Thus, it is used judiciously and handled as a cytotoxic drug in the clinical setting. Summary guideline for therapeutic drug monitoring tdm in. Monitoring of trough plasma ganciclovir levels and. Case report ganciclovir concentrations in the cerebral. Ganciclovir, postnatal cytomegalovirus infection, therapeutic drug monitoring, extremely low. To the editor ganciclovir is a firstline agent for the treatment of human. Raman spectroscopy may offer an effective tool for the noninvasive assessment of the local concentration of ganciclovir in the ocular media. C max, c min and auc are highly correlated, allowing for the possibility of steadystate drug monitoring to confirm that the recommended dosing algorithm produces appropriate plasma levels. Importance and methods of therapeutic drug monitoring. Her urine was positive for cytomegalovirus cmv dna. Evidence of sub therapeutic levels suzanne luck, andrew lovering, paul griffiths, mike sharland. Pharmacokinetic assessment of oral ganciclovir in lung. The authors use a previously published decisionmaking algorithm to address the role of clinical pharmacokinetic monitoring of ganciclovir, the drug of choice for prophylaxis and treatment of cytomegalovirus cmv in solid organ transplant recipients.
The drug is converted intracellularly to ganciclovir 5monophosphate by a viral kinase, which is encoded by the cytomegalovirus cmv gene ul97 during infection. Therapeutic drug monitoring an overview sciencedirect. Therapeutic drug monitoring of ganciclovir treatment for cytomegalovirus infections among immunocompromised children. 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. 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. Diagnostic mutations in the cytomegalovirus ul97 kinase gene are used to assess the level of associated ganciclovir resistance and therapeutic options. Since then, therapeutic drug monitoring tdm approaches have been progressively applied to a variety of drug classes among others antiepileptics, antidepressants, cardiovascular drugs, immunosuppressants or antibiotics. A pregnancy test will be done before you start ganciclovir systemic to show that you are not pregnant. This is a comprehensive sourcebook that details 964. Analytical methods for therapeutic drug monitoring and.
Human herpes virus6 encephalitis in a paediatric bone. Noninvasive detection of ganciclovir in ocular tissue by. The appropriate dose is estimated based on through and peak concentrations and area under the curve values auc. Aug 22, 2016 we have recently experienced a case of an extremely premature infant with severe postnatal cmv infection. Data regarding suitable drug levels for use in therapeutic drug monitoring tdm in the paediatric age group do not currently exist. Find patient medical information for ganciclovir sodium intravenous on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings.
Technology for therapeutic drug monitoring in cancer. Pharmacogenetics biomarkers predictive of drug pharmacodynamics as an additional tool to therapeutic drug monitoring haufroid, vincent. The first patient is diagnosed with thymoma a, the second is a heart transplant recipient. We can use a validated liquid chromatographytandem mass spectrometry method. In this paper, we report the pharmacokinetics of ganciclovir in three anuric heart transplant patients under continuous venovenous hemodialysis cvvhd. Ganciclovir is considered a potential human carcinogen, teratogen, and mutagen. Traditionally therapeutic drug monitoring involves measuring drug concentration in a biological matrix most commonly serum or plasma and interpreting these concentrations in terms of relevant clinical parameters. Three days of oral ganciclovir results in therapeutically useful plasma drug levels in the cf lt population, despite a background of general malabsorption.
Therapeutic drug monitoring of antipsychotics mdedge. The target trough concentrations for ganciclovir in our hospital are 12 mgl and 24 mgl. Therapeutic drug monitoring of serum gcv was carried out using a mass spectrometry method. The bestknown mutations at codons 460, 520, or 591 to 607 individually confer 5 to 10folddecreased ganciclovir susceptibility, except that a 3fold decrease occurs in the case of the amino acid substitution c592g. Treatment courses are generally derived from adult studies and there are few data relating to the pharmacokinetics of gcv in children. 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. Therapeutic drug monitoring of 21day oral etoposide in. Gcv treatment has been associated with serious toxic hematological effects such as neutropenia and leukopenia, thus drug monitoring is needed, especially in the case of. Ganciclovir 91,3,dihydroxy2propoxymethyl guanine, or dhpg is an acyclic analog of the nucleoside guanosine. The clinical utility of ganciclovir therapeutic drug monitoring tdm is. Nms labs does not assume responsibility for billing errors due to reliance on the cpt codes listed in this document. Dec 21, 2018 ganciclovir is a prescription medicine approved by the u. Differentiated levels of ganciclovir resistance conferred. However, the optimal exposure for the treatment of cmv disease is unknown.
