High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis after renal transplantation

Abstract

Background: The correct valganciclovir dose for cytomegalovirus (CMV) prophylaxis depends on renal function estimated by the Cockcroft-Gault (CG) estimated creatinine clearance (CG-CrCl) formula. Patients with delayed or rapidly changing graft function after transplantation (tx) will need dose adjustments. Methods: We performed a retrospective investigation of valganciclovir dosing in renal transplant patients receiving CMV prophylaxis between August 2003 and August 2011, and analysed valganciclovir dosing, CG-CrCl, CMV viraemia (CMV-PCR <750 copies/mL), leucopenia (<3500/mL) and neutropenia (<1500/mL) in the first year post-transplant. On Days 30 and 60 post-transplant, dosing pattern in relation to estimated creatinine clearance was analysed regarding CMV viraemia, leucopenia and neutropenia. Results: Six hundred and thirty-five patients received valganciclovir prophylaxis that lasted 129 6 68 days with a mean dose of 248 6 152 mg/day of whom 112/635 (17.7%) developed CMV viraemia, 166/635 (26.1%) leucopenia and 48/635 (7.6%) neutropenia. CMV resistance within 1 year post-transplant was detected in three patients. Only 137/609 (22.6%) patients received the recommended dose, while n ¼ 426 (70.3%) were underdosed and n ¼ 43 (7.1%) were overdosed at Day 30 post-tx. Risk factors for CMV viraemia were donor positive D (þ)/receptor negative R () status and short prophylaxis duration, but not low valganciclovir dose. Risk factors for developing leucopenia were Dþ/R status and low renal function. No significant differences in dosing frequency were observed in patients developing neutropenia or not (P ¼ 0.584). Conclusion: Most patients do not receive the recommended valganciclovir dose. Despite obvious underdosing in a large proportion of patients, effective prophylaxis was maintained and it was not associated as a risk factor for CMV viraemia or leucopenia.