However, the results of a 5year international proficiency program. This paper presents three cases of immunocompromised patients for whom therapeutic drug monitoring tdm of ganciclovir in combination with cytomegalovirus cmv viral load measurement was used to guide treatment. Ganciclovir capsules are used to treat cmv retinitis after the condition has been controlled by intravenous injected into a vein ganciclovir. This book is a compilation of summarized analytical methods designed to serve the needs of pharmacologists, toxicologists, and other allied health professionals involved the development, use, or monitoring of pharmaceuticals. Valganciclovir tdm in transplant recipients full text view.
Manufacturer advises avoid inhalation of the powder or direct contact of the powder or reconstituted solution with the skin or mucous membranes. Change in dose or even stopping the drug may be needed if any of these side effects happen. Ganciclovir gcv resistance is an emerging therapeutic challenge and should be suspected in patients failing to show a clinical and virological response to prolonged therapy. Ganciclovir is an oxopurine that is guanine substituted by a 1,3dihydroxypropan2yloxymethyl group at position 9. Cytovene ganciclovir side effects, images, uses, dosage. Conclusions monitoring the therapeutic drug levels and cytomegalovirus loads is useful in obtaining a proper treatment effect and preventing overdosage during ganciclovir therapy in premature. Comparative studies of preemptive and prophylactic ganciclovir therapies in bone marrow transplant bmt recipients have shown similar rates of cytomegalovirus cmv infection, disease and patient mortality. Relationship of ganciclovir therapeutic drug monitoring with clinical efficacy and patient safety. Very bad and sometimes lifethreatening blood and bone marrow problems like anemia, low platelet counts, or low white blood cell counts have happened with ganciclovir systemic. The primary outcome was an association between ganciclovir tdm and clinical efficacy endpoints within 30 days, defined by viral. Ganciclovir is a white to offwhite crystalline powder. Relationship of ganciclovir therapeutic drug monitoring. Therapeutic drug monitoring of ganciclovir for postnatal. The objective of this study was to develop and validate a reliable and clinically applicable limited sampling strategy using bayesian estimation for individualizing valganciclovir dose in pediatric kidney transplant patients.
Onsite therapeutic drug monitoring has the potential to improve patient outcomes and drastically reduce healthcare costs. Monitoring plasma levels of ganciclovir in aids patients. Individualization of valganciclovir prophylaxis for cytomega. Ganciclovir drug information indications, dosage, side. Ganciclovir is an antiviral drug that slows the growth and spread of the cytomegalovirus. Treat initially with ganciclovir 5 mgkgdose iv q12hr. Their report suggested that in some cases, particularly among young patients with a high rate of kidney excretion, conventional ganciclovir dosage regimens may not reach effective concentrations. Gancyclovir definition of gancyclovir by medical dictionary. Pdf neurotoxicity related to valganciclovir in a child. Learn how to pronounce the drug s name, its indications, dosage, how to take, when. Nov 09, 2018 ganciclovir is an antiviral drug that slows the growth and spread of the cytomegalovirus cmv. Despite being on the radar of the scientific community for almost two decades, sensorbased approaches have yet to break through and support the clinical application of therapeutic drug monitoring, potentially due to the gap between scientific and clinical communities. Ganciclovir is a polar hydrophilic compound with a solubility of 2. Sensitive human viruses include cmv, herpes simplex virus1 and 2 hsv1, hsv2, epsteinbarr virus, and varicellazoster virus.
Human herpes virus6 encephalitis in a paediatric bone. Ganciclovir is used to treat cmv retinitis in people with immunosuppression caused by. Ganciclovir is a potential teratogen and carcinogen. In this study, the mean ratio of prescribed daily dose to the standard dose shows that antiviral drugs are totally used more than the recommended daily dose which can emerge drug resistance and increase the cost of treatment and adverse drug effects. Ganciclovir is also fdaapproved for the prevention of cmv disease in recipients of organ transplants who are at risk for cmv diseases. Cytomegalovirus cmv infection is a common complication following solid organ transplantation that may severely affect the outcome of transplantation. Protein precipitation with acetonitrile was followed by hydrophilic interaction liquid chromatography on a silica column with 4 min run time. Dailymed ganciclovir ganciclovir sodium injection, powder. To the editor ganciclovir is a firstline agent for the treatment of human cytomegalovirus cmv.
