Literature DB >> 24178903

Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine.

M Stephenson1, A Wong, J A Rotella, N Crump, F Kerr, S L Greene.   

Abstract

INTRODUCTION: Fingolimod is an immunomodulating agent used in multiple sclerosis (MS). It is a sphingosine-1-phosphate (S1P) receptor agonist prescribed for relapsing forms of MS to delay onset of physical disability. As fingolimod is known to cause first-dose bradycardia, telemetry is recommended for the first 6 h post-dose. We present the first reported case of deliberate fingolimod overdose requiring atropine administration for bradycardia and hemodynamic instability. CASE REPORT: A 33-year-old woman ingested 14 mg of fingolimod and 2 g of phenoxymethylpenicillin. After presenting to the emergency department 19 h later, she was initially hemodynamically stable (heart rate (HR) 60, blood pressure (BP) 113/89 mmHg). Two hours later, she then developed bradycardia (HR 48) and hypotension (87/57 mmHg). Despite intravenous fluids, stabilisation was only achieved after administration of atropine (300 μg). She was then admitted to the intensive care unit (ICU) for further monitoring where another episode of bradycardia and hypotension required atropine. She was monitored in the ICU for 48 h and then discharged on day 5 with no further episodes. DISCUSSION: Fingolimod is known to cause bradycardia in the first 6 h post first therapeutic dose. Following intentional overdose, onset of bradycardia occurred at 21 h post-ingestion and was associated with hypotension. Atropine was successful in treating bradycardia and associated hypotension.

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Year:  2014        PMID: 24178903      PMCID: PMC4057535          DOI: 10.1007/s13181-013-0354-3

Source DB:  PubMed          Journal:  J Med Toxicol        ISSN: 1556-9039


  10 in total

Review 1.  Clinical pharmacokinetics of fingolimod.

Authors:  Olivier J David; John M Kovarik; Robert L Schmouder
Journal:  Clin Pharmacokinet       Date:  2012-01-01       Impact factor: 6.447

Review 2.  FTY720: targeting G-protein-coupled receptors for sphingosine 1-phosphate in transplantation and autoimmunity.

Authors:  Volker Brinkmann; Kevin R Lynch
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3.  Prolonged and symptomatic bradycardia following a single dose of fingolimod.

Authors:  Hans Faber; Hans-Jörg Fischer; Frank Weber
Journal:  Mult Scler       Date:  2012-06-22       Impact factor: 6.312

4.  The heart rate decrease caused by acute FTY720 administration is mediated by the G protein-gated potassium channel I.

Authors:  Lev Koyrakh; Maria I Roman; Volker Brinkmann; Kevin Wickman
Journal:  Am J Transplant       Date:  2005-03       Impact factor: 8.086

5.  Immunomodulator FTY720 Induces eNOS-dependent arterial vasodilatation via the lysophospholipid receptor S1P3.

Authors:  Markus Tölle; Bodo Levkau; Petra Keul; Volker Brinkmann; Günter Giebing; Gilbert Schönfelder; Michael Schäfers; Karin von Wnuck Lipinski; Joachim Jankowski; Vera Jankowski; Jerold Chun; Walter Zidek; Markus Van der Giet
Journal:  Circ Res       Date:  2005-03-31       Impact factor: 17.367

6.  Oral-intravenous crossover study of fingolimod pharmacokinetics, lymphocyte responses and cardiac effects.

Authors:  John M Kovarik; Stefan Hartmann; Michael Bartlett; Gilles-Jacques Riviere; Daniel Neddermann; Yibin Wang; Andreas Port; Robert L Schmouder
Journal:  Biopharm Drug Dispos       Date:  2007-03       Impact factor: 1.627

Review 7.  Signaling and biological actions of sphingosine 1-phosphate.

Authors:  Timothy Hla
Journal:  Pharmacol Res       Date:  2003-05       Impact factor: 7.658

8.  A method for estimating the probability of adverse drug reactions.

Authors:  C A Naranjo; U Busto; E M Sellers; P Sandor; I Ruiz; E A Roberts; E Janecek; C Domecq; D J Greenblatt
Journal:  Clin Pharmacol Ther       Date:  1981-08       Impact factor: 6.875

9.  Delayed fingolimod-associated asystole.

Authors:  Patricio S Espinosa; Joseph R Berger
Journal:  Mult Scler       Date:  2011-06-07       Impact factor: 6.312

10.  A mechanistic study to assess whether isoproterenol can reverse the negative chronotropic effect of fingolimod.

Authors:  John M Kovarik; Gilles-Jacques Riviere; Daniel Neddermann; Steve Maton; Thomas L Hunt; Robert L Schmouder
Journal:  J Clin Pharmacol       Date:  2008-01-24       Impact factor: 3.126

  10 in total
  1 in total

Review 1.  Abuse and dependence potential of sphingosine-1-phosphate (S1P) receptor modulators used in the treatment of multiple sclerosis: a review of literature and public data.

Authors:  Kerri A Schoedel; Carine Kolly; Anne Gardin; Srikanth Neelakantham; Kasra Shakeri-Nejad
Journal:  Psychopharmacology (Berl)       Date:  2021-11-13       Impact factor: 4.530

  1 in total

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