Vorapaxar and diplopia: Possible off-target PAR-receptor mismodulation

Thrombosis and Haemostasis

Volumn 115, Issue 5, 2016, Pages 905-910

  Serebruany, Victor L ^a,b   Fortmann, Seth D ^b   Rao, Sunil V ^c   Tanguay, Jean Francois ^d   Lordkipanidze, Marie ^d   Hanley, Daniel F ^a   Can, Mehmet ^e   Kim, Moo Hyun ^f   Marciniak, Thomas A ^g  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b HeartDrug Research Laboratories   (United States)

^c DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d MONTREAL HEART INSTITUTE   (Canada)

^e Haseki Education and Training Hospital   (Turkey)

^f Dong A University College of Medicine   (South Korea)

^g NONE   (United States)

Author keywords

Adverse events; Clinical trials; Diplopia; PAR receptor; Safety; Vorapaxar

Indexed keywords

ACETYLSALICYLIC ACID PLUS CLOPIDOGREL; PLACEBO; PROTEINASE ACTIVATED RECEPTOR; PROTEINASE ACTIVATED RECEPTOR 1; PROTEINASE ACTIVATED RECEPTOR 2; PROTEINASE ACTIVATED RECEPTOR 3; PROTEINASE ACTIVATED RECEPTOR 4; VORAPAXAR; ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; LACTONE; PYRIDINE DERIVATIVE; TICLOPIDINE;

ARTICLE; BLEEDING; CONJUNCTIVA; CORNEA; DIPLOPIA; DRUG EFFICACY; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; FOLLOW UP; HEART INFARCTION; HUMAN; LACRIMAL GLAND; LENS; MULTICENTER STUDY (TOPIC); NONHUMAN; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RETINA; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; DRUG APPROVAL; DRUG EFFECTS; EYE; FOOD AND DRUG ADMINISTRATION; METABOLISM; UNITED STATES;

ANIMALS; ASPIRIN; DIPLOPIA; DRUG APPROVAL; EYE; HUMANS; LACTONES; PERIPHERAL ARTERIAL DISEASE; PLATELET AGGREGATION INHIBITORS; PYRIDINES; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECEPTOR, PAR-1; RECEPTORS, PROTEINASE-ACTIVATED; TICLOPIDINE; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84964835087     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH15-11-0882     Document Type: Article

References (43)

