Other safety alerts
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| Canada: REVOLADE (eltrombopag) - Risk of Severe Hepatotoxicity |
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Health Canada reported that a recent review of all clinical trial and post-marketing cases identified five (5) cases fulfilling Hy’s law criteria (severe drug-induced liver injury).
REVOLADE (eltrombopag) tablets are indicated:
． For adult chronic immune thrombocytopenia purpura (cITP) to increase platelet counts in splenectomized patients who are refractory to first-line treatments (e.g. corticosteroids, immunoglobulins). REVOLADE may be considered as second line treatment for adult non-splenectomized patients where surgery is contraindicated,
． To increase platelet counts in thrombocytopenic patients with chronic hepatitis C virus (HCV) infection to allow the initiation and maintenance of interferon-based therapy, and
． For the treatment of adult patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy.
A systematic analysis of the different trials in the clinical database (across the entire REVOLADE development program) and the post-marketing safety database was conducted by Novartis Pharmaceuticals Canada Inc. to identify cases fulfilling Hy’s Law criteria for drug-induced liver injury.
Based on this review, two (2) cases fulfilling Hy’s law criteria were identified in adult cITP patients; three (3) further cases were identified in patients treated for other, non-approved indications. The elevation of laboratory values typically occurred within three (3) months of initiation; in all five (5) cases the event resolved following REVOLADE discontinuation. In clinical trials in patients with chronic HCV infection, 11 patients treated with REVOLADE (1%) experienced drug-induced liver injury.
The Canadian Product Monograph for REVOLADE has been updated to reflect the risk of severe hepatotoxicity (i.e., severe hepatotoxicity and potentially fatal liver injury) in the existing Hepatotoxicity section under the Warnings and Precautions and to add an adverse drug reaction to the Adverse Reactions section.
In addition, an upper limit on the extent of serum alanine aminotransferase (ALT) elevation in patients with elevated ALT at baseline was added, to prohibit continuation of REVOLADE in patients with pre-existing hepatic disease, and in line with discontinuation criteria in the pivotal trials conducted in the approved indications.
Healthcare professionals should measure serum ALT, aspartate aminotransferase (AST) and bilirubin prior to initiation of REVOLADE, every 2 weeks during the dose adjustment phase, and then monthly following establishment of a stable dose. Healthcare professionals should discontinue REVOLADE if ALT levels:
． increase greater than or equal to 3x upper limit of normal (ULN) in patients with normal liver function or;
． increase greater than or equal to 3x baseline or greater than 5x ULN, whichever is the lower, in patients with elevations in transaminases before treatment and that are:
- progressive, or
- persistent for greater than or equal to 4 weeks, or
- accompanied by increased direct bilirubin, or
- accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation.
Please refer to the following website in Health Canada for details:
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/../59916a-eng.php
In Hong Kong, there are 4 registered pharmaceutical products containing eltrombopag, namely Revolade Tab 25mg (HK-60349), Revolade Tab 50mg (HK-60350), Revolade Tablets 25mg (Spain) (HK-62055) and Revolade Tablets 50mg (Spain) (HK-62056), which are registered by Novartis Pharmaceuticals (HK) Limited, and are prescription only medicines. So far, the Department of Health (DH) has received one adverse drug reaction case in connection with eltrombopag but it is not related to severe hepatotoxicity. In view of Health Canada's announcement, letters to local healthcare professionals to draw their attention to the risk will be issued. The matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board and DH will remain vigilant on the safety updates on the products from other overseas drug regulatory authorities.
Ends/ Friday, August 26, 2016
Issued at HKT 15:30
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