This article presents 3 cases of immunocompromised patients for whom therapeutic drug monitoring of ganciclovir in combination with cytomegalovirus viral load measurement was used to guide treatment. Effects of ganciclovir on pharmacokinetic parameters of coadministered drug. Therapeutic drug monitoring of ganciclovir after valganciclovir administration is. Ganciclovir, postnatal cytomegalovirus infection, therapeutic drug monitoring, extremely low. Ganciclovir indications, dosage, side effects and precautions.
Oral valganciclovir and intravenous ganciclovir are used for prophylaxis. Pdf therapeutic drug monitoring of ganciclovir for postnatal. In the april 2019 issue of therapeutic drug monitoring, in the article ganciclovir therapeutic drug monitoring. Summary guideline for therapeutic drug monitoring tdm in. Inclusion or absence of a drug label on the aidsinfo site does not imply endorsement or lack thereof by aidsinfo. Therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant. It is also considered likely to cause inhibition of spermatogenesis.
Nov 12, 2012 ganciclovir is a nucleoside guanosine analogue which incorporates ganciclovir triphosphate the active moiety into dna during elongation, thereby inhibiting viral replication. Population pharmacokinetics of ganciclovir after intravenous. Pdf neurotoxicity related to valganciclovir in a child with. Dec 21, 2018 ganciclovir is a prescription medicine approved by the u. Aug 22, 2016 therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant.
Ganciclovir gcv and its prodrug valganciclovir are successfully used to prevent and treat cmv infection. Ganciclovir may lower the number of all types of cells in your blood, causing serious and lifethreatening problems. Neurotoxicity related to valganciclovir in a child with. Otherwise, therapeutic drug monitoring tdm may represent a useful alternative. The lexicomp content is intended to serve the user as a rapidly accessible, concise initial reference resource and not as a complete reference resource. To assure adequate ganciclovir drug exposure, therapeutic drug monitoring tdm is an easytouse tool to assess ganciclovir serum concentrations and to guide. Ganciclovir fda label injection powder, lyophilized. Valganciclovir therapeutic monitoring showed high ganciclovir concentrations in the plasma 3.
Statistical analyses were performed using stata software version 8. A case series, it should be noted that author annegrete martson was funded by marie sklodowskacurie actions, grant agreement number. Ganciclovir was the first antiviral agent approved for the treatment of cytomegalovirus cmv infection. Thus, it is used judiciously and handled as a cytotoxic drug in the clinical setting. The role of therapeutic drug monitoring in the treatment. Drug interactions and toxicities associated with the antiviral management of cytomegalovirus cmv infection are described. Nms labs does not assume responsibility for billing errors due to reliance on the cpt codes listed in this document. Jun 27, 2017 therapeutic drug monitoring tdm is eventually considered when side effects are seen at a lower doses or inadequate efficacy is observed at a higher doses than expected.
Results of drug interaction studies with ganciclovir. The first patient is diagnosed with thymoma a, the second is a heart transplant recipient, and the third is an hivpositive patient. Therapeutic drug monitoring tdm in its initial years, the 19601970s, was mainly equated with the measurement of drug concentrations in serum, plasma, or whole blood to individualize dosage with the goal of maintaining drug concentrations within a therapeutic target range pharmacokinetic pk tdm. Individualized dosing algorithms and therapeutic monitoring. We retrospectively analyzed adult patients treated for cytomegalovirus cmv infection with ganciclovir with tdm between 2005 and 2015.
