其 他 安 全 警 示
|
| |
| The United Kingdom: Dimethyl fumarate (Tecfidera): updated advice on the risk of progressive multifocal leukoencephalopathy (PML) associated with mild lymphopenia (English only) |
| |
Medicines and Healthcare products Regulatory Agency (MHRA) announces a small number of reports of progressive multifocal leukoencephalopathy (PML) in patients with mild lymphopenia treated with dimethyl fumarate.
A recent European review of safety data identified 11 cases of PML with lymphopenia associated with Tecfidera treatment, including 3 cases in patients with mild lymphopenia (lymphocyte counts defined as lymphocyte counts between 0.8x10⁹ per litre and the lower limit of normal [per local laboratory]). These reports were received within an estimated exposure to Tecfidera of more than 475,000 patients.
The risk of PML in patients with mild lymphopenia has been added to the product information (summary of product characteristics), alongside a new contraindication for suspected or confirmed PML.
MHRA has not received any United Kingdom reports via the Yellow Card scheme of confirmed PML cases associated with Tecfidera.
Lymphocyte counts should be checked before starting Tecfidera and continue to be monitored routinely every 3 months during treatment. Lymphocyte counts and neurological symptoms should be monitored more closely in patients with lymphopenia. Prescribers should be aware that the following factors may further increase the risk of PML in individuals with lymphopenia: duration of treatment – PML has been diagnosed after approximately 1–5 years of Tecfidera treatment; previous immunosuppressive or immunomodulatory treatment; marked reductions in CD4+ and CD8+ T cell counts. Magnetic resonance imaging (MRI) may be considered as part of increased vigilance for patients considered at increased risk of PML in accordance with local recommendations.
Physicians should continue to re-assess the balance of benefits and risks of Tecfidera treatment in patients with sustained moderate lymphopenia (defined as lymphocyte counts between 0.5x10⁹ per L and 0.8x10⁹ per L) for longer than 6 months. Patients who have recently stopped natalizumab (Tysabri) may develop PML in the absence of lymphopenia. Healthcare professionals should continue to monitor patients on dimethyl fumarate for any signs of neurological dysfunction. In any patient developing signs or symptoms suggestive of PML, dimethyl fumarate treatment should be stopped immediately and appropriate investigations conducted, including testing for John Cunningham virus (JCV) DNA in the cerebrospinal fluid using a quantitative polymerase chain reaction assay.
Advice for healthcare professionals:
- A small number of patients receiving dimethyl fumarate (Tecfidera) for the treatment of multiple sclerosis have developed PML associated with mild lymphopenia (defined as lymphocyte counts between 0.8x10⁹ per litre and the lower limit of normal [per local laboratory]); until now, other reported cases of PML were reported in patients with moderate to severe lymphopenia.
- Tecfidera is contraindicated in patients with suspected or confirmed PML.
- Before starting treatment: do not start treatment in patients with severe lymphopenia (lymphocyte count of less than 0.5x10⁹ per litre); investigate patients with low lymphocyte counts for underlying causes of this before initiation.
- During treatment: all patients should have a lymphocyte count at least every 3 months; conduct enhanced vigilance with close monitoring of lymphocyte counts and neurological symptoms in patients with lymphopenia and consider additional factors that may increase the risk of PML; revaluate treatment in patients who have sustained moderate reductions of absolute lymphocyte counts (between 0.5x10⁹ per litre and 0.8x10⁹ per litre) for longer than 6 months; stop treatment in patients who have prolonged severe lymphopenia for longer than 6 months; Tecfidera must be permanently discontinued in any patient developing PML.
Please refer to the following website in MHRA for details:
http://www.gov.uk/drug-safety-update/dimethyl-fumarate-tecfidera-updated-advice-on-the-risk-of-progressive-multifocal-leukoencephalopathy-pml-associated-with-mild-lymphopenia
In Hong Kong, Tecfidera Gastro-Resistant Capsules 240mg (HK-64410) and Tecfidera Gastro-Resistant Capsules 120mg (HK-64411) are registered pharmaceutical products containing dimethyl fumarate. Both products are registered by Eisai (Hong Kong) Co Ltd, and are prescription-only medicines. So far, the Department of Health (DH) has not received any case of adverse drug reaction related to dimethyl fumarate.
Related news on the risk of progressive multifocal leukoencephalopathy associated with the use of dimethyl fumarate was previously issued by various overseas drug regulatory authorities, and was was posted on the Drug Office website since 26 Nov 2014, with the latest update posted on 19 Apr 2016. Letters to inform local healthcare professionals were issued by the DH on 19 Apr 2016.
The current package insert of the above registered products in Hong Kong include safety information on progressive multifocal leukoencephalopathy.
Related news on cases of progressive multifocal leukoencephalopathy in patients with mild lymphopenia and updated recommendations to help minimise the risk was previously issued by Taiwan Food and Drug Administration, and was posted on the Drug Office website on 31 Dec 2020. Letters to inform local healthcare professionals were issued by the DH on the same date. 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
|
| |
|
