honestly [2:<13 years of age, and 0.7 for boys 13 16 years of age. To prevent overdosage, estimated Cl cr used to calculate pediatric dose should not exceed 150 mL/minute per 1.73 m 2 , regardless of value calculated using the modified Schwartz formula. 1 11 If estimated Cl cr is> 150 mL/minute per 1.73 m 2 , use the value of 150 mL/minute per 1.73 m 2 to calculate the dose. 1 11 Round calculated dose to nearest 25-mg increment. 1 Maximum dose is 900 mg. 1 11 Adults CMV Retinitis Oral Initial (induction) therapy: 900 mg twice daily for 21 days. 1 8 13 CDC, NIH, and IDSA recommend a duration of 14 21 days. 13 After completion of induction therapy or in patients with inactive CMV retinitis, use a maintenance dosage of 900 mg once daily. 1 8 13 Prevention of CMV Disease in Transplant Recipients Oral Heart or kidney-pancreas transplant patients at high risk: 900 mg once daily starting within 10 days of transplantation and continued until 100 days posttransplantation. 1 Kidney transplant patients at high risk: 900 mg once daily starting within 10 days of transplantation and continued until 200 days posttransplantation. 1 Prescribing Limits Pediatric Patients Prevention of CMV Disease in Transplant Recipients Oral Maximum 900 mg daily. 1 11 To avoid overdosage, Cl cr used to calculate pediatric dosage should not exceed 150 mL/minute per 1.73 m 2 . 1 11 If patient's estimated Cl cr exceeds 150 mL/minute per 1.73 m 2 , use 150 mL/minute per 1.73 m 2 in the pediatric dosage equation. 1 11 (See Pediatric Patients under Dosage and Administration.) Special Populations Renal Impairment Adjust adult dosage if Cl cr is <60 mL/minute. 1 Dosage for Treatment of CMV Retinitis in Adults with Renal Impairment1 Cl cr (mL/min) Induction Dosage Maintenance Dosage 40 59 450 mg twice daily 450 mg once daily 25 39 450 mg once daily 450 mg every 2 days 10 24 450 mg every 2 days 450 mg twice weekly Do not use in adults undergoing hemodialysis (Cl cr> <10 mL/minute). 1 (See Renal Impairment under Cautions.) Calculate dosage for pediatric patients with renal impairment using the usually recommended pediatric dosage equation. 1 (See Pediatric Dosage under Dosage and Administration.) Cautions for Valganciclovir Hydrochloride Contraindications Known hypersensitivity to valganciclovir, ganciclovir, or any ingredient in the formulation. 1 Warnings/Precautions Warnings Hematologic Effects Toxicity of valganciclovir, following metabolism to ganciclovir, includes granulocytopenia, anemia, and thrombocytopenia. 1 Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been reported with valganciclovir or ganciclovir. 1 Cytopenia may occur at any time during therapy; 1 degree of cytopenia may increase with continued valganciclovir therapy. 1 Cell counts usually begin to return to baseline 3 7 days after discontinuance of the drug. 1 Perform CBCs and platelet counts frequently, especially in those with baseline neutrophil counts> <1000/mm 3 or in those who previously developed leukopenia while receiving ganciclovir or other nucleoside analogs. 1 Do not use in those with absolute neutrophil count> <500/mm 3 , platelet count> <25,000/mm 3 , or hemoglobin concentration> <8 g/dL. 1 Use with caution in those with preexisting cytopenias and those receiving myelosuppressive drugs or irradiation. 1 More frequent monitoring for cytopenias may be warranted if therapy is changed from oral ganciclovir to valganciclovir. 1 Teratogenicity and Impairment of Fertility In animals, ganciclovir is teratogenic, suppresses fertility in females, and inhibits spermatogenesis with subsequent infertility in males. 1 Since valganciclovir is metabolized to ganciclovir, consider valganciclovir a potential teratogen and expect the drug to have adverse effects on fertility. 1 (See Pregnancy under Cautions.) Mutagenicity and Carcinogenicity In animals, ganciclovir is mutagenic and carcinogenic. 1 Since valganciclovir is metabolized to ganciclovir, consider valganciclovir a potential carcinogen or mutagen in humans. 1 Other Warnings/Precautions Renal Effects Acute renal failure may occur in geriatric patients (with or without impaired renal function), patients receiving potentially nephrotoxic drugs, and inadequately hydrated patients. 