DISCLAIMER: This publication is intended for healthcare professionals. The information provided aims to update on medication safety issues and should not substitute clinical judgement. While reasonable care has been taken to verify the accuracy of the information at the time of publication, the NPRA shall not be held liable for any loss arising from the use of or reliance on this publication.

 

Overview of Product

Lamotrigine is indicated for the treatment of epilepsy and for the prevention of mood episodes in bipolar disorder.¹ In Malaysia, a total of 20 lamotrigine-containing products have been registered with the Drug Control Authority (DCA) since 1993.² All registered products are available as tablets, including conventional and dispersible forms. Careful dose titration is required based on the indication and concomitant medications, due to the risk of severe cutaneous adverse reactions.^3,4

 

Overview of Safety Concern

Photosensitivity reactions occur following exposure to certain medicinal products or chemicals that increase the skin’s sensitivity to sunlight, particularly ultraviolet (UV) radiation, thereby triggering skin reactions.⁵ These reactions are broadly classified into phototoxic and photoallergic types, which differ in their underlying mechanisms and typical clinical presentation.

Phototoxic reactions represent the most common form and result from direct cellular or tissue damage following UV exposure in the presence of a phototoxic agent. These reactions typically occur once a sufficient concentration of the drug or chemical is reached. Clinically, phototoxicity typically presents as an exaggerated sunburn within minutes to hours after sun exposure and is usually confined to exposed areas of the skin.

In contrast, photoallergic reactions are less common and involve a cell-mediated immune response in previously sensitised individuals, even at low levels of exposure. These reactions generally present as pruritic, eczematous eruptions occurring 24 to 48 hours after sun exposure and may extend beyond sun-exposed areas.

 

Source of Safety Concern

The National Pharmaceutical Regulatory Agency (NPRA), through its global safety signal monitoring activities, identified an update by the European Medicines Agency (EMA) regarding the risk of photosensitivity reactions associated with the use of lamotrigine.⁶ This update was based on the EMA’s review of evidence from published literature, the EudraVigilance database, the Dutch pharmacovigilance database, as well as the pharmacological properties of lamotrigine. Consequently, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) recommended updating the product information for lamotrigine-containing products to include this risk.

 

Background of the Safety Issue

The evidence reviewed by the EMA included reports of photosensitivity reactions in association with lamotrigine use.^7,8 In several cases, these reactions occurred at higher doses (400 mg or above), particularly following dose escalation or rapid up-titration.

A plausible mechanism supporting these observations is that lamotrigine absorbs UV radiation and generates reactive chemical species, including singlet oxygen and superoxide radical anions, which can induce lipid oxidation and damage skin lipids.⁹ This may increase the skin’s susceptibility to sunburn and trigger phototoxic reactions. Furthermore, lamotrigine may also undergo photodecomposition under UV light, forming reactive compounds such as aryl radicals. These breakdown products may modify cellular proteins, triggering a cell-mediated immune response in previously sensitised individuals, potentially contributing to rare photoallergic reactions.

 

Local Adverse Drug Reaction Reports¹⁰

To date, the NPRA has received 595 reports involving 1,095 adverse events suspected to be related to lamotrigine-containing products. Of these, two reports involved photosensitivity reactions associated with lamotrigine use.

 

Regulatory Action

The NPRA has completed a review of the potential risk of photosensitivity reaction associated with lamotrigine. On 14 April 2026, a directive [NPRA.600-1/9/13(6) Jld. 2] was issued for all registration holders of lamotrigine-containing products to update the local package inserts and consumer medication information leaflets (Risalah Maklumat Ubat untuk Pengguna) to reflect this safety information.

