Usual Pediatric Dose for CMV Prophylaxis 1 month to 16 years (heart transplant recipients) or 4 months to 16 years (kidney transplant recipients) : The recommended once-daily oral dose is based on BSA and CrCl derived from a modified Schwartz formula, and is calculated using the following equation Oral ganciclovir has been replaced by valganciclovir for prophylaxis and preemptive therapy because of bioavailability issues. Prophylaxis is provided to all patients who have positive CMV. with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday unti Conclusions: Three months of low-dose valganciclovir (450 mg/day) was as effective as ganciclovir (3 g/day) for prophylaxis of CMV disease after kidney and/or pancreas transplantation CMV Colitis or Esophagitis in HIV-Infected Patients (Off-label) Treat initially with ganciclovir 5 mg/kg/dose IV q12hr; once therapy is tolerated, change to valganciclovir 900 mg PO q12hr for 21-42..
For chronic suppressive therapy of cytomegalovirus (CMV) disease, including CMV retinitis (i.e., secondary cytomegalovirus (CMV) retinitis prophylaxis) in HIV-infected patients. NOTE: Ganciclovir intravenous injection has been designated an orphan drug by the FDA for CMV retinitis CMV Colitis or Esophagitis in HIV-Infected Patients (Off-label) Treat initially with ganciclovir 5 mg/kg/dose IV q12hr; once therapy is tolerated, change to valganciclovir 900 mg PO q12hr for 21-42 days or until signs and symptoms have resolved. Dosage Modifications Renal impairment. Induction dose. CrCl 50-69 mL/min: 2.5 mg/kg IV q12h This technique has been widely used in other fields, particularly cardiovascular disease [ 3 ]. Kalil et al [ 2] included only studies in which valganciclovir at a dosage of 900 mg/day (12 studies) or 450 mg/day (8 studies) was used for CMV prophylaxis, with a comparator arm consisting of oral ganciclovir, oral valacyclovir, or preemptive therapy
The initial patients received CMV prophylaxis with high-dose intravenous (i.v.) acyclovir at 500 mg/m 2 every 8 h from day −7 until engraftment, followed by oral acyclovir 800 mg four times. Prevention of CMV after SOT can be achieved with antiviral prophylaxis. Prophylaxis is the administration of antiviral drugs to all patients or higher risk patients for predetermined time periods after transplantation. Common antiviral regimens include oral valganciclovir (VGCV) or intravenous ganciclovir Thereafter secondary prophylaxis was given using 900 mg (2×450 mg) per day valganciclovir tablets for 28 days. In case of CMV disease or if the patient was unable to take oral medication, intravenous ganciclovir at 2×5 mg/kg body weight per day was permitted Considering the dosage of Ganciclovir and Valganciclovir used in this population, the mean ratio of the prescribed daily dose to the optimal daily dose was 2.9 in the first dose, 2.0 in the second dose, 1.3 in the third dose, and 1.5 in the fourth dose, considering prevention and treatment doses as a whole
Ganciclovir and Valganciclovir: Ganciclovir is an analogue of 2-deoxyguanosine, a competitive substrate for UL54-encoded CMV DNA polymerase. 10 Ganciclovir is triphosphorylated intracellularly by kinases and incorporated into DNA during viral replication, resulting in premature termination of DNA synthesis. 10 IV ganciclovir has significantly. In contrast, patients in the non-valganciclovir prophylaxis group did not receive any prophylaxis for CMV. Preemptive antiviral therapy with ganciclovir and CMV-specific intravenous immunoglobulin started when the CMV viral load exceeded 1000 copies/mL in both groups of patients The Lancet Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients D.J. Winston MD * a * Correspondence to: Dr Drew J Winston D. Wirin RN a A. Shaked MD b R.W. Busuttil MD b a Hematology-Oncology, Department of Medicine, UCLA Medical Center, Los Angeles, CA 90024, U.S.A . b Dumont-UCLA Transplant Center, Department. SummaryDespite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients.At the time of transplant, patients were. concentrations for CMV prophylaxis. Clinical Studies in Children The first report of ganciclovir treatment in an infant with CMV was published in 1988. 9 Since that time, a variety of case reports and clinical studies have been published describ ing the use of ganciclovir in infants and children. In addition,
