confidence: 98%

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Tolvaptan for the treatment of the syndrome of inappropriate antidiuresis (SIAD)

Tzoulis

Kaltsas

Baldeweg

et al. 2023

Therapeutic Advances in Endocrinology

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The syndrome of inappropriate antidiuresis (SIAD), the commonest cause of hyponatraemia, is associated with significant morbidity and mortality. Tolvaptan, an oral vasopressin V2-receptor antagonist, leads through aquaresis to an increase in serum sodium concentration and is the only medication licenced in Europe for the treatment of euvolaemic hyponatraemia. Randomised controlled trials have shown that tolvaptan is highly efficacious in correcting SIAD-related hyponatraemia. Real-world data have confirmed the marked efficacy of tolvaptan, but they have also reported a high risk of overly rapid sodium increase in patients with a very low baseline serum sodium. The lower the baseline serum sodium, the higher the tolvaptan-induced correction rate occurs. Therefore, a lower starting tolvaptan dose of 7.5 mg has been evaluated in small cohort studies, demonstrating its efficacy, but it still remains unclear as to whether it can reduce the risk of overcorrection. Most international guidelines, except for the European ones, recommend tolvaptan as second-line treatment for SIAD after fluid restriction. However, the risk of unduly rapid sodium correction in combination with its high cost have limited its routine use. Prospective controlled studies are warranted to evaluate whether tolvaptan-related sodium increase can improve patient-related clinical outcomes, such as mortality and length of hospital stay in the acute setting or neurocognitive symptoms and quality of life in the chronic setting. In addition, the potential role of a low tolvaptan starting dose needs to be further explored. Until then, tolvaptan should mainly be used as second-line treatment for SIAD, especially when there is a clinical need for prompt restoration of normonatraemia. Tolvaptan should be used with specialist input according to a structured clinical pathway, including rigorous monitoring of electrolyte and fluid balance and, if needed, implementation of appropriate measures to prevent, or when necessary reverse, overly rapid hyponatraemia correction.

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Section: Real-world Data On the Effectiveness And Safety Of Tolvaptan...mentioning

confidence: 98%

Section: Real-world Data On the Effectiveness And Safety Of Tolvaptan...mentioning

confidence: 99%

Tolvaptan for the treatment of the syndrome of inappropriate antidiuresis (SIAD)

Tzoulis

Kaltsas

Baldeweg

et al. 2023

Therapeutic Advances in Endocrinology

View full text Add to dashboard Cite

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Section: Impact Of Treatment Of Hyponatraemia; Why Should We Treat It?mentioning

confidence: 99%

“…Resistance to the aquaretic effects of tolvaptan occurred in the setting of progression of malignant disease, with escalating plasma AVP concentrations which we postulate overwhelmed the drug at the V2 receptor. 67 The European guidelines specifically advised against the use of tolvaptan, because of concerns about overcorrection of hyponatraemia. 11 Overcorrection was reported in 1.8% of patients treated with tolvaptan in the SALT studies, 68 and no patient displayed symptoms of osmotic demyelination.…”

Section: Treatment Of Siadmentioning

confidence: 99%

The management of acute and chronic hyponatraemia

Lawless

Thompson

Garrahy

2022

Therapeutic Advances in Endocrinology

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Hyponatraemia is the most common electrolyte abnormality encountered in clinical practice; despite this, the work-up and management of hyponatraemia remain suboptimal and varies among different specialist groups. The majority of data comparing hyponatraemia treatments have been observational, up until recently. The past two years have seen the publication of several randomised control trials investigating hyponatraemia treatments, both for chronic and acute hyponatraemia. In this article, we aim to provide a background to the physiology, cause and impact of hyponatraemia and summarise the most recent data on treatments for acute and chronic hyponatraemia, highlighting their efficacy, tolerability and adverse effects.

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“…This reflects a sense that the doses of tolvaptan used in the early SALT studies may have been higher than needed for clinical effects and that better dosing studies are needed in SIAD ( Sterns 2018 a ). Although tolvaptan may be efficacious in reversing hyponatraemia associated with the SIAD of cancer, a loss of effect has been reported, associated with rising plasma AVP concentrations, as small cell lung cancer tumour mass progresses and cancer becomes more active ( Garrahy et al 2018 ). In the patients reported, escalating doses of tolvaptan were needed to maintain normonatreamia as plasma AVP concentrations increased, with eventual loss of drug effect.…”

Section: Treatment Of Said In Malignancymentioning

confidence: 99%

Hyponatraemia and the syndrome of inappropriate antidiuresis (SIAD) in cancer

2022

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Hyponatraemia is a common electrolyte abnormality seen in a wide range of oncological and haematological malignancies, and confers poorer performance status, prolonged hospital admission and reduced overall survival, in patients with cancer. Syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia in malignancy, and is characterised by clinical euvolaemia, low plasma osmolality, and concentrated urine, with normal renal, adrenal and thyroid function. Causes of SIAD include ectopic production of vasopressin (AVP) from an underlying tumour, cancer treatments, nausea and pain. Cortisol deficiency is an important differential in the assessment of hyponatraemia, as it has an identical biochemical pattern to SIAD, and is easily treatable. This is particularly relevant with the increasing use of immune checkpoint inhibitors, which can cause hypophysitis and adrenalitis, leading to cortisol deficiency. Guidelines on the management of acute, symptomatic hyponatraemia recommend 100ml bolus of 3% saline with careful monitoring of the serum sodium to prevent overcorrection. In cases of chronic hyponatraemia, fluid restriction is recommended as first line treatment, however this is frequently not feasible in patients with cancer and has been shown to have limited efficacy. Vasopressin-2 receptor antagonists (vaptans), may be preferable, as they effectively increase sodium levels in SIAD and do not require fluid restriction. Active management of hyponatraemia is increasingly recognised as an important component of oncological management; correction of hyponatraemia is associated with shorter hospital stay and prolonged survival. The awareness of the impact of hyponatraemia, and the positive benefits of active restoration of normonatraemia, remain challenging in oncology.

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Secondary resistance to tolvaptan in two patients with SIAD due to small cell lung cancer

Cited by 7 publications

References 3 publications

Tolvaptan for the treatment of the syndrome of inappropriate antidiuresis (SIAD)

Tolvaptan for the treatment of the syndrome of inappropriate antidiuresis (SIAD)

The management of acute and chronic hyponatraemia

Hyponatraemia and the syndrome of inappropriate antidiuresis (SIAD) in cancer

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