Drug Interactions between mycophenolic acid and valacyclovir

Coadministration with mycophenolic acid may increase the plasma concentrations of acyclovir. The mechanism of interaction has not been described. In 15 healthy subjects, coadministration of a single oral dose each of mycophenolate mofetil (1 gram) and acyclovir (800 mg) increased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and time to reach Cmax (Tmax) of acyclovir by 40%, 31% and 0.38 hour, respectively, compared to administration of acyclovir alone. In contrast, coadministration of mycophenolate mofetil with valacyclovir (2 gram) did not significantly alter acyclovir pharmacokinetics with the exception of a 0.5 hour decrease in Tmax. During coadministration with acyclovir or valacyclovir, pharmacokinetics of mycophenolic acid and its glucuronide metabolite, MPAG, were generally not significantly altered, although the AUC of MPAG decreased by 12% with valacyclovir. None of these changes are considered clinically relevant in healthy individuals. However, because both MPAG and acyclovir plasma concentrations are increased in the presence of renal impairment, the potential exists for the two drugs to compete for active tubular secretion, further increasing the concentrations of both drugs. Caution may be appropriate in patients with decreased renal function.