What medications can cause aseptic meningitis?

From the Guidelines

Aseptic meningitis can be caused by various medications, including intrathecal (IT) administration of chemotherapeutics such as methotrexate (MTX) and liposomal cytarabine, with symptoms typically resolving spontaneously with symptomatic treatment. The medications most commonly associated with aseptic meningitis include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Antibiotics
• Immunosuppressants
• Antiepileptic medications
• Intrathecal agents, such as MTX and liposomal cytarabine, which can cause aseptic meningitis in 10%–50% of patients, as reported in the study published in the Annals of Oncology 1. The occurrence of aseptic meningitis is typically characterized by signs of meningeal irritation, including headache, nuchal stiffness, vomiting, fever, and lethargy, which develop within 2–4 hours after drug injection and usually last for about 12–72 hours 1. Management of aseptic meningitis involves immediate discontinuation of the suspected medication and symptomatic treatment, with the option of using IT corticosteroids, such as 4 mg IT dexamethasone, to prevent aseptic meningitis, although the evidence for this is limited 1. Cerebrospinal fluid (CSF) examination may show pleocytosis without other features of bacterial infection, and CSF culture should be carried out for differential diagnosis 1. It is essential to note that rechallenge with the same medication should be avoided, as recurrence is common and may be more severe.

From the FDA Drug Label

Aseptic Meningitis Aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a patient taking carbamazepine in combination with other medications

• Ibuprofen and carbamazepine have been associated with aseptic meningitis in rare cases.
• The exact relationship between these medications and aseptic meningitis is not fully understood, but it is considered a potential risk.
• Patients taking these medications should be monitored for signs and symptoms of meningitis, such as fever, headache, and stiff neck.
• If aseptic meningitis is suspected, the medication should be discontinued and the patient should be evaluated by a healthcare professional 2 3.

From the Research

Medications Causing Aseptic Meningitis

• Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen 4, 5 are known to cause aseptic meningitis.
• Antibiotics like trimethoprim-sulfamethoxazole (TMP-SMX) 6, 7, 8 have also been reported to induce aseptic meningitis.
• Other medications that can cause aseptic meningitis include intravenous immunoglobulin, OKT3 monoclonal antibodies, and vaccines 4, 5.

Clinical Findings

• Common clinical findings in patients with drug-induced aseptic meningitis include fever, headache, stiffness, and altered level of consciousness 6, 4, 7, 8.
• Cerebrospinal fluid findings may include elevated white blood cell count, elevated protein, and normal glucose levels 4, 8.

Patient Characteristics

• Patients with autoimmune diseases are more frequently observed to have drug-induced aseptic meningitis 4, 8.
• Both immunocompromised and immunocompetent patients can develop aseptic meningitis due to medications like TMP-SMX 7.
• Female patients are more commonly reported to have TMP-SMX-induced aseptic meningitis 8.

Diagnosis and Treatment

• Diagnosis of drug-induced aseptic meningitis can be confirmed with drug challenge or graded test dosing when necessary 4, 8.
• Prompt discontinuation of the offending medication can lead to complete recovery 6, 7, 8.
• Patients who have experienced aseptic meningitis due to TMP-SMX should be advised to avoid both trimethoprim and sulfamethoxazole in the future 8.