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Cryptococcal meningitis

To date, two cases of CM have been reported with siponimod. Cases of fatal CM and disseminated cryptococcal infections have been reported with another S1P receptor modulator1,2

Clinical and postmarketing_CM_v1

As of March 25, 2023, with a cumulative clinical trial exposure of 8,757 patient-years, two cases of CM have been reported with siponimod3

As of March 25, 2023, with a cumulative postmarketing exposure of 31,187 patient-years, no cases of CM have been reported with siponimod4


About CM

CM background

  • Cryptococcosis is a pulmonary or disseminated infection acquired by inhalation of soil contaminated with the encapsulated yeast Cryptococcus neoformans or C. gattii5
  • After inhalation, Cryptococcus may disseminate frequently to the brain and meninges, typically manifesting as microscopic multifocal intracerebral lesions5
  • CM signs/symptoms result from cerebral edema and include nonspecific symptoms such as headache, blurred vision, confusion, depression, agitation, and other behavioral changes. Except for ocular or facial palsies, focal signs are rare until relatively late in the course5
  • CM diagnosis is suggested by symptoms of an indolent infection in immunocompetent patients and a more severe, progressive infection in immunocompromised patients and unexplained progressive brain dysfunction, particularly in those with depressed cell-mediated immunity5
    • Chest x-ray, urine collection, and lumbar puncture are frequently the initial diagnostic tests done
    • Elevated CSF protein and a mononuclear cell pleocytosis are usual in CM
    • The latex test for cryptococcal capsular antigen is positive in CSF or blood specimens or both in >90% of patients with meningitis and is generally specific
  • General recommendations for CM management5
    • Amphotericin B, flucytosine, and fluconazole are antifungal medications shown to improve survival in patients with cryptococcal infections5
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CM, cryptococcal meningitis; CSF, cerebrospinal fluid; S1P, sphingosine 1-phosphate receptor modulator
1. Siponimod® Prescribing Information (US), Accessed Aug 30, 2023.
2. Del Poeta M, Neurol Neuroimmunol Neuroinflamm. 2022 Mar 22;9(3):e1156. doi: 10.1212/NXI.0000000000001156.
3. Data on File, cutoff date 25-March-2023, Novartis Pharma AG.
4. Data on File, PSUR, cutoff date 25-March-2023, Novartis Pharma AG.
5. Centers for Disease Control and Prevention. CDC. Cryptococcal meningitis. Accessed June 26, 2023. Preventing Deaths from Cryptococcal Meningitis | Fungal Diseases | CDC.
* Indication varies in different countries. Current website is a global information resource. Local Prescribing Information/ Summary of Product Characteristics approved by individual country’s regulatory authority is the primary source of information for the indication of siponimod in the individual country.

The Pregnancy outcome Intensive Monitoring (PRIM) program is based on enhanced pharmacovigilance of the Novartis spontaneous reporting system. PRIM is an adverse event outcomes intensive monitoring program to collect information (targeted follow-up checklists) about pregnancy in patients exposed to siponimod immediately before or during pregnancy and infant outcomes 12 months after delivery.