Drugs Causing Aseptic Meningitis

Introduction to Causative Agents

The American Academy of Family Physicians and other medical societies note that the most common drugs that cause aseptic meningitis include NSAIDs, trimethoprim-sulfamethoxazole, certain antibiotics, intrathecal chemotherapeutic agents, and immunomodulatory drugs 1, 2

Ibuprofen is most frequently implicated in NSAID-induced aseptic meningitis 1, 2
Naproxen is another common NSAID associated with aseptic meningitis 1
NSAID-induced aseptic meningitis occurs more frequently in patients with underlying systemic lupus erythematosus 1

Methotrexate (MTX) is associated with aseptic meningitis in 10-50% of patients receiving intrathecal administration 3, 4
Cytarabine, particularly liposomal cytarabine, can cause aseptic meningitis 3, 4
Other chemotherapeutic agents reported to cause aseptic meningitis include cisplatin, carmustine, and thiotepa 3

Underlying autoimmune diseases, particularly systemic lupus erythematosus, increase the risk of drug-induced aseptic meningitis 1

For intrathecal chemotherapy-induced aseptic meningitis, concomitant use of intrathecal corticosteroids (4 mg dexamethasone) may help prevent occurrence 3, 4

Aseptic meningitis is characterized by symptoms of meningism (neck stiffness, headache, photophobia), raised numbers of cells in the cerebrospinal fluid (CSF), and sterile bacterial culture, according to the Journal of Infection guidelines 6

Drug-induced aseptic meningitis is rare, with NSAIDs being one of the causative agents, as reported by the Journal of Allergy and Clinical Immunology 7
The American Academy of Allergy, Asthma, and Immunology recommends avoiding all NSAIDs in the same chemical class in severe cases of aseptic meningitis, and considering alternative pain management options from different drug classes 7

The Journal of Allergy and Clinical Immunology suggests that supportive care for symptoms and avoidance of all NSAIDs in the same chemical class may be necessary for patients with naproxen-induced aseptic meningitis 7

Cross-reactivity between NSAIDs has been reported, though it is not universal, and patients with naproxen-induced aseptic meningitis may also react to other NSAIDs, as noted by the Journal of Allergy and Clinical Immunology 7

The National Comprehensive Cancer Network recommends corticosteroid therapy, such as dexamethasone 4-8 mg IV every 6 hours for 3-5 days, with gradual tapering for chemical meningitis treatment 8
Empiric antibiotic therapy should be initiated if bacterial meningitis cannot be confidently excluded, with options including Ceftriaxone 2g IV q12h or Cefotaxime 2g IV q6h for adults <60 years, and adding Amoxicillin 2g IV q4h to cover Listeria for adults ≥60 years 9