Abstract
Dendritic epithelial keratitis is most commonly caused by infections of herpes simplex virus (HSV) type 1 (HSV-1), and less frequently by HSV type 2 (HSV-2). Ganciclovir, a guanosine nucleoside analogue, is a well established broad-spectrum antiviral agent that inhibits replication of viral DNA and is active against both HSV-1 and -2 and several other viruses. Ganciclovir ophthalmic gel 0.15% is a five-times-daily topical preparation that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers).
A randomized, open-label, phase III trial in immunocompetent patients with acute herpetic keratitis showed that ganciclovir ophthalmic gel 0.15% applied five times daily provided effective clinical resolution of dendritic ulcers following 7 days of treatment (primary endpoint). Moreover, a retrospective analysis of noninferiority showed that ganciclovir ophthalmic gel 0.15% was no less effective than aciclovir (acyclovir) ointment 3%.
A pooled analysis of three randomized, single-masked, phase II multinational trials also showed high rates of dendritic ulcer healing at day 7 for eyes treated with ganciclovir ophthalmic gel 0.15% and aciclovir ointment 3%. Furthermore, in the individual phase II trials, most patients showed evidence of healed dendritic and geographic ulcers at day 14 in either treatment arm. Median healing times with either treatment ranged from 6 to 10 days.
Ganciclovir ophthalmic gel 0.15% was generally well tolerated and was associated with a significantly lower incidence of visual disturbances than aciclovir ointment 3% in the phase III trial.
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References
Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea 2001 Jan; 20(1): 1–13
Chaney SM, Warren KG, Kettyls J, et al. A comparative analysis of restriction enzyme digests of the DNA of herpes simplex virus isolated from genital and facial lesions. J Gen Virol 1983 Feb; 64 (Pt 2): 357–71
Xu F, Sternberg MR, Kottiri BJ, et al. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA 2006 Aug 23; 296(8): 964–73
Wilhelmus KR. The treatment of herpes simplex virus epithelial keratitis. Trans Am Ophthalmol Soc 2000; 98: 505–32
National Eye Institute. Facts about the cornea and corneal disease [online]. Available from URL: http://www.nei.nih.gov/health/cornealdisease/ [Accessed 2010 Dec 21]
Foster C. Ganciclovir gel: a new topical treatment for herpetic keratitis. US Ophthal Rev 2008; 3: 52–6
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res 2006 Jul; 25(4): 355–80
Tabbara KF. Pharmacologic strategies in the prevention and treatment of corneal transplant rejection. Int Ophthalmol 2008 Jun; 28(3): 223–32
Wilhelmus K. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev 2010; (12): CD002898
O’Brien JJ, Campoli-Richards DM. Acyclovir: an updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1989 Mar; 37(3): 233–309
Kaufman HE. Ganciclovir: a promising topical antiviral gel for herpetic keratitis. Expert Rev Ophthalmol 2009; 4(4): 367–75
McGavin JK, Goa KL. Ganciclovir: an update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients. Drugs 2001; 61(8): 1153–83
Faulds D, Heel RC. Ganciclovir: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in cytomegalovirus infections. Drugs 1990 Apr; 39(4): 597–638
Crumpacker CS. Ganciclovir. N Engl J Med 1996 Sep 5; 335(10): 721–9
Trousdale MD, Goldschmidt PL, Nobrega R. Activity of ganciclovir against human adenovirus type-5 infection in cell culture and cotton rat eyes. Cornea 1994 Sep; 13(5): 435–9
Drug Information Online. Virgan eye gel [online]. Available from URL: http://www.drugs.com/uk/virgan-eye-gel-spc-3322.html [Accessed 2011 Mar 2]
Bausch & Lomb Inc. Zirgan (ganciclovir ophthalmic gel 0.15%): US prescribing information [online]. Available from URL: http://www.bausch.com/en_US/downloads/ecp/pharma/Zirganpackage_insert.pdf [Accessed 2011 Mar 2]
Matthews T, Boehme R. Antiviral activity and mechanism of action of ganciclovir. Rev Infect Dis 1988 Jul 31; 10 Suppl 3: S490–4
Colin J. Ganciclovir ophthalmic gel, 0.15%: a valuable tool for treating ocular herpes. Clin Ophthalmol 2007 Dec; 1(4): 441–53
Levin MJ, Bacon TH, Leary JJ. Resistance of herpes simplex virus infections to nucleoside analogues in HIV-infected patients. Clin Infect Dis 2004 Nov 1; 39 Suppl 5: S248–57
Duan R, de Vries RD, Osterhaus AD, et al. Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis. J Infect Dis 2008 Sep 1; 198(5): 659–63
Hoh HB, Hurley C, Claoue C, et al. Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis: a multicentre study. Br J Ophthalmol 1996 Feb; 80(2): 140–3
Chribret H, Elena PP, Khosravi E. Ocular pharmacokinetics of topically-applied ganciclovir in rabbits with intact or removed corneal epithelium [abstract no. 1712]. Invest Ophthalmol Vis Sci 1993; 34(4): 1050
Elena PP, Goldschimdt P, Chast F, et al. Distribution of ganciclovir in the anterior uvea after topical application of 0.15% ganciclovir gel to the intact HSV-infected eyes of rabbits [abstract no. 1984]. Invest Ophthalmol Vis Sci 1994; 35(4): 1682
Khosravi E, Elena PP, Goldschimdt P, et al. Ocular bioavailability of ganciclovir gel, an anti-herpetic formulation, after topical administration to intact or removed corneal epithelium of rabbit eyes [abstract no. 383]. Invest Ophthalmol Vis Sci 1996; 37(3): S81
Colin J, Hoh HB, Easty DL, et al. Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis. Cornea 1997 Jul; 16(4): 393–9
US FDA. NDA 22-211 Medical review(s): ganciclovir ophthalmic gel 0.15% [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022211s000_MedR.pdf [Accessed 2011 Jan 17]
Acknowledgements and Disclosures
This manuscript was reviewed by J. Colin, Centre Hospitalier Universitaire Pellegrin, Bordeaux Cedex, France; A. D. Osterhaus, Department of Virology, Erasmus University, Rotterdam, the Netherlands; K. R. Wilhelmus, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA.
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
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Croxtall, J.D. Ganciclovir Ophthalmic Gel 0.15%. Drugs 71, 603–610 (2011). https://doi.org/10.2165/11207240-000000000-00000
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DOI: https://doi.org/10.2165/11207240-000000000-00000