valganciclovir and Anemia

Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT.. We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs.. Of 2081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μl, ranged from 13% to 48% within 1-year post-transplant; ANC <500/μl ranged from 15% to 20%. Leukopenia, defined as white blood cell counts <3500/μl, was 19% to 83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for granulocyte colony-stimulating factor (G-CSF) use were common with L/N.. Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.

Topics: Adult; Anemia; Graft Rejection; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukopenia; Mycophenolic Acid; Neutropenia; Opportunistic Infections; Transplant Recipients; Valganciclovir

High HHV-8 viral load (VL) in Kaposi Sarcoma (KS) has been associated with Severe Immune Reconstitution Inflammatory Syndrome (Severe-IRIS-KS), which can occur after initiating cART, and leads to high mortality, particularly in patients with pulmonary involvement. We investigate if valganciclovir (as an anti-HHV-8 agent) initiated before cART reduces the mortality associated with Severe-IRIS-KS and the incidence of Severe-IRIS-KS.. Open-label parallel-group randomized clinical trial in AIDS cART naïve patients with disseminated KS (DKS) as defined by at least two of the following: pulmonary, lymph-node, or gastrointestinal involvement, lymphedema, or ≥30 skin lesions. In the experimental group (EG), patients received valganciclovir 900 mg BID four weeks before cART and continued until week 48; in the control group (CG), cART was initiated on week 0. Non-severe-IRIS-KS was defined as: an increase in the number of lesions plus a decrease of ≥one log10 HIV-VL, or an increase of ≥50cells/mm3 or ≥2-fold in baseline CD4+cells. Severe-IRIS-KS was defined as abrupt clinical worsening of KS lesions and/or fever after ruling out another infection following cART initiation, and at least three of the following: thrombocytopenia, anemia, hyponatremia, or hypoalbuminemia.. 40 patients were randomized and 37 completed the study. In the ITT analysis, at 48 weeks, total mortality was the same in both groups (3/20), severe-IRIS-KS attributable mortality was 0/20 in the EG, compared with 3/20 in the CG (p = 0.09), similar to the per-protocol analysis: 0/18 in the EG, and 3/19 in the control group (p = 0.09). The crude incidence rate of severe-IRIS-KS was four patients developed a total of 12 episodes of Severe-IRIS-KS in the CG and two patients developed one episode each in the EG. Mortality in patients with pulmonary KS was nil in the EG (0/5) compared with 3/4 in the CG (P = 0.048). No difference was found between groups in the number of non-S-IRIS-KS events. Among survivors at week 48, 82% achieved >80% remission.. Although mortality attributable to KS was lower in the EG the difference was not statistically significant.

Topics: Anemia; Antiretroviral Therapy, Highly Active; Herpesvirus 8, Human; HIV Infections; Humans; Sarcoma, Kaposi; Valganciclovir

Treatment of solid-organ transplant (SOT) patients with ganciclovir (GCV)-valganciclovir (VGCV) according to the manufacturer's recommendations may result in over- or underexposure. Bayesian prediction based on a population pharmacokinetics model may optimize GCV-VGCV dosing, achieving the area under the curve (AUC) therapeutic target. We conducted a two-arm, randomized, open-label, 40% superiority trial in adult SOT patients receiving GCV-VGCV as prophylaxis or treatment of cytomegalovirus infection. Group A was treated according to the manufacturer's recommendations. For group B, the dosing was adjusted based on target exposures using a Bayesian prediction model (NONMEM). Fifty-three patients were recruited (27 in group A and 26 in group B). About 88.6% of patients in group B and 22.2% in group A reached target AUC, achieving the 40% superiority margin (P< 0.001; 95% confidence interval [CI] difference, 47 to 86%). The time to reach target AUC was significantly longer in group A than in group B (55.9 ± 8.2 versus 15.8 ± 2.3 days,P< 0.001). A shorter time to viral clearance was observed in group B than in group A (12.5 versus 17.6 days;P= 0.125). The incidences of relapse (group A, 66.67%, and group B, 9.01%) and late-onset infection (group A, 36.7%, and group B, 7.7%) were higher in group A. Neutropenia and anemia were related to GCV overexposure. GCV-VCGV dose adjustment based on a population pharmacokinetics Bayesian prediction model optimizes GCV-VGCV exposure. (This study has been registered at ClinicalTrials.gov under registration no. NCT01446445.).

