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| The United Kingdom: Cladribine (Mavenclad): New advice to minimise risk of serious liver injury (English only) |
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Medicines and Healthcare products Regulatory Agency (MHRA) announces that liver monitoring requirements for cladribine in the treatment of multiple sclerosis have been introduced following uncommon cases of serious liver injury.
A recent European review of safety data has identified 16 cases of liver injury post-marketing, including serious cases requiring discontinuation and one fatal case of hepatic failure in a patient with alcohol-related liver disease and who was undergoing tuberculosis treatment with isoniazid. Within the cases of liver injury reviewed, there were rare reports of jaundice and serum transaminase levels greater than 1000 IU/L. However, the majority of cases had mild clinical symptoms.
A small number of cases of liver injury have also been seen in clinical trials. In some of these cases, patients developed significantly increased serum transaminase levels related to treatment. These serious events resolved within 4 months after cladribine was discontinued (in the cases reporting a final outcome). Alternative causes were excluded in one patient, and none required a liver biopsy. Data from clinical trials did not suggest a dose-dependent effect.
Time to onset of liver injury varied, with most cases occurring within 8 weeks after start of the first treatment course. Some patients had underlying hepatic disorders or a history of hepatic injury related to other medicines. A causal mechanism has not been identified.
The product information and the educational materials will be revised to include updated advice for healthcare professionals and patients on the risk of serious liver injury. Liver injury will be included as an adverse drug reaction of uncommon frequency (may affect up to 1 in 100 patients).
In the United Kingdom, up to 25 Jan 2022, MHRA has received 2 reports of hepatic injury in patients receiving cladribine for multiple sclerosis via the Yellow Card scheme. Both patients developed liver injury within a month of starting cladribine treatment and in one case the alanine aminotransferase (ALT) level exceeded 1000 IU/L.
Cladribine is also available in other medicines. Leustat injection and Litak 2mg/ml solution for injection are authorised to treat patients with hairy cell leukaemia and Leustat injection is also approved for the treatment of B-cell chronic lymphocytic leukaemia. Prescribers of these medicines should continue to follow the current recommendations on patient monitoring.
Advice for healthcare professionals:
- A small number of cases of clinically significant liver injury have been reported during cladribine treatment for multiple sclerosis.
- Most events occurred within 8 weeks of the start of the first treatment course of cladribine.
- Before starting cladribine check if there is a history of liver disorders, including hepatic injury related to other medicines.
- Monitor liver function tests (including total bilirubin) before each treatment course in years 1 and 2; and, if clinically necessary, during treatment.
- Urgently check liver function tests (including bilirubin) in patients with symptoms or signs of liver injury.
- Discontinue or interrupt cladribine treatment in patients with hepatic dysfunction or unexplained increases in liver enzymes.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/cladribine-mavenclad-new-advice-to-minimise-risk-of-serious-liver-injury
In Hong Kong, there is one registered pharmaceutical product containing cladribine, namely Mavenclad Tablets 10mg (HK-65910). The product is registered by Merck Pharmaceutical (HK) Limited. It is a prescription-only medicine. So far, the Department of Health (DH) has not received any case of adverse drug reaction related to cladribine. Related news was previously issued by European Medicines Agency and Singapore Health Sciences Authority, and was posted on the Drug Office website on 15 Jan 2022 and 19 Feb 2022. Letters to inform local healthcare professionals were issued by the DH on 15 Jan 2022. The matter will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/Wednesday, Mar 16, 2022
Issued at HKT 15:00
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