The Role of Ganciclovir for the Management of Cytomegalovirus Retinitis in HIV Patients: Pharmacological Review and Update on New Developments

Abstract

OBJECTIVE: To review the pharmacology and pharmacokinetics of intravenous, oral and intraocular ganciclovir, and to discuss the role of these various formulations in the management of cytomegalovirus (CMV) retinitis in AIDS patients.DATA SOURCES: A MEDLINE search (1987 through November 1995) of English-language literature using the main medical subject headings ‘ganciclovir’ and ‘cytomegalovirus’, and the subheading ‘acquired immunodeficiency syndrome’. Relevant articles were also selected from references of identified articles. Abstracts from recent medical conferences of infectious diseases, pharmacology and human immunodeficiency virus were screened for additional data.STUDY SELECTION AND DATA EXTRACTION: All articles and abstracts discussing the use of ganciclovir for the management or prophylaxis of CMV retinitis in AIDS patients were considered for inclusion. Pertinent information, as judged by the authors, was selected and synthesized for discussion.DATA SYNTHESIS: Ganciclovir has demonstrated virustatic activity against CMV, and is often administered 5 mg/kg intravenously every 12 h as first-line therapy for CMV retinitis. Intravenous maintenance therapy at 5 mg/kg daily is usually effective at delaying retinitis progression for approximately 60 to 70 days. Neutropenia and thrombocytopenia are observed frequently, often necessitating interruption or discontinuation of therapy. Local drug administration may delay disease progression even further, and may be considered for patients who are intolerant to or failing intravenous therapy. However, systemic ganciclovir should be encouraged to reduce the risk of developing contralateral eye or end-organ CMV disease. Oral ganciclovir at 1 g tid is almost as effective as intravenous ganciclovir 5 mg/kg/day in delaying retinitis progression and is associated with fewer line-related complications. Absorption, drug interactions, cost and compliance should also be considered.CONCLUSIONS: Until recently, ganciclovir was available only for intravenous use. Recent developments allow for intraocular and oral administration of this agent. A clear understanding of the advantages and disadvantages of these new formulations is required in order to select the most appropriate product for managing CMV retinitis in AIDS patients.