Ganciclovir is a therapeutic choice for extremely premature infants with severe postnatal cytomegalovirus disease, but little is known about its optimal dose size and dosing interval for them. Ganciclovir is a polar hydrophilic compound with a solubility of 2. Improving global outcomes kdigo acute kidney in jury work group. See actual entry in rtecs for complete information. Therapeutic drug monitoring tdm is the use of drug concentration measurements in body fluids as an aid to the management of drug therapy for the cure, alleviation or prevention of disease. Ganciclovir is used to treat cmv retinitis in people with immunosuppression caused by. Ganciclovir gcv is used to treat babies and older children with cytomegalovirusrelated disease. Although the precise mechanisms of these drug interactions have not been elucidated, they are most likely due to the additive or synergistic effects of ganciclovir and drugs with a similar toxicity profile. Ganciclovir side effects, dosage, interactions drugs. Therapeutic drug monitoring of ganciclovir for postnatal.
Monitoring of trough plasma ganciclovir levels and peripheral. This supports supplementation of ganciclovir in patients receiv ing this antiviral agent when they are undergoing hemodialysis. It is also considered likely to cause inhibition of spermatogenesis. Ganciclovir gcv and its prodrug valganciclovir are successfully used to prevent and treat cmv infection. Oral route capsule the clinical toxicity of ganciclovir includes granulocytopenia, anemia, and thrombocytopenia. Whole blood is the preferred matrix for therapeutic drug monitoring of immunosuppressants, except for mycophenolic acid. 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. Monitoring renal function during therapy with cytoveneiv is essential, especially for elderly patients and those patients receiving concomitant agents that may cause. The importance of therapeutic drug monitoring is the following. The first patient is diagnosed with thymoma a, the second is a heart transplant recipient, and the third is an hivpositive patient. Pdf therapeutic drug monitoring of ganciclovir for postnatal. 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. The role of therapeutic drug monitoring in the treatment of cytomegalovirus disease in kidney transplantation. Vancomycin monitoring practices are highly variable in children admitted to pediatric hospitals 46% of patients had no monitoring no correlation with length of therapy source.
The healthcare team responsible for administration and monitoring of opat should appropriately monitor patients to avoid and address poor clinical responses, therapeutic failure, adverse effects, drug toxicity, or infusion device and vascular access issues. The clinical utility of ganciclovir therapeutic drug monitoring tdm is unknown. Ganciclovir is also fdaapproved for the prevention of cmv disease in recipients of organ transplants who are at risk for cmv diseases. Request pdf on mar 8, 2016, chris stockmann and others published therapeutic drug monitoring of ganciclovir treatment for cytomegalovirus infections among immunocompromised children find, read. Pharmacokinetics of ganciclovir in a patient undergoing. Clinical oncologists are well aware of the narrow therapeutic index of antineoplastic drugs and make dose adjustments after toxicity is encountered.
The primary outcome was an association between ganciclovir tdm and clinical efficacy endpoints within 30 days, defined by viral. This book is valuable for pharmacologists, toxicologists, and health professionals working in academic, industrial, and regulatory agencies who are involved in therapeutic drug monitoring. Neurotoxicity related to valganciclovir in a child with impaired function. Ganciclovir is an antiviral drug that slows the growth and spread of the cytomegalovirus cmv. Therapeutic drug monitoring of ganciclovir for postnatal cytomegalovirus infection in an extremely low birth weight infant. We retrospectively analyzed adult patients treated for cytomegalovirus cmv infection with ganciclovir.
