What is the treatment for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

From the Guidelines

The treatment for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should prioritize addressing the underlying cause while managing hyponatremia, with first-line treatment including fluid restriction to 800-1000 mL/day and consideration of pharmacological options like vasopressin receptor antagonists (vaptans) such as tolvaptan. The management of SIADH involves a multifaceted approach, focusing on correcting the hyponatremia and addressing the underlying cause, which could be malignancy, medications, CNS disorders, or pulmonary disease 1. Key considerations in the treatment of SIADH include:

• Fluid restriction to less than 1 L/day as a first-line measure to reduce free water intake and correct sodium levels.
• For acute, severe, or symptomatic hyponatremia, the use of hypertonic (3%) saline intravenously, with careful monitoring to avoid rapid correction and prevent osmotic demyelination syndrome, ensuring the correction rate does not exceed 8-10 mEq/L in 24 hours 1.
• Pharmacological options such as oral salt tablets, loop diuretics like furosemide, and vasopressin receptor antagonists (vaptans) like tolvaptan, which can be effective in blocking ADH action at the kidney and improving serum sodium levels 1.
• Regular monitoring of serum sodium, fluid status, and neurological signs is crucial, with careful control of sodium correction rates to prevent complications. Given the potential side effects and the need for careful monitoring, the choice of treatment should be individualized, considering the severity of hyponatremia, the presence of symptoms, and the underlying cause of SIADH 1. In the context of real-life clinical practice, prioritizing the most recent and highest quality evidence, the use of tolvaptan, starting at 15 mg daily, is supported for the management of SIADH, especially in cases where fluid restriction is not sufficient or feasible 1.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

El tratamiento para el Síndrome de Secreción Inapropiada de Hormona Antidiurética (SIADH) es tolvaptan, que se administra por vía oral.

• La dosis inicial recomendada es de 15 mg una vez al día.
• La dosis puede aumentarse a 30 mg una vez al día, después de al menos 24 horas, hasta un máximo de 60 mg una vez al día, según sea necesario para alcanzar el nivel deseado de sodio sérico.
• Es importante monitorear estrechamente el sodio sérico y el estado de volumen durante la iniciación y la titulación de la dosis.
• Se debe evitar la restricción de líquidos durante las primeras 24 horas de terapia para evitar una corrección demasiado rápida de la hiponatremia. 2

From the Research

Treatment Options for SIADH

The treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) aims to correct hyponatremia and alleviate symptoms. The following are some treatment options:

• Fluid restriction: This is a common treatment approach, especially for patients with mild to moderate hyponatremia 3, 4.
• Hypertonic saline: This is used to treat severe hyponatremia, especially in patients with acute symptoms 3, 4.
• Urea: Oral urea is considered an effective and safe treatment for SIADH, especially for patients who do not respond to fluid restriction 4.
• Demeclocycline: This is sometimes used to treat SIADH, but its efficacy is based solely on laboratory endpoints, and it has adverse effects shared by all tetracyclines 5.
• Vasopressin receptor antagonists (vaptans): These include conivaptan and tolvaptan, which have been shown to be effective in treating hyponatremia in SIADH patients 3, 4, 6.

Considerations for Treatment

When treating SIADH, it is essential to:

• Limit the daily increase of serum sodium to less than 8-10 mmol/liter to avoid osmotic demyelination 3.
• Monitor serum sodium levels closely, especially during the first 24 hours of treatment with vaptans 3.
• Be aware of the potential for hyponatremic relapse after discontinuation of vaptan therapy 3.
• Consider the risk of pharmacokinetic interactions with vaptans, especially with drugs metabolized by cytochrome P450 isoenzyme CYP 3A4 5.

Emerging Therapies

New therapies, such as vasopressin-receptor antagonists, are being developed to treat SIADH-induced hyponatremia 7. These therapies aim to provide a more effective method to treat hyponatremia by selectively increasing solute-free water excretion by the kidneys (aquaresis).