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.

 

Overview of Products

Moxifloxacin is a fluoroquinolone antibiotic with a broad spectrum of activity and bactericidal properties.¹ It demonstrates in vitro activity against a wide range of Gram-positive and Gram-negative organisms, anaerobes, and acid-fast bacteria.

Moxifloxacin is mainly indicated for the treatment of respiratory tract infections, pelvic inflammatory disease, skin infections, and intra-abdominal infections.¹ There are currently 13 moxifloxacin-containing products for systemic use (as oral and injectable formulations) registered with the Drug Control Authority (DCA).²

 

Overview of Safety Concerns

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction that primarily affects the skin, presenting as a morbilliform skin rash, and is often accompanied by fever, facial oedema, lymphadenopathy, and involvement of multiple internal organs, which can be fatal in severe cases.^3,4 Incidence of DRESS varies by drug type and patient immune status, and many cases may remain undiagnosed or untreated.³

Fixed drug eruption (FDE) is also a cutaneous hypersensitivity reaction associated with medications such as analgesics, anticonvulsants, and antibiotics.⁵ It typically presents as a sudden onset of round and/or oval, oedematous, dusky-red macules on the skin or mucosa, often accompanied by a burning sensation or itching.^5,6 Acute lesions typically resolve into residual hyperpigmentation. The incidence of FDE induced correlates with the drug’s usage frequency.⁶

Drug-induced photosensitivity is a common adverse drug reaction characterised by cutaneous eruptions triggered by exposure to ultraviolet (UV) or visible light in patients taking topical or systemic photosensitising agents, including antibiotics.⁷ Triggers may include artificial light sources like medical phototherapy lamps and tanning beds. These reactions fall into two main categories, photoallergic and phototoxic, with the latter being more common.⁸

 

Source of Safety Concern

The National Pharmaceutical Regulatory Agency (NPRA) was notified by the product registration holder for moxifloxacin of updates to its product information after an assessment by the European Medicines Agency (EMA). Based on the evaluation of available data from the literature and spontaneous reports, the Pharmacovigilance Risk Assessment Committee (PRAC) of EMA concluded that the product information of moxifloxacin should be updated to include the risk of DRESS, FDE, and photosensitivity associated with systemic use, with the frequency classified as ‘not known’.^9,10

 

Background of the Safety Issue

Although the exact mechanism underlying moxifloxacin-induced DRESS is still unclear, it has been proposed that a drug-specific immune response may trigger virus reactivation and subsequent activation of cytotoxic CD8+ T lymphocytes, resulting in tissue damage.⁴ The onset of DRESS is usually delayed, ranging from 2 to 8 weeks after initiation of the suspected drug, although the time to onset may be shorter or vary depending on individual immune response and predisposing factors.^3,11,12

In contrast, FDE is a distinct condition with a different pathogenesis, thought to involve a localised T-cell–mediated cytotoxic response.¹³ FDE typically presents earlier, within 2 weeks following initial exposure and rapidly upon re-exposure (within 30 minutes to 16 hours).

With regard to photosensitivity reactions, many therapeutic agents, notably the fluoroquinolone class, exhibit photosensitising potential.¹⁴ In these cases, the drug or its metabolites within the cutaneous tissue absorb UV radiation, and this induces phototoxic (dose-dependent direct tissue damage) or photoallergic (type IV hypersensitivity) reactions.⁷ There are data suggesting that moxifloxacin is associated with a lower risk of photosensitivity, primarily phototoxic reactions, compared with other fluoroquinolones such as ciprofloxacin, levofloxacin, norfloxacin, and ofloxacin.¹⁴

 

Local Adverse Drug Reaction Reports¹⁵

To date, NPRA has received 389 reports with 710 adverse events suspected to be related to moxifloxacin-containing products. The most frequently reported adverse events were pruritus (82), rash (63), and erythema (30). Three reports of FDE were identified, while no reports of DRESS or photosensitivity following the systemic use of moxifloxacin have been identified.

 

Advice for Healthcare Professionals

• While NPRA is still reviewing this safety issue, be aware that DRESS, FDE, and photosensitivity are cutaneous adverse reactions that may occur with the systemic use of moxifloxacin.
• Prioritise a thorough patient assessment and drug reaction history-taking before initiating therapy with moxifloxacin.
• Educate patients to monitor closely for early signs and symptoms of these adverse reactions to ensure prompt recognition.
• If suspected, discontinue the drug immediately and initiate appropriate treatment such as corticosteroids and antihistamines depending on the severity of the reactions.
• Advise patients to avoid prolonged exposure to sunlight and not to use a sunbed or any other UV lamp during treatment with moxifloxacin.
• Report all adverse events suspected to be related to the use of moxifloxacin-containing products to the NPRA.