1. Storey RF, Kotha J, Smyth SS, et al. Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy. Thromb Haemost 2014; 111: 883-891.
2. Tricoci P, Huang Z, Held C, et al.; the TRACER Investigators. Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes. N Engl J Med 2012; 366: 20-33.
3. Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012; 366: 1404-1413.
4. NDA 294-886. Medical reviews on Vorapaxar. June 18th, 2014 Available at: www.accessdata.fda.gov/drugsatfda_docs/nda/2014/204886Orig1s000MedR. pdf. Accessed May 15, 2015.
5. NDA 294-886. Cross-discipline Team Leader review on Vorapaxar. April 18th, 2014 Available at: http://www.accessdata.fda.gov/drugsatfda_docs/ nda/2014/204886Orig1s000SumR.pdf. Accessed May 15, 2015.
6. Sowka J. Neurogenic diplopia: paralysis of cranial nerves III, IV, and VI. Optom Clin 1996; 5: 53-76.
7. Dinkin M. Diagnostic approach to diplopia. Continuum 2014; 20: 942-965.
8. Fraine L. Nonsurgical management of diplopia. Am Orthopt J 2012; 62: 13-18.
9. Chhabra MS, Golnik KC. Recovery of ocular motor cranial nerve palsy after herpes zoster ophthalmicus. J Neuroophthalmol 2014; 34: 20-22.
10. Schmidt RF, Yick F, Boghani Z, et al. Malignant peripheral nerve sheath tumors of the trigeminal nerve: a systematic review of 36 cases. Neurosurg Focus 2013; 34: E5.
11. Fraser CL, Skalicky SE, Gurbaxani A, et al. Ocular myositis. Curr Allergy Asthma Rep 2013; 13: 315-321.
12. Penedones A, Mendes D, Alves C, et al. Drug-induced ocular adverse reactions: review of the safety alerts issued during the last decade. J Ocul Pharmacol Ther 2015; 31: 258-268.
13. Lucca JM, Ramesh M, Parthasarathi G, et al. Lorazepam-induced diplopia. Indian J Pharmacol 2014; 46: 228-229.
14. Karadag H, Acar M, Özdel K. Aripiprazole Induced Acute Transient Bilateral Myopia: A Case Report. Balkan Med J 2015; 32: 230-232.
15. Mellon G, Stitou H, Aoun O, et al. Lateral rectus muscle paralysis induced by ribavirin and pegylated interferon-α2a in a patient with HIV/HCV co-infection. J Infect Chemother 2012; 18: 937-938.
16. Fraunfelder FW, Fraunfelder FT. Diplopia and fluoroquinolones. Ophthalmology 2009; 116: 1814-1817.
17. Fraunfelder FW, Richards AB. Diplopia, blepharoptosis, and ophthalmoplegia and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor use. Ophthalmology 2008; 115: 2282-2285.
18. Mowla A, Ghanizadeh A, Ashkani H. Diplopia with citalopram: a case report. J Clin Psychopharmacol 2005; 25: 623-624.
19. Kalis MM, Huff NA. Oxcarbazepine, an antiepileptic agent. Clin Ther 2001; 23: 680-700.
20. Openshaw H, Slatkin NE, Smith E. Eye movement disorders in bone marrow transplant patients on cyclosporin and ganciclovir. Bone Marrow Transplant 1997; 19: 503-505.
21. Wutthiphan S, Kowal L, O'Day J, et al. Diplopia following subcutaneous injections of botulinum A toxin for facial spasms. J Pediatr Ophthalmol Strabismus 1997; 34: 229-234.
22. Digre KB, Varner MW, Schiffman JS. Neuroophthalmologic effects of intravenous magnesium sulfate. Am J Obstet Gynecol 1990; 163: 1848-1852.
23. Rubin ML, Thomas WC Jr. Diplopia and loss of accommodation due to chloroquine. Arthritis Rheum 1970; 13: 75-82.
24. Luo W, Wang Y, Reiser G. Two types of protease-activated receptors (PAR-1 and PAR-2) mediate calcium signaling in rat retinal ganglion cells RGC-5. Brain Res 2005; 1047: 159-167.
25. Rohatgi T, Sedehizade F, Sabel BA, et al. Protease-activated receptor subtype expression in developing eye and adult retina of the rat after optic nerve crush. J Neurosci Res 2003; 73: 246-254.
26. Joyal JS, Nim S, Zhu T, et al. Subcellular localisation of coagulation factor II receptor-like 1 in neurons governs angiogenesis. Nat Med 2014; 20: 1165-1173.
27. Cowan C, Muraleedharan CK, O'Donnell JJ 3rd, et al. MicroRNA-146 inhibits thrombin-induced NF-κB activation and subsequent inflammatory responses in human retinal endothelial cells. Invest Ophthalmol Vis Sci 2014; 55: 4944-4951.
28. Bastiaans J, van Meurs JC, van Holten-Neelen C, et al. Factor Xa and thrombin stimulate proinflammatory and profibrotic mediator production by retinal pigment epithelial cells: a role in vitreoretinal disorders? Graefes Arch Clin Exp Ophthalmol 2013; 251: 1723-1733.
29. Peng Y, Zhang J, Xu H, et al. Neuroprotective effect of protease-activated receptor-2 in the hypoxia-induced apoptosis of rat RGC-5 cells. J Mol Neurosci 2013; 50: 98-108.
30. Narayan S, Prasanna G, Tchedre K, et al. Thrombin-induced endothelin-1 synthesis and secretion in retinal pigment epithelial cells is rho kinase dependent. J Ocul Pharmacol Ther 2010; 26: 389-397.
31. James C, Collison DJ, Duncan G. Characterisation and functional activity of thrombin receptors in the human lens. Invest Ophthalmol Vis Sci 2005; 46: 925-932.
32. Lang R, Song PI, Legat FJ, et al. Human corneal epithelial cells express functional PAR-1 and PAR-2. Invest Ophthalmol Vis Sci 2003; 44: 99-105.
33. Tripathi T, Abdi M, Alizadeh H. Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2014; 55: 3912-3921.
34. Satpathy M, Gallagher P, Jin Y, et al. Extracellular ATP opposes thrombin-induced myosin light chain phosphorylation and loss of barrier integrity in corneal endothelial cells. Exp Eye Res 2005; 81: 183-192.
35. Yeoh S, Church M, Lackie P, et al. Increased conjunctival expression of protease activated receptor 2 (PAR-2) in seasonal allergic conjunctivitis: a role for abnormal conjunctival epithelial permeability in disease pathogenesis? Br J Ophthalmol 2011; 95: 1304-1308.
36. Nickel TJ, Kabir MH, Talreja J, et al. Constitutive expression of functionally active protease-activated receptors 1 and 2 in human conjunctival epithelial cells. Mediators Inflamm 2006; 3: 61359.
37. Asano-Kato N, Fukagawa K, Okada N, et al. Tryptase increases proliferative activity of human conjunctival fibroblasts through protease-activated receptor-2. Invest Ophthalmol Vis Sci 2005; 46: 4622-4626.
38. Oikawa M, Saino T, Kimura K, et al. Effects of protease-activated receptors (PARs) on intracellular calcium dynamics of acinar cells in rat lacrimal glands. Histochem Cell Biol 2013; 140: 463-476.
39. Oh SJ, Han KS, Park H, et al. Protease activated receptor 1-induced glutamate release in cultured astrocytes is mediated by Bestrophin-1 channel but not by vesicular exocytosis. Mol Brain 2012; 5: 38.
40. Huang H, Vasilakis P, Zhong X, et al. Parstatin suppresses ocular neovascularisation and inflammation. Invest Ophthalmol Vis Sci 2010; 51: 5825-5832.
41. Serebruany VL. Redesigning TRACER after TRITON. Intern J Cardiol 2015; 197: 44-47.
42. Vries MJ, van der Meijden PE, Henskens YM, et al. Assessment of bleeding risk in patients with coronary artery disease on dual antiplatelet therapy. A systematic review.Thromb Haemost 2016; 115: 7-24.
43. Serebruany VL, Cherepanov V, Cabrera-Fuentes HA, et al. Solid cancers after antiplatelet therapy: Confirmations, controversies, and challenges. Thromb Haemost 2015; 114: 1104-1112.