Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Vistide (Pharmacia & Upjohn)
75 mg/mL sterile concentrate for infusion in 5 mL vials
Approved indication: cytomegalovirus retinitis
Australian Medicines Handbook Section 5.3.2
Patients who are immuno compromised may develop significant cytomegalovirus infections. In patients with AIDS, there is a risk of retinitis which may lead to blindness. Cytomegalovirus retinitis can be treated with ganciclovir or foscarnet. Cidofovir provides another option.
Cidofovir is an analogue of cytosine. It is active against herpes viruses including cytomegalovirus (CMV). Unlike ganciclovir, which is activated by viral enzymes, cidofovir is converted by host enzymes. This may slow the development of resistance.
A randomised controlled trial studied cidofovir in 48 patients with AIDS and retinitis. The patients were either treated immediately or after the retinitis progressed. The median time to progression was 120 days in the immediate treatment group and 22 days in the deferred treatment group.1 (Inpatients taking ganciclovir or foscarnet, the median time to progression is approximately 50 days.)
In a study of patients who were intolerant of, or failed to respond to, ganciclovir or foscarnet, the median time to retinal progression was 115 days.
Cidofovir is infused once a week for two weeks. After this induction, maintenance treatment is given every two weeks. As nephrotoxicity is a common adverse event, patients must be well hydrated and be given probenecid. The probenecid reduces the clearance, probably by blocking renal tubular secretion. The half-life of the active drug in cells is 17-65 hours.
Proteinuria occurs in 41% of patients. Approximately 25% of patients had to withdraw from clinical trials of the drug because of this nephrotoxicity or other adverse effects such as neutropenia. Patients may complain of asthenia, nausea, alopecia, rashes and fever. They may also have adverse reactions to probenecid.
Cidofovir does delay the progression of retinitis due to CMV infection; however, visual acuity may not significantly change. The drug has an advantage over foscarnet and ganciclovir as it needs to be given less frequently, but there are insufficient data to establish which drug is the most effective in practice.
- Lalezari JP, Stagg RJ, Kuppermann BD, Holland GN, Kramer F, Ives DV, et al. Intravenous cidofovir for peripheral cytomegalovirus retinitis in patients with AIDS. Ann Intern Med 1997;126:257-63.