Cytovene-IV
Cytovene-IV - General Information
An acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Cytovene-IV is used to treat complications from AIDS-associated cytomegalovirus infections. [PubChem]
Pharmacology of Cytovene-IV
Cytovene-IV 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. Cytovene-IV 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.
Cytovene-IV for patients
All patients should be informed that the major toxicities of ganciclovir are granulocytopenia
(neutropenia), anemia and thrombocytopenia and that dose modifications may be required, including
discontinuation. The importance of close monitoring of blood counts while on therapy should be emphasized.
Patients should be informed that ganciclovir has been associated with elevations in serum creatinine.
Patients should be instructed to take CYTOVENE capsules with food to maximize bioavailability.
Patients should be advised that ganciclovir has caused decreased sperm production in animals and may cause
infertility in humans. Women of childbearing potential should be advised that ganciclovir causes birth
defects in animals and should not be used during pregnancy. Women of childbearing potential should be
advised to use effective contraception during treatment with CYTOVENE-IV or CYTOVENE. Similarly, men
should be advised to practice barrier contraception during and for at least 90 days following treatment
with CYTOVENE-IV or CYTOVENE.
Patients should be advised that ganciclovir causes tumors in animals. Although there is no information
from human studies, ganciclovir should be considered a potential carcinogen.
All HIV+ Patients: These patients may be receiving zidovudine (Retrovir?*). Patients should be counseled
that treatment with both ganciclovir and zidovudine simultaneously may not be tolerated by some patients
and may result in severe granulocytopenia (neutropenia). Patients with AIDS may be receiving didanosine
(Videx?#). Patients should be counseled that concomitant treatment with both ganciclovir and didanosine
can cause didanosine serum concentrations to be significantly increased.
HIV+ Patients With CMV Retinitis: Ganciclovir is not a cure for CMV retinitis, and immunocompromised
patients may continue to experience progression of retinitis during or following treatment. Patients
should be advised to have ophthalmologic follow-up examinations at a minimum of every 4 to 6 weeks while
being treated with CYTOVENE-IV or CYTOVENE. Some patients will require more frequent follow-up.
Transplant Recipients: Transplant recipients should be counseled regarding the high frequency of impaired
renal function in transplant recipients who received CYTOVENE-IV solution in controlled clinical trials,
particularly in patients receiving concomitant administration of nephrotoxic agents such as cyclosporine
and amphotericin B. Although the specific mechanism of this toxicity, which in most cases was reversible,
has not been determined, the higher rate of renal impairment in patients receiving CYTOVENE-IV solution
compared with those who received placebo in the same trials may indicate that CYTOVENE-IV played a
significant role.
Cytovene-IV Interactions
No drug interactions have been observed with the Vitrasert Implant. There is limited experience with use of retinal tamponades in conjunction with the Vitrasert Implant.
Cytovene-IV Contraindications
The Vitrasert Implant is contraindicated in patients with hypersensitivity to ganciclovir or acyclovir, and in patients with any contraindications for intraocular surgery, such as external infection or severe thrombocytopenia.
Additional information about Cytovene-IV
Cytovene-IV Indication: For 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.
Mechanism Of Action: Cytovene-IV'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. Cytovene-IV inhibits viral DNA polymerases more effectively than it does cellular polymerase, and chain elongation resumes when ganciclovir is removed.
Drug Interactions: Didanosine The antiviral agent increases the effect and toxicity of didanosine
Probenecid Probenecid increases the effect and toxicity of ganciclovir/valganciclovir
Zidovudine Hematotoxicity
Food Interactions: Take with food, food increases bioavailability.
Generic Name: Ganciclovir
Synonyms: Ganciclovir Sodium; GA2
Drug Category: Antiviral Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Ganciclovir: Cytovene; Cytovene IV; Cytovene-IV; Vitrasert;
Absorption: Poorly 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).
Toxicity (Overdose): Oral, 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.
Protein Binding: 1 to 2%
Biotransformation: Little to no metabolism, about 90% of plasma ganciclovir is eliminated unchanged in the urine.
Half Life: 2.5 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).
Dosage Forms of Cytovene-IV: Implant Intravitreal
Powder, for solution Intravenous
Capsule Oral
Chemical IUPAC Name: 2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)-3H-purin-6-one
Chemical Formula: C9H13N5O4
Ganciclovir on Wikipedia: https://en.wikipedia.org/wiki/Ganciclovir
Organisms Affected: Human Herpes Virus
