Description

Simple

A medication used to treat multiple sclerosis (MS) and being studied to help manage lung problems caused by COVID-19.

Clinical

A sphingosine 1-phosphate receptor modulator used to treat patients with the relapsing-remitting form of multiple sclerosis (MS) and studied to manage lung complications of COVID-19.

Overview

Multiple sclerosis or MS is a devastating inflammatory disease that often progresses and causes severe neurological, physical, and cognitive effects.[3] Fingolimod is a sphingosine 1-phosphate receptor modulator for the treatment of relapsing-remitting multiple sclerosis. It was developed by Novartis and initially approved by the FDA in 2010.[12]

Fingolimod is currently being studied for the treatment of COVID-19, the disease caused by infection with the SARS-CoV-2 virus. Phase 2 clinical trials are currently underway and completion is expected in July 2020.[13]

Pharmacology

Indication

Fingolimod is indicated for the treatment of patients aged 10 and above with relapsing forms of multiple sclerosis, which may include clinically isolated syndrome, relapsing-remitting disease, as well as active secondary progressive disease.[ Read more

Pharmacodynamic

In multiple sclerosis, fingolimod binds to sphingosine receptors, reducing its associated neuroinflammation.[12]In COVID-19, it may reduce lung inflammation and improve the clinica... Read more

Mechanism of action

Sphingosine‐1‐phosphate (S1P) is an important phospholipid that binds to various G‐protein‐coupled receptor subtypes, which can be identified as S1P1–5R. S1P and the receptors it binds to perform regular functions in the immune, cardiovascular, pulmonary, and nervous system.[ Read more

Absorption

Fingolimod is slowly but efficiently absorbed in the gastrointestinal tract. AUC varies greatly, depending on the patient, and pharmacokinetic studies demonstrate a range of AUC values for fingolimod.[ Read more

Protein binding

The protein binding of fingolimod and its active metabolite exceeds 99.7%.[5, Read more

Volume of distribution

The volume of distribution of fingolimod is about 1200±260 L. It is approximately 86% distributed in the red blood cells (RBC).[ Read more

Clearance

Fingolimod blood clearance is 6.3±2.3 L/h[12], according to prescribing information. Another resource mentions it ranges from 6-8 L/h.[ Read more

Half life

The half-life of fingolimod and its active metabolite ranges from 6-9 days.[5,... Read more

Route of elimination

About 81% of an oral dose of fingolimod is excreted in the urine in the form of inactive metabolites. Intact fingolimod and its active metabolite account for less than 2.5% of the dose, and can be found excreted in the feces.[ Read more

Toxicity

The LD50 of fingolimod in rats ranges from 300-600 mg/kg.[7]

Prescribing information for fingolimod does not mention symptoms or management of an overdos... Read more

Adverse Effects

Contraindications

  • Regions: US
  • With Categories Coadmin:
      • Name: Antiarrhythmics, Class III
      • Drugbank Id: DBCAT002208
  • Regions: US
  • With Categories Coadmin:
      • Name: Antiarrhythmics, Class Ia
      • Drugbank Id: DBCAT002277
  • Lab Values:
    • Baseline QTc interval ≥500 msec
  • Regions: US
  • Time Period: last 6 months
  • Regions: US
  • Patient Conditions:
      • Name: Class IV heart failure
      • Drugbank Id: DBCOND0108522
  • Time Period: last 6 months
  • Regions: US
  • Patient Conditions:
      • Name: Class III heart failure
      • Drugbank Id: DBCOND0108521
  • Time Period: last 6 months
  • Regions: US
  • Patient Conditions:
      • Name: Decompensated Heart Failure
      • Drugbank Id: DBCOND0035248
  • Time Period: last 6 months
  • Regions: US
  • Patient Conditions:
      • Name: Transient Ischemic Attack
      • Drugbank Id: DBCOND0029275
  • Time Period: last 6 months
  • Regions: US
  • Patient Conditions:
      • Name: Stroke
      • Drugbank Id: DBCOND0020609
  • Time Period: last 6 months
  • Regions: US
  • Patient Conditions:
      • Name: Unstable Angina
      • Drugbank Id: DBCOND0030047
  • Time Period: last 6 months
  • Regions: US
  • Patient Conditions:
      • Name: Myocardial Infarction
      • Drugbank Id: DBCOND0027900
  • Regions: US
  • Patient Conditions:
      • Name: Sick Sinus Syndrome
      • Drugbank Id: DBCOND0000493
  • Regions: US
  • Patient Conditions:
      • Name: Mobitz Type II third-degree AV block
      • Drugbank Id: DBCOND0108520
  • Regions: US
  • Patient Conditions:
      • Name: History of Mobitz Type II third-degree AV block
      • Drugbank Id: DBCOND0108519
  • Regions: US
  • Patient Conditions:
      • Name: Mobitz Type II second-degree Av block
      • Drugbank Id: DBCOND0108518
  • Regions: US
  • Patient Conditions:
      • Name: History of Mobitz Type II second-degree AV block
      • Drugbank Id: DBCOND0108517

Food Interactions

  • Take with or without food.

