其他安全警示

Singapore: Valproate-containing medicines and risk of teratogenicity – An update (English Only)

Health Sciences Authority (HSA) announces an update on valproate-containing medicines and risk of teratogenicity. Valproate is a known teratogen that has been associated with congenital malformations and developmental disorders in children born to women taking the medicine during pregnancy. Clinical studies have suggested an increased incidence of congenital malformations in children born to epileptic women exposed to valproate monotherapy during pregnancy as compared to the general population, and up to 30% to 40% of in utero exposed children experienced neurodevelopmental disorders such as delayed locomotor skills, lower intellectual capacities, poor language abilities and impaired memory.

HSA has not received any local cases of adverse events associated with the exposure of valproate during pregnancy. Several risk mitigation measures have been put in place locally to manage the teratogenic risks of valproate so as to ensure the continued positive benefit-risk balance of valproate-containing medicines. These measures include the strengthening of the Singapore package inserts for Epilim® by including warnings and precautions regarding the risk of teratogenicity and that valproate should not be used during pregnancy and in women of childbearing potential (WOCP) unless other treatment options are ineffective or intolerable. Two Dear Healthcare Professional Letters have also been issued by the product registrant (sanofi aventis Singapore) in Feb 2016 and Mar 2018 respectively, to remind healthcare professionals of the teratogenic potential of valproate. Physician educational materials and a pocket-sized Patient Alert Card were also developed as educational tools to counsel patients about the potential risks to the unborn child as a result of in utero valproate exposure and the need to use effective contraception during treatment.

Healthcare professionals are advised to discuss the benefits versus the risks of valproate with their patients, including the importance for WOCP to use effective and reliable contraception while taking valproate. Healthcare professionals are encouraged to submit any suspected congenital abnormalities associated with in utero exposure of valproate to the Vigilance and Compliance Branch of HSA.

Please refer to the following website in HSA for details: http://www.hsa.gov.sg/content/hsa/../valproate-containingmedicinesandriskofteratogenicityanupdate.html

In Hong Kong, there are 11 registered pharmaceutical products containing valproic acid and/or valproate, and all products are prescription-only medicines. So far, the Department of Health (DH) has received 9 cases of adverse drug reaction related to valproic acid or valproate, but these cases are not related to adverse effects in new-born babies whose mothers took valproate for their medical conditions.

Related news on the recent review of valproate was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 13 Mar 2017, with the latest update posted on 25 Apr 2018. Letters to local healthcare professionals to draw their attention to the European Medicines Agency (EMA) recent review were also issued on 12 Feb 2018.

In Dec 2014, the Registration Committee of the Pharmacy and Poisons Board (Registration Committee) discussed the findings of an EMA previous review on the risk of valproate products in pregnancy and had decided that warnings and precautions on the risk of pregnancy should be included in valporate products. The safety information in the above HSA’s announcement, together with the safety updates issued by other overseas drug regulatory authorities (including the EMA recent review), will be discussed by the Registration Committee.

Ends/Wednesday, Sep 19, 2018
Issued at HKT 16:00

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