Sep 30, 2012 read the role of therapeutic drug monitoring in the treatment of cytomegalovirus disease in kidney transplantation, international urology and nephrology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Thrombocytopenia was observed, antibiotic and immunoglobulin therapy were initiated for suspected sepsis. Drug interactions involving ganciclovir have been associated with nephrotoxicity, myelosuppression, and seizures. Ganciclovir investigated as a drug, mutagen and tumorigen. Oral valganciclovir and intravenous ganciclovir are used for prophylaxis, treatment, and preemptive treatment of cytomegalovirus and. The cpt codes provided in this document are based on ama guidelines and are for informational purposes only. Therapeutic drug monitoring of ganciclovir treatment for. The first patient is diagnosed with thymoma a, the second is a heart transplant recipient and the third is an hiv positive patient. Relationship of ganciclovir therapeutic drug monitoring. Hemodialysis reduced ganciclovir levels by approximately 62% with an extraction coefficient of 0. In cancer therapy, however, therapeutic drug monitoring has not found a standard role except for methotrexate measurements to guide leucovorin rescue after highdose therapy 2. For cmv treatment, the standard dosing of ganciclovir is 900 mg every 12 hours for oral valganciclovir and 5 mgkg every 12 hours. Analysis of vancomycin therapeutic drug monitoring trends at.
Dailymed ganciclovir ganciclovir sodium injection, powder. Cmv cytomegalovirus, tdm therapeutic drug monitoring, auc area under the concentrationtime curve. Only select registry of toxic effects of chemical substances rtecs data is presented here. Ganciclovir is used to treat cmv retinitis in people with immunosuppression caused by hiv or aids. Therapeutic drug monitoring analysis was performed for ganciclovir. Pdf neurotoxicity related to valganciclovir in a child. Valganciclovir therapeutic monitoring showed high ganciclovir concentrations in the plasma 3. Ganciclovir for injection, usp is available as sterile lyophilized powder in strength of 500 mg per vial for intravenous administration only. We use cookies to make interactions with our website easy and meaningful, to better understand the use of our services, and to tailor advertising.
Valganciclovir, an oral prodrug of ganciclovir is now available and an. Valganciclovir, a guanine analogue, is a prodrug of ganciclovir. The role of therapeutic drug monitoring in the treatment. Clinical monitoring of outpatient parenteral antimicrobial. Pharmacokinetics of ganciclovir in heart transplant patients. Gilquin j et al 2000 monitoring plasma levels of ganciclovir in aids patients receiving oral ganciclovir as maintenance therapy for cmv retinitis.
University of groningen determination of ganciclovir and. Troughs ganciclovir gcv is used to treat babies and older children with cytomegalovirusrelated disease. University of groningen ganciclovir therapeutic drug. Aliquots of 100 l serum samples were transferred to filter vials and ultracentrifuged for 10 min at 14 600g. This is a comprehensive sourcebook that details 964 different analytical methods for 511 different drugs.
Despite a long history of therapeutic drug monitoring tdm within psychiatry, routine monitoring of antipsychotic serum levels has not been unanimously adopted as standard practice. Determination of ganciclovir in plasma of newborns with. The amplitudes of the spectral peaks corresponding to ganciclovir exhibited a linear dependence on the local concentration of the drug in the anterior chamber of the eye. During the treatment with ganciclovir, we performed therapeutic drug monitoring tdm and measurement of cmv load in the peripheral blood that were useful to obtain a proper therapeutic effect and avoid overdosage. Nov 14, 2018 ganciclovir is a synthetic guanine derivative active against cytomegalovirus cmv. Feb 03, 2020 if you are 65 or older, use ganciclovir systemic with care. Filtrates 100 l were vortexed after addition of penciclovir as internal standard, and 1 l of the sample was injected into a liquid. Nov 09, 2018 ganciclovir is an antiviral drug that slows the growth and spread of the cytomegalovirus cmv. Treatment guideline for infants with congenital cmv disease. Sep 30, 2012 cytomegalovirus cmv infection is a common complication following solid organ transplantation that may severely affect the outcome of transplantation.