1 Maintain adequate hydration in all patients. 1 Use caution and adjust dosage based on Cl cr . 1 (See Renal Impairment under Dosage and Administration.) Use caution in patients receiving concomitant therapy with potentially nephrotoxic drugs. 1 Adherence to Dosage Regimen Adherence to recommended dosage regimens is essential to avoid overdosage. 1 In pediatric patients, adhere to recommended pediatric dosage equation, maximum estimated Cl cr , and maximum daily dosage. 1 11 (See Pediatric Dosage under Dosage and Administration.) Bioavailability of ganciclovir from valganciclovir tablets is substantially higher than from ganciclovir capsules, and the tablets and capsules cannot be substituted on a one-to-one basis. 1 Handling and Disposal Because valganciclovir is considered a potential teratogen and carcinogen, observe caution when handling the drug. 1 Do not break or crush valganciclovir tablets. 1 Avoid direct contact of broken or crushed tablets, powder for oral solution, or reconstituted oral solution with skin or mucous membranes. 1 If such contact occurs, wash thoroughly with soap and water; rinse eyes thoroughly with water. 1 Specific Populations Pregnancy Category C. 1 Expected to have reproductive toxicity similar to ganciclovir. 1 Likely to produce temporary or permanent inhibition of spermatogenesis and also may suppress fertility in females. 1 (See Teratogenicity and Impairment of Fertility under Cautions.) Advise women of childbearing potential to use an effective method of contraception during and for at least 30 days after valganciclovir therapy. 1 Advise men to use a reliable method of barrier contraception during and for at least 90 days after valganciclovir therapy. 1 Lactation Not known if distributed into human milk. 1 Because of potential for serious adverse effects in the infant, women should not breast-feed infants while receiving valganciclovir. 1 Instruct HIV-infected women not to breast-feed because of the risk of HIV transmission. 1 Pediatric Use Safety and efficacy not established in pediatric patients> <4 months of age. 1 Use for prevention of CMV disease in pediatric kidney or heart transplant recipients 4 months to 16 years of age at high risk is based on pharmacokinetic, safety, and efficacy data from an open-label study in this age group and efficacy extrapolated from a study in adults. 1 Safety and efficacy not established for prevention of CMV disease in any other pediatric solid organ transplant recipients. 1 Safety and efficacy not established for treatment of congenital CMV disease. 1 7 Geriatric Use Insufficient experience in those 65 years of age to determine whether they respond differently than younger adults. 1 Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. 1 Assess renal function before and during therapy; make appropriate dosage adjustments as necessary. 1 (See Renal Impairment under Dosage and Administration.) Hepatic Impairment Safety and efficacy not established. 1 Renal Impairment Dosage adjustment necessary in adults if Cl cr> <60 mL/minute. 1 (See Renal Impairment under Dosage and Administration.) Do not use in adults undergoing hemodialysis; 1 use ganciclovir (with appropriate dosage adjustment) instead. 1 Common Adverse Effects Abdominal pain, anemia, diarrhea, graft rejection, increased serum creatinine, headache, insomnia, leukopenia, nausea, neutropenia, paresthesia, peripheral neuropathy, pyrexia, retinal detachment, thrombocytopenia, tremors, vomiting. 1 Upper respiratory tract infection, pyrexia, nasopharyngitis, anemia, and neutropenia reported more frequently in children than adults. 1 Interactions for Valganciclovir Hydrochloride No formal drug interaction studies have been performed using valganciclovir. 1 Interactions associated with ganciclovir are expected to occur in patients receiving valganciclovir. 1 Specific Drugs Drug Interaction Comments Didanosine Potential increased AUC and peak plasma concentration of didanosine 1 Monitor closely for didanosine toxicity 1 Mycophenolate Potential increased metabolite concentrations of both drugs 1 Monitor closely in patients with renal impairment 1 Myelosuppressive agents or irradiation Potential additive hematologic toxicity 1 Use with caution 1 Probenecid Potential increased AUC of ganciclovir 1 Monitor closely for ganciclovir toxicity 1 Zidovudine Potential increased AUC of zidovudine and decreased AUC of ganciclovir 1 Potential additive hematologic toxicity 1 Valganciclovir Hydrochloride Pharmacokinetics Absorption Bioavailability Valganciclovir, a prodrug of ganciclovir, is well absorbed from GI tract 1 2 3 and metabolized by intestinal and hepatic esterases to ganciclovir. 