Home / Drugs / Starting with G /
indicationFor induction and maintenance in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). Also used in the treatment of severe cytomegalovirus (CMV) disease, including CMV pneumonia, CMV gastrointestinal disease, and disseminated CMV infections, in immunocompromised patients.
pharmacologyGanciclovir is a synthetic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Sensitive human viruses include cytomegalovirus (CMV), herpes simplex virus -1 and -2 (HSV-1, HSV-2), Epstein-Barr virus (EBV) and varicella zoster virus (VZV), however clinical studies have been limited to assessment of efficacy in patients with CMV infection. Ganciclovir is a prodrug that is structurally similar to acyclovir. It inhibits virus replication by its encorporation into viral DNA. This encorporation inhibits dATP and leads to defective DNA, ceasing or retarding the viral machinery required to spread the virus to other cells.
mechanism of actionGanciclovir's antiviral activity inhibits virus replication. This inhibitory action is highly selective as the drug must be converted to the active form by a virus-encoded cellular enzyme, thymidine kinase (TK). TK catalyzes phosphorylation of ganciclovir to the monophosphate, which is then subsequently converted into the diphosphate by cellular guanylate kinase and into the triphosphate by a number of cellular enzymes. In vitro, ganciclovir triphosphate stops replication of herpes viral DNA. When used as a substrate for viral DNA polymerase, ganciclovir triphosphate competitively inhibits dATP leading to the formation of 'faulty' DNA. This is where ganciclovir triphosphate is incorporated into the DNA strand replacing many of the adenosine bases. This results in the prevention of DNA synthesis, as phosphodiester bridges can longer to be built, destabilizing the strand. Ganciclovir inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.
toxicityOral, mouse LD50: > 2g/kg. Intravenous, dog LD50: > 150mg/kg. Symptoms of overdose include irreversible pancytopenia, worsening GI symptoms, and acute renal failure. Suspected cancer agent.
biotransformationLittle to no metabolism, about 90% of plasma ganciclovir is eliminated unchanged in the urine.
absorptionPoorly absorbed systemically following oral administration. Bioavailability under fasting conditions is approximately 5%, and when administered with food, 6 to 9% (about 30% with a fatty meal).
half life2.5 to 3.6 hours (mean 2.9 hours) when administered intravenously in adults. 3.1 to 5.5 hours when administered orally in adults. Renal function impairment causes a marked increase in half life (9 to 30 hours intravenously, 15.7 to 18.2 hours orally).
route of eliminationRenal excretion of unchanged drug by glomerular filtration and active tubular secretion is the major route of elimination of ganciclovir.
drug interactionsAbacavir: The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Ganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is required.
Didanosine: The antiviral agent, ganciclovir, may increase the effect and toxicity of didanosine.
Probenecid: Probenecid increases the effect and toxicity of ganciclovir/valganciclovir
Zidovudine: Increased risk of hematologic toxicity. Concomitant therapy should be avoided.