When using ganciclovir as universal prophylaxis to prevent CMV, there is an established AUC 0-24 target range of 40-60 μg ∙ hour/mL, which was also used to develop the pediatric dosing algorithm of valganciclovir. Our simulations demonstrate that i.v. ganciclovir at the adult dose of 5 mg/kg q.d. fails to reach the target exposure for. Valganciclovir is shown to be more active than oral ganciclovir, and as good as intravenous (i.v.) ganciclovir in treating newly diagnosed CMV retinitis. The use of valganciclovir for CMV prophylaxis post stem cell transplantation was never tested in controlled study Data on CMV prophylaxis medication were collected from the date of transplantation and 90 (±7) days forward; other biochemical and clinical data were collected up to a year post-tx. Data on valganciclovir and ganciclovir dosage were recorded from a medical prescription database and were cross-referenced with clinical journals Anti-CMV drugs currently available for either treatment or prophylaxis include ganciclovir, valganciclovir (the orally administered prodrug), foscarnet, cidofovir, and letermovir. Ganciclovir targets both UL97 and UL54, while cidofovir and foscarnet target only UL54
Cytomegalovirus (CMV) Retinitis is an acquired immunodeficiency syndrome (AIDS)-related opportunistic infection that can lead to blindness. CMV retinitis occurred with higher frequency prior to the advent of antiretroviral therapy, but has since been decreasing in well-developed countries, although still remains a prevalent condition in developing countries Valganciclovir at a dose of 900 mg (two 450-mg tablets) orally results in ganciclovir blood levels similar to those obtained with a dose of 5 mg/kg intravenous ganciclovir, and has been shown to be similar in efficacy to intravenous ganciclovir as induction therapy in treating HIV-associated CMV retinitis Kidney recipients (n = 51) at risk of cytomegalovirus (CMV) disease, and requiring anti‐lymphocyte globulin therapy because of biopsy‐proven rejection, received high‐dose ganciclovir, three times a week, for a total of nine doses. CMV disease was observed in seven (14%) patients within 6 months. Six of these patients were in a group of 45 CMV‐seropositive recipients, and one was in a. Because CMV viremia is uncommon while taking valgancicolvir prophylaxis, surveillance CMV PCR testing was not performed during the period of antiviral prophylaxis, which is consistent with clinical guidelines. 8,17 Valganciclovir (or intravenous ganciclovir) use for the first 10 days after transplant prior to randomization per local standards.
3 • Pediatrics!have!anincreasedriskof!primary!CMVinfection;!more!experience!with pharmacologic!prophylaxis!thanpreemptive!management! • Recommended!CMV. , safer, and lower cost drugs (high-dose acyclovir, valacyclovir, ganciclovir), our results do not favor the use of valganciclovir as a first-line agent for CMV preemptive or universal prophylaxis in SOT patients
Drug / Dose Comments; Retinitis, Immediate sight-threatening lesions ganciclovir 5 mg/kg bid iv: 3 weeks, then secondary prophylaxis: OR foscarnet 90 mg/kg bid iv: Foscarnet used as alternative therapy if toxicity or resistance to ganciclovir. Some experts would add intravitreal injections of ganciclovir (2 mg) or foscarnet (2.4 mg) for 1-4. Drugs used for CMV prophylaxis in patients with solid organ transplants include CMV immune globulin i.v., acyclovir, valacyclovir, ganciclovir, and valganciclovir. The mechanisms of action and. Ganciclovir prophylactic regimens have been shown to be effective in renal transplant recipients at risk for primary (donor seropositive/recipient seronegative) and secondary (recipient seropositive) cytomegalovirus (CMV) disease. However, in addition to serologic factors, the type and intensity of the administered immunosuppression is a strong risk factor for CMV disease Ganciclovir is an acyclic nucleoside analogue of 2-deoxyguanosine that inhibits replication of herpes viruses. Ganciclovir has been shown to be active against cytomegalovirus (CMV) and herpes simplex virus (HSV) in human clinical studies. Indication : Prevention of cytomegalovirus (CMV) disease in advanced HIV infection at risk for CMV diseas
Randomized comparison of ganciclovir and high-dose acyclovir for long- term cytomegalovirus prophylaxis in liver-transplant recipients. Lancet 1995;346:69-74. 222. Winston DJ, Wirin D, Shaked A, Busuttil RW. Randomized comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver transplant recipients Dosage is based on BSA and CrCl; not to exceed 900 mg/day PO for prophylaxis; 1,800 mg/day PO is used off-label for treatment of CMV infection in children old enough to receive adult dosage. Infants Dosage is based on BSA and CrCl; alternatively, 32 mg/kg/day PO has been used off-label for congenital CMV disease In this three-arm, randomized, open-label, parallel group trial, conducted between June 1991 and August 1993, patients with AIDS and stable CMV retinitis following from 4 weeks to 4 months of treatment with Ganciclovir Injection solution were randomized to receive maintenance treatment with Ganciclovir Injection solution, 5 mg/kg once daily. Another trial of 9 lung transplant recipients (ages 6 to 18 years), reported no cases of neutropenia (defined as ANC less than 500/mm3) after 12 weeks of intravenous ganciclovir for prophylaxis (5 mg/kg/dose IV every 12 hours for 21 days, then 5 mg/kg/dose IV once daily to complete 12 weeks)
In a prospective study, 36 severely immunocompromised paediatric patients (6 months - 16 years of age) with HIV and CMV infection received intravenous ganciclovir at a dose of 5 mg/kg per day for 2 days followed by oral ganciclovir for a median of 32 weeks CMV infection (second or later episode) was deﬁned as the development of a new positive CMV test occur-ring after a 50-day interval free of CMV infection. Another endpoint was the dose-limiting toxicities, deﬁned as the dose adjustment or withdrawal because of related toxicity, of prophylaxis with ganciclovir and valganciclovir The primary endpoint of the study was the area-under-the-curve. Authors concluded that a single dose of 900 mg of oral valganciclovir was non-inferior to a single dose 5 mg/kg of IV ganciclovir. Conclusions: Research question 1. There were no studies of IV ganciclovir versus placebo for preventative CMV treatment in stem cell transplant patients A comparative randomised study of valacyclovir vs. oral ganciclovir for cytomegalovirus prophylaxis in renal transplant recipients. 2005. Ioanna Pavlopoulou. Download PDF. Download Full PDF Package. This paper. A short summary of this paper. 37 Full PDFs related to this paper. READ PAPER , in the context of prophylaxis and treatment of CMV infections, in order to provide the patient with an adequate dose
Low-dose valaciclovir prophylaxis resulted in a statistically significant decrease (8.5 vs 37%, P=0.004) in CMV disease zyx report our experience with low-dose in the study group at 6 months. On zyxwvutsrqpo valaciclovir prophylaxis of up to 3 g/ subgroup analysis the decrease was day, adjusted to creatinine clearance Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipient Ganciclovir is a potential teratogen and carcinogen. Manufacturer advises avoid inhalation of the powder or direct contact of the powder or reconstituted solution with the skin or mucous membranes; if contact occurs, wash thoroughly with soap and water; rinse eyes thoroughly with plain water
Virus that exhibits low-level ganciclovir resistance has a mutation at UL97. High-level resistance is also associated with a DNA polymerase mutation, which results in cross-resistance to cidofovir. There have been a number of studies looking at prophylaxis of CMV disease. ACTG 204 compared high-dose valacyclovir with two doses of acyclovir An open, prospective, randomised study was conducted to compare the safety and efficacy of valacyclovir vs. oral ganciclovir for cytomegalovirus (CMV) prophylaxis in renal transplant recipients. Eighty-three renal transplant recipients were assigned randomly to receive valacyclovir (n = 43) or oral ganciclovir (n = 40) for the first 3 months after transplantation PET comprises antiviral agents like ganciclovir, valganciclovir, and foscarnet. However, these agents are associated with significant adverse effects such as myelo- or nephrotoxicity [7, 8], precluding their routine use for CMV prophylaxis. Accordingly, CMV viremia still represents a time-dependent risk factor for mortality after alloHCT Low-Dose Valganciclovir for Cytomegalovirus Prophylaxis in Intermediate-Risk Liver Transplantation Recipients Salman Khan ,1 Timothy Sullivan,1 Mohsin Ali,2 Dallas Dunn,1 Gopi Patel,1 and Shirish Huprikar1 1Division of Infectious Diseases; 2Icahn School of Medicine at Mount Sinai, New York, NY Liver transplantation recipients (LTRs) who are seropositive for cytomegalovirus (CMV) (recipient.
