Ganciclovir is similar to aciclovir in its mode of action, but is much more toxic. It is given i.v. or orally and is eliminated in the urine, mainly unchanged (t'/2 4 h). Ganciclovir is active against several types of virus but because of toxicity, its i.v. use is limited to life- or sight-threatening cytomegalovirus (CMV) infection in immunocompromised patients, and (by mouth) for maintenance suppressive treatment of retinitis in patients with AIDS, and to prevent CMV disease in patients receiving immunosuppressive therapy following organ transplantation (especially liver transplants). Ganciclovir-resistant cytomegalovirus isolates have been reported.
Adverse reactions include neutropenia and thrombocytopenia which are usually but not always reversible after withdrawal. Concomitant use of potential marrow-depressant drugs, e.g. cotrimox-azole, amphotericin B, zidovudine, should be avoided. Other reactions are fever, rash, gastrointestinal symptoms, confusion and seizure (the last especially if imipenem is coadministered).
Foscarnet 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.
Cidofovir is given by i.v. infusion (usually every 1-2 weeks) for CMV retinitis in patients with AIDS
when other drugs are unsuitable. Nephrotoxicity is common, but is reduced by hydration with i.v. fluids before each dose and co-administration with probenecid. A variety of other side effects has been reported, including bone marrow suppression, nausea and vomiting, and iritis and uveitis.
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