Valganciclovir

354.36168

354.36

1312995-182-4

DTXSID8048288

2933990090

171.37000

-1.28

Solid

1.59±0.1 g/cm3(Predicted)

629.1±65.0 °C at 760 mmHg

334.3±34.3 °C

1.678

1.81X10+5 mg/L at 25 °C (est)

Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. Store in a refrigerator. This material is hygroscopic.

1.08E-16mmHg at 25°C

5.2X10-18 mm Hg at 25 °C (est)

Henry's Law constant = 4.87X10-27 atm-cu m/mol at 25 °C (est)

pKa1 = 4.03 (amine); pKa2 = 6.31 (amine) (est)

MW: 390.82. Crystals from water + isopropanol, undergoes phase change at 142 °C; decomposes at 175 °C /Valganciclovir hydrochloride/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/|For more Disposal Methods (Complete) data for Valganciclovir (9 total), please visit the HSDB record page.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including valganciclovir hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Valganciclovir hydrochloride/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/|For more Personal Protective Equipment (PPE) (Complete) data for Valganciclovir (7 total), please visit the HSDB record page.

This material is assumed to be combustible.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately; a spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/|Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Wash spill site with ethanol. Place spillage and all contaminated cleanup materials in a thick plastic hazardous waste disposal bag or leakproof container and label it CAUTION: HAZARDOUS CHEMICAL WASTE.

Because valganciclovir is considered a potential teratogen and carcinogen, observe caution when handling the drug. Valganciclovir tablets should not be broken or crushed. Avoid direct contact of broken or crushed tablets, powder for oral solution, or reconstituted oral solution with skin or mucous membranes. If such contact occurs, wash thoroughly with soap and water; rinse eyes thoroughly with water.|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/|For more Preventive Measures (Complete) data for Valganciclovir (24 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /Antineoplastic agents/

Intravenous administration of ganciclovir is associated with transient mild-to-moderate elevations in serum ALT levels in 2% of patients. These episodes have usually been asymptomatic and self-limited. CMV infection itself can cause liver enzyme elevations and may account for some abnormalities found during therapy. There is little evidence that either ganciclovir or valganciclovir can cause clinically apparent liver injury. Ganciclovir also has activity against HBV and HBV DNA levels decrease on treatment and can rebound when therapy is stopped, leading to an acute flare of hepatitis B, which can be symptomatic and severe.

Potential pharmacologic interaction (additive hematologic toxicity (neutropenia, anemia)) /with concomitant use of valganciclovir and zidovudine.|Potential pharmacokinetic interaction /with concomitant use of valganciclovir and probenecid/ (decreased renal clearance and increased AUC of ganciclovir); monitor for ganciclovir toxicity.|Potential pharmacologic interactions (additive hematologic toxicity) /with concomitant use of valganciclovir and myelosuppressive agents or irradiation/.|Potential pharmacokinetic interaction /with concomitant use of valganciclovir and mycophenolate mofetil/ in patients with renal impairment (increased plasma concentrations of the metabolites of both drugs).|For more Interactions (Complete) data for Valganciclovir (6 total), please visit the HSDB record page.

Experience in those 65 years of age or older/is/ insufficient to determine whether they respond differently from younger adults. Pharmacokinetics not studied in geriatric patients. Because geriatric individuals frequently have decreased renal function (e.g., glomerular filtration), particular attention should be paid to assessing renal function before and during therapy. If evidence of renal impairment exists or develops, appropriate dosage adjustments should be made. Drug dosage should be selected carefully, taking into account the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.

Ganciclovir is a nucleoside analogue and antiviral agent used in therapy of cytomegalovirus infections. Valganciclovir is the valyl ester prodrug of ganciclovir which can be given orally. When given intravenously, ganciclovir can cause mild, transient and asymptomatic elevations in serum aminotransferase levels, but neither ganciclovir nor valganciclovir have been associated with clinically apparent liver injury.