 

Advice for Health Care Professionals

• Be aware that photosensitivity reactions have been reported with lamotrigine.
• Screen patients for a history of drug-induced dermatological reactions before initiating lamotrigine. Use with caution in patients who previously developed a rash following treatment with lamotrigine or other medicines used for epilepsy or bipolar disorder.
• Exercise caution during dose escalation or rapid up-titration of lamotrigine, as photosensitivity reactions have been reported more frequently at higher doses (400 mg or above).
• Advise patients to seek medical advice if they develop a rash or sunburn after taking lamotrigine, particularly following exposure to sunlight or artificial UV light (e.g., solarium).
• If lamotrigine-associated photosensitivity is suspected in patients presenting with signs such as exaggerated sunburn, consider discontinuation of treatment.
• If continuation of lamotrigine is deemed clinically necessary, advise patients to avoid exposure to sunlight and artificial UV light, as well as to adopt appropriate protective measures such as use of sunscreen and protective clothing.
• Report all suspected adverse events related to lamotrigine use to the NPRA.

 

References

1. National Pharmaceutical Regulatory Agency (NPRA). LAMICTAL TABLET 50MG [Package Insert]. QUEST3+ Product Search. 2025 Mar 18 [cited 2025 Dec 24] Available from: https://www.npra.gov.my
2. National Pharmaceutical Regulatory Agency (NPRA). QUEST3+ Product Search [Internet]. 2025 [cited 2025 Dec 24] Available from: https://www.npra.gov.my
3. Ministry of Health Malaysia. Clinical Practice Guidelines: Management of Bipolar Disorder (2^nd). [Internet]. 2024. [cited 2026 Feb 23]. Available from: https://www.moh.gov.my/images/04-penerbitan/penerbitan-klinikal/panduan-amalan-klinikal/e-CPG_Management_of_Bipolar_Disorder_Second_Edition_300824_1_1.pdf
4. Brickel N, Shaikh H, Kirkham A, Davies G, Chalker M, Yoshida P. Collaboration in pharmacovigilance: lamotrigine and fatal severe cutaneous adverse reactions – a review of spontaneous reports. Therapeutics and Clinical Risk Management. 2017;13:897–903. Available from: https://doi.org/10.2147/TCRM.S131021
5. Netherlands Pharmacovigilance Centre Lareb. Lamotrigine and photosensitivity. ’s-Hertogenbosch: Lareb; 2020 Feb 6. [cited 2026 Jan 28]. Available from: https://www.lareb.nl/Knowledge/FilePreview?id=38403&p=33379
6. European Medicines Agency (EMA). 26-29 Oct 2020 PRAC meeting minutes [Internet]. 2021 Jan 8 [cited 2025 Dec 25]. Available from: https://www.ema.europa.eu/en/documents/minutes/minutes-prac-meeting-26-29-october-2020_en.pdf
7. European Medicines Agency (EMA). PRAC recommendations on signals: Adopted at the 26–29 Oct 2020 PRAC meeting. 2021 Jul 6 [cited 2025 Dec 25]. Available from: https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-26-29-october-2020-prac-meeting_en.pdf
8. European Medicines Agency (EMA). New product information wording – Extracts from PRAC recommendations on signals: Adopted at the 26–29 Oct 2020 PRAC meeting. 2020 Nov 23 [cited 2025 Dec 24]. Available from: https://www.ema.europa.eu/en/documents/prac-recommendation/new-product-information-wording-extracts-prac-recommendations-signals-adopted-26-29-october-2020-prac_en.pdf
9. Bilski PJ, Wolak MA, Zhang V, Moore DE, Chignell CF. Photochemical reactions involved in the phototoxicity of the anticonvulsant and antidepressant drug lamotrigine (Lamictal). Photochem Photobiol. 2009;85(6):1327–1335. Available from: https://doi.org/10.1111/j.1751-1097.2009.00590.x
10. National Pharmaceutical Regulatory Agency. The Malaysian National ADR Database [Internet]. 2025 [cited 2025 Dec 26]. Available from https://www.npra.gov.my (access restricted)

 

Written by: Nafiza Mohd. Ismail

Reviewed/Edited by: Lim Sze Gee, Dr Rema Panickar, Noor'ain Shamsuddin, Norleen Mohamed Ali