Long-term cardiac safety and tolerability of fingolimod in multiple sclerosis: A postmarketing study

J Clin Pharmacol. 2015 Oct;55(10):1131-6. doi: 10.1002/jcph.519. Epub 2015 Jun 17.

Abstract

Fingolimod is the first oral disease-modifying therapy approved for multiple sclerosis (MS). The risks associated with the use of fingolimod include cardiovascular adverse events (AEs). First-dose observation (FDO) is required for all patients for at least 6 hours. We describe FDO data and long-term cardiac tolerability in a cohort of fingolimod-treated relapsing MS patients. Two hundred and twelve patients started fingolimod 0.5 mg once daily. Before the first administration, all subjects had an electrocardiogram (ECG) with cardiologist interpretation. Following administration they were monitored for 6 hours and underwent a cardiac monitoring every 3 months. In this cohort, there was a heart rate reduction at the VI hour of 9.6 ± 8 beats per minute (P < .001). Fifty-four individuals (25.5%) presented an abnormal ECG during the 6 hours. We experienced 1 case (0.22%) of symptomatic second-degree atrioventricular block. The mean follow-up period was 1.5 ± 0.7 years. During this period, 1 patient showed atrial fibrillation that needed to be treated. We also observed 5 cases of persistent increase in blood pressure. This postmarketing study shows that fingolimod is well tolerated and tha tcardiologic AEs are generally self-limited in the long term.

Keywords: cardiac; fingolimod; first-dose observation; long-term safety; multiple sclerosis.

MeSH terms

  • Adult
  • Atrial Fibrillation / chemically induced
  • Atrioventricular Block / chemically induced
  • Blood Pressure / drug effects
  • Electrocardiography / drug effects
  • Female
  • Fingolimod Hydrochloride / adverse effects*
  • Fingolimod Hydrochloride / therapeutic use
  • Heart / drug effects
  • Heart Rate / drug effects
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / physiopathology*
  • Product Surveillance, Postmarketing

Substances

  • Immunosuppressive Agents
  • Fingolimod Hydrochloride