Interactions

Type in a drug name to check for interaction with Fingolimod
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
2-Methoxyethanol
2-Methoxyethanol may increase the immunosuppressive activities of Fingolimod.
9-(N-methyl-L-isoleucine)-cyclosporin A
9-(N-methyl-L-isoleucine)-cyclosporin A may increase the immunosuppressive activities of Fingolimod.
Abatacept
Abatacept may increase the immunosuppressive activities of Fingolimod.
Abetimus
Abetimus may increase the immunosuppressive activities of Fingolimod.
Acebutolol
Acebutolol may increase the bradycardic activities of Fingolimod.
Acetaminophen
Fingolimod may increase the hepatotoxic activities of Acetaminophen.
Acteoside
Acteoside may increase the immunosuppressive activities of Fingolimod.
Adalimumab
Adalimumab may increase the immunosuppressive activities of Fingolimod.
Ademetionine
The metabolism of Fingolimod can be decreased when combined with Ademetionine.
Adenovirus type 7 vaccine live
The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Fingolimod.
Afelimomab
Afelimomab may increase the immunosuppressive activities of Fingolimod.
Agmatine
Agmatine may increase the bradycardic activities of Fingolimod.
Ajmaline
Fingolimod may increase the arrhythmogenic activities of Ajmaline.
Aldesleukin
Aldesleukin may increase the immunosuppressive activities of Fingolimod.
Aldosterone
Aldosterone may increase the immunosuppressive activities of Fingolimod.
Alefacept
Alefacept may increase the immunosuppressive activities of Fingolimod.
Alemtuzumab
Alemtuzumab may increase the immunosuppressive activities of Fingolimod.
Alfentanil
Alfentanil may increase the bradycardic activities of Fingolimod.
Alprenolol
Alprenolol may increase the bradycardic activities of Fingolimod.
Altretamine
Altretamine may increase the immunosuppressive activities of Fingolimod.
15 References
  1. 1 . An X, Kezuka T, Usui Y, Matsunaga Y, Matsuda R, Yamakawa N, Goto H: Suppression of experimental autoimmune optic neuritis by the novel agent fingolimod. J Neuroophthalmol. 2013 Jun;33(2):143-8. doi: 10.1097/WNO.0b013e31828ea2fc.PubMed: 23609767
  2. 2 . Ali R, Nicholas RS, Muraro PA: Drugs in development for relapsing multiple sclerosis. Drugs. 2013 May;73(7):625-50. doi: 10.1007/s40265-013-0030-6.PubMed: 23609782
  3. 3 . Ghasemi N, Razavi S, Nikzad E: Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. 2017 Apr-Jun;19(1):1-10. Epub 2016 Dec 21.PubMed: 28367411
  4. 4 . Fakhoury M, Negrulj R, Mooranian A, Al-Salami H: Inflammatory bowel disease: clinical aspects and treatments. J Inflamm Res. 2014 Jun 23;7:113-20. doi: 10.2147/JIR.S65979. eCollection 2014.PubMed: 25075198
  5. 5 . David OJ, Kovarik JM, Schmouder RL: Clinical pharmacokinetics of fingolimod. Clin Pharmacokinet. 2012 Jan 1;51(1):15-28. doi: 10.2165/11596550-000000000-00000.PubMed: 22149256
  6. 6 . Tran JQ, Hartung JP, Tompkins CA, Frohna PA: Effects of High- and Low-Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator. Clin Pharmacol Drug Dev. 2018 Aug;7(6):634-640. doi: 10.1002/cpdd.409. Epub 2017 Nov 10.PubMed: 29125718
  7. 7 . Dumont FJ: Fingolimod. Mitsubishi Pharma/Novartis. IDrugs. 2005 Mar;8(3):236-53.PubMed: 15772896
  8. 8 . Stephenson M, Wong A, Rotella JA, Crump N, Kerr F, Greene SL: Deliberate fingolimod overdose presenting with delayed hypotension and bradycardia responsive to atropine. J Med Toxicol. 2014 Jun;10(2):215-8. doi: 10.1007/s13181-013-0354-3.PubMed: 24178903
  9. 9 . Enjeti AK, D'Crus A, Melville K, Verrills NM, Rowlings P: A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia. Anticancer Drugs. 2016 Jul;27(6):560-8. doi: 10.1097/CAD.0000000000000358.PubMed: 26967515
  10. 10 . Tran JQ, Hartung JP, Peach RJ, Boehm MF, Rosen H, Smith H, Brooks JL, Timony GA, Olson AD, Gujrathi S, Frohna PA: Results From the First-in-Human Study With Ozanimod, a Novel, Selective Sphingosine-1-Phosphate Receptor Modulator. J Clin Pharmacol. 2017 Aug;57(8):988-996. doi: 10.1002/jcph.887. Epub 2017 Apr 11.PubMed: 28398597
  11. 11 . Chaudhry BZ, Cohen JA, Conway DS: Sphingosine 1-Phosphate Receptor Modulators for the Treatment of Multiple Sclerosis. Neurotherapeutics. 2017 Oct;14(4):859-873. doi: 10.1007/s13311-017-0565-4.PubMed: 28812220
  12. 12 . FDA Approved Products: Gilenya (fingolimod) oral capsules Link
  13. 13 . Clinicaltrials.gov: Fingolimod in COVID-19 Link
  14. 14 . Clinical trials on drug repositioning for COVID-19 treatment Link
  15. 15 . European Medicines Agency Public Assessment Report: Gilenya (fingolimod) Link