Ganciclovir is used to treat cmv retinitis in people with immunosuppression caused by hiv or aids. Ganciclovir fda label injection powder, lyophilized, for. The first patient is diagnosed with thymoma a, the second is a heart transplant recipient and the third is an hiv positive patient. Coadministered drug ganciclovir dosage n coadministered drug pharmacokinetic pk parameter.
They used therapeutic drug monitoring to reach the targeted plasma concentrations. Aciclovir and ganciclovir levels are common virology request for tdm. Oct 06, 2017 ganciclovir is a white to offwhite crystalline powder with a molecular formula of c 9 h n 5 0 4 and a molecular weight of 255. Drug interactions and toxicities associated with the. Learn how to pronounce the drugs name, its indications, dosage, how to take, when.
The chemical name for ganciclovir is 92hydroxy1hydroxymethylethoxymethylguanine. Monitoring the therapeutic drug levels and cytomegalovirus loads is useful in obtaining a proper treatment effect and preventing overdosage during ganciclovir therapy in premature infants with postnatal cytomegalovirus infection. Requesters have found these assays to be of value in patients with renal failure andor on ecmo, in cases of suspected neurotoxicity, or suspected poor absorption and in some patients receiving valaciclovir. Diagnosis of gcvresistant cmv infection is established by demonstration of mutations in the ul97 kinase or ul54 dna polymerase genes with analysis of cmv dna 9. Ganciclovir is an antiviral agent, prescribed for cytomegalovirus cmv retinitis eye infection that can cause blindness in people who have received organ or bone marrow transplants. Human herpes virus6 encephalitis in a paediatric bone marrow. Reed ec, wolford jl, kopecky kj, et al ganciclovir for the treatment of cytomegalovirus gastroenteritis in bone marrow transplant patients. Therapeutic drug monitoring tdm may assist to overcome this problem. It is widely used for the treatment of cmv infections among patients with impaired cellmediated immunity, particularly persons with poorly controlled and advanced hivaids, and recipients of solid organ and bone marrow transplantation, who are at high risk for invasive cmv. Ganciclovirresistant cytomegalovirus infection in a kidney. Nov 14, 2018 ganciclovir is a white to offwhite crystalline powder. It is used to prevent disease caused by a virus called cytomegalovirus cmv in people who have received organ or. The drug is converted intracellularly to ganciclovir 5monophosphate by a viral kinase, which is encoded by the cytomegalovirus cmv gene ul97 during infection. Ganciclovir 91,3,dihydroxy2propoxymethyl guanine, or dhpg is an acyclic analog of the nucleoside guanosine.
Comparative studies of preemptive and prophylactic ganciclovir therapies in bone marrow transplant bmt recipients have shown similar rates of cytomegalovirus cmv infection, disease and patient. Valganciclovir vgc is an oral prodrug of ganciclovir gcv recently introduced for. Valganciclovir drug monograph pediatric care online. Therapeutic drug monitoring of ganciclovir treatment for. This study was the first medication use evaluation on ganciclovir and valganciclovir in kidney transplanted patients. Cytovene, ganciclovir dosing, indications, interactions. Relationship of ganciclovir therapeutic drug monitoring with. The aim of valganciclovir therapeutic drug monitoring tdm is to gain more insight into the pharmacodynamics and pharmacokinetics of. Summary guideline for therapeutic drug monitoring tdm in adults. Ganciclovir is a nucleoside guanosine analogue which incorporates ganciclovir triphosphate the active moiety into dna during elongation, thereby inhibiting viral replication.
To assure adequate ganciclovir drug exposure, therapeutic drug monitoring tdm is an easytouse tool to assess ganciclovir serum. The summaries are structured monographs on 511 different drug entities detailing 964 different analytical methods, providing the reader with a thorough description of. Therapeutic drug monitoring tdm is eventually considered when side effects are seen at a lower doses or inadequate efficacy is observed at a higher doses than expected. Piketty c1, bardin c, gilquin j, gairard a, kazatchkine md, chast f. The results of therapeutic drug monitoring in adult solid organ transplant recipients receiving prophylaxis indicated that a 24hour. It is changed in the body to the active form of the drug called ganciclovir. Vgc is rapidly converted into gcv by enzymes in the organism and also by chemical hydrolysis at higher ph. Ganciclovirresistant cytomegalovirus infection in a. Ganciclovir is a prescription medicine approved by the u.
