Version November 2024
Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow failure including aplastic anemia have been reported in patients treated with valganciclovir.
Based on animal data and limited human data, valganciclovir may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females.
Based on animal data, valganciclovir has the potential to cause birth defects in humans.
Based on animal data, valganciclovir has the potential to cause cancers in humans.
Cytomegalovirus, mild to moderate, treatment in solid organ transplant recipients (off-label use): Oral: 900 mg twice daily until symptom resolution and 1 or 2 consecutive weekly undetectable CMV viral load samples are obtained and clinical resolution of disease (minimum treatment course: 2 weeks) (Ref).
Cytomegalovirus, preemptive therapy in hematopoietic cell transplant recipients (off-label use): Oral:
<100 days post-transplant: 900 mg twice daily for 7 days (autologous transplant) or 7 to 14 days (allogenic transplant), then 900 mg once daily for 1 to 2 weeks or until the indicator test is negative (minimum total induction and maintenance treatment is 2 weeks when 14 days of twice daily is used and 3 weeks when a 7-day induction course is used) (Ref).
>100 days post-transplant: 900 mg twice daily for 7 to 14 days, then 900 mg once daily for 1 to 2 weeks or until the indicator test is negative (Ref).
Cytomegalovirus, prophylaxis in solid organ transplant recipients: Oral:
900 mg once daily; duration of prophylaxis is dependent on type of transplant, as well as donor and recipient CMV serostatus (Ref). Note: Based on limited data (Ref), some centers utilize a lower dose of 450 mg once daily in intermediate-risk (CMV-seropositive [CMV R+] transplant recipients). This dosing strategy has not been studied prospectively and has only been primarily described in renal transplant recipients (Ref).
Cytomegalovirus, treatment, esophagitis or colitis in patients with HIV (off-label use): Oral: Treat initially with ganciclovir IV; once patient is able to absorb and tolerate oral therapy, may switch to oral valganciclovir 900 mg twice daily for a total duration of 21 to 42 days, or until signs and symptoms have resolved (Ref).
Cytomegalovirus retinitis, treatment: Oral:
Induction: 900 mg twice daily for 14 to 21 days followed by maintenance therapy (Ref).
Maintenance: 900 mg once daily; may consider discontinuation of chronic maintenance therapy in patients that have received 3 to 6 months of treatment, have inactive lesions, and CD4 count >100 cells/mm3 for 3 to 6 months in response to antiretroviral therapy. Discontinue only after consultation with an ophthalmologist (Ref).
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
Note: Dosing recommendations are based on CrCl as calculated by the Cockcroft-Gault equation (Ref). Dose adjustments based on Modification of Diet in Renal Disease Study equation eGFR have been associated with underdosing and subtherapeutic drug concentrations (Ref).
|
CrCl |
Induction/treatment dosea |
Maintenance/prophylaxis dosea |
|---|---|---|
|
a The optimal dose adjustments for valganciclovir are not well defined. Data suggest an increased risk for cytomegalovirus infection among patients with renal dysfunction, possibly associated with valganciclovir renal dose adjustment (Posadas Salas 2013; Schaenman 2020). A pharmacokinetic study with Monte Carlo simulations of different dose adjustments in kidney impairment suggests using valganciclovir doses higher than manufacturer-recommended dosing in order to achieve target exposure. However, the risks and benefits of utilizing higher doses have not been evaluated and are likely to be patient specific (Tängdén 2018). | ||
|
≥60 (mL/minute) |
900 mg twice daily |
900 mg once daily |
|
40 to <60 (mL/minute) |
450 mg twice daily |
450 mg once daily |
|
25 to <40 (mL/minute) |
450 mg once daily |
450 mg every 2 days |
|
10 to <25 (mL/minute) |
450 mg every 2 days |
450 mg twice weekly |
|
<10 (mL/minute) |
Not recommended by manufacturer; may consider using oral solution 200 mg 3 times weekly (Lucas 2014) |
Not recommended by manufacturer; may consider using oral solution 100 mg 3 times weekly (Lucas 2014) |
Hemodialysis, intermittent (thrice weekly): Dialyzable (50%; (Ref)). Avoid use per manufacturer labeling. Alternatively, consider using valganciclovir oral solution 200 mg (induction/treatment) or 100 mg (maintenance/prophylaxis) 3 times per week (after dialysis on dialysis days) (Ref).
Peritoneal dialysis: Extent of dialyzability is unknown: Use generally should be avoided; however, if necessary, in the absence of peritoneal dialysis patient-specific data, may consider utilizing doses recommended for CrCl <10 mL/minute (Ref).
CRRT: Avoid use due to substantial interpatient variability in pharmacokinetic parameters (Jarrell 2020); recommend treatment with ganciclovir instead (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Avoid use due to anticipated substantial interpatient variability in pharmacokinetic parameters; recommend treatment with ganciclovir instead (Ref).
