其 他 安 全 警 示
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| Canada: ZOLGENSMA (onasemnogene abeparvovec) and fatal cases of acute liver failure (English only) |
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Health Canada announces that two cases of fatal acute liver failure associated with ZOLGENSMA have recently been reported internationally. The deaths occurred 6-7 weeks post-ZOLGENSMA infusion, following the initiation of corticosteroid taper. No fatal cases of acute liver failure have been reported in Canada.
Hepatotoxicity (acute liver failure, acute liver injury and elevated liver aminotransferases) is an identified risk associated with ZOLGENSMA that is included in the Serious Warnings and Precautions Box, Warnings and Precautions, and Adverse Reactions (Post-Market Adverse Reactions) sections of the current Canadian Product Monograph. Recently, two fatal cases of acute liver failure have been reported internationally in patients who were at 4 and 28 months of age with spinal muscular atrophy (SMA) treated with ZOLGENSMA. Common clinical characteristics of the two fatal cases are summarized below:
- The first manifestation was asymptomatic elevation of liver aminotransferases within the first 1-2 weeks post-ZOLGENSMA infusion, which was treated with an increased prednisolone dose.
- The clinical presentation of hepatotoxicity included vomiting, weakness and a second elevation of liver aminotransferases, starting between 5 to 6 weeks post-ZOLGENSMA infusion, approximately 1-10 days following the initiation of prednisolone taper.
- Rapid deterioration in liver function, and progression to hepatic encephalopathy and multi-organ failure followed. Death occurred 6-7 weeks after ZOLGENSMA infusion.
To date, ZOLGENSMA has been used to treat more than 2,300 patients worldwide across clinical trials, managed access programs, and in the post-market setting. At this time, the benefits of ZOLGENSMA to treat SMA continues to outweigh the risks.
Healthcare professionals are advised to:
- Assess liver function by clinical examination and laboratory testing (AST and ALT, total bilirubin, prothrombin time, albumin, PTT, and INR) before ZOLGENSMA infusion. Continue to monitor liver function for at least 3 months after ZOLGENSMA infusion through to the end of the corticosteroid tapering period.
- Administer corticosteroid (oral prednisolone or equivalent) to all patients before and for 30 days after ZOLGENSMA infusion.
- Taper the corticosteroid dose gradually over 28 days, with careful monitoring, in patients with unremarkable liver function findings after the first 30 days. Do not stop systemic corticosteroids abruptly.
- Consider adjusting the corticosteroid treatment regimen, including longer duration, and/or increased dose, or more gradual taper to manage hepatotoxicity.
- Monitor any suspected hepatic injury closely, and consult a pediatric gastroenterologist or hepatologist if patients do not respond adequately to the equivalent of 1 mg/kg/day oral prednisolone and/or if acute serious liver injury and acute liver failure is suspected.
Health Canada is currently working with the manufacturer to update the Canadian Product Monograph, including the Serious Warnings and Precautions Box, to include fatal cases of acute liver failure and revise the guidance for monitoring liver function.
Please refer to the following website in Health Canada for details:
http://recalls-rappels.canada.ca/en/alert-recall/zolgensma-onasemnogene-abeparvovec-and-fatal-cases-acute-liver-failure
In Hong Kong, the above product is not a registered pharmaceutical product.
Ends/Tuesday, Sep 13, 2022
Issued at HKT 15:00
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