title: Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Emergency Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Stephenson
authors.forename: A
authors.initials: A
authors.lastname: Wong
authors.forename: J A
authors.initials: JA
authors.lastname: Rotella
authors.forename: N
authors.initials: N
authors.lastname: Crump
authors.forename: F
authors.initials: F
authors.lastname: Kerr
authors.forename: S L
authors.initials: SL
authors.lastname: Greene
mesh_terms: D000328:Adult; D000931:Antidotes / Q000627:therapeutic use; D001285:Atropine / Q000627:therapeutic use*; D001919:Bradycardia / Q000188:drug therapy* / Q000209:etiology; D003131:Combined Modality Therapy / Q000009:adverse effects; D062787:Drug Overdose / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007022:Hypotension / Q000188:drug therapy* / Q000209:etiology; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000506:poisoning*; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D011409:Propylene Glycols / Q000037:antagonists & inhibitors / Q000506:poisoning*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000506:poisoning; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000931:Antidotes; D007166:Immunosuppressive Agents; D018727:Muscarinic Antagonists; D011409:Propylene Glycols; D001285:Atropine; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine