Review and analysis of differing regulatory indications and expert panel guidelines for the treatment of hyponatremia

Abstract

Introduction and objective:

As evidence grows about the management of hyponatremia, a number of different international and national recommendations/guidelines from professional organizations have recently been published that offer guidance on decision-making. However, they include several important differences that could confuse practising physicians. This article summarizes the key differences in guideline recommendations by various independent groups, taking the marketing authorizations granted by different regulatory agencies into account. It proposes a synthesis of implications for practising physicians as a practical method for resolving these differences as they relate to everyday clinical practice.

Methods:

The authors reviewed all recent guidelines and consensus documents worldwide to assess differences and similarities. They also reviewed licensed indications for therapeutic agents in hyponatremia.

Results:

The actual indications for the only pharmacological therapy approved across three continents for the treatment of hyponatremia—the vaptans—differ substantially around the world. The numerous treatment guidelines published to date also fail to achieve agreement on hyponatremia management. The possible reasons for these differences are explored in this paper. The authors emphasize the crucial role that clinical judgment must continue to play in decision-making about the management of hyponatremia in individual patients. Such judgments should take into account appropriate appraisals of evidence by authoritative experts in the field, as well as the decisions of regulatory agencies that have based their approvals on a critical review of the efficacy and safety data for approved treatments for hyponatremia.

Conclusion:

It is clinical judgment rather than guidelines that should dictate the ultimate choices physicians make for their patients, not only in hyponatremia, but in all aspects of medicine.

Keywords::

• Hyponatremia
• Tolvaptan
• Mozavaptan
• Conivaptan
• Syndrome of inappropriate anti-diuretic hormone secretion (SIADH)
• Sodium
• Guidelines

Transparency

Declaration of funding

This paper was commissioned by Otsuka Pharmaceutical Europe Ltd. and publication costs for this article were supported by the company. The authors have not received any honorarium in relation to this paper.

Declaration of financial/other relationships

Charlotte Höybye has been an investigator for Otsuka and has received lecture fees from Otsuka for lectures on hyponatremia. Ashley Grossman is on the Otsuka Speakers’ Bureau, and receives funds for research from Otsuka. Isabelle Runkle has received research funding from Otsuka and has been an advisor and speaker for Otsuka. She has also given talks for Novo Nordisk. Dr Verbalis has served as a consultant, Advisory Board and Speaker Bureau member, and has received both research grants and travel support from Otsuka Pharmaceuticals for development and educational programs related to the use of tolvaptan for treatment of hyponatremia. He has also served as a consultant and provided expert testimony on behalf of Cornerstone Pharmaceuticals related to their application to the FDA for approval of lixivaptan for the treatment of hyponatremia.

CMRO Peer Reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

The authors would like to thank Lorraine Law from apothecom for proofreading the manuscript, and Eman Zaman and James Williams from apothecom for their assistance in compiling the tables.