1 Systemic exposure to prodrug is transient and low. 1 3 GI absorption of valganciclovir substantially greater than absorption of oral ganciclovir resulting in plasma ganciclovir concentrations comparable to those achieved with IV ganciclovir. 1 2 4 6 Absolute bioavailability of ganciclovir approximately 60% when oral valganciclovir given with food. 1 2 Time to peak ganciclovir concentrations 1 3 hours. 1 Food Administration of valganciclovir with a high-fat meal (approximately 600 calories, 31 g fat) increases AUC and peak plasma concentrations of ganciclovir at steady-state by 30 and 14%, respectively. 1 Distribution Extent Ganciclovir crosses the placenta (based on an ex vivo human placental model). 1 Not known whether ganciclovir or valganciclovir distributed into human milk. 1 Plasma Protein Binding Ganciclovir plasma protein binding 1 2%; 1 protein binding of valganciclovir not determined because of rapid conversion to ganciclovir. 1 Elimination Metabolism Valganciclovir rapidly hydrolyzed to ganciclovir; no other metabolites detected. 1 Ganciclovir phosphorylated to ganciclovir phosphate in CMV-infected cells. 1 Elimination Route Major route of elimination of valganciclovir is renal excretion as ganciclovir by glomerular filtration and active tubular secretion. 1 Half-life Adults: Mean half-life of ganciclovir after oral administration of valganciclovir is approximately 4 hours in healthy or HIV-positive/CMV-positive adults (with or without retinitis) and 6.6 6.8 hours in adult heart, kidney, and kidney-pancreas transplant recipients. 1 Children: Mean half-life of ganciclovir after oral administration of valganciclovir is 2.8 4.8 hours in pediatric solid organ transplant recipients 4 months through 11 years of age and 4.4 6 hours in pediatric solid organ transplant recipients 12 years of age. 1 Clearance is influenced by BSA and renal function. 1 Special Populations Pharmacokinetics not evaluated in hepatic impairment. 1 Half-life increased in renal impairment. 1 2 Data from otherwise healthy adults with renal impairment indicate the mean half-life is about 22 hours if Cl cr is 11 20 mL/minute and about 68 hours if Cl cr is 10 mL/minute. 1 Stability Storage Oral Tablets 25 C (may be exposed to 15 30 C). 1 For Solution 25 C (may be exposed to 15 30 C). 1 After reconstitution, refrigerate at 2 8 C for up to 49 days. 1 Do not freeze. 1 Actions and Spectrum Valganciclovir is the l-valyl ester of ganciclovir. 1 Prodrug with no antiviral activity until converted in vivo to ganciclovir and subsequently to the active ganciclovir triphosphate. 1 2 Rapidly converted to ganciclovir by intestinal and hepatic esterases and then phosphorylated within CMV-infected cells to ganciclovir triphosphate, which has in vitro and in vivo inhibitory activity against CMV. 1 Ganciclovir triphosphate exerts its antiviral activity on CMV by interfering with DNA synthesis. 1 Resistance to ganciclovir reported after prolonged treatment with valganciclovir; 1 ganciclovir resistance also reported in patients not previously treated with the drug. 1 Advice to Patients Importance of not substituting valganciclovir tablets for ganciclovir capsules on a one-to-one basis. 1 Risk of adverse effects, including hematologic adverse effects. 1 Necessity of monitoring blood counts and serum creatinine concentration. 1 Necessity of dosage adjustment or discontinuance of valganciclovir if toxicity occurs. 1 Importance of taking with food for optimum absorption. 1 Risk of CNS adverse effects (e.g., seizures, sedation, dizziness, ataxia and/or confusion), which may affect tasks requiring alertness. 1 Advise patients that valganciclovir is not a cure for CMV retinitis and that regular ophthalmologic examinations during therapy (at least every 4 6 weeks) are important. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or nonprescription drugs. 