There are no dosage adjustments provided in the manufacturer labeling (has not been studied).
Refer to adult dosing.
(For additional information see "Valganciclovir: Pediatric drug information")
Note: Valganciclovir oral solution is the preferred oral dosage form in pediatric patients for accuracy in dosing; round to the nearest 25 mg for use with manufacturer-provided oral dispenser. Valganciclovir tablets can be considered if the calculated dose is within 10% of the available tablet strength (450 mg per tablet).
Congenital cytomegalovirus (CMV) infection, treatment, continuation from neonatal period: Limited data available: Infants 1 to 6 months: Oral: 16 mg/kg/dose every 12 hours for 6 months (Ref).
Dosing based on a pharmacokinetic study of 24 neonates which demonstrated that 16 mg/kg/dose twice daily produced similar serum concentrations to ganciclovir 6 mg/kg IV twice daily with a 6-week recommended duration of therapy based on ganciclovir experience (Ref). A longer duration of therapy (6 months) was evaluated in a randomized trial of 96 neonates (GA >32 weeks weighing ≥1.8 kg; PNA at time of therapy initiation <30 days) which compared treatment with 6 weeks of therapy (n=47) to 6 months of therapy (n=49); results demonstrated a modest improvement in long-term hearing and developmental outcomes (evaluated at 12 and 24 months of age) with the longer duration of therapy (6-month course); however, short-term improvement (evaluated at 6 months of age) in hearing was not demonstrated (Ref).
Cytomegalovirus (CMV) disease, mild to moderate, treatment in solid organ transplant recipients (Ref): Limited data available: Note: Limit CrCl value used in equation below to 150 mL/minute/1.73 m2 regardless of CrCl calculated in order to avoid overexposure (Ref).
Infants, Children, and Adolescents: Oral: Dosing based on BSA and CrCl calculation using modified Schwartz formula which bases k constant on age*:
Dose (mg) = 7 × BSA × CrCl* administered every 12 hours
Maximum dose: 900 mg/dose.
Continue therapy for ≥2 weeks, until symptoms resolve, and until 1 to 2 weekly CMV viral load samples are undetectable or below a test-specific threshold; may also be used as step-down therapy in patients who initially received IV ganciclovir when clinical and virologic control is adequate (Ref).
Cytomegalovirus (CMV), treatment, esophagitis or colitis in patients with HIV: Adolescents: Oral: Treat initially with ganciclovir IV; once patient is able to absorb and tolerate oral therapy, may switch to oral valganciclovir 900 mg twice daily for a total duration of 21 to 42 days, or until signs and symptoms have resolved (Ref).
Cytomegalovirus (CMV), preemptive therapy in hematopoietic cell transplant recipients: Limited data available: Note: Valganciclovir should be avoided in patients with CMV gastritis or intestinal graft-versus-host disease (GVHD) (Ref).
BSA-based dosing (Ref): Infants ≥9 months, Children, and Adolescents:
Maintenance (following induction): Oral: Dosing based on BSA and CrCl calculation using modified Schwartz formula which bases k constant on age*:
Dose (mg) = 7 × BSA × CrCl* administered every 12 hours; use a maximum of 150 mL/minute/1.73 m2 for CrCl in equation even if calculated value is higher.
Maximum dose: 900 mg/dose.
Dosing based on a retrospective evaluation of 46 patients who received preemptive therapy upon CMV reactivation; patients were screened for CMV DNA twice weekly starting 9 days prior to transplantation; 40 of the 46 patients received initial IV induction therapy with ganciclovir; 22 patients received only ganciclovir and 24 patients received valganciclovir; outcomes were similar between the groups (Ref).
Fixed dosing (Ref): Children and Adolescents weighing ≥40 kg: Note: Only use in patients with good oral intake.
<100 days post-transplant:
Induction: Oral: 900 mg twice daily for 7 days (autologous transplant) or 7 to 14 days (allogenic transplant).
Maintenance: Oral: 900 mg once daily for 1 to 2 weeks or until the indicator test is negative (minimum total induction and maintenance treatment for autologous transplant is 2 weeks; for allogeneic transplants minimum is 2 weeks when 14 days of twice-daily therapy is used and 3 weeks when a 7-day induction course is used).
>100 days post-transplant:
Induction: Oral: 900 mg twice daily for 7 to 14 days.
Maintenance: Oral: 900 mg once daily for 1 to 2 weeks until the indicator test is negative (minimum treatment course is 2 weeks).
Cytomegalovirus (CMV), primary prophylaxis in HIV-exposed/-infected patients: Limited data available:
Infants ≥4 months, Children, and Adolescents ≤16 years (Ref): Oral: Dosing based on BSA and CrCl calculation using modified Schwartz formula which bases k constant on age*:
Dose (mg) = 7 × BSA × CrCl* administered once daily; use a maximum of 150 mL/minute/1.73 m2 for CrCl in the equation even if calculated value is higher.
