What drugs can cause aseptic meningitis?

Drugs Causing Aseptic Meningitis

The most common drugs that cause aseptic meningitis include NSAIDs (particularly ibuprofen and naproxen), trimethoprim-sulfamethoxazole, certain antibiotics, intrathecal chemotherapeutic agents, and immunomodulatory drugs. 1

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• 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
• The FDA label for ibuprofen specifically warns that aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen therapy 2

Antibiotics

• Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the most commonly reported antibiotics causing aseptic meningitis 3, 4
• Amoxicillin has been reported to cause aseptic meningitis, though this is rare 5, 6
• Ciprofloxacin has been implicated in some cases, particularly when used in combination with other antibiotics 4

Chemotherapeutic Agents (Intrathecal Administration)

• 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

Anticonvulsants

• Carbamazepine has been reported to cause aseptic meningitis, particularly when used in combination with other medications 7
• The FDA label for carbamazepine specifically mentions aseptic meningitis as a potential adverse reaction 7

Immunomodulatory Drugs

• Intravenous immunoglobulin (IVIG) has been associated with aseptic meningitis 8
• Monoclonal antibodies can trigger aseptic meningitis in some patients 8

Clinical Presentation and Diagnosis

• Typical symptoms include headache, neck stiffness, fever, photophobia, nausea, vomiting, and altered mental status 9, 8
• Symptoms typically develop within hours to days after drug exposure 3, 4
• CSF analysis typically shows lymphocytic pleocytosis with normal glucose and variable protein levels 5, 8
• Diagnosis requires exclusion of infectious causes of meningitis 8, 4

Risk Factors

• Female gender appears to be a risk factor for drug-induced aseptic meningitis 4
• Underlying autoimmune diseases, particularly systemic lupus erythematosus, increase the risk 1, 2
• Previous history of drug-induced aseptic meningitis increases risk of recurrence with re-exposure 5, 6

Management

• Immediate discontinuation of the suspected causative drug is the primary treatment 8, 4
• Symptoms typically resolve within 24-48 hours after drug discontinuation, though some patients may experience neurological deterioration before improvement 4
• For intrathecal chemotherapy-induced aseptic meningitis, concomitant use of intrathecal corticosteroids (4 mg dexamethasone) may help prevent occurrence 1
• Rechallenge with the suspected drug should be avoided, as recurrence is common and may be more severe 8, 6

Prognosis

• The outcome is generally good with prompt recognition and discontinuation of the offending drug 8
• Most cases resolve without long-term sequelae 9, 8
• Recurrence is common with re-exposure to the causative agent 5, 6

Remember that drug-induced aseptic meningitis is a diagnosis of exclusion, and infectious causes must be ruled out before attributing meningitis to a medication.