Open Access Highly Accessed Research article

Safety of the first dose of fingolimod for multiple sclerosis: results of an open-label clinical trial

Alice Laroni1, Davide Brogi1, Vincenzo Brescia Morra2, Leonello Guidi3, Carlo Pozzilli4, Giancarlo Comi5, Alessandra Lugaresi6, Renato Turrini7, Debora Raimondi7, Antonio Uccelli1, Giovanni Luigi Mancardi1* and on behalf of the EAP Investigators

Author Affiliations

1 Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Largo Daneo 3, 16132 Genoa, Italy

2 Department of Neurological Sciences, University Federico II, Naples, Italy

3 Neurology Unit, S. Giuseppe Hospital, Empoli, Italy

4 Department of Neurology, University La Sapienza, Rome, Italy

5 Department of Neurology, INSPE, Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan, Italy

6 Department of Neuroscience and Imaging, University G. D’Annunzio, Chieti, Italy

7 Novartis Farma, Origgio, Varese, Italy

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BMC Neurology 2014, 14:65  doi:10.1186/1471-2377-14-65

Published: 1 April 2014



In patients with relapsing-remitting MS (RRMS) fingolimod prevents disease relapses and delays disability progression. First dose administration of fingolimod is associated with a transient, dose-dependent decrease in heart rate (HR) in the 6 hours after drug intake.

The aim of the study is to to assess safety and tolerability of the first dose of fingolimod in a cohort of Italian patients with RRMS without alternative therapeutic options.


Open-label, single arm, multicentre study. After the first dose of fingolimod, patients were observed for 6 hours and had their vital signs monitored hourly. Extended on-site monitoring was provided when required.


Of the 906 patients enrolled in the study, most (95.2%) did not experience any adverse event (AE) following fingolimod administration. Cardiovascular AEs occurred in 18 patients and included bradycardia (1.3%), first-and second-degree atrioventricular block (0.1% and 0.2%), palpitations (0.1%), sinus arrhythmia (0.1%) and ventricular premature beats (0.1%). All events were self-limiting and did not require any intervention. Extended monitoring was required in 34 patients.


These results, in a population who better resembled real-world clinical practice in terms of concomitant diseases and medications, are consistent with previous clinical trials and confirmed that the first dose administration of fingolimod is generally safe and well tolerated.

Trial registration

EudraCT 2011-000770-60

Atrioventricular block; Bradycardia; Multiple sclerosis; Fingolimod; Safety; Tolerability