Maximum daily dose: 900 mg/day.
Primary prophylaxis can be considered in in CMV-seropositive patients <6 years of age who have a CD4 percentage <5% or ≥6 years of age who have CD4 cell counts <50 cells/mm3. Discontinuation of primary prophylaxis can be considered when CD4 cell count is >10% in <6 years of age or >100 cells/mm3 for children ≥6 years of age. Secondary prophylaxis may be considered in patients with prior disseminated disease, retinitis, neurologic disease, or GI disease with relapse.
Cytomegalovirus (CMV), prophylaxis in solid organ transplant recipients:
Note: To avoid supratherapeutic exposure, especially in patients with normal renal function and low body weight, the CrCl used in dosage calculations should be capped; most hospitals with pediatric solid organ transplant recipients limit the CrCl used to calculate dosage to a value of 150 mL/minute/1.73 m2, regardless of value calculated with the Schwartz equation, to avoid overexposure (Ref).
Infants, Children, and Adolescents: Limited data available except for kidney and heart transplants (Ref):
Oral: Dosing based on BSA and CrCl calculation using modified Schwartz formula which bases k constant on age*:
Dose (mg) = 7 × BSA × CrCl* administered once daily
Maximum daily dose: 900 mg/day.
Initiate therapy within 10 days after transplant; duration of prophylaxis varies depending on organ(s) transplanted, donor and recipient CMV serostatus, and immunosuppressive regimen; typically continued for 3 to 6 months; may be continued up to 12 months in certain cases (Ref).
Cytomegalovirus (CMV) retinitis, treatment (AIDS-related): Adolescents (Ref):
Induction (active retinitis): Oral: 900 mg twice daily for 14 to 21 days followed by maintenance therapy. For patients with immediate sight-threatening lesions, concomitant use of intravitreal ganciclovir is required.
Maintenance: Oral: 900 mg once daily; may consider discontinuation of chronic maintenance therapy in patients who have received 3 to 6 months of treatment, have inactive lesions, and CD4 count >100 cells/mm3 for 3 to 6 months in response to antiretroviral therapy. Discontinue only after consultation with an ophthalmologist (Ref).
*CrCl calculation (based on the modified Schwartz formula):
CrCl (mL/minute/1.73 m2) = [k × height (cm)] ÷ SCr (mg/dL)
Calculated using a modified Schwartz formula where k =
• 0.33 in infants <1 year of age with low birthweight for GA
• 0.45 in infants <1 year of age with birthweight appropriate for GA
• 0.45 in children 1 to <2 years
• 0.55 in boys age 2 to <13 years
• 0.55 in girls age 2 to <16 years
• 0.7 in boys age 13 to 16 years
Infants ≥1 month, Children, and Adolescents ≤16 years: BSA and CrCl based dosing calculation: No additional dosage adjustments required; dosing equation adjusts for renal function using modified Schwartz equation*.
Adolescents >16 years (tablet formulation):
Induction dose:
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl 40 to 59 mL/minute: 450 mg twice daily.
CrCl 25 to 39 mL/minute: 450 mg once daily.
CrCl 10 to 24 mL/minute: 450 mg every 2 days.
CrCl <10 mL/minute:
Manufacturer's labeling: Use not recommended; ganciclovir (with appropriately specified renal dosage adjustment) should be used instead of valganciclovir.
Alternate recommendations: HIV-1 infected persons: Consider valganciclovir solution 200 mg 3 times weekly (Ref).
End-stage renal disease (ESRD) on intermittent hemodialysis (IHD):
Manufacturer's labeling: Use not recommended; ganciclovir (with appropriately specified renal dosage adjustment) should be used instead of valganciclovir.
Alternate recommendations: HIV-1 infected persons: Consider valganciclovir solution 200 mg 3 times weekly (Ref); valganciclovir is dialyzable and should be administered following dialysis.
Maintenance/prevention dose:
CrCl ≥60 mL/minute: No dosage adjustment necessary.
CrCl 40 to 59 mL/minute: 450 mg once daily.
CrCl 25 to 39 mL/minute: 450 mg every 2 days.
CrCl 10 to 24 mL/minute: 450 mg twice weekly.
CrCl <10 mL/minute:
Manufacturer's labeling: Use not recommended; ganciclovir (with appropriately specified renal dosage adjustment) should be used instead of valganciclovir.
Alternate recommendations: HIV-infected persons: Consider valganciclovir solution 100 mg 3 times weekly (Ref).
End-stage renal disease (ESRD) on intermittent hemodialysis (IHD):
Manufacturer's labeling: Use not recommended; ganciclovir (with appropriately specified renal dosage adjustment) should be used instead of valganciclovir.
Alternate recommendations: HIV-1 infected persons: Consider valganciclovir solution 100 mg 3 times weekly (Ref); valganciclovir is dialyzable and should be administered following dialysis.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension (12% