title: [Clinical significance of the cardiovascular effects of fingolimod treatment in multiple sclerosis].
abstract: Fingolimod is a sphingosine-1 phosphate receptor modulator, which is effective in the treatment of severe relapsing-remitting form of multiple sclerosis. Once daily oral use of fingolimod decreased the annualized relapse rate, inflammatory brain lesion activity and the rate of brain atrophy compared both to placebo and intramuscular administered interferon beta-1a. The drug targets the cardiovascular system as well via sphingosine-1 phosphate receptors. After initiation of fingolimod therapy transient sinus bradycardia and slowing of the atrioventricular conduction develops. The onset of the effect is as early as 1 hour post administration, while heart rate and conduction normalized in 24 hours in most of the cases. According to the clinical trials symptomatic bradycardia developed in 0.5% of the cases, responding to the appropriate therapy. The incidence of Mobitz I type II atrioventricular blocks and blocks with 2:1 atrioventricular conduction was 0.2% and 0.1%, respectively. All of these cardiovascular events showed regression during observation and no higher degree atrioventricular blocks were detected at the approved therapeutic dose. Following the first dose effect, fingolimod had a moderate hypertensive effect on long-term. For the safety of fingolimod treatment detailed cardiovascular risk stratification of all patients, adequate patient monitoring after the first dose and competency in treating the possible side effects is necessary. In patients with increased cardiovascular risks, treatment should be considered only if anticipated benefits outweigh potential risks and extended monitoring is required.
authors.affiliation: Semmelweis Egyetem, Altalános Orvosi Kar, Kardiológiai Központ--Kardiológia Tanszék, Budapest. szeplaki.gabor@kardio.sote.hu
authors.forename: Gábor
authors.initials: G
authors.lastname: Széplaki
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
mesh_terms: D054537:Atrioventricular Block / Q000139:chemically induced; D001919:Bradycardia / Q000139:chemically induced; D002319:Cardiovascular System / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D000068876:Fingolimod Hydrochloride; D006329:Heart Conduction System / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000517:prevention & control*; D011409:Propylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000187:drug effects; D055502:Secondary Prevention; D013110:Sphingosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D000068556:Interferon beta-1a