Tolvaptan (Samsca▼): over-rapid increase in serum sodium risking serious neurological events
- Medicines and Healthcare products Regulatory Agency
- 20 April 2012
- Therapeutic area:
- Endocrinology, diabetology and metabolism
Careful monitoring of serum sodium important, co-administration of other drugs that may increase serum sodium not recommended.
Article date: April 2012
Tolvaptan (Samsca▼) is a selective vasopressin V2-receptor antagonist. It has been licensed in the UK since 2009 for the treatment of adults with hyponatraemia secondary to inappropriate antidiuretic hormone secretion (SIADH) at a dose of 15–60 mg once a day.
Risk of over-rapid increase in serum sodium
Tolvaptan achieves its therapeutic effect by increasing free water clearance without affecting sodium excretion, thereby raising serum sodium. However, there have been reports of serious neurological events (see below: advice for healthcare professionals) in patients treated with tolvaptan where the correction of serum sodium has exceeded the suggested rate. Further information on the rates at which serum sodium should increase is also set out in the advice for healthcare professionals.
Serum sodium should be closely monitored in patients receiving tolvaptan, especially those with very low serum sodium (<120 mmol/L) at baseline or where there is increased risk of demyelination syndromes (eg, hypoxia, alcoholism, or malnutrition).
Product information for tolvaptan has been updated to reflect the new advice.
Interaction with high sodium content medicines or other treatments for hyponatraemia
There is also a risk of a rapid rise in serum sodium when tolvaptan is given concomitantly with medicines with a high sodium content or with other treatments for hyponatraemia (for example normal or hypertonic saline). Treatment with such combinations is therefore not recommended.
Interaction with vasopressin analogues
In addition to its effect on the renal tubule, tolvaptan can block vasopressin V2-receptors involved in the release of coagulation factors (eg, von Willebrand factor). Therefore, tolvaptan may interact with vasopressin analogues such as desmopressin used to prevent or control bleeding, reducing their effect.
Advice for healthcare professionals:
- increases in serum sodium which are too rapid can be harmful and cause osmotic demyelination, resulting in dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, or death
- close monitoring of serum sodium during tolvaptan treatment is recommended, especially in patients with very low serum sodium (<120 mmol/L) at baseline or in those at high risk of demyelination syndromes—for example, those with hypoxia, alcoholism, or malnutrition
- sodium correction that exceeds 6 mmol/L during the first 6 hours of administration or 8 mmol/L during the first 6–12 hours may be too rapid; in such patients close monitoring of serum sodium and administration of hypotonic fluid is recommended
- if the increase in serum sodium exceeds 12 mmol/L in 24 hours, or 18 mmol/L in 48 hours tolvaptan treatment should be interrupted or discontinued and followed by administration of hypotonic fluid
- co-administration of tolvaptan with medicines with a high sodium content or with other treatments for hyponatraemia (for example normal or hypertonic saline) is not recommended
- the effect of vasopressin analogues such as desmopressin may be attenuated in patients using them to prevent or control bleeding when given with tolvaptan
BNF section 6.5.2 Tolvaptan
Article citation: Drug Safety Update April 2012, vol 5 issue 9: A3.
Published: 20 April 2012
Therapeutic area: Endocrinology, diabetology and metabolism