Unpredictable Nature of Tolvaptan in Treatment of Hypervolemic Hyponatremia: Case Review on Role of Vaptans

Malhotra, Ishan; Gopinath, Shilpa; Janga, Kalyana; Greenberg, Sheldon; Sharma, Shree Krishna; Tarkovsky, Regina

doi:10.1155/2014/807054

Cited by 30 publications

(29 citation statements)

References 12 publications

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“…Only two of those cases have been published (S.A.A. Harb and C. Alraies, unpublished data) (73). However, some other factors could have contributed to PNa overcorrection in the published cases.…”

Section: Vasopressin Receptor Antagonists (Vaptans)mentioning

confidence: 94%

Mild Chronic Hyponatremia in the Ambulatory Setting

Rondon‐Berrios

Berl

2015

Clinical Journal of the American Society of Nephrology

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Mild chronic hyponatremia, as defined by a persistent (>72 hours) plasma sodium concentration between 125 and 135 mEq/L without apparent symptoms, is common in ambulatory patients and generally perceived as being inconsequential. The association between increased mortality and hyponatremia in hospitalized patients in various settings and etiologies is widely recognized. This review analyzes the significance of mild chronic hyponatremia in ambulatory subjects and its effects on mortality and morbidity. It addresses whether this disorder should even be treated and if so, which patients are likely to benefit from treatment. The available approaches to correct hyponatremia in such patients in the context of recently published panel-generated recommendations and guidelines are described.

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Section: Vasopressin Receptor Antagonists (Vaptans)mentioning

confidence: 94%

Mild Chronic Hyponatremia in the Ambulatory Setting

Rondon‐Berrios

Berl

2015

Clinical Journal of the American Society of Nephrology

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“…Man beachte, dass auch im Kontrollarm einer Metaanalyse zu Vaptanen [6] Auch unter Tolvaptan-Monotherapie, insbesondere bei nicht bestimmungsgemäßem Gebrauch, kann es aufgrund seiner aquaretischen Potenz im Rahmen einer überschnellen Korrektur zu einem ODS kommen. Dies wird an einem "gut" dokumentierten ODS-Fall nach extremer Fehlbehandlung mit Tolvaptan deutlich [18]. Trotz täglicher Dokumentation der Natriumwerte und der in diesem Fall erheblichen Ausfuhr wurde mit zunehmendem Natriumanstieg die Tolvaptan-Therapie nicht abgesetzt oder reduziert, sondern sogar grob fehlerhaft gesteigert, was schließlich eine schwere Hypernatriämie und ein ODS zur Folge hatte [18].…”

Section: Osmotisches Demyelinisationssyndromunclassified

“…Dies wird an einem "gut" dokumentierten ODS-Fall nach extremer Fehlbehandlung mit Tolvaptan deutlich [18]. Trotz täglicher Dokumentation der Natriumwerte und der in diesem Fall erheblichen Ausfuhr wurde mit zunehmendem Natriumanstieg die Tolvaptan-Therapie nicht abgesetzt oder reduziert, sondern sogar grob fehlerhaft gesteigert, was schließlich eine schwere Hypernatriämie und ein ODS zur Folge hatte [18].…”

Section: Osmotisches Demyelinisationssyndromunclassified

Hyponatriämie und Tolvaptan

Hensen

2015

Internist

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The diuretic tolvaptan has been approved for more than 5 years for the indications of euvolemic hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH) secretion. In recent years many patients have been treated with tolvaptan and many physicians could gather practical experience. Other countries, such as the USA had already gained greater experience, also in the indications for hypervolemic hyponatremia. After approval was granted more than 5000 patients worldwide were included in the so-called hyponatremia register and 22 active centers in Germany with 317 patients participated. Although some details from this now concluded register have been published, the final publication of the multinational post-authorization safety study on tolvaptan in the treatment of SIADH has not yet been published. In the years 2012 and 2013 two warning letters were issued on tolvaptan. The first letter warned of the risk of a faster increase in serum sodium using tolvaptan and provided detailed information on how the risk of osmotic demeyelination can be minimized. So far only one proven case of osmotic demelination syndrome (ODS) is known; however, this occurred following incorrect use of tolvaptan in a monotherapy. The second warning letter provided information on the potential risk (reversible) of liver damage by tolvaptan, which resulted from the TEMPO 3:4 study. In this study tolvaptan was used in a higher dosage for therapy of autosomal dominant polycystic kidney disease. Although the European renal best practice (ERBP) guidelines from 2014 did not recommend tolvaptan for the indications of SIADH, other guidelines came to different conclusions. In summary, 5 years after the approval of tolvaptan there is still no consensus. At the current time many questions still remain unanswered. Initiation of therapy with tolvaptan remains reserved for experienced physicians in hospitals. Treatment must be adapted on the basis of a clinical estimation of the individual situation of each patient.

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“…11,12 However, so far only one case of human ODS has been published in which the use of vaptans unfortunately led to an excessive correction gradient (66 mEq/l over 72 h) along with hyperosmolarity. 13 Another option for the treatment of hyponatremia is urea, and our team has reported that urea is effective in correcting euvolemic and even hypervolemic hyponatremia. 14,15 Interestingly, urea, through an unclear mechanism, acts as a cryoprotectant and an osmoprotectant in amphibians.…”

mentioning

confidence: 99%

Urea minimizes brain complications following rapid correction of chronic hyponatremia compared with vasopressin antagonist or hypertonic saline

Kengne

Couturier

Soupart

et al. 2015

Kidney International

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Hyponatremia is a common electrolyte disorder that carries significant morbidity and mortality. However, severe chronic hyponatremia should not be corrected rapidly to avoid brain demyelination. Vasopressin receptor antagonists (vaptans) are now being widely used for the treatment of hyponatremia along with other alternatives like hypertonic saline. Previous reports have suggested that, in some cases, urea can also be used to correct hyponatremia. Correction of severe hyponatremia with urea has never been compared to treatment with a vaptan or hypertonic saline with regard to the risk of brain complications in the event of a too rapid rise in serum sodium. Here, we compared the neurological outcome of hyponatremic rats corrected rapidly with urea, lixivaptan, and hypertonic saline. Despite similar increase in serum sodium obtained by the three drugs, treatment with lixivaptan or hypertonic saline resulted in a higher mortality than treatment with urea. Histological analysis showed that treatment with urea resulted in less pathological change of experimental osmotic demyelination than was induced by hypertonic saline or lixivaptan. This included breakdown of the blood-brain barrier, microglial activation, astrocyte demise, and demyelination. Thus, overcorrection of hyponatremia with urea resulted in significantly lower mortality and neurological impairment than the overcorrection caused by lixivaptan or hypertonic saline.

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Unpredictable Nature of Tolvaptan in Treatment of Hypervolemic Hyponatremia: Case Review on Role of Vaptans

Cited by 30 publications

References 12 publications

Mild Chronic Hyponatremia in the Ambulatory Setting

Mild Chronic Hyponatremia in the Ambulatory Setting

Hyponatriämie und Tolvaptan

Urea minimizes brain complications following rapid correction of chronic hyponatremia compared with vasopressin antagonist or hypertonic saline

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