Ganciclovir toxicity

The clinical toxicity of ganciclovir includes granulocytopenia, anemia, and thrombocytopenia. In animal studies, ganciclovir was carcinogenic, teratogenic, and caused aspermatogenesis. 

IV Do not administer by rapid or bolus IV injection. The toxicity may be increased as a result of excessive plasma levels. Do not exceed the recommended infusion rate. IM or subcutaneous injection of reconstituted ganciclovir may result in severe tissue irritation because of high pH. 

Children Safety and efficacy in children have not been established. The use of ganciclovir in children warrants extreme caution to the probability of long-term carcinogenicity and reproductive toxicity. Administer to children only after careful evaluation and only if the potential benefits of treatment outweigh the risks. Oral ganciclovir has not been studied in children younger than 13 years of age. 

Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation of therapy. Other potential adverse effects include headache and asthenia. Tenofbvir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D, and preclinical studies in several animal species have demonstrated bone toxicity (eg, osteomalacia). Monitoring of bone mineral density should be considered with long-term use in those with risk factors for or with known osteoporosis, as well as in children. Reduction of renal function over time, as well as cases of acute renal failure and Fanconi s syndrome, have been reported in patients receiving tenofovir alone or in combination with emtricitabine. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. 

Allopurinol increases didanosine plasma concentrations and their coadministration is not recommended. Ganciclovir, tenofovir and disoproxil also increase didanosine plasma concentrations, and dose reduction is recommended. Conversely, methadone decreases didanosine plasma concentrations, and appropriate doses for the combination have not been established. Didanosine should not be administered with drugs that cause pancreatic or neurotoxicity. Ribavirin increases its risk of toxicity and should not be coadministered. 

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. 

Famciclovir [fam SYE kloe ver], another acyclic analog of 2 -deoxyguanosine, is a prodrug that is metabolized to the active pen-ciclovir (pen SYE kloe ver). The antiviral spectrum is similar to that of ganciclovir but it is presently approved only for treatment of acute herpes zoster. The drug is effective orally. Adverse effects include headaches and nausea. Studies in experimental animals have shown an increased incidence in mammary adenocarcinomas and testicular toxicity. 

MYCOPHENOLATE ANTIVIRALS -ACICLOVIR, GANCICLOVIR t plasma concentrations of both drugs. Toxic effects of both drugs likely Attributed to competition for renal tubular excretion Monitor blood counts - For signs and symptoms of immunosuppression, see Oinical Features of Some Adverse Drug Interactions, Immunosuppression and blood dyscrasias... 

TRIMETHOPRIM GANCICLOVIR/ VALGANCICLOVIR Possibly t adverse effects (e.g, myelosuppression) when trimethoprim is co administered with ganciclovir or valgancidovir Small t in bioavailability possible additive toxicity Well tolerated in a study. For patients at risk of additive toxicities, use only if benefits outweigh risks, and monitor FBC closely... 

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS GANCICLOVIRAfALGANCIC LOVIR 1. T adverse effects with tenofovir, zidovudine and possibly didanosine, lamivudine and zalcitabine 2. Possibly 1 efficacy of ganciclovir 1. Uncertain possibly additive toxicity. Lamivudine may compete for active tubular secretion in the kidneys 2. Uncertain L bioavailability 1. Avoid if possible otherwise monitor FBC and renal function weekly. It has been suggested that the dose of zidovudine should be halved from 600 mg to 300 mg daily. Monitor for peripheral neuropathy, particularly with zalcitabine 2. Uncertain clinical significance if in doubt, consider alternative cytomegalovirus prophylaxis... 

Ganciclovir Intravenous administration Intravitreal injection Intravitreal implant Oral administration (valganciclovir) Primary toxicity = neutropenia... 

Hochster H, Dieterich D, Bozzette S et al. Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS An AIDS clinical trials group study. Ann Intern Med 1990 113 111-17. 

Foscamet is used i.v. for retinitis due to CMV in patients with HIV infection when ganciclovir is contraindicated it has also been used to treat aciclovir-resistant herpes simplex virus infection (see p. 258). It causes numerous adverse effects, including renal toxicity, nausea and vomiting, neurological reactions and marrow suppression. 

J.) Ganciclovir This is a guanosine derivative exhibiting a good action profile in HBV, EBV, CMV and VZV infection. Ganciclovir triphosphate inhibits virus replication. The half-life is about 4 hours. Elimination is via the kidneys. Only a minor fraction of this substance is absorbed after oral administration application (e.g. in CMV infection) is usually intravenous (10 mg/kg BW/ day). It has severe toxic side effects. Ganciclovir was... 

Lewis RA, Clogston P, Fainstein V, et al. Morbidity and toxic effects associated with ganciclovir or foscamet therapy in a randomized cytomegalovirus retinitis trial. Studies of ocular complications of AIDS Research Group, in collaboration with the AIDS Clinical Trials Group. Arch Intern Med I995 I55(I) 65-74. 

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