Ganciclovir 91,3dihydroxy2 propoxymethyl guanine, gcv is a synthetic acyclic nucleoside which has shown activity against cytomegalovirus. The results of therapeutic drug monitoring in adult solid organ transplant recipients receiving prophylaxis indicated that a 24hour ganciclovir area under the curve auc 24 of 4050 ghr per ml was associated with delayed development of cmv viremia 2. Refer to the respective prescribing information of the coadministered drug s to confirm compatibility of simultaneous coadministration. The international association of therapeutic drug monitoring and clinical toxicology adopted the following definition for drug monitoring. The pharmacokinetics of ganciclovir in patients with severe renal dysfunction is poorly defined. Neurotoxicity related to valganciclovir in a child with. We retrospectively analyzed adult patients treated for cytomegalovirus cmv infection with ganciclovir with tdm between 2005 and 2015. Ganciclovir was administered at a dose of 5 mgkg every 48 h for at least 9 days. Challenges of therapeutic drug monitoring in paediatrics. Chqgdl01005 treatment guideline for infants with congenital cmv disease ccmv 4 side effects ganciclovir gcv, and less frequently valganciclovir, use is associated with bone marrow suppression. Clinical practice typically results in mostly a subjective assessment of the safety and efficacy of antipsychotics. List of compatible drug products when prevymis and drug products are prepared in 0. Therapeutic drug monitoring is defined as the measurement made in the laboratory of a parameter that, with appropriate interpretation, will directly influence prescribing procedures. The role of therapeutic drug monitoring tdm during treatment with gcv is unclear.
Human herpes virus6 encephalitis in a paediatric bone marrow recipient. Recommended indications for voriconazole and posaconazole tdm in the. Therapeutic drug monitoring an overview sciencedirect topics. Women must use birth control while taking ganciclovir systemic and for some time after the last. Ganciclovir concentrations in the cerebral extracellular. 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. In principle, the concept of tdm aims to control for pharmacokinetic variability among patients which might otherwise lead to. Although no data are available to inform therapeutic target levels or levels associated with toxicity, therapeutic drug monitoring is recommended to ensure that patients are absorbing drug. She was administered antiviral therapy with iv ganciclovir at 5 mgkg per dose every 12 hours. Chqgdl01005 treatment guideline for infants with congenital cmv disease ccmv 1 treatment guideline for infants with congenital cmv disease ccmv document id chqgdl01005 version no.
Drug interactions and toxicities associated with the. University of groningen ganciclovir therapeutic drug monitoring. Therapeutic drug monitoring tdm of antifungal agents is warranted, especially where noncompliance, nonlinear pharmacokinetics, inadequate absorption, a narrow therapeutic window, suspected drug interaction or unexpected toxicity are encountered. Summary guideline for therapeutic drug monitoring tdm in adults. Consensus guidelines for optimising antifungal drug. In adults, low trough gcv levels have been associated with treatment failure and virological resistance. To assure adequate ganciclovir drug exposure, therapeutic drug monitoring tdm is an easytouse tool to assess ganciclovir serum. Who will benefit from therapeutic drug monitoring of. Who will benefit from therapeutic drug monitoring of ganciclovir. As we know that therapeutic drug monitoring is a branch of clinical chemistry and clinical pharmacology as discussed in the previous tutorial overview and steps involved in tdm. Ganciclovir capsules are indicated only for prevention of cytomegalovirus cmv disease in patients with advanced hiv infection at risk for cmv disease, for maintenance treatment of cmv retinitis in immunocompromised patients, and for prevention of cmv disease in solid. Food and drug administration fda for the treatment of cytomegalovirus retinitis cmv retinitis in individuals with aids.
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