From the Guidelines
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should be managed with fluid restriction as the first-line treatment, and for severe cases, hypertonic saline may be administered with careful monitoring to avoid rapid correction, as recommended by recent guidelines 1. The management of SIADH involves treating the underlying cause while addressing fluid and sodium imbalances.
- Fluid restriction to less than 1 L/day is recommended for asymptomatic mild SIADH and as an adjunct to other therapy for severe cases, as stated in the American College of Chest Physicians evidence-based clinical practice guidelines 1.
- For symptomatic or severe hyponatremia (sodium <120 mEq/L), 3% hypertonic saline may be administered at 1-2 mL/kg/hr with careful monitoring to avoid rapid correction, as suggested by expert opinion 1.
- Pharmacologic options include demeclocycline, lithium, and vasopressin 2 receptor antagonists (conivaptan, lixivaptan, tolvaptan, and satavaptan) to correct hyponatremia, as mentioned in the guidelines 1. The underlying pathophysiology involves inappropriate ADH secretion despite normal or low serum osmolality, which increases water reabsorption in the kidneys, diluting serum sodium, as explained in the study published in the Journal of the National Comprehensive Cancer Network 1. Regular monitoring of serum sodium, osmolality, and urine output is essential during treatment to ensure safe correction rates and prevent complications, such as osmotic demyelination syndrome, as highlighted in the guidelines 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)
Tolvaptan is indicated for the treatment of SIADH. The drug label states that tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including patients with SIADH 2.
- Key points:
- Tolvaptan is used to treat SIADH.
- The treatment should be initiated and re-initiated in a hospital where serum sodium can be monitored closely.
- The dose of tolvaptan can be increased at 24-hour intervals to 30 mg once daily, then to 60 mg once daily, until either the maximum dose of 60 mg or normonatremia (serum sodium >135 mEq/L) is reached 2.
- Tolvaptan has been shown to cause a statistically greater increase in serum sodium compared to placebo in patients with SIADH 2.
From the Research
Definition and Diagnosis of SIADH
- The syndrome of inappropriate antidiuretic hormone secretion (SIADH) accounts for approximately one-third of all cases of hyponatremia, which is the most frequent electrolyte disorder 3.
- In the diagnosis of SIADH, it is essential to ascertain the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements 3.
Treatment of SIADH
- Therapeutic modalities for SIADH include nonspecific measures such as fluid restriction, hypertonic saline, urea, and demeclocycline, as well as specific treatments like vasopressin receptor antagonists (vaptans) 3.
- Vaptans, such as tolvaptan, have been introduced as a direct therapy for SIADH, offering advantages like no need for fluid restriction and rapid correction of hyponatremia 3, 4, 5, 6, 7.
- Low-dose tolvaptan (3.75-7.5mg) has been shown to effectively increase serum sodium in SIADH-associated hyponatremia, with a recommended starting dose of 7.5mg or 3.75mg in high-risk patients 4.
- Long-term low-dose tolvaptan therapy has been found to be safe and effective in SIADH treatment, with no cases of overcorrection or osmotic demyelination syndrome reported 6.
Safety and Efficacy of Tolvaptan
- Tolvaptan has been associated with mild side effects such as thirst, polydipsia, and frequency of urination 3, 6, 7.
- The risk of overcorrection and osmotic demyelination syndrome can be minimized by limiting the daily increase of serum sodium to less than 8-10 mmol/liter and monitoring sodium levels closely 3, 4, 6.
- Tolvaptan has been shown to improve hyponatremia in patients with SIADH, with significant positive treatment effects on physical and mental components of the SF-12 Health Survey 7.