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The Journal of Pediatrics Jul 2022From 2009-2015 to 2016-2019, the proportion of infants in the US with congenital cytomegalovirus treated with valganciclovir roughly doubled for infants enrolled with...
From 2009-2015 to 2016-2019, the proportion of infants in the US with congenital cytomegalovirus treated with valganciclovir roughly doubled for infants enrolled with employer-sponsored insurance (from 16% to 29%) and Medicaid (from 16% to 36%). The proportion treated with valganciclovir increased for all congenital cytomegalovirus disease severity groups.
Topics: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Humans; Infant; Medicaid; United States; Valganciclovir
PubMed: 35358586
DOI: 10.1016/j.jpeds.2022.03.042 -
Medecine Et Maladies Infectieuses Feb 2005
Review
Topics: Acquired Immunodeficiency Syndrome; Adult; Antiviral Agents; Cytomegalovirus Infections; Drug Resistance, Viral; Ganciclovir; Humans; Male; Treatment Failure; Valganciclovir
PubMed: 15780901
DOI: 10.1016/j.medmal.2004.11.005 -
Nederlands Tijdschrift Voor Geneeskunde Jun 2004Valganciclovir is an orally administered prodrug of ganciclovir, the most widely used drug in the clinical management of Cytomegalovirus infections. The good... (Review)
Review
Valganciclovir is an orally administered prodrug of ganciclovir, the most widely used drug in the clinical management of Cytomegalovirus infections. The good bioavailability and the rapid conversion into ganciclovir provide oral valganciclovir with pharmacokinetic properties approaching those of intravenously administered ganciclovir. The first-reported clinical applications confirm the efficacy of valganciclovir in the treatment of Cytomegalovirus retinitis in AIDS patients and the prophylaxis of Cytomegalovirus disease after organ transplantations, which are the currently approved indications. Broader application of valganciclovir is to be expected in the pre-emptive treatment of organ as well as stem-cell transplant recipients. This drug also increases the potential for prophylactic applications, which may lead to the development of viral resistance.
Topics: Administration, Oral; Antiviral Agents; Biological Availability; Cytomegalovirus Infections; Drug Resistance, Viral; Ganciclovir; Humans; Immunocompromised Host; Treatment Outcome; Valganciclovir
PubMed: 15301386
DOI: No ID Found -
International Journal of Infectious... Sep 2020Ganciclovir and its prodrug valganciclovir are elective treatments for cCMV. Neonates with important symptoms undergo 6 months of therapy to ameliorate/prevent symptoms...
Ganciclovir and its prodrug valganciclovir are elective treatments for cCMV. Neonates with important symptoms undergo 6 months of therapy to ameliorate/prevent symptoms and late sequelae, but evidence of resistance is emerging. Over the last 5 years, we took care of 59 cCMV infants and experienced two cases of resistance among nine cCMV infants receiving long-term valganciclovir therapy. In the first case, valganciclovir therapy was prolonged beyond 6 months due to severity of symptoms, control of viral load, and absence of adverse events. Resistance was detected in the 8th month of therapy. In the second case, after a significant reduction following valganciclovir administration and no adverse events, CMV viral load suddenly increased in the 6th month of therapy due to resistance. Both events were associated with UL97 gene mutation. The cCMV infants, affected by severe symptoms, remained in a steady state during treatment, and their later neurological development was coherent with initial seriousness of diagnosis. Prolonged therapeutic exposure may therefore be a risk for resistance, suggesting that constant dosage/weight adjustments, monthly surveillance of viral load, and therapeutic drug monitoring could be proposed to monitor resistance onset and optimize the therapy regime. The risk-benefit ratio for long-term therapy, including the possibility of resistance onset, alongside SNHL and neurodevelopmental improvement, should also be evaluated.
Topics: Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Resistance, Viral; Female; Ganciclovir; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Mutation; Valganciclovir; Viral Load
PubMed: 32615325
DOI: 10.1016/j.ijid.2020.06.087 -
American Journal of Transplantation :... Dec 2023Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing...
Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, P <.001), lymphopenia (51% vs 15.0%, P <.001), and acute kidney injury causing treatment modification (8.0% vs 1.8%, P <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.
Topics: Child; Humans; Valganciclovir; Antiviral Agents; Cytomegalovirus Infections; Body Surface Area; Retrospective Studies; Cytomegalovirus; Neutropenia; Organ Transplantation; Body Weight; Lymphopenia; Ganciclovir
PubMed: 37499799
DOI: 10.1016/j.ajt.2023.07.013 -
The Journal of Pediatrics Aug 2018To evaluate the efficacy of antiviral treatment for infants with congenital cytomegalovirus (cCMV) with isolated sensorineural hearing loss (SNHL). (Observational Study)
Observational Study
OBJECTIVE
To evaluate the efficacy of antiviral treatment for infants with congenital cytomegalovirus (cCMV) with isolated sensorineural hearing loss (SNHL).
STUDY DESIGN
Data were reviewed retrospectively for infants with isolated SNHL who received prolonged antiviral treatment between 2005 and 2017. Hearing status was evaluated for infants who had been followed for >1 year.
RESULTS
Among 329 infants treated for cCMV, 59 (18%) were born with isolated SNHL. Hearing impairment was unilateral in 38 (64.4%) infants and bilateral in 21 (35.6%). Of the 80 affected ears at baseline, 55 (68.8%) improved, and only 2 (2.5%) deteriorated. Most of the improved ears (53/55 = 96.3%) returned to normal hearing with no deterioration observed in the ears that were unaffected at baseline. On best ear evaluation, of 21 infants who had bilateral hearing loss, 16 (76.1%) improved (93.7% regaining normal functional hearing); none deteriorated.
