From the FDA Drug Label
In patients with hyponatremia (defined as <135 mEq/L), serum sodium concentration increased to a significantly greater degree in tolvaptan-treated patients compared to placebo-treated patients as early as 8 hours after the first dose, and the change was maintained for 30 days The primary endpoint for these studies was the average daily AUC for change in serum sodium from baseline to Day 4 and baseline to Day 30 in patients with a serum sodium less than 135 mEq/L. Patients were randomized to receive either placebo (N = 220) or tolvaptan (N = 223) at an initial oral dose of 15 mg once daily. For patients with a serum sodium of <130 mEq/L or <125 mEq/L, the effects at Day 4 and Day 30 remained significant
The patient has a sodium level of 121 mmol/L, which is less than 135 mEq/L and also less than 130 mEq/L and 125 mEq/L.
- Tolvaptan can be used to treat hyponatremia in this patient.
- The initial dose of tolvaptan is 15 mg once daily.
- 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 1.
- Fluid restriction should be avoided if possible during the first 24 hours of therapy to avoid overly rapid correction of serum sodium.
- The patient is on Lisinopril and cortisone for adrenal insufficiency, but there is no direct interaction between these medications and tolvaptan mentioned in the provided drug labels.
- However, patients with uncontrolled adrenal insufficiency were excluded from the studies, so it is essential to ensure that the patient's adrenal insufficiency is well-controlled before starting tolvaptan.
From the Research
To treat hyponatremia in a patient on Lisinopril and cortisone with a sodium level of 121 mmol/L, I recommend first evaluating the patient's volume status and reducing the Lisinopril dose, as ACE inhibitors can contribute to hyponatremia, and then consider administering 3% hypertonic saline if the patient is symptomatic, aiming for a sodium correction rate of 4-6 mmol/L in the first 24 hours to avoid osmotic demyelination syndrome, as suggested by the most recent guidelines 2.
When managing hyponatremia, it is crucial to categorize patients according to their fluid volume status (hypovolemic, euvolemic, or hypervolemic) and treat the underlying cause, as emphasized in a review on the diagnosis and management of hyponatremia 3. For patients with severe hyponatremia (Na <125 mmol/L), particularly those who are symptomatic, the use of hypertonic saline is recommended to rapidly correct the sodium level and prevent neurological complications, with the goal of increasing the serum sodium level by 4-6 mEq/L within the first 24 hours, but not exceeding a correction limit of 10 mEq/L within the first 24 hours, as highlighted in a study on hypertonic saline for hyponatremia 4.
Key considerations in the management of hyponatremia include:
- Evaluating the patient's volume status to guide treatment decisions
- Reducing or discontinuing medications that may contribute to hyponatremia, such as ACE inhibitors
- Implementing fluid restriction, particularly in euvolemic patients
- Using hypertonic saline for severe, symptomatic hyponatremia
- Optimizing cortisone replacement therapy in patients with adrenal insufficiency to prevent worsening of hyponatremia
- Monitoring serum sodium levels closely during correction to avoid overly rapid correction and the risk of osmotic demyelination syndrome, as noted in guidelines on the treatment of hyponatremia 2, 5.
The use of vasopressin receptor antagonists may also be considered in certain cases of euvolemic or hypervolemic hyponatremia, as discussed in a commentary on the use of these agents 6. However, the primary approach should focus on addressing the underlying cause of hyponatremia, managing fluid balance, and carefully correcting the sodium level to improve patient outcomes.