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 additive or synergistic effects have been demonstrated in vitro with other
antiviral drugs, including
ganciclovir and
zidovudine.
Foscarnet appears to have negligible effects on host
enzymes and cells. Complete or partial clinical resolution of ocular symptoms is obtained in more than 89% of patients with
acquired immunodeficiency syndrome (
AIDS) and CMV
retinitis during
foscarnet induction
therapy, but relapse occurs soon after ceasing treatment. Maintenance treatment given daily can extend the period of remission considerably.
Foscarnet and
ganciclovir monotherapy had similar efficacy in the treatment of CMV
retinitis in patients 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 with 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. Reversible nephrotoxicity is common during
foscarnet therapy, but may be reduced by dosage adjustment and adequate hydration. Anaemia,
nausea and
vomiting, disturbances in
electrolyte levels and genital ulceration have also been associated with administration of the
drug. The different tolerability profiles of
foscarnet and
zidovudine facilitate the use of these agents in combination in patients with
AIDS and CMV
infection; whereas
ganciclovir, like
zidovudine, is associated with dose-limiting haematological toxicity. The apparent survival benefits seen in these patients when receiving
foscarnet and
zidovudine (possibly linked to synergy between
zidovudine and
foscarnet and/or the inherent anti-HIV activity of
foscarnet), appear to offer potentially important advantages for
foscarnet over
ganciclovir in the treatment of selected patients with
AIDS and CMV
infections.