CONCLUSION
Infants born with isolated SNHL due to cCMV were found to benefit from prolonged antiviral treatment. These children (and ears) showed significant improvement in hearing status and no deterioration of unaffected ears at baseline. Our data serve as observational evidence of the benefits of antiviral treatment in these children. Avoiding treatment of these children due to the lack of prospective data is debatable.
Topics: Antiviral Agents; Cytomegalovirus Infections; Female; Follow-Up Studies; Hearing Loss, Sensorineural; Humans; Infant; Infant, Newborn; Male; Retrospective Studies; Treatment Outcome; Valganciclovir
PubMed: 29605391
DOI: 10.1016/j.jpeds.2018.02.028 -
Clinical Infectious Diseases : An... Feb 2011
Topics: Antiviral Agents; Chemoprevention; Cytomegalovirus Infections; Ganciclovir; Humans; Organ Transplantation; Treatment Outcome; Valganciclovir
PubMed: 21190935
DOI: 10.1093/cid/ciq145 -
Transplant International : Official... Mar 2020Ganciclovir (GCV) inhibits spermatogenesis in preclinical studies but long-term effects on fertility in renal transplant patients are unknown. In a prospective,... (Clinical Trial)
Clinical Trial
Ganciclovir (GCV) inhibits spermatogenesis in preclinical studies but long-term effects on fertility in renal transplant patients are unknown. In a prospective, multicenter, open-label, nonrandomized study, male patients were assigned to Cohort A [valganciclovir (VGCV), a prodrug of GCV] (n = 38) or B (no VGCV) (n = 21) by cytomegalovirus prophylaxis requirement. Changes in semen parameters and DNA fragmentation were assessed via a mixed-effects linear regression model accounting for baseline differences. Sperm concentration increased post-transplant, but between baseline and treatment end (mean 164 days Cohort A, 211 days Cohort B), the model-based change was lower in Cohort A (difference: 43.82 × 10 /ml; P = 0.0038). Post-treatment, sperm concentration increased in Cohort A so that by end of follow-up (6 months post-treatment) changes were comparable between cohorts (difference: 2.09 × 10 /ml; P = 0.92). Most patients' sperm concentration improved by end of follow-up; none with normal baseline concentrations (≥20 × 10 /ml) were abnormal at end of follow-up. Changes in seminal volume, sperm motility/morphology, DNA fragmentation, and hormone levels were comparable between cohorts at end of follow-up. Improvement in semen parameters after renal transplant was delayed in men receiving VCGV, but 6 months post-treatment parameters were comparable between cohorts.
Topics: Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Male; Prospective Studies; Sperm Motility; Spermatogenesis; Valganciclovir
PubMed: 31729770
DOI: 10.1111/tri.13558 -
Clinical Pharmacokinetics Nov 2018Valganciclovir is used as oral prophylaxis for cytomegalovirus (CMV) infection in kidney transplant recipients. However, limited pharmacokinetic data exist to guide...
BACKGROUND AND OBJECTIVES
Valganciclovir is used as oral prophylaxis for cytomegalovirus (CMV) infection in kidney transplant recipients. However, limited pharmacokinetic data exist to guide dosing in this patient group. This study aimed to describe the population pharmacokinetics of valganciclovir in a large sample of kidney transplant recipients and predict optimal dosing based on Monte Carlo simulations.
METHODS
Therapeutic drug monitoring (TDM) data from adult kidney transplant recipients who received valganciclovir prophylaxis during a 10-year study period were collected retrospectively. A non-parametric pharmacokinetic analysis and Monte Carlo simulations to determine the probabilities of reaching an area under the drug concentration-time curve (AUC) target of 40-50 mg·h/L with various dosing regimens at different levels of renal function were conducted using the Pmetrics™ package for R.
RESULTS
This study included 792 ganciclovir concentration measurements derived from 97 patients. A one-compartment oral absorption model best described the data. The final covariate model was as follows: CL(ganciclovir) = TVCL × (CL/51), where CL is the clearance, TVCL is the typical value of ganciclovir clearance, creatinine clearance (CL) according to the Cockcroft-Gaultt equation and 51 is the mean CL determined in the study. In the simulations, the probability of reaching the targeted AUC was insufficient when using the recommended dosing regimens for prophylaxis, especially in patients with impaired renal function at CL < 50 mL/min.
CONCLUSIONS
Higher doses of valganciclovir corrected to renal function are suggested for use as oral prophylaxis for CMV infection in kidney transplant recipients. Further study is required to establish TDM targets to ensure adequate drug concentrations while avoiding potentially toxic drug exposures.
Topics: Administration, Oral; Adult; Aged; Antiviral Agents; Cytomegalovirus Infections; Drug Administration Schedule; Drug Monitoring; Female; Humans; Kidney Transplantation; Male; Middle Aged; Models, Biological; Monte Carlo Method; Prodrugs; Retrospective Studies; Valganciclovir
PubMed: 29546589
DOI: 10.1007/s40262-018-0638-5 -
The National Medical Journal of India 2016
Topics: AIDS-Related Opportunistic Infections; Adult; Antiretroviral Therapy, Highly Active; Antiviral Agents; Cytomegalovirus Retinitis; Ganciclovir; Humans; Male; Valganciclovir
PubMed: 27492038
DOI: 10.4103/0970-258x.186919