Underdosing of Prophylactic Valganciclovir Due to Inaccurate Estimation of Glomerular Filtration Rate Leading to Severe Cytomegalovirus Disease in a Kidney Transplant Recipient

Penne, E. Lars; Nurmohamed, Shaikh A.

doi:10.1128/aac.01816-13

Cited by 3 publications

(3 citation statements)

References 6 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical drug level monitoring of free GCV in plasma or serum samples is often used in studies as a surrogate for intracellular GCV triphosphate, which is the active component of the drug. Suboptimal GCV blood concentrations during treatment for CMV infection result from (1) hemodialysis where ~50% of the administered GCV was eliminated from the plasma after 4 hours of dialysing, (2) use of an inappropriate dosing algorithm, and (3) inaccurate estimation of glomerular filtration rate (GFR) . Suboptimal GCV concentrations may promote the emergence of resistant CMV strains .…”

Section: Introductionmentioning

confidence: 99%

“…Suboptimal GCV blood concentrations during treatment for CMV infection result from (1) hemodialysis where~50% of the administered GCV was eliminated from the plasma after 4 hours of dialysing, (2) use of an inappropriate dosing algorithm, and (3) inaccurate estimation of glomerular filtration rate (GFR). [20][21][22][23][24] Suboptimal GCV concentrations may promote the emergence of resistant CMV strains. 25 Despite these reports, contrasting results were found in pharmacodynamic studies investigating the relationship between the therapeutic effect of different GCV blood concentrations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Wong

Zuylen

Craig

et al. 2018

Reviews in Medical Virology

View full text Add to dashboard Cite

Summary Human cytomegalovirus (CMV) represents the most common infection among recipients of solid organ transplants (SOTs). Previous meta‐analysis showed 0.8% of SOT recipients developed CMV disease whilst receiving valganciclovir (ValGCV) prophylaxis. However, the clinical utility of monitoring ganciclovir (GCV) blood concentrations is unclear. We systematically reviewed the association between GCV concentrations during prophylaxis and the incidence of CMV. MEDLINE and EMBASE databases were searched for studies between 1946 and 2018, where GCV pharmacokinetics and incidence of CMV viraemia or disease in SOT were available. Research designs included randomised trials, comparative, prospective cohort, retrospective, or case report studies. Only human adult studies were included, with English language restriction. The 11 studies that met the eligibility criteria included 610 participants receiving GCV or ValGCV prophylaxis. Quality assessment showed 2/4 randomised trials, 4/6 cohort studies, and 1/1 case report were of high quality. Despite dose adjustments for renal impairment, mean GCV exposures for patients were heterogeneous and ranged between 28 and 53.7 μg·h/mL across three randomised trials. The incidence of CMV infection and disease ranged from 0% to 50% and 0% to 3.1%, respectively, with follow up between 3 to 9 months. One study showed statistical power in determining relationship, where GCV exposure at 40 to 50 μg·h/mL in high‐risk SOT recipients was associated with a reduced risk of viraemia. Clinical monitoring for GCV exposure can be applied to high‐risk SOT recipients during ValGCV prophylaxis; however, further studies are needed to determine the utility of monitoring in all SOT recipients.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Wong

Zuylen

Craig

et al. 2018

Reviews in Medical Virology

View full text Add to dashboard Cite

show abstract

“…[19][20][21] Cytomegalovirus disease resistance has been reported as a result of lower valganciclovir dose given after underestimation of GFR by Modification of Diet in Renal Disease formula, which responded well after adjustment of the valganciclovir dose to the Cockcroft-Gault formula. 22 In a multivariate analysis, 12 trials with 900 mg valganciclovir (1543 patients) and 8 trials with 450 mg valganciclovir (1531 patients) were included. 23 In the high-risk group (D+/R−), 900 mg valganciclovir showed equivalent efficacy to 450 mg valganciclovir (statistical power: 97%) for CMV universal prophylaxis.…”

Section: Introductionmentioning

confidence: 99%

Untitled

Halim

Al-Otaibi²,

Gheith³

et al. 2016

Exp Clin Transplant

View full text Add to dashboard Cite

Objectives: Prophylaxis for cytomegalovirus infection is highly recommended for kidney transplant recipients. The use of daily 900 mg valganciclovir is the usual prophylactic dose, whereas 450 mg daily is under investigation. We evaluated the outcome of using 2 different doses of valganciclovir prophylaxis for cytomegalovirus infection after kidney transplant. Materials and Methods: We randomized kidney transplant recipients (1:1) to receive 450 mg daily valganciclovir (group 1) or 900 mg daily valganciclovir (group 2) for the first 6 months after kidney transplant. Serologically, all patients were at moderate risk for cytomegalovirus infection. Patients were studied for incidence of cytomegalovirus disease, leukopenia attacks, rejection episodes, and graft outcomes for 1 year. Results: Demographic features of group 1 (98 patients) and group 2 (98 patients) were comparable. More than 50% of patients received thymoglobulin induction therapy without difference between the groups. There were more leukopenia attacks in group 2 (P = .03) requiring higher doses of granulocyte colonystimulating factor (P = .03). Group 2 patients received lower doses of mycophenolate mofetil (P= .04) and required reduced doses of valganciclovir (P = .045). Compared with group 1, the high-dose group developed numerically more rejection episodes (P = .057) and more cytomegalovirus infections requiring full treatment (P = .17). Graft and patient outcomes were satisfactory in both groups. Conclusion:Six months of low-dose valganciclovir prophylaxis for intermediate-risk kidney transplant recipients was as effective as high-dose valganciclovir with a better safety profile.

show abstract

Kidney Transplantation in Developing Countries

Muller¹

2019

Kidney Transplantation - Principles and Practice

View full text Add to dashboard Cite

Underdosing of Prophylactic Valganciclovir Due to Inaccurate Estimation of Glomerular Filtration Rate Leading to Severe Cytomegalovirus Disease in a Kidney Transplant Recipient

Cited by 3 publications

References 6 publications

Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Untitled

Kidney Transplantation in Developing Countries

Contact Info

Product

Resources

About