Deliberate Fingolimod Overdose Presenting with Delayed Hypotension and Bradycardia Responsive to Atropine

• Published in: Journal of medical toxicology 2014-06, Vol.10 (2), p.215-218
• Main Authors: Stephenson, M., Wong, A., Rotella, J. A., Crump, N., Kerr, F., Greene, S. L.
• Format: Article
• Language: English
• Subjects: Adult; Antidotes - therapeutic use; Atropine; Atropine - therapeutic use; Biomedical and Life Sciences; Biomedicine; Blood pressure; Bradycardia; Bradycardia - drug therapy; Bradycardia - etiology; Combined Modality Therapy - adverse effects; Drug Overdose - physiopathology; Drug Overdose - therapy; Emergency medical services; Female; Fingolimod Hydrochloride; Heart rate; Hemodynamics; Humans; Hypotension; Hypotension - drug therapy; Hypotension - etiology; Immunosuppressive Agents - antagonists & inhibitors; Immunosuppressive Agents - poisoning; Ingestion; Intravenous administration; Multiple sclerosis; Muscarinic Antagonists - therapeutic use; Overdose; Pharmacology; Pharmacology/Toxicology; Poisoning; Propylene Glycols - antagonists & inhibitors; Propylene Glycols - poisoning; Sphingosine - analogs & derivatives; Sphingosine - antagonists & inhibitors; Sphingosine - poisoning; Sphingosine 1-phosphate; Telemetry; Time Factors; Toxicity; Toxicology Observation; Treatment Outcome
• ISSN: 1556-9039; 1937-6995
• DOI: 10.1007/s13181-013-0354-3

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.