FOSCARNET - A REAPPRAISAL OF ITS ANTIVIRAL ACTIVITY, PHARMACOKINETIC PROPERTIES AND THERAPEUTIC USE IN IMMUNOCOMPROMISED PATIENTS WITH VIRAL-INFECTIONS

The DNA polymerase of human herpes viruses, including cytomegalovirus (CMV), and the reverse transcriptase of human immunodeficiency virus ( HIV) are selectively inhibited in vitro by the pyrophosphate analogue foscarnet. Inhibition is reversible on withdrawal of foscarnet and add itive or synergistic effects have been demonstrated in vitro with othe r antiviral drugs, including ganciclovir and zidovudine. Foscarnet app ears to have negligible effects on host enzymes and cells. Complete or partial clinical resolution of ocular symptoms is obtained in more th an 89% of patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis during foscarnet induction therapy, but relapse occurs s oon after ceasing treatment. Maintenance treatment given daily carl ex tend the period of remission considerably. Foscarnet and ganciclovir m onotherapy had similar efficacy in the treatment of CMV retinitis in p atients with AIDS in several studies, and have been used concomitantly in immunocompromised patients with recalcitrant CMV infections. In 1 trial, patients receiving foscarnet survived for significantly longer than those receiving ganciclovir. Foscarnet has been used successfully in the treatment of limited numbers of immunocompromised patients wit h CMV-associated gastrointestinal (improvement in over 67% of patients ) and other infections. Aciclovir-resistant herpes simplex infections in immunocompromised patients have also been treated successfully with foscarnet. Almost 90% of a foscarnet dose is excreted in the urine. R eversible nephrotoxicity is common during foscarnet therapy, but may b e reduced by dosage adjustment and adequate hydration. Anaemia, nausea and vomiting, disturbances in electrolyte levels and genital ulcerati on have also been associated with administration of the drug. The diff erent tolerability profiles of foscarnet and zidovudine facilitate the use of these agents in combination in patients with AIDS and CMV infe ction: whereas ganciclovir, like zidovudine, is associated with dose-l imiting haematological toxicity. The apparent survival benefits seen i n these patients when receiving foscarnet and zidovudine (possibly lin ked to synergy between zidovudine and foscarnet and/or the inherent an ti-HIV activity of foscarnet), appear to offer potentially important a dvantages for foscarnet over ganciclovir in the treatment of selected patients with AIDS and CMV infections.