Other safety alerts
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| The United Kingdom: Fingolimod (Gilenya▼): updated advice about the risks of serious liver injury and herpes meningoencephalitis |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that liver monitoring requirements and discontinuation criteria for fingolimod have been updated following reports of serious liver injury. Fatal cases of encephalitis and meningitis caused by herpes simplex and varicella zoster viruses have been reported during treatment.
A recent European review of safety data identified 7 cases of clinically significant liver injury that developed between 10 days and 5 years after the start of fingolimod treatment, including 3 post-marketing reports of acute hepatic failure requiring liver transplantation. Liver samples showed submassive hepatic necrosis in 2 patients, and one of these samples also contained features of acute hepatitis. MHRA has not received any United Kingdom reports via the Yellow Card scheme of acute hepatic failure or serious liver injury (defined as AST or ALT at 3-times ULN or higher with increased bilirubin or jaundice) considered causally related to fingolimod treatment. Due to the severity of recently reported cases, recommendations for liver monitoring and the discontinuation criteria have been strengthened to minimise the risks of liver injury.
Advice in the product information regarding the risks of herpes zoster/herpes simplex infections with fingolimod has also been updated following the review’s consideration of reported cases of infections with visceral or CNS dissemination, some of which were fatal. Remind patients to seek immediate medical attention if they have a fever or signs of infection (including influenza or shingles) or if they have symptoms of meningitis or encephalitis during fingolimod treatment and up to 2 months after the last dose.
The product information and the educational materials will be revised to include updated advice for healthcare professionals and patients on the risks of serious liver injury and of herpes meningoencephalitis and cryptococcal meningitis.
Advice for healthcare professionals:
- A small number of cases of clinically significant liver injury, including acute hepatic failure requiring transplantation, have been reported during fingolimod treatment.
- Monitor liver function tests (including bilirubin) routinely: before starting treatment; during treatment at months 1, 3, 6, 9 and 12; and then periodically until 2 months after discontinuation.
- In patients without signs and symptoms of liver injury, the updated advice is: monitor liver function tests more frequently if serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) levels exceed 3-times the upper limit of normal (ULN) but less than 5-times ULN with a normal bilirubin level; discontinue fingolimod if ALT or AST levels exceed 5-times ULN or if they are at least 3-times the ULN and bilirubin is increased – fingolimod may be re-started following a careful benefit-risk assessment of the underlying cause when serum levels have returned to normal.
- In patients with symptoms or signs of hepatic dysfunction: check liver function tests urgently; discontinue fingolimod if significant hepatic injury is confirmed; further treatment with fingolimod may be considered following recovery only if an alternative cause of hepatic dysfunction is established.
- Continue to be vigilant for infections with fingolimod; information has been updated to include herpes zoster/herpes simplex infections with visceral or CNS dissemination.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/fingolimod-gilenyav-updated-advice-about-the-risks-of-serious-liver-injury-and-herpes-meningoencephalitis
In Hong Kong, there are 3 registered pharmaceutical products containing fingolimod, namely Gilenya Hard Capsules 0.5mg (HK-61192) and Gilenya Hard Capsules 0.25mg (HK-66472) which are registered by Novartis Pharmaceuticals (HK) Limited; and Fingolimod Teva Capsules 0.5mg (HK-66882) which is registered by Teva Pharmaceutical Hong Kong. All products are prescription-only medicines. So far, the Department of Health (DH) has received 14 cases of adverse drug reaction related to fingolimod, but these cases are not related to liver injury and herpes meningoencephalitis.
Related news on the risk of infections (including central nervous system infections caused by herpes simplex and varicella zoster viruses) and liver injury (with strengthening of recommendations for liver monitoring and the discontinuation criteria) was previously issued by the MHRA and Taiwan Food and Drug Administration, and was posted on the Drug Office website on 19 Apr 2016 and 16 Dec 2020 respectively. Letters to inform local healthcare professionals were issued by DH on 19 Apr 2016 and 16 Dec 2020. In light of the above MHRA’s announcement, the matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/Friday, Jan 8, 2021
Issued at HKT 18:00
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