Tolvaptan

Red

Brand Name(s):Jinarc

Indication:Autosomal dominant polycystic kidney disease (ADPKD)

Rationale:1,2,3

Considered:Jun-15

Review Date:Nov-20

Comments:
MHRA Drug Safety Update
Drug-induced liver injury has been observed in clinical trials investigating potential use in patients with autosomal dominant polycystic kidney disease (ADPKD, an unlicensed indication) at higher doses than those for the approved indication and in long-term use.

Liver-function tests should be done in patients taking tolvaptan who report signs or symptoms that suggest liver injury. Treatment with tolvaptan should be stopped during investigations into the probable cause of liver injury and patients treated with alternative appropriate treatment
Advice for healthcare professionals:
Tolvaptan is licensed only for the treatment of adults with hyponatraemia secondary to inappropriate antidiuretic hormone secretion (SIADH) at a dose of 15 to 60 mg once a day
Patients taking tolvaptan who report symptoms that may indicate liver injury should receive prompt liver-function testing. These symptoms include fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice
Patients with liver enzyme abnormalities (such as elevations of ALT, AST, or bilirubin) should be investigated to exclude significant hepatotoxicity

Prescribers should stop tolvaptan treatment in patients if liver injury is suspected and use alternative appropriate treatment. Tolvaptan should not be restarted in patients, unless the cause of the observed liver injury is definitively established to be unrelated to tolvaptan treatment
Suspected hepatic adverse drug reactions to tolvaptan should be reported to us on a Yellow Card
Volume 6, Issue 10 May 2013
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MHRA Drug Safety Update
Tolvaptan (Samsca): over-rapid increase in serum sodium and risk of serious neurological events

Summary
Treatment with tolvaptan (Samsca) can result in over-rapid correction of hyponatraemia, which can lead to serious neurological events. Careful monitoring of serum sodium is therefore important and co-administration of other drugs that may increase serum sodium is not recommended.

Tolvaptan may also reduce the effect of vasopressin analogues used to control or prevent bleeding.

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 to 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 Volume 5, Issue 9 April 2012 ..............................