Drug-induced aseptic meningitis

Medicinal products can be overlooked as triggers of aseptic meningitis.

Meningitis may be attributable to both infectious and non-infectious (what is called aseptic meningitis) causes. In addition to systemic diseases with a meningeal component, such as Behçet's disease or sarcoidosis (neurosarcoidosis), or cancer, the causes of aseptic meningitis may include medicines. The medicinal products that have been associated with meningitis include non-steroidal anti-inflammatories (NSAIDs), antibiotics (sulfonamides, penicillins), intravenous immunoglobulin and monoclonal antibodies ^[1].

aseptic meningitis, non-steroidal anti-inflammatories (NSAIDs), ibuprofen, mefenamic acid, Ponstan®, antibiotics (sulfonamides, penicillins), sulfamethoxazole, trimethoprim, co-trimoxazole, Bactrim® forte, intravenous immunoglobulin (IVIg), human immunoglobulin, Intratect® 10%, monoclonal antibodies
Incident data	Description
Year: 2003 Age group: Adult Gender: Female Medicinal product: Ponstan® capsules Active substance: Mefenamic acid Indication: Pain ADR: Aseptic meningitis Outcome: Recovered	Two hours after taking a single 250-mg capsule of mefenamic acid, a young patient with several episodes of meningoradiculitis in her history once again developed symptoms of meningitis. From her history, the patient was known to have had cutaneous lupus erythematosus, post-infectious sensory neuropathy and thoracic herpes zoster. She received immediate antibiotic and antiviral treatment. Cerebrospinal fluid testing produced abnormal results; leucocytes and elevated protein were both detected, but there were no indications of bacterial infection and a cranial scan was normal. Just two days later, there was a clear improvement in the patient’s clinical condition and lab test results. A systematic review of the patient’s files from previous hospital stays showed that she had taken various NSAIDs (mefenamic acid, ibuprofen) immediately before each episode of meningoradiculitis and never took NSAIDs outside these episodes.
Year: 2001 Age group: Adult Gender: Male Medicinal product: Bactrim® forte Active substance: Co-trimoxazole Indication: Prevention of infections ADR: Aseptic meningitis Outcome: Recovered	A young, male adult patient with HIV infection had to be hospitalised with aseptic meningitis after taking a daily prophylactic dose of 800 mg of co-trimoxazole for 4 days. The investigations conducted in the emergency department revealed no abnormalities. The symptoms subsided after the co-trimoxazole had been discontinued. The same symptoms occurred again two weeks later following renewed exposure to co-trimoxazole (400 mg).

Summary and recommendation

Aseptic meningitis can be a rare or very rare side effect of certain medicines as e.g. ibuprofen, mefenamic acid or co-trimoxazole. Patients with autoimmune diseases such as lupus erythematosus are predisposed to it after taking NSAIDs. However, the side effect can also occur in healthy people^[1].

The pathophysiology has not been explained definitively. Immunological hypersensitivity reactions (type III/IV) are being discussed, as is direct chemical irritation of the meninges for co-trimoxazole and IVIg ^[2-4]. In the case of IVIg, an IgG antigen interaction at the meningeal vessels could be causing cytokine secretion^[4]. The symptoms generally begin within hours or days of initial exposure, or often within a matter of minutes to a few hours after renewed exposure. They normally subside quickly and without any complications after the medicine has been discontinued ^[5]. Aseptic meningitis should be considered in the differential diagnosis when patients present with typical symptoms in conjunction with suspicious medicines.

Statutory duty of healthcare professionals to report adverse drug reactions (ADRs)

In Switzerland, healthcare professionals who are authorised to dispense or administer medicinal products are obligated to report severe and/or previously unknown side effects. Reports to Swissmedic can be entered and sent in the Electronic Vigilance Reporting Portal “ElViS” (ElViS login).

Supplementary information

^1. _{Medicinal product information (ibuprofen, mefenamic acid, co-trimoxazolewww.swissmedicinfo.ch)}

^2. _{Elmedani, S., Albayati, A., Udongwo, N., Odak, M., & Khawaja, S. (2021). Trimethoprim-Sulfamethoxazole-Induced Aseptic Meningitis: A New Approach. Cureus, 13(6), e15869. https://doi.org/10.7759/cureus.15869}

^3. _{Desgranges, F., Tebib, N., Lamy, O., & Kritikos, A. (2019). Meningitis due to non-steroidal anti-inflammatory drugs: an often-overlooked complication of a widely used medication. BMJ case reports, 12(11), e231619. https://doi.org/10.1136/bcr-2019-231619}

^4. _{Kretowska-Grunwald, A., Krawczuk-Rybak, M., & Sawicka-Zukowska, M. (2022). Intravenous Immunoglobulin-Induced Aseptic Meningitis-A Narrative Review of the Diagnostic Process, Pathogenesis, Preventative Measures and Treatment. Journal of clinical medicine, 11(13), 3571. https://doi.org/10.3390/jcm11133571}

^5. _{Bernasconi, G. F., Milani, G. P., De Felice, E. L. T., Laurence, C., Faré, P. B., Terziroli Beretta-Piccoli, B., Bianchetti, M. G., & Lava, S. A. G. (2025). Acute aseptic meningitis temporally associated with trimethoprim and sulfamethoxazole: Systematic review. British journal of clinical pharmacology, 91(1), 236–243. https://doi.org/10.1111/bcp.16346}

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Drug-induced aseptic meningitis

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