Topics: Adult; Aged; Anemia; Antiviral Agents; Area Under Curve; Bayes Theorem; Cytomegalovirus; Cytomegalovirus Infections; Drug Combinations; Drug Dosage Calculations; Female; Ganciclovir; Heart Transplantation; Humans; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Neutropenia; Recurrence; Valganciclovir; Viral Load

There are two approaches for treating cytomegalovirus (CMV) infection occurring after kidney transplantation (KTx). One is preemptive therapy in which treatment is started after confirming positive CMV antigenemia using periodic antigenemia assay. The other approach is prophylactic therapy in which oral valganciclovir (VGCV) is started within 10 days after KTx and continued for 200 days. The Transplantation Society guidelines recommend prophylactic therapy for high-risk (donor's CMV-IgG antibody positive and recipient's negative) pediatric recipients. However, the adequate dose and side effects of VGCV are not clear in children, and there is no sufficient information about prophylaxis for Japanese pediatric recipients.. A single-center retrospective analysis was conducted on case series of high-risk pediatric patients who underwent KTx and received oral VGCV prophylaxis at the Department of Pediatric Nephrology, Tokyo Women's Medical University, between August 2018 and March 2019. Data were collected using medical records.. The dose of administration was 450 mg in all the study patients (n = 5). Reduction or discontinuation was required in four of five patients due to adverse events, which included neutropenia in one patient, anemia in two patients, and neutropenia and digestive symptoms in one patient. Late-onset CMV disease occurred in all patients. No seroconversion was observed during prophylaxis.. Our preliminary study suggests that the dosage endorsed by The Transplantation Society may be an overdose for Japanese pediatric recipients. Further studies are required to examine the safety and efficacy of VGCV prophylaxis in Japanese pediatric recipients.

Topics: Adolescent; Anemia; Antibodies, Viral; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Digestive System Diseases; Female; Humans; Kidney Transplantation; Male; Neutropenia; Retrospective Studies; Valganciclovir; Young Adult

Valganciclovir (2/d) therapy for 6 months in neonates with symptomatic congenital cytomegalovirus (cCMV) infection improves hearing and neurodevelopmental outcome. The only reported adverse event was neutropenia. Since 2009, our protocol for symptomatic cCMV infection was a 1-year treatment of 2/d for the first 3 months followed by 9 months of 1/d.. A retrospective study. Infants with cCMV treated with valganciclovir for 1 year were recruited. Data of drug-related hematologic adverse events were collected.. One hundred sixty infants were eligible; 46 (28.8%) had experienced at least 1 episode of neutropenia (58 episodes), the majority (39/46, 84.8%) during the first 3 months of treatment and 7 (15.2%) during the last 9 months of treatment. Grades 3 and 4 neutropenia occurred in 9 (5.6%) children, almost exclusively during the first 3 months of treatment. Anemia (hemoglobin <9 g/dL) was recorded in 12 (7.5%) children during the first 3 months of 2/d treatment. Four children presented with hemoglobin levels <7 g/dL and needed a blood transfusion. One child was diagnosed with transient pure red cell aplasia. No long-term adverse events were recorded.. Although prolonged valganciclovir treatment for cCMV is safe, a close monitoring of the white blood cell count and hemoglobin levels is warranted. Much lower rates of grades 3 and 4 neutropenia were observed than previously reported, probably owing to our unique treatment protocol. Nevertheless, drug-induced anemia should be of primary concern. The optimal protocol assessing clinical outcome, concurrently with potential side effects, has not yet been determined.

Topics: Anemia; Antiviral Agents; Cytomegalovirus Infections; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Humans; Infant; Male; Neutropenia; Retrospective Studies; Valganciclovir

A 3-month-old male infant was admitted to hospital with anemia. Follow-up controls revealed the presence of specific cytomegalovirus (CMV) antibodies. Virus was isolated from urine, blood, and saliva. At 7 months of age, he presented with melena. Polymerase chain reaction (PCR) of biopsy samples from the duodenum was positive for CMV. Anemia resolved after starting antiviral therapy with oral valganciclovir.

Topics: Anemia; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Diagnosis, Differential; Ganciclovir; Humans; Infant; Male; Melena; Valganciclovir

Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Anemia; Antiviral Agents; Biological Availability; Cytomegalovirus Retinitis; Fever; Ganciclovir; Gastrointestinal Diseases; Headache; Humans; Infusions, Intravenous; Neutropenia; Paresthesia; Peripheral Nervous System Diseases; Prodrugs; Randomized Controlled Trials as Topic; Retinal Detachment; Sleep Initiation and Maintenance Disorders; Thrombocytopenia; Valganciclovir