A neutropenia suggesting an interaction between valacyclovir and mycophenolate mofetil

Abstract

Mycophenolate mofetil (MMF) is a drug which decreases the frequency of renal transplantation rejection. However, cytomegalovirus infections are a common feature of this treatment leading the physicians to prescribe antiviral prophylactic drugs like valacyclovir. During this association, neutropenia occur and the cause of this adverse effect is difficult to define. This report presents a case of neutropenia in a woman treated with MMF and valacyclovir. As the duration of the valacyclovir treatment exactly corresponds to the neutropenia duration, and the mycophenolate trough levels increased with the neutrophil count, the responsibility of this neutropenia was ascribed to valacyclovir. However, an examination of the literature for cases of neutropenia led to the suspicion of an interaction between MMF and valacyclovir. Mycophenolate may increase intracellular concentrations of valacyclovir up to haematotoxic levels. This mechanism may explain the interaction and further research is needed to confirm this interaction.

Special Issue: KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients

“…However, the alternative antiviral valacyclovir was not associated with more leucopenia compared to placebo in a RCT of CMV prophylaxis in KTRs, but drug‐induced leucopenia in the treatment arm may have offset the CMV‐induced leucopenia in the control arm (742). Combined therapy with antiviral and antiproliferative agents may increase the incidence of leucopenia (743).…”

Mycophenolate mofetil in dermatology

“…9 In addition, there may be an increased risk of neutropenia with coadministration of valacyclovir and MMF, as demonstrated in one case report. 151 MMF is contraindicated in patients who have experienced allergic reactions to MMF, MMA, or Polysorbate 80 (TWEEN 80; ICI Americas, Inc, Bridgewater, NJ). It is also recommended that MMF not be taken with azathioprine because both have the potential to cause bone marrow suppression, and clinical studies are not yet available regarding this combination.…”

Poor Outcomes Associated With Neutropenia After Kidney Transplantation: Analysis of United States Renal Data System

“…There are no current practice guidelines for management of PTN in kidney transplant recipients, and PTN or leukopenia has been reported with many transplant medications to include anti-lymphocyte globulin (4), thymoglobulin (5,6), azothioprine (4,(7)(8)(9), mycophenolate (10), sirolimus (11), valacyclovir (12), valgancyclovir (13), and trimethoprimsulfamethoxazole (14). Generally, the above medications are not given individually, and cytopenias have been reported from various combinations (12,14) of medications, possibly related to idiosyncratic drug-drug interactions.…”