Oral Valganciclovir Is Noninferior to Intravenous Ganciclovir for the Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients

Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i.v. ganciclovir twice daily for 21 days, followed by 900 mg daily valganciclovir for 28 days. A total of 321 patients were evaluated (valganciclovir [n = 164]; i.v. ganciclovir [n = 157]). The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI -14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS). Treatment success, as assessed by investigators, was 77.4% versus 80.3% at Day 21 and 85.4% versus 84.1% at Day 49 (p = NS). Baseline viral loads were not different between groups and decreased exponentially with similar half-lives and median time to eradication (21 vs. 19 days, p = 0.076). Side-effects and discontinuations of assigned treatment (18 of 321 patients) were comparable. Oral valganciclovir shows comparable safety and is not inferior to i.v. ganciclovir for treatment of cytomegalovirus disease in organ transplant recipients and provides a simpler treatment strategy, but care should be taken in extrapolating to organ transplant recipients not properly represented in the present study.     

Cytomegalovirus Disease in High-Risk Transplant Recipients Despite Ganciclovir or Valganciclovir Prophylaxis

The clinical patterns and predictors of cytomegalovirus (CMV) disease in kidney and/or pancreas transplant patients on ganciclovir (1.0 g po t.i.d.) or valganciclovir (450 mg po q.d.) prophylaxis were studied. This is a retrospective analysis of 129 transplant recipients. Median follow up was 12 months (range, 6-18 months). The overall incidence of CMV disease at 1-year post-transplant was 14% (4% tissue-invasive, 10% noninvasive). Seventeen of 18 patients were diagnosed with CMV after completion of 3 months' prophylaxis (median 8 weeks, range, 2-28 weeks). Induction treatment with thymoglobulin, and Donor +/Recipient - CMV status were the strongest predictors for the development of CMV disease. Cytomegalovirus incidence was not different between patients treated with ganciclovir or valganciclovir (15 vs. 17%, respectively). Valganciclovir (450 mg q.d.) is as effective as oral ganciclovir in CMV prophylaxis. High-risk individuals might require higher doses or longer duration of valganciclovir treatment.     

Valganciclovir Dosing According to Body Surface Area and Renal Function in Pediatric Solid Organ Transplant Recipients

Oral valganciclovir is effective prophylaxis for cytomegalovirus (CMV) disease in adults receiving solid organ transplantation (SOT). However, data in pediatrics are limited. This study evaluated the pharmacokinetics and safety of valganciclovir oral solution or tablets in 63 pediatric SOT recipients at risk of CMV disease, including 17 recipients ≤2 years old. Patients received up to 100 days' valganciclovir prophylaxis; dosage was calculated using the algorithm: dose (mg) = 7 × body surface area × creatinine clearance (Schwartz method; CrCLS). Ganciclovir pharmacokinetics were described using a population pharmacokinetic approach. Safety endpoints were measured up to week 26. Mean estimated ganciclovir exposures showed no clear relationship to either body size or renal function, indicating that the dosing algorithm adequately accounted for both these variables. Mean ganciclovir exposures, across age groups and organ recipient groups were: kidney 51.8 ± 11.9 μg * h/mL; liver 61.7 ± 29.5 μg * h/mL; heart 58.0 ± 21.8 μg * h/mL. Treatment was well tolerated, with a safety profile similar to that in adults. Seven serious treatment-related adverse events (AEs) occurred in five patients. Two patients had CMV viremia during treatment but none experienced CMV disease. In conclusion, a valganciclovir-dosing algorithm that adjusted for body surface area and renal function provides ganciclovir exposures similar to those established as safe and effective in adults     

口服抗病毒新药——缬更昔洛韦

缬更昔洛韦 (valganciclovir)是抗病毒药更昔洛韦的前体药物 ,用于治疗AIDS病人发生的巨细胞病毒 (CMV)视网膜炎。缬更昔洛韦口服后迅速吸收 ,并水解为更昔洛韦 ,其口服给药的生物利用度较高 (60 % )。试验表明 ,口服缬更昔洛韦 (90 0mg)与静脉注射更昔洛韦 (5mg·kg-1) ,bid,3wk后改为 qd ,治疗 1 60例AIDS病人发生的CMV视网膜炎有相同疗效 ,且耐受性相似。缬更昔洛韦维持治疗中最常见的不良反应为中性粒细胞减少症、贫血、胃肠道反应 (腹泻、恶心、呕吐 )、发热、头痛和失眠等     

Oral valganciclovir in human immunodeficiency virus-positive patients suffering from cytomegalovirus retinitis at a tertiary care hospital in North India

Purpose:To study clinical efficacy of valganciclovir in cytomegalovirus retinitis (CMVR) in human immunodeficiency virus (HIV)-positive-positive patients in a tertiary care clinic in a developing nation.Methods: In a retrospective study, systemic and ocular records of HIV patients suffering from CMVR and treated with valganciclovir, were analyzed. Primary outcome measures were involvement of the other eye, incidence of retinal detachment, systemic involvement, and mortality encountered. Secondary outcome measures included change in BCVA.Results: Out of nine patients who were included, two patients developed CMVR in the other eye and only one patient (11.11%) developed retinal detachment during the course of the study. No patient developed any systemic manifestations or had mortality during the course of the study. The change in BCVA was not statistically significant.Conclusion: Use of oral valganciclovir showed good outcome and was found to be a better alternative compared to the use of intravitreal ganciclovir in the literature. Introduction of valganciclovir at an affordable price in developing nations can decrease disease burden.     

Prophylactic CMV therapy does not improve three‐yr patient and graft survival compared to preemptive therapy

Despite increasing evidence in favor of prophylactic valganciclovir treatment in kidney transplant recipients for the prevention of cytomegalovirus (CMV) infection, the impact of preemptive vs. prophylactic treatment on long‐term clinical outcomes is unclear. In this retrospective study, 187 kidney transplant recipients with serologic intermediate‐risk constellation (recipient CMV IgG positive) received either preemptive or prophylactic treatment with valganciclovir. Patient survival (primary endpoint), graft survival, viremia rates, and other CMV‐related outcomes were analyzed. Prophylactic therapy reduced the rates for CMV viremia during the first year (hazard ratio: 0.48, 95% confidence interval [CI] 0.30–0.75; p < 0.001). There was a trend for higher three‐yr patient mortality in the prophylactic group (hazard ratio: 5.08, 95% CI 0.62–41.3; p = 0.091), and the rate of graft loss was not reduced (hazard ratio: 0.93, 95% CI 0.32–2.68; p = 0.894). Estimated glomerular filtration rate over three yr was on average 6.8 mL/min/1.73 m² lower in the prophylactic group (95% CI −11.68 to −1.81; p = 0.007) using a multivariate random effects model but showed more improvement over time. Prophylactic valganciclovir treatment reduced the rate of CMV infections during the first year post‐transplant but no effects of prophylactic treatment on patient and graft survival or kidney function over three yr were observed.