 

References:

1. National Pharmaceutical Regulatory Agency (NPRA). Avelox 400mg Tablet and Solution for Infusion. [Package Insert]. 2021 Jan [Cited 2025 Oct 11]. The Malaysian Product Registration Database (QUEST). Available from: https://www.npra.gov.my
2. National Pharmaceutical Regulatory Agency (NPRA). QUEST3+ Product Search [Internet]. 2025 [cited 2025 Oct 15]. Available from: https://www.npra.gov.my
3. Calle AM, Aguirre N, Ardila JC, Villa RC. DRESS syndrome: A literature review and treatment algorithm. World Allergy Organization Journal [Internet]. 2023 Mar 1;16(3):100673. Available from: https://doi.org/10.1016/j.waojou.2022.100673
4. Zhang Y, Wang X, Cheng Y, Wang X, Zhang Y. A typical presentation of moxifloxacin-induced DRESS syndrome with pulmonary involvement: a case report and review of the literature. BMC Pulmonary Medicine. 2022 Jul 19;22(1):279. Available from: https://doi.org/10.1186/s12890-022-02064-1
5. Hager JL, Mir MR, Hsu S. Fluoroquinolone-induced generalized fixed drug eruption. Dermatology Online Journal. 2009 Dec 1;15(12):8. Available from: https://escholarship.org/uc/item/5cz3r80b
6. Sánchez-Morillas L, Pérez-Ezquerra PR, Morales MLG, Mayorga C, González-Mendiola R, Martínez JJL. Fixed drug eruption due to norfloxacin and cross-reactivity with other quinolones. Allergologia Et Immunopathologia [Internet]. 2012 Jan 21;41(1):60-69. Available from: https://doi.org/10.1016/j.aller.2011.10.004
7. Di Bartolomeo L, Irrera N, Campo GM, Borgia F, Motolese A, Vaccaro F, et al. Drug-Induced Photosensitivity: clinical types of phototoxicity and photoallergy and pathogenetic mechanisms. Frontiers in Allergy. 2022 Jun 20;3:876695. Available from: https://doi.org/10.3389/falgy.2022.876695
8. Epstein JH, Phototoxicity and photoallergy. Semin Cutan Med Surg. 1999;18(4):274–284. Available from: https://pubmed.ncbi.nlm.nih.gov/10604793/
9. European Medicines Agency (EMA). Pharmacovigilance Risk Assessment Committee (PRAC): Minute of the meeting on 8-11 January 2024 [Internet]. 2024 Feb 29 [cited 2025 Oct 10]. Available from: https://www.ema.europa.eu/system/files/documents/minutes/minutes-prac-meeting-08-11-january-2024_en.pdf
10. European Medicines Agency (EMA). Scientific conclusions and grounds for the variation to the terms of the marketing authorisation(s): Moxifloxacin (systemic use) [Internet]. 2024 Feb 29 [cited  2025 Oct 10]. Available from: https://www.ema.europa.eu/en/documents/psusa/moxifloxacin-systemic-use-cmdh-scientific-conclusions-grounds-variation-amendments-product-information-timetable-implementation-psusa-00009231-202305_en.pdf
11. Wang S, Kang Y, He C, Jin H. The systemic treatments for drug reaction with eosinophilia and systemic symptoms (DRESS) beyond corticosteroids. World Allergy Organization Journal. 2024 Jul 20;17(8):100935. Available from: https://doi.org/10.1016/j.waojou.2024.100935
12. Nam YH, Park, Nam HJ, Lee SK, Kim KH, Roh, et al. Drug reaction with eosinophilia and systemic symptoms syndrome is not uncommon and shows better clinical outcome than generally recognised. Allergologia Et Immunopathologia. 2014 Jan 3;43(1):19–24. Available from: https://doi.org/10.1016/j.aller.2013.08.003
13. Butler DF. Fixed Drug Eruptions. [Internet] Medscape [cited 2026 Jan 29]. Available from: https://emedicine.medscape.com/article/1336702-print
14. Van Bambeke F, Tulkens PM. Safety profile of the respiratory fluoroquinolone moxifloxacin. Drug Safety. 2009 Jan 1;32(5):359–78. Available from: https://doi.org/10.2165/00002018-200932050-00001
15. National Pharmaceutical Regulatory Agency (NPRA). The Malaysian National ADR Database (QUEST) [Internet]. 2025 [cited 2025 Nov 12]. Available from: https://www.npra.gov.my (access restricted)

 

Written by: Azura Abdullah

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