Antihistamines in Ocular Allergy: Are They All Created Equal?
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Use of topical antihistamines in the treatment of allergic conjunctivitis has evolved over the past several decades as our knowledge of the nature of the underlying disease has progressed. Formulations for the eye typically employ H1-receptor antagonists with a dual action, both directly as competitors for histamine receptor occupancy and as mast cell–stabilizing agents. Many of these compounds also display activity against late-phase allergic symptoms. Of the newest available drugs, several have a prolonged duration of action allowing once-daily dosing. Future development is likely to focus on long-acting agents such as these and on drugs that can target additional histamine receptor subtypes.
KeywordsConjunctivitis CAC Olopatadine Alcaftadine
Dr. Abelson has served as a consultant for Alcon.
Dr. McLaughlin and Mr. Gomes are employees of Ora Inc.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 5.Collum LMT, Kilmartin DJ. Acute allergic conjunctivitis. In Allergic Diseases of the Eye. Philadelphia: WB Saunders Co; 2000. p. 108–32.Google Scholar
- 6.Label and approval history, Vasocon; Available at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist. Accessed February 21, 2011.
- 16.Abelson MB, Berdy GJ, Mundorf T, Amdahl LD. Pemirolast study group. Pemirolast potassium 0.1% ophthalmic solution is an effective treatment for allergic conjunctivitis: a pooled analysis of two prospective, randomized, double-masked, placebo-controlled, phase III studies. J Ocul Pharmacol Ther. 2002;18:475–88.PubMedCrossRefGoogle Scholar
- 17.Abelson MB, Wun PJ, Nevius JM. Mast cell stabilizers. In Allergic Diseases of the Eye. Philadelphia: WB Saunders Co; 2000. p. 228–34.Google Scholar
- 18.Butrus S, Portela R. Ocular allergy: diagnosis and treatment. Ophthalmol Clin N Am. 2005;18:485–92.Google Scholar
- 24.Secchi A, Leonardi A, Discepola M, Deschenes J, Abelson MB, the Emadine Study Group. An efficacy and tolerance comparison of emedastine difumarate 0.05% and levocabastine hydrochloride 0.05%: reducing chemosis and eyelid swelling in subjects with seasonal allergic conjunctivitis. Acta Ophthalmol. 2000;78 Suppl 230:48–51.CrossRefGoogle Scholar
- 25.• Qasem AR, Bucolo C, Baiula M, Spartà A, Govoni P, Bedini A, Fascì D, Spampinato S. Contribution of alpha4beta1 integrin to the antiallergic effect of levocabastine. Biochem Pharmacol. 2008;76:751–62. This was one of several studies providing insight into mechanisms of late-phase effects of antihistamines.Google Scholar
- 27.Secchi A, Ciprandi G, Leonardi A, Deschenes J, Abelson MB. Safety and efficacy comparison of emedastine 0.05% ophthalmic solution compared to levocabastine 0.05% ophthalmic suspension in pediatric subjects with allergic conjunctivitis. Emadine Study Group. Acta Ophthalmol Scand Suppl. 2000;230:42–7.PubMedCrossRefGoogle Scholar
- 30.• Leonardi A, Quintieri L. Olopatadine: a drug for allergic conjunctivitis targeting the mast cell. Expert Opin Pharmacother. 2010;116:969–81. This article provides an excellent synopsis of this first-in-class medication. Google Scholar
- 39.Avunduk AM, Tekelioglu Y, Turk A, Akyol N. Comparison of the effects of ketotifen fumarate 0.025% and olopatadine HCl 0.1% ophthalmic solutions in seasonal allergic conjunctivities: a 30-day, randomized, double-masked, artificial tear substitute-controlled trial. Clin Ther. 2005;27:1392–402.PubMedCrossRefGoogle Scholar
- 42.• Abelson MB, Gomes PJ. Olopatadine 0.2% ophthalmic solution: the first ophthalmic anti-allergy agent with once-daily dosing. Expert Opin Drug Metab Toxicol. 2008; 4:453–61. This article provided a clinical description of this paradigm-shifting reformulation, the first once-daily ocular antihistamine. Google Scholar
- 43.Abelson MB, Spangler DL, Epstein AB, Mah FS, Crampton HJ. Efficacy of once-daily olopatadine 0.2% ophthalmic solution compared to twice-daily olopatadine 0.1% ophthalmic solution for the treatment of ocular itching induced by conjunctival allergen challenge. Curr Eye Res. 2007;32(12):1017–22.PubMedCrossRefGoogle Scholar
- 48.• Borazan M, Karalezli A, Akova YA, Akman A, Kiyici H, Erbek SS. Efficacy of olopatadine HCI 0.1%, ketotifen fumarate 0.025%, epinastine HCI 0.05%, emedastine 0.05% and fluorometholone acetate 0.1% ophthalmic solutions for seasonal allergic conjunctivitis: a placebo-controlled environmental trial. Acta Ophthalmol. 2009; 87:549–54. This was a rare head-to- head clinical study with five of the most commonly used topical agents. Google Scholar
- 50.• Kida T, Fujii A, Sakai O, Iemura M, Atsumi I, Wada T, Sakaki H. Bepotastine besilate, a highly selective histamine H1 receptor antagonist, suppresses vascular hyperpermeability and eosinophil recruitment in in vitro and in vivo experimental allergic conjunctivitis models. Exp Eye Res. 2010; 91:85–91. This was yet another one of several studies providing insight into mechanisms of late-phase effects of antihistamines.Google Scholar
- 51.Bohets H, McGowanC, Mannens G, Schroeder N, Edwards-Swanson K, Shapiro A. Clinical pharmacology of alcaftadine, a novel antihistamine for the prevention of allergic conjunctivitis. J Ocul Pharmacol Ther. 2011 Feb 12 (Epub ahead of print).Google Scholar
- 52.• Engelhardt H, Smits RA, Leurs R, Haaksma E, de Esch IJ. A new generation of anti-histamines: histamine H4 receptor antagonists on their way to the clinic. Curr Opin Drug Discov Devel. 2009; 12:628–43. This article provides an excellent perspective on the potential for H 4 -targeted pharmacotherapy. Google Scholar
- 53.Saravanan C, Bharti SK, Jaggi S, Singh SK. Histamine H(4) receptor: a novel target for inflammation therapy. Mini Rev Med Chem. 2011 Jan 11 (Epub ahead of print).Google Scholar
- 61.Smuda C, Bryce PJ. New developments in the use of histamine and histamine receptors. Curr Allergy Asthma Rep. 2010 Nov 23 (Epub ahead of print).Google Scholar
- 64.• Nakano Y, Takahashi Y, Ono R, Kurata Y, Kagawa Y, Kamei C. Role of histamine H4 receptor in allergic conjunctivitis in mice. Eur J Pharmacol. 2009;608:71–5. This was a simple, elegant study establishing the potential importance of H 4 -receptors in ocular allergy. Google Scholar
- 67.Greiner JV, Edwards-Swanson K, Ingerman A. Evaluation of alcaftadine 0.25% ophthalmic solution in acute allergic conjunctivitis at 15 min and 16 h after instillation versus placebo and olopatadine 0.1%. Clinical. Ophthalmology. 2011;5:87–93.Google Scholar
- 68.• Ono SJ, Lane K. Comparison of effects of alcaftadine and olopatadine on conjunctival epithelium and eosinophil recruitment in a murine model of allergic conjunctivitis. Drug Design, Development and Therapy 2011;5:77–84. This was yet another one of several studies providing insight into mechanisms of late-phase effects of antihistamines.Google Scholar