Antiviral Agents

Antiviral Agents|Valganciclovir hydrochloride tablets are used for initial (induction) treatment and maintenance treatment (secondary prophylaxis) of cytomegalovirus (CMV) retinitis in adults with human immunodeficiency virus (HIV) infection, including those with acquired immunodeficiency syndrome (AIDS). /Included in US product labeling/|The US Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), and Infectious Diseases Society of America (IDSA) also recommend use of oral valganciclovir for treatment and secondary prophylaxis of CMV retinitis in HIV-infected older children and adolescents who can receive adult dosage. /NOT included in US product labeling/|Valganciclovir hydrochloride tablets are used for prevention of cytomegalovirus (CMV) disease in adult kidney, heart, and kidney-pancreas transplant recipients considered at high risk for the disease (CMV-seronegative recipient of an organ from a CMV-seropositive donor). /Included in US product labeling/|Cytomegalovirus (CMV) is the most common viral infection after solid organ transplantation (SOT). Safe and effective prophylactic regimens that decrease its incidence after SOT are essential for long-term graft survival. Although valganciclovir is not Food and Drug Administration-approved for CMV prophylaxis in liver transplant recipients, postmarketing studies have shown valganciclovir to be as effective as ganciclovir in high-risk adult patients undergoing SOT. Currently, data are lacking for pediatric liver transplantation. The purpose of this study was to compare the efficacy and safety of valganciclovir and ganciclovir for CMV infection prophylaxis in pediatric liver transplant recipients. This was a retrospective study of 56 pediatric liver transplant recipients who were prescribed either oral ganciclovir (n = 37) or valganciclovir (n = 19). Patients were followed until 200 days after transplantation or death. The primary outcome measure compared the rates of early-onset CMV infection and CMV disease in the 2 medication groups. Secondary outcome measures identified patient-specific factors that contributed to CMV acquisition and the incidence of late-onset CMV infection or disease. The rates of adverse drug effects and discontinuation were also evaluated. Early-onset CMV disease was documented in 0% of valganciclovir patients and in 5.4% of ganciclovir patients (P = 0.54). There were no statistically significant differences in the secondary outcomes. An increased incidence of late-onset CMV disease was seen in the valganciclovir group versus the ganciclovir group (22.2% versus 8.1%, P = 0.23). No differences in adverse events were reported. In conclusion, no statistically significant differences were found in the incidence of CMV infection or disease between patients receiving oral valganciclovir and patients receiving oral ganciclovir.

/BOXED WARNING/ WARNING: HEMATOLOGIC TOXICITY, CARCINOGENICITY, TERATOGENICITY, AND IMPAIRMENT OF FERTILITY. Clinical toxicity of Valcyte, which is metabolized to ganciclovir, includes granulocytopenia, anemia, and thrombocytopenia. In animal studies, ganciclovir was carcinogenic, teratogenic, and caused aspermatogenesis.|Toxicity of valganciclovir, which is metabolized to ganciclovir, includes granulocytopenia, anemia, and thrombocytopenia. Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been reported in patients receiving valganciclovir or ganciclovir. Cytopenia may occur at any time and the degree of cytopenia may increase with continued valganciclovir therapy. Cell counts usually begin to return to baseline 3-7 days after discontinuance of the drug. Complete blood cell counts (CBCs) and platelet counts should be performed frequently, especially in those with baseline neutrophil counts less than 1000/cu mm and in those who have experienced leukopenia while receiving ganciclovir or other nucleoside analogs. More frequent monitoring for cytopenias may be warranted if therapy is changed from oral ganciclovir to valganciclovir (because of comparatively increased plasma ganciclovir concentrations with valganciclovir). Valganciclovir should not be used in patients with an absolute neutrophil count less than 500/cu mm, a platelet count less than 25,000/cu mm, or a hemoglobin concentration less than 8 g/dL. Use with caution in patients with preexisting cytopenias and in those who have received or are receiving concomitant myelosuppressive drugs or irradiation.|Animal data indicate that ganciclovir is carcinogenic, mutagenic, teratogenic, and causes aspermatogenesis. Valganciclovir is converted to ganciclovir and is expected to have carcinogenic and reproductive toxic effects similar to those of ganciclovir. Valganciclovir can be considered a potential carcinogen in humans and may be teratogenic or embryotoxic at usual therapeutic doses. It is considered likely that valganciclovir will produce temporary or permanent inhibition of spermatogenesis and also may suppress fertility in females. Women of childbearing potential should be advised to use an effective method of contraception during and for at least 30 days after valganciclovir therapy. Men should be advised to use a reliable method of barrier contraception during and for at least 90 days after valganciclovir therapy.|Acute renal failure may occur in geriatric patients (with or without renal impairment), patients receiving potentially nephrotoxic drugs, and inadequately hydrated patients. Adequate hydration should be maintained in all patients. Use caution and adjust valganciclovir dosage based on creatinine clearance. Use caution in patients receiving concomitant therapy with potentially nephrotoxic drugs.|For more Drug Warnings (Complete) data for Valganciclovir (16 total), please visit the HSDB record page.