Cytomegalovirus (CMV) is a substantial cause of morbidity in pulmonary allograft recipients. In an attempt to decrease the prevalence of this infection, we treated 13 recipients at risk for cytomegalovirus with 3 wk of intravenous ganciclovir (5 mg/kg twice a day for 14 days, starting 5 days after the procedure, followed by 1 wk of the drug at a dose of 5 mg/kg/day) Adult Dosage (2.2) Treatment of CMV Induction: 900 mg (two 450 mg tablets) twice a retinitis . Ganciclovir coadministered with didanosine may increase Monitor serum creatinine levels regularly and consider changes in height and body weight and adapt the dose as appropriate during prophylaxis period
Regarding CMV prophylaxis, patients in the val-ganciclovir prophylaxis group received valganci-clovir 450mg per day, from the day of absolute neutrophil engraftment to approximately 100 days after allo-HSCT. The median duration of valgan-ciclovir prophylaxis was 98.5 (range: 21-107) days. In contrast, patients in the non-valganciclo CMV management in kidney/pancreas transplantation In all cases of CMV prophylaxis, a 3 month course of oral valganciclovir is given. Dose of valganciclovir depends on the patient's renal function (see Appendix 3 for details) and it is crucial to review dose regimen regularly to ensure effective CMV prophylaxis and avoid drug toxicity Primary prophylaxis (CMV retinitis in patients with AIDS) Ganciclovir 1000 mg orally three times daily OR valganciclovir 900 mg orally daily. Intravitreal therapy (for CMV retinitis) induction ganciclovir 400mg two to three times a week . maintenance therapy ganciclovir 400 mg weekly. Disease state based dosing: Renal Impairment
Cytomegalovirus (CMV) All transplant recipients except CMV recipients of CMV donors receive CMV prophylaxis with valganciclovir for 6 months. If T-Cell depleting induction [ATG/Alemtuzumab (Campath)] is used, CMV D-/R- cases will also receive 6 months valganciclovir. The initial valganciclovir dose is dependent on renal function as shown in the. CMV prophylaxis and treatment with valganciclovir in patient 7. valganciclovir dosage (red rectangle), ganciclovir plasma concentration (closed white circle: concentration measured at trough, closed white triangle: concentration measured 3 h after last dose, red line: concentration predicted by population pharmacokinetic model), CMV viremia (blue square and solid blue line), symptoms period.
Ganciclovir Susceptibilities of Cytomegalovirus (CMV) Isolates from Solid Organ Transplant Recipients with CMV Viremia after Antiviral Prophylaxis Henry H. Balfour , Guy Boivin, Alejo Erice, Deborah D. Crane, David Dun Kliem V, Fricke L, Wollbrink T, et al. Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial. Am J Transplant 2008; 8:975. Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis 2004; 4:725
Valacyclovir has been used for prophylaxis against cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT). We investigated the efficacy and safety of high-dose Valacyclovir as pre-emptive therapy in patients with CMV antigenemia after HSCT. In a retrospective single center study of 61 patients, we compared the rates of viral clearance, recurrent antigenemia and.
Table 2: Currently available drugs for cmv prophylaxis Drug Usual adult Prophylaxis dose Comments on use and major toxicity Valganciclovir 900 mg once daily Ease of administration; leukopenia Oral Ganciclovir 1 g three times daily Low oral bioavailability; high pill burden IV Ganciclovir 5 mg/kg once daily Intravenous access; leukopeni
Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 studies; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 studies; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 studies; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality. CMV disease, which traditionally occurs during the first three months after transplantation12. Subsequent clinical trials have therefore ex-tended the duration of prophylaxis to three months after solid organ transplantation21-23. The adminis-tration of IV ganciclovir for 90-100 days reduced the incidence of CMV disease in CMV D+/R- liver trans Administration. Type: Antiviral Routes of Administration: IV, PO; Common Trade Names: Cytovene; Adult Dosing. CMV prophylaxis, solid organ transplant . IV route: 5mg/kg IV q12h x7-14 days, then 5mg/kg IV q24h or 6mg/kg IV 5x/w If CMV viremia recurs during continuous treatment with ganciclovir, researchers report restarting ganciclovir induction (100) or stopping ganciclovir and starting foscarnet (CIII). Limited data were found regarding the use of foscarnet among HSCT recipients for either CMV prophylaxis or preemptive therapy (92,93)