It has a role as an antiviral drug and an antiinfective agent. Determination of ganciclovir and its prodrug valganciclovir. Ganciclovir will not cure this eye infection, but it may help to keep the symptoms from becoming worse. Therapeutic drug monitoring tdm is a good tool to estimate drug exposure in. Ganciclovir is an antiviral drug used to treat or prevent aidsrelated cytomegalovirus infections. Therapeutic drug monitoring of antiinfective agents in. Aidsinfo provides the following drug label solely as an example of the labels available for ganciclovir.
Who will benefit from therapeutic drug monitoring of. The purpose was to evaluate the effect of accuracy of therapy with ganciclovir and valganciclovir correct indication, drug dosage, duration of treatment, etc. Ganciclovir is used to treat the symptoms of cytomegalovirus infection of the eyes in people whose immune system is not working fully. The results of therapeutic drug monitoring in adult solid organ transplant recipients receiving prophylaxis indicated that a 24hour ganciclovir. Ganciclovir is also used to prevent cmv disease in people with immunosuppression due to an organ transplant. Individualization of valganciclovir prophylaxis for. Ganciclovir side effects, dosage, interactions drugs. Monitoring plasma levels of ganciclovir in aids patients receiving oral ganciclovir as maintenance therapy for cmv retinitis. In addition, because the treatment schedule was fixed for all patients, the results can only provide indices of alternative treatment strategies, for example, treating until results are negative for viremia or targeting ganciclovir or valganciclovir with therapeutic drug monitoring. Ganciclovir is an antiviral drug active against cytomegalovirus cmv.
Ganciclovir is considered a potential human carcinogen, teratogen, and mutagen. Food and drug administration fda for the treatment of cytomegalovirus retinitis cmv retinitis in individuals with aids. Several fdaapproved drug labels may be available for ganciclovir. After recovery of neurologic function, valganciclovir was resumed at a lower dosage 225 mg twice a week with therapeutic drug monitoring and was well tolerated. This includes patients with acquired immune deficiency syndrome aids. Population pharmacokinetics of ganciclovir in solidorgan. Who will benefit from therapeutic drug monitoring of ganciclovir. Ganciclovir is also used to prevent cytomegalovirus cmv disease in people who have acquired immunodeficiency syndrome aids or who have received an organ transplant and are at risk of cmv disease. It does not include information concerning every therapeutic agent, laboratory or diagnostic test or procedure available.
More frequent monitoring is recommended for patients who have previously experienced leukopenia with ganciclovir or another nucleoside analog or in whom neutrophil counts are less than cu mm prior to initiating therapy with the drug. However, a clinically feasible tool for valganciclovir dosage adjustment based on individual auc is not available. Nhs grampian acute sector summary guideline for therapeutic drug monitoring tdm in adults version 2 antibiotic assays on the microbiology request card for serum levels, please supply details of the antibiotic level required, the time and date of the sample. On the other hand, in some cases dosing regimens may be selected that aim at reaching steady. It is used to prevent disease caused by a virus called cytomegalovirus cmv in. Determination of gcv and vgc in human and animal plasma is required in therapeutic drug monitoring, further clinical development i. Sep 30, 2012 cytomegalovirus cmv infection is a common complication following solid organ transplantation that may severely affect the outcome of transplantation. Methods high performance liquid chromatography tandem mass spectrometry lcmsms. Ganciclovir is a white to offwhite crystalline powder with a molecular formula of c 9 h n 5 0 4 and a molecular weight of 255. Sep 01, 2010 drug interactions and toxicities associated with the antiviral management of cytomegalovirus cmv infection are described.