Ganciclovir therapy

Elderly Pharmacokinetic profile in elderly patients is not established. Because elderly individuals frequently have a reduced glomerular filtration rate, pay particular attention to assessing renal function before and during ganciclovir therapy. 

Male patients should use barrier contraception during ganciclovir therapy and for 90 days afterward because of the drug s mutagenic potential... 

Bilbao R, Gerolami R, Bralet MR et al. Transduction efficacy, antitumoral effect, and toxicity of adenovirus-mediated herpes simplex virus thymidine kinase/ ganciclovir therapy of hepatocellular carcinoma the woodchuck animal model. Cancer Gene Ther 2000 7(5) 657-662. 

The dose-limiting and most common adverse effect wdth intravenous and oral ganciclovir is bone marrow suppression (anemia, leukopenia, neutropenia, and thrombocytopenia). These effects are usually reversible upon w ithdraw al of the drug. CNS side effects are less common and range in severity from headache to behavioral changes to convulsions and coma. Fever, edema, phlebitis, disorientation, nausea, anorexia, rash, and myalgias have also been reported w ith ganciclovir therapy (Markham and Faulds, 1994). 

Roche, B., Samuel, D., Gigou, M., Feray, C., Virot, V., Majno, P., Ser-raf, L., David, M.F., Dusseaix, E., Reynes, M., Bismuth, H. Long-term ganciclovir therapy for hepatitis B virus infection after transplantation. J. Hepatol. 1999 31 584-592... 

The proportion of patients in whom ganciclovir therapy is subsequently interrupted or withdrawn because of adverse effects is estimated at 32% (1). 

Thomson MH, Jeffries DJ. Ganciclovir therapy in iatrogeni-cally immunosuppressed patients with cytomegalovirus disease. J Antimicrob Chemother 1989 23(Suppl E) 61-70. 

Luscombe, C., Pederson, J., Bowden, S., and Locarnini, S. (1994) Alterations in intrahepat.ic expression of duck hepatitis B viral markers with ganciclovir therapy. Liver 14, 182-192. 

Roberts TC, Brennan DC, Buller RS, Gaudreault-Keener M, Schnitzler MA, Sternahell KA, et al. Quantitative polymerase chain reaction to predict occurrence of symptomatic cytomegalovirus infection and assess response to ganciclovir therapy in renal transplant recipients. J Infect Dis 1998 178 626-35. 

Singh N, Yu VL, Mieles L, et al. High-dose acyclovir compared with short-course preemptive ganciclovir therapy to prevent cytomegalovirus disease in liver transplant recipients. Ann Intern Med 1994 120 375-381. 

Studies of Ocular Complications of AIDS Research Group in Collaboration with the AIDS Clinical Trial Group. Combination foscarnet and ganciclovir therapy vs monotherapy for the treatment of relapsed cytomegalovirus retinitis in patients with AIDS. Arch Ophthamol 1996 114 23-33. 

Sanborn GE, Anand R, Torti RE, et al. Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Arch Ophthalmol 1992 110 188-195. 

Heinemann MH. Long-term intravitreal ganciclovir therapy for cytomegalovirus retinopathy. Arch Ophthalmol 1989 107 1767. 

CNS side effects occur in 5 to 15% of patients, and range in severity from headache to behavioral changes to convulsions and coma. About one-third of patients have had to interrupt or prematurely stop intravenous ganciclovir therapy because of bone marrow or CNS toxicity. Infusion-related phlebitis, azotemia, anemia, rash, fever, liver function test abnormahties, nausea or vomiting, and eosinophiha also have been described. 

Ganciclovir therapy (5 mg/kg every 12 hours for 14 to 21 days) may benefit other CMV syndromes in AIDS patients or solid-organ-transplant recipients. Response rates of 67% or higher have been found in combination with a decrease in immunosuppressive therapy. The duration of therapy depends on demonstrating clearance of viremia an early switch from intravenous ganciclovir to oral valganciclovir is feasible. Recurrent CMV disease occurs commonly after initial treatment. In bone marrow transplant... 

Cidofovir resistance in CMV is due to mutations in viral DNA polymerase. Low-level resistance to cidofovir develops in up to 30% of retinitis patients by 3 months of therapy. Highly ganciclovir-resistant CMV isolates that possess DNA polymerase and UL97 kinase mutations are resistant to cidofovir, and prior ganciclovir therapy may select for cidofovir resistance. Some fos-carnet-resistant CMV isolates show cross-resistance to cidofovir, and triple-drug-resistant variants with DNA polymerase mutations occur. 

Foscamet [73,74](Scheme 8.18) is a first line treatment for CMV retinitis and a treatment for CMV colitis if ganciclovir therapy is ineffective or not tolerated. Foscamet crosses the blood-brain barrier and can treat susceptible infection in the... 

Hematologic Howell-Jolly body-like inclusions have been observed in neutrophils in a transplant recipient in association with ganciclovir therapy in a 31-year-old man they disappeared after a few days of therapy [ll ]. The authors concluded that ganciclovir may cause nuclear fragmentation in such patients, but that a role of cytomegalovirus infection could not be excluded. 

Hall SJ, Sanford MA Atkinson G, Chen SH. Induction of potent antitumor natural killer cell activity by herpes simplex virus-thyntidine kinase and ganciclovir therapy in an orthotopic mouse model of prostate cancer. Cancer Res 1998 58 3221-3225. 

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