Cidofovir is a nucleoside analogue and antiviral agent which is used in therapy of serious cytomegalovirus infections in immunocompromised patients. Cidofovir has been associated with mild-to-moderate serum aminotransferase elevations during intravenous therapy but has not been convincingly linked to cases of clinically apparent acute liver injury.
Cidofovir (sye dof' oh vir) is an acyclic nucleoside monophosphate and cytosine analogue with potent activity against replication of several herpes viruses, including cytomegalovirus (CMV). Cidofovir is phosphorylated intracellularly and competes with cytosine resulting in DNA chain termination and inhibition of DNA viral synthesis. Cidofovir has activity in cell culture against several herpes viruses, papilloma, polyoma, pox and adenoviruses. Cidofovir is poorly absorbed orally and must be given intravenously, usually administered with probenecid to inhibit its rapid renal excretion. Cidofovir is indicated for therapy of cytomegalovirus retinitis and off label is used to treat serious adenovirus and acyclovir-resistant herpes simplex infections in immunocompromised individuals. Cidofovir was approved for use in the United States in 1996 and has limited use, largely because of its potential for nephrotoxicity. Cidofovir is available as an intravenous formulation of 75 mg/mL under the brand name of Vistide. The usually recommended dose in adults is 5 mg/kg infused over one hour, once weekly for two weeks, but dose modifications are required if there is renal insufficiency. Probenecid is given concurrently. Side effects include headache, dizziness, confusion, fever, fatigue, abdominal pain, renal dysfunction and rash.
Intravenous cidofovir therapy is associated with mild-to-moderate elevations in serum ALT levels in a proportion of patients, but the elevations are usually self-limited and do not require dose modification. Nephrotoxicity is often dose limiting which may account for the absence of clinically significant cases of liver injury associated with cidofovir therapy. Cases of clinically apparent liver injury have been reported during cidofovir therapy, but the role of this agent has been difficult to define because most patients who receive cidofovir have severe immunodeficiency and are receiving multiple other agents, some of which are known hepatotoxins. Several instances of acute liver failure, lactic acidosis and fatty liver have been described in patients taking cidofovir, but other nucleoside analogues such as zidovudine, stavudine or didanosine were being taken concurrently.
Mechanism of Injury
The absence of hepatotoxicity from cidofovir is probably related to the fact that it is rapidly excreted in the urine and binds to the anion transported in the convoluted tubules leading to its accumulation and renal toxicity.
Outcome and Management
The minor aminotransferase elevations associated with cidofovir therapy are usually self-limited and do not require dose modification or discontinuation of therapy.
REPRESENTATIVE TRADE NAMES
Cidofovir – Vistide®
Product labeling at DailyMed, National Library of Medicine, NIH
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