What medications can cause aseptic meningitis?

Medications That Can Cause Aseptic Meningitis

Several classes of medications can cause aseptic meningitis, with NSAIDs (particularly ibuprofen), trimethoprim-sulfamethoxazole, certain antibiotics, intrathecal chemotherapeutic agents, and immunomodulatory drugs being the most common causative agents. 1

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Ibuprofen is the most frequently implicated NSAID in drug-induced aseptic meningitis 1, 2
• Naproxen is another common NSAID associated with aseptic meningitis 1, 3
• NSAID-induced aseptic meningitis occurs more frequently in patients with underlying systemic lupus erythematosus 1, 4
• Clinical presentation includes fever, headache, neck stiffness, and altered mental status, mimicking infectious meningitis 4

Antibiotics

• Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the most common antibiotics associated with aseptic meningitis 1, 5, 6
• Amoxicillin has been reported to cause aseptic meningitis, though this is relatively rare 7, 8
• Penicillins as a class have been implicated in drug-induced aseptic meningitis 7
• Symptoms typically resolve rapidly after discontinuation of the offending antibiotic 6

Chemotherapeutic Agents

• Methotrexate (MTX) is associated with aseptic meningitis in 10-50% of patients receiving intrathecal administration 1
• Cytarabine, particularly liposomal cytarabine, can cause aseptic meningitis 1
• Other chemotherapeutic agents reported to cause aseptic meningitis include cisplatin, carmustine, and thiotepa 1

Immunomodulatory Drugs

• Intravenous immunoglobulins can cause aseptic meningitis 4, 8
• OKT3 antibodies (monoclonal antibodies against the T3 receptor) have been implicated 4

Clinical Features and Diagnosis

• Drug-induced aseptic meningitis presents with symptoms indistinguishable from infectious meningitis, including:
  • Fever, headache, neck stiffness 4, 6
  • Altered level of consciousness 4
  • Photophobia 8
• CSF typically shows neutrophilic pleocytosis, making it difficult to distinguish from bacterial meningitis 4
• Diagnosis requires:
  • Exclusion of infectious causes 7
  • Temporal relationship between drug administration and symptom onset 8
  • Resolution of symptoms after drug discontinuation 7
  • Recurrence with rechallenge (though intentional rechallenge is not recommended) 7

Risk Factors

• Underlying autoimmune diseases, particularly systemic lupus erythematosus, significantly increase the risk of drug-induced aseptic meningitis, especially with NSAIDs 1, 3
• Previous episodes of drug-induced aseptic meningitis increase the risk of recurrence with re-exposure to the same medication 8

Management

• Immediate discontinuation of the suspected causative medication 6, 8
• Symptomatic treatment for headache and fever 8
• For intrathecal chemotherapy-induced aseptic meningitis, concomitant use of intrathecal corticosteroids (4 mg dexamethasone) may help prevent occurrence 1
• Documentation of the reaction to prevent re-exposure to the offending drug 8

Prognosis

• Most cases resolve completely without long-term sequelae after discontinuation of the offending medication 1, 8
• Recovery typically occurs within several days of drug discontinuation 4