Overview

Topiramate is indicated for the treatment of epilepsy, and also as prophylaxis against migraine headaches.¹ (please see package insert for full prescribing details). Topiramate exerts the blockade of sodium channels, enhance inhibitory effect of gamma-aminobutyrate (GABA) while inhibiting the action of kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype glutamate receptor.² 

Uveitis refers to a condition in which the middle layer of the eyeball (uvea) becomes inflamed. Uveitis can cause damage to vital eye tissues and may result in permanent vision loss.³

Background of the safety issue

In July 2019, the National Pharmaceutical Regulatory Agency (NPRA) received information from the European Medicines Agency (EMA) regarding the updates of topiramate product package insert with the risk of uveitis. 

Based on EMA’s safety review and product registration holder’s cumulative review, there are a few reports of bilateral uveitis with a short time to onset after topiramate initiation in patients whom have no confounding diseases. The adverse event resolved relatively fast following drug withdrawal. Looking at all available evidence, EMA concluded that there is a causal association between topiramate and uveitis.⁴

Adverse Drug Reaction (ADR) Reports:

To date, NPRA has received 35 reports with 61 adverse events suspected to be related to topiramate. However, no event related to uveitis associated with topiramate has been reported locally.⁵

Advice for Healthcare Professionals:

• Be aware on the risk of uveitis associated with the use of topiramate.
• Advise patients to inform their doctor immediately if they have signs and symptoms of uveitis, such as eye redness, pain and blurring of vision.
• Report all suspected adverse events associated with topiramate use to the NPRA.

NPRA has completed the review of this safety issue and a directive [Ruj. Kami: NPRA.600-1/9/13 (5)] has been issued for registration holders of topiramate products to update the local package inserts and consumer medication information leaflet (Risalah Maklumat Ubat untuk Pengguna) to reflect this safety information.

References: 

1. National Pharmaceutical Regulatory Agency. Malaysian Product Registration Database (Quest 3+). Topiramate local package insert [Internet]. Last revision date: 2020 May 5 [Cited 2020 May 5]. Available from: https://www.npra.gov.my
2. Goldberg JL, Lau AG, Fan B, Ford L, Greenberg HE. Is uveitis associated with topiramate use? A cumulative review. Clinical Ophthalmology [Internet]. 2016 August 2 [Cited 2020 July 27] 10, 1467-1470. Available at: http://www.dx.doi.org/10.2147/OPTH.S104847
3. Boyd K. What Is Uveitis? American Academy of Ophthalmology 2020 [Internet]. 2019 August 29 [Cited on 2020 July 27]. Available at: https://www.aao.org/eye-health/diseases/what-is-uveitis
4. European Medicines Agency. PRAC recommendations on signals: Adopted at the 11-14 June 2019 PRAC meeting. 2019 July 8 [Cited on 2020 May 5]. EMA/PRAC/303951/2019.
5. National Pharmaceutical Regulatory Agency. The Malaysian National ADR Database [Internet]. 2020 [Cited 2020 May 5]. Available from: https://www.npra.gov.my

DISCLAIMER: 

This publication is aimed at health professionals. The information is meant to provide updates on medication safety issues, and not as a substitute for clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.