Tolerability of Foscarnet As a Continuous Infusion for Treatment of Herpesvirus Infections

Foscarnet (FOS) remains the primary antiviral option in the setting of intolerance of and/or resistance to ganciclovir (GCV) and other inhibitors of viral kinase.   However, FOS-associated nephrotoxicity often limits it utility.  Because this nephrotoxicity can be attenuated by substantially increasing the infusion time and ensuring adequate hydration, we report a successful approach to the administration of FOS as a continuous infusion (CI) in both the inpatient and outpatient settings. The decision regarding administering FOS as a CI was solely at the discretion of the treating team with most common reasons cited as attenuation of nephrotoxicity, management of fluid balance, and facilitation of outpatient care.   Results:  Data regarding both groups is summarized in Table 1.  Throughout administration, total daily dose was adjusted per recommendations based on creatinine clearance and adjusted ideal body weight with an additional liter of hydration daily.  Median duration of treatment was 23 days (4-123d).  22 of the 25 treatment courses (23 patients) resulted in successful resolution of the disease process; however, 3 patients died with a detectable viral load despite the concomitant administration of ganciclovir in 2 patients.  The median serum creatinine (SCr) (mg/dl, range) prior to, during, and post-FOS CI were 1.3 (0.7-2.2), 1.15 (0.7-2.0), and 1.9 (0.9-7.1), respectively.  In the analysis of individual data, median net change in SCr was 0.3 mg/dl (range:  -0.9 to +5.7) from the pre- to the post-FOS period, although one patient developed renal failure shortly before dying of multi-organ failure, GVHD and persistent CMV disease.

Conclusion:  FOS CI permitted the safe administration of outpatient treatment in patients at high risk for nephrotoxicity with CMV reactivation and/or disease which, in our experience, has increased the utility of this drug. Data regarding comparative efficacy to standard infusion will require additional study.