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

Abstract

BackgroundIn 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.MethodsOpen-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.ResultsOf 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.ConclusionsThese 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 registrationEudraCT 2011-000770-60

Neurological safety of fingolimod: An updated review

“…The most common AE were cardiovascular events, including bradycardia and first‐degree or second‐degree atrioventricular block, after administration of the first dose 12. These AE usually occur within 1 h after administration of the drug, and bradycardia usually lasts for several days.…”

The real-life experience with cardiovascular complications in the first dose of fingolimod for multiple sclerosis

“…As yet, there has been no report on the safety of the first dose of fingolimod in Brazilian patients with MS where the protocol recommends medical observation and cardiovascular monitoring for at least six hours. In fact, except for results on clinical trials with very strict inclusion criteria for patients 4 , there are few reports on the real life experience with the first dose of fingolimod 2,5 . Retrospective data were collected for 180 patients aged over 18 years diagnosed with MS according to the revised McDonald criteria 6 .…”

“…The study of Ontaneda et al which dealt with clinical practice data also demonstrated 1% rate of bradycardia as a complication of fingolimod initiation 2 . A recent Italian study reported 2% cardiovascular adverse events in patients taking the first dose of fingolimod, mainly bradycardia and atrio-ventricular block 5 . The Italian study used a method similar to ours, reporting the results of daily medical practices.…”

Fertility, Pregnancy and Childbirth in Patients with Multiple Sclerosis: Impact of Disease-Modifying Drugs

“…S1P receptors are expressed in many body tissues, explaining a number of unwarranted effects of fingolimod. After the first dose of fingolimod, bradycardia and atrioventricular conduction block have been reported in fewer than 2 % of patients [31][32][33]. Other side effects are macula oedema, elevated liver function tests, an increased risk of infections (fatal herpes virus in a few cases) and hypertension [31,32].…”