1 Advise patients that ganciclovir is a potential carcinogen. 1 Importance of both women and men using effective contraception during valganciclovir therapy. 1 Advise women to use effective barrier contraception while receiving and for at least 30 days after therapy with the drug. 1 Advise men to use effective barrier contraception while receiving and for at least 90 days after therapy with the drug. 1 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Advise women to avoid pregnancy and to not breast-feed infants. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses. 1 Importance of advising patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. valGANciclovir Hydrochloride Routes Dosage Forms Strengths Brand Names Manufacturer Oral For solution 250 mg (of valganciclovir) per 5 mL Valcyte Roche Tablets, film-coated 450 mg (of valganciclovir) Valcyte Roche AHFS DI Essentials. Copyright 2017, Selected Revisions February 1, 2011. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. Use is not currently included in the labeling approved by the US Food and Drug Administration. References 1. Roche. Valcyte (valganciclovir hydrochloride) tablets prescribing information. South San Francisco, CA; 2010 Aug. 2. Brown F, Banken L, Saywell K et al. Pharmacokinetics of valganciclovir and ganciclovir following multiple oral dosages of valganciclovir in HIV- and CMV-seropositive volunteers. Clin Pharmacokinet . 1999; 37:167-76. [PubMed 10496303] 3. Martin DF, Sierra-Madero J, Walmsley S et al. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med . 2002; 346:1119-26. [PubMed 11948271] 4. Jung D, Dorr A. Single-dose pharmacokinetics of valganciclovir in HIV- and CMV-seropositive subjects. J Clin Pharmacol . 1999; 39:800-4. [PubMed 10434231] 6. Pescovitz MD, Rabkin J, Merion RM et al. Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother . 2000; 44:2811-5. [PubMed 10991864] 7. Roche, Nutley, NJ: Personal communication. 8. . Drugs for Non-HIV Viral Infections. Treat Guidel Med Lett . 2010; 8:71-82. [PubMed 20864902] 9. Lange WR. Dear healthcare provider letter: 2003 safety alert: valcyte (valganciclovir HCL tablets). Nutley, NJ; 2003 Sept 30. From FDA website (). 10. Vaudry W, Ettenger R, Jara P et al. Valganciclovir dosing according to body surface area and renal function in pediatric solid organ transplant recipients. Am J Transplant . 2009; 9:636-43. [PubMed 19260840] 11. US Food and Drug Administration (FDA). FDA drug safety communication: New dosing recommendations to prevent potential Valcyte (valganciclovir) overdose in pediatric transplant patients. 2010 Sep 15. From FDA website. 12. Humar A, Lebranchu Y, Vincenti F et al. The efficacy and safety of 200 days of valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant . 2010; 10:1228-37. [PubMed 20353469] 13. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep . 2009; 58(RR-4):1-207; quiz CE1-4. 14. Mofenson LM, Brady MT, Danner SP et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep . 2009; 58(RR-11):1-166. [PubMed 19730409] Next Interactions Print this page Add to My Med List More about valganciclovir Side Effects During Pregnancy Dosage Information Drug Images Drug Interactions Support Group Pricing & Coupons En Español 1 Review Add your own review/rating Drug class: purine nucleosides Consumer resources Valganciclovir ... +3 more Professional resources Valganciclovir (FDA) Valganciclovir Solution (FDA) ValGANciclovir (Wolters Kluwer) Other brands: Valcyte Related treatment guides CMV Prophylaxis CMV Retinitis> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Manufacturers Dr. Reddy's Laboratories, Inc. Teva Pharmaceuticals USA, Inc. Aurobindo Pharma Limited Camber Pharmaceuticals, Inc. More... Drug Class Purine nucleosides Related Drugs CMV Prophylaxis valacyclovir , Valcyte , valganciclovir , Prevymis , cytomegalovirus immune globulin , Cytovene , CytoGam , More... CMV Retinitis Valcyte , valganciclovir , foscarnet , cidofovir , Foscavir , Cytovene , Vistide , More... Valganciclovir Rating 1 User Review 8.0 /10 1 User Review 8.0 Rate it! Valganciclovir Images Valganciclovir systemic 450 mg (E114 ) View all images} } workers
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