U.K. Regulator Warns of Tolvaptan Side Effects

A U.K. regulator just issued a warning over side effects linked to Tolvaptan. Side effects include serious neurological events.

Tolvaptan is a selective vasopressin V2-receptor antagonist used for the treatment of adults diagnosed with hyponatremia, secondary to inappropriate anti-diuretic hormone secretion (SIADH). Hyponatremia is a metabolic condition in which there insufficient sodium (salt) in the body’s fluids outside of the cells, explained the National Institutes of Health (NIH).

Tolvaptan has been licensed in the U.K. since 2009 at a dose of 15-60 mg daily for the approved condition.

The Medicines and Healthcare products Regulatory Agency (MHRA) warns that treatment with Tolvaptan (Samsca▼) can lead to an over-rapid correction of hyponatremia. This, in turn, can lead to serious neurological events. Careful monitoring of serum sodium critical; co-administration of other drugs that may increase serum sodium is not recommended.

Tolvaptan may also reduce the effect of vasopressin analogues, which are prescribed to control or prevent bleeding.

Tolvaptan increases free water clearance without affecting sodium excretion, which raises serum sodium; however, reports of serious neurological events have been seen in patients treated with Tolvaptan where the correction of serum sodium has exceeded the suggested rate. Because of this, serum sodium should be closely monitored in patients receiving Tolvaptan, especially in those patients with very low serum sodium (<120 mmol/L) at baseline or where there is increased risk of demyelination syndromes, such as with hypoxia, alcoholism, or malnutrition.

According to the MHRA, product information for Tolvaptan has been updated to reflect the new advice.

There is also a risk of a rapid rise in serum sodium when Tolvaptan is received along with (concomitantly) with medicines that contain a high sodium content or with other treatments for hyponatraemiam, such as normal or hypertonic saline. Because of this, treatment with these combinations is not recommended.

In addition to its effect on the renal tubule, Tolvaptan can block vasopressin V2-receptors involved in the release of coagulation factors (e.g., von Willebrand factor); Tolvaptan may interact with vasopressin analogues such as desmopressin, which is used to prevent or control bleeding. Tolvaptan may reduce the effect of these vasopressin analogues.