Prophylaxis or preemptive treatment (actively monitoring patients by viral load and giving antiviral drugs to those with evidence of infection) is effective for preventing CMV disease in solid organ or hematopoietic cell transplant recipients infected with CMV and at risk of CMV disease. Drugs used include ganciclovir, valganciclovir, and. CMV prophylaxis was administered with anti-CMV HI G, 150 mglkg at week I and 3, then 100 mglkg every 2 weeks until week 12, and then a final dose at 16 weeks. Ganciclovir, 10 mglkgld, was given IV for 2 weeks, and then a dose of 5 mglkg/d was given IV three times per week until week 12. Diagnosis of CMV Diseas CMV retinitis, prophylaxis and treatment of systemic CMV infections in immunocompromised patients including HIV-positive and transplant patients. Contraindications. Hypersensitivity to ganciclovir or acyclovir, lactation. Cautious Use. Renal impairment, older adults, pregnancy (category C). Safety and efficacy in children are not established
Ganciclovir (5mg/kg IV daily, adjusted for renal clearance) and valganciclovir (900mg per os daily, adjusted for renal clearance) are currently the most effective antiviral drugs used for CMV disease prevention in SOT. When used for prophylaxis, the duration of antiviral administration most commonly used is 100 days CMV viremia while on study drug was more common in oral ganciclovir-treated patients (10.4%) than in valganciclovir recipients (2.5%)(P = .001), which may have resulted in a higher rate of ganciclovir-resistant CMV being recovered from ganciclovir-treated patients (2%) than from patients on the valganciclovir arm (0%)
To assess whether ganciclovir prophylaxis can reduce IL-6 levels in critically ill nonimmunosuppressed patients, investigators conducted a randomized phase 2 clinical trial. A total of 160 CMV-seropositive patients with sepsis or trauma and respiratory failure, requiring intubation and ventilatory support, were randomized to receive ganciclovir. INTRODUCTION: CMV infection is a major cause of morbidity and mortality in transplant recipients. For this reason patients are often prophylaxed against CMV infections in the postoperative period. The advent of new oral medications has broadened the options for prophylaxis, but there is a paucity of data attesting to their efficacy. We analyzed our data of lung transplant patients before and. Indications and Dosage. Intravenous. Cytomegaloviral infections. Adult: Induction: 5 mg/kg 12 hrly for 14-21 days. Maintenance: 5 mg/kg once daily for 7 days per wk or 6 mg/kg once daily for 5 days per wk. Doses to be given by IV infusion over 1 hr. Intravenous. Prophylaxis of cytomegaloviral infections in immunocompromised patients
Anti- CMV drugs currently available for either treatment or prophylaxis include ganciclovir, valganciclovir (the orally administered prodrug), foscarnet, cidofovir, and letermovir. Ganciclovir targets both UL97 and UL54, while cidofovir and foscarnet target only UL54. The newest CMV drug, Letermovir, targets subunit 2 of the viral terminase. 10. Snydman DR. Combined CMV-IGIV and ganciclovir prophylaxis in CMV seronegative transplant recipients from CMV seropositive donors. Report on file. 11. Martin M. CMV prophylaxis with combination ganciclovir and CMV hyperimmune globulin followed by high-dose acyclovir in solid organ transplant recipients. Report on file. 12 Graft loss occurred in 1 patient in the low-dose group. No patients had ganciclovir resistant infection. Conclusions: Rates of CMV disease, hematologic events, ganciclovir-resistance, and graft loss were similar among intermediate-risk patients who received renallyadjusted VGC 900 mg and VGC 450 mg for CMV prophylaxis post-kidney transplant
ciclovir for prophylaxis remain contro-versial and unresolved. First, a brief description of the ter-minology used to describe various ap-proaches to CMV prophylaxis would be relevant. Universal prophylaxis in-volves administration of ganciclovir, usu-ally for a prolonged period, to all trans-plant recipients, irrespective of the risk of CMV. and ganciclovir, respectively, is similar to that previ-ously reported by Gane et al.2 (4.8% with ganciclovir at 6 months). In addition, the incidence of CMV disease in our high risk group of 7% and 22% with valganciclovir and ganciclovir, respectively, was similar to that re-ported by others using ganciclovir (9.3-21.4%).2-4 Fi Valantine and Luikart 12 compared prophylaxis with CMV-IGIV (biweekly for three months) in combination with ganciclovir prophylaxis (IV at 5 mg/kg twice a day for the initial 14 days post-transplant, then at 6 mg/kg through day 28) in 16 CMV seronegative recipients of hearts from CMV seropositive donors with 16 matched controls receiving. The health technologies studied were oral ganciclovir (dosage of 1g tid (Cymevene; Hoffman-La Roche, UK)), and oral valacyclovir (dosage of 2g qid (Valtrex; Glaxo Wellcome, UK)). These were then compared to deferred therapy with no prophylaxis (i.e. frequent monitoring by highly sensitive nested PCR for cytomegalovirus (CMV) DNA for whole blood. Conclusions. Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high- dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group. AB - Background The presence of known ganciclovir resistance-associated amino acid substitutions was evaluated in a study that extended valganciclovir cytomegalovirus (CMV) prophylaxis from 100 days to 200 days post-transplant in adult kidney transplant patients at high risk for CMV disease (D+/R-)