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-). Five subjects from the 100 day group and four subjects from the 200 day group meeting the resistance analysis criteria had known ganciclovir resistance-associated amino acid substitutions detected. In six subjects, the following resistance-associated amino acid substitutions were detected within pUL97: 100 day group: A440V, M460V, C592G; 200 day group: M460V, C603W. In three subjects, the following resistance-associated amino acid substitutions were detected within pUL54: 100 day group: E315D, 200 day group: E315D, P522S. Overall, the detection of known ganciclovir resistance-associated amino acid substitutions was observed more frequently in patients during prophylaxis therapy than after the completion of prophylaxis therapy (during therapy: 5/12 (42%) versus after therapy: 4/58 (7%)). The possibility of viral resistance should be considered in patients who show poor clinical response or experience persistent viral excretion during therapy.|Cytomegalovirus (CMV) isolates with reduced susceptibility to ganciclovir have been selected in cell culture. Growth of CMV strains in the presence of ganciclovir resulted in the selection of pUL97 amino acid substitutions (M460I, M460V, L595S, and K599T) and pUL54 amino acid substitutions (D301N, N410K, F412V, L516R, L545S, V812L, P829S and D879G). Insufficient data are available on the development of resistance to ganciclovir and many pathways to resistance exist with no single pathway predominating. Viruses resistant to ganciclovir can arise after prolonged treatment or prophylaxis with valganciclovir by selection of amino acid substitutions in either the viral protein kinase, pUL97, responsible for ganciclovir monophosphorylation and/or in the viral DNA polymerase, pUL54. Virus with mutations in the UL97 gene is resistant to ganciclovir alone, whereas virus with mutations in the UL54 gene may show cross-resistance to other antivirals that target the viral DNA polymerase.

The major route of elimination of valganciclovir is by renal excretion as ganciclovir through glomerular filtration and active tubular secretion. Systemic clearance of intravenously administered ganciclovir was 3.07 + or - 0.64 mL/min/kg (n=68) while renal clearance was 2.99 + or - 0.67 mL/min/kg (n=16).|Due to the rapid conversion of valganciclovir to ganciclovir, plasma protein binding of valganciclovir was not determined. Plasma protein binding of ganciclovir is 1% to 2% over concentrations of 0.5 and 51 ug/mL. When ganciclovir was administered intravenously, the steady-state volume of distribution of ganciclovir was 0.703 + or - 0.134 L/kg (n=69). After administration of Valcyte tablets, no correlation was observed between ganciclovir AUC and reciprocal weight; oral dosing of Valcyte tablets according to weight is not required.|When Valcyte tablets were administered with a high fat meal containing approximately 600 total calories (31.1 g fat, 51.6 g carbohydrates and 22.2 g protein) at a dose of 875 mg once daily to 16 HIV-positive subjects, the steady-state ganciclovir AUC increased by 30% (95% CI 12% to 51%), and the Cmax increased by 14% (95% CI -5% to 36%), without any prolongation in time to peak plasma concentrations (Tmax). Valcyte should be administered with food.|The absolute bioavailability of ganciclovir following oral administration of valganciclovir is about tenfold higher than that following oral administration of ganciclovir (60 versus 5.6%, respectively). Results from pharmacokinetic studies in adults indicate that oral administration of valganciclovir 900 mg once daily with food provides a mean area under the plasma concentration-time curve 0-24 hour (AUC0-24 hour) for ganciclovir comparable to that following IV ganciclovir 5 mg/kg once daily and exceeding that following oral ganciclovir 1 g 3 times daily with food. However, at these dosages, oral valganciclovir produces lower peak plasma ganciclovir concentrations than IV ganciclovir, and lower trough plasma ganciclovir concentrations than oral ganciclovir. The clinical importance, if any, of these differences in peak and trough plasma drug concentrations with these 3 ganciclovir delivery systems has not been determined.|For more Absorption, Distribution and Excretion (Complete) data for Valganciclovir (7 total), please visit the HSDB record page.

Valganciclovir is an L-valyl ester (prodrug) of ganciclovir that exists as a mixture of two diastereomers. After oral administration, both diastereomers are rapidly converted to ganciclovir by intestinal and hepatic esterases. ...|Valganciclovir is rapidly hydrolyzed to ganciclovir; no other metabolites have been detected. No metabolite of orally administered radiolabeled ganciclovir (1000 mg single dose) accounted for more than 1% to 2% of the radioactivity recovered in the feces or urine.

...Ten patients were evaluated. Patients were 56.8 + or - 3.4 years old and had a mean creatinine clearance of 69 + or - 9 mL/min. Oral bioavailability of ganciclovir after administration of valganciclovir was 59%, and mean half-life was 3.73 + or - 1.15 hours. ...|The terminal half-life of ganciclovir following oral administration of Valcyte tablets to either healthy or HIV-positive/CMV-positive subjects was 4.08 + or - 0.76 hours (n=73), and that following administration of intravenous ganciclovir was 3.81 + or - 0.71 hours (n=69). In heart, kidney, kidney-pancreas, and liver transplant patients, the terminal elimination half-life of ganciclovir following oral administration of Valcyte was 6.48 + or - 1.38 hours, and following oral administration of ganciclovir capsules was 8.56 + or - 3.62 hours.

