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, the NPRA shall not be held liable for any loss whatsoever arising from the use of or reliance on this publication.

Background

Vancomycin is an important antimicrobial for prophylactic, empirical and directed therapy of Gram-positive pathogens. It is a tricyclic glycopeptide antibiotic that inhibits the synthesis of the cell wall in sensitive bacteria by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units and is slowly bactericidal for dividing microorganisms. In addition, it impairs the permeability of the bacterial cell membrane and RNA synthesis.¹

Severe cutaneous adverse drug reactions (SCARs) comprise Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP) and generalised bullous fixed drug eruptions (GBFDE). T-cell-mediated delayed hypersensitivity reactions, triggered by interactions between small-molecule drugs, Human Leukocyte Antigen (HLA) class I molecules and T-cell receptors, underlie the pathogenesis of most SCARs.²

Trigger of the Safety Signal

This signal, particularly for vancomycin-associated TEN, was triggered from the WHO global database of adverse event reports for medicines and vaccines (VigiBase), that prompted a disproportionality analysis on local ADR reports.

TEN is a type of SCAR that is potentially life-threatening characterised by widespread erythema, necrosis, and bullous detachment of the epidermis and mucous membranes, resulting in exfoliation and possible sepsis and/or death.³ TEN and SJS are clinically similar except for their distribution:

• changes affect < 10% of body surface area in SJS;
• changes affect > 30% of body surface area in TEN;
• involvement of 10 to 30% of body surface area is considered SJS/TEN overlap.⁴  

Disproportionality Analysis*^5-6

Based on the cut-off date of 30^th September 2025, the IC₀₂₅ value for vancomycin-TEN pair was 0.3 with 10 local reports received. It was also noted that the IC₀₂₅ value for vancomycin-DRESS was 1.5 with 32 local reports, whereas the IC₀₂₅ value was negative for SJS and AGEP. However, globally, the IC₀₂₅ values were positive for all SCARs, prompting further assessment.

A signal assessment into both local and global pharmacovigilance databases, scientific literature, and regulatory actions taken by other regulatory agencies for SCARs showed the signal was validated by other National Regulatory Authorities (NRAs), and further risk minimisation measures were needed. 

Signal Assessment Outcome⁷

The outcome of the review led to an NPRA directive [NPRA.600-1/9/13 (10) Jld. 2] issued for product registration holders of vancomycin-containing products to update the local package inserts to reflect the risk of SCARs.

Recommendations for Healthcare Professionals

• Be aware that SCARs including SJS, TEN, DRESS and AGEP have been reported in association with vancomycin treatment, mostly occuring within a few days and up to eight weeks after commencing treatment. Educate patients  to seek medical attention immediately if they develop early signs and symptoms of SCARs such as fever, rash, eye irritation, sore throat or widespread redness of the skin.  
• If SCARs are suspected, discontinue the drug immediately and initiate appropriate treatment depending on the severity of the reactions.
• Report all suspected adverse events associated with vancomycin-containing products to the NPRA.

References:

1. National Pharmaceutical Regulatory Agency (NPRA). VANCO 500 (vancomycin hydrochloride) [Package Insert]. QUEST3+ Product Search. 2024 Feb 26 [cited 2026 Jul 30]. Available from: http://www.npra.gov.my.
2. Severe cutaneous adverse reactions (SCAR). (2025). Council for International Organizations of Medical Sciences (CIOMS). [cited 2026 Jul 30]. Available from: https://doi.org/10.56759/lrty1600
3. Jellinek-Cohen, S. P. (2024, December 18). Toxic Epidermal Necrolysis (TEN). Medscape. [cited 2026 Jul 30]. Available from: https://emedicine.medscape.com/article/229698-overview
4. Benedetti J. Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) [Internet]. Merck Manual Professional Version. 2024 May [cited 2026 Jul 30]. Available from: https://www.msdmanuals.com/professional/dermatologic-disorders/hypersensitivity-and-reactive-skin-disorders/stevens-johnson-syndrome-sjs-and-toxic-epidermal-necrolysis-ten
5. Uppsala Monitoring Centre (UMC). The WHO Global ICSR Database (VigiLyze) [Internet]. 2023 [cited 2023 Jan 5]. Available from: https://www.vigilyze.who-umc.org(access restricted)
6. Information from the Uppsala Monitoring Centre (UMC). The UMC Measures of Disproportionate Reporting [Internet]. 2016 [cited 2023 Jan 5]. Available from: https://who-umc.org/media/164041/measures-of-disproportionate-reporting_2016.pdf
7. National Pharmaceutical Regulatory Agency (NPRA). 197 MADRAC meeting minutes. 2026 February 26 [cited 2026 Jul 30] (access restricted)

Written by: Dr Vidhya Hariraj
Reviewed/Edited by: Dr Rema Panickar, Nora Ashikin Mohd Ali, Norleen Mohamed Ali