Valganciclovir is an L-valyl ester (prodrug) of ganciclovir that exists as a mixture of two diastereomers. After oral administration, both diastereomers are rapidly converted to ganciclovir by intestinal and hepatic esterases. Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in cell culture and in vivo. In CMV-infected cells ganciclovir is initially phosphorylated to ganciclovir monophosphate by the viral protein kinase, pUL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly metabolized intracellularly (half-life 18 hours). As the phosphorylation is largely dependent on the viral kinase, phosphorylation of ganciclovir occurs preferentially in virus-infected cells. The virustatic activity of ganciclovir is due to inhibition of the viral DNA polymerase, pUL54, synthesis by ganciclovir triphosphate.

Specific drugs and antidotes: There are no specific antidotes for these agents. Anecdotal cases of patients with severe lactic acidosis suggest that vitamin deficiency may be a contributor to the development of a life-threatening condition. Riboflavin ... and/or thiamine ... may be beneficial if levels are low. /Antiviral and antiretroviral agents/|Decontamination: Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small to moderate ingestions if activated charcoal can be given promptly. /Antiviral and antiretroviral agents/|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/CASE REPORTS/ A 13-year-old boy with acute lymphoblastic leukemia was treated for cytomegalovirus retinitis with valganciclovir 450 mg every 2 days in the course of hematopoietic stem cell transplantation. Concomitant medication included omeprazole, furosemide, and acetaminophen. During treatment, when creatinine clearance decreased to 20 mL/min, the child presented with acute neurotoxicity, consisting of mental confusion and hallucinations, which resolved when all medications were stopped. Valganciclovir therapeutic monitoring showed high ganciclovir concentrations in the plasma (3.85 microg/mL) and cerebrospinal fluid (2.6 ug/mL) 48 hours after the last valganciclovir dose. 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. However, the cytomegalovirus infection was not resolved. The leukemia relapsed, and the patient had terminal renal failure and died. The Naranjo probability scale indicated a probable relationship between valganciclovir and neurotoxicity. Drugs taken by this child (acyclovir, valganciclovir, omeprazole) have been reported to induce neurotoxicity, with the pharmacokinetics of the first 2 being altered by renal failure. At the time when acyclovir was first administered, symptoms of neurotoxicity were already apparent. Moreover, plasma concentrations of ganciclovir were very high during the course of the neurotoxicity. Thus, the adverse effects seemed related to an overdosage of valganciclovir and were worsened by the addition of acyclovir. This case is informative because few clinical and pharmacokinetic data are available concerning the use of valganciclovir in children. A study should be performed to determine the proper pediatric dose of valganciclovir with and without renal impairment to prevent the occurrence of adverse effects.|/CASE REPORTS/ One adult developed fatal bone marrow depression (medullary aplasia) after several days of dosing that was at least 10-fold greater than recommended for the patient's estimated degree of renal impairment.|/CASE REPORTS/ ... Valganciclovir has been reported to cause usually mild to moderate hematologic adverse effects such as leukopenia, neutropenia, anemia, thrombocytopenia, and pancytopenia. Severe and fatal bone marrow depression has been described in 1 adult patient. Herein, we describe the cases of 4 patients with end-stage renal disease who underwent cadaveric renal transplantation and received valganciclovir prophylaxis for CMV at a standard dose of 900 mg/d despite persistant renal failure. This therapy resulted in severe bone marrow failure after 18 to 20 days in all 4 patients, with fatal infections in 2 patients. This report demonstrates the in vivo pharmacodynamics of valganciclovir overdose in terms of hematotoxicity in the setting of renal impairment. ...|/CASE REPORTS/ Three cases of nonrespiratory acidosis in kidney transplant recipients receiving ganciclovir or valganciclovir as anti-CMV therapy or prophylaxis are presented. Lactic acidosis developed in 2 patients, and the other patient had nonrespiratory acidosis of unknown origin. The possible mechanism of the development of lactic acidosis in presented cases is explored. The analysis of the described cases cannot eliminate the potential negative influence of anti-CMV therapy on acid-base equilibrium, especially with coexisting active viral infection.|For more Human Toxicity Excerpts (Complete) data for Valganciclovir (6 total), please visit the HSDB record page.

Table: Valganciclovir Hydrochloride Preparations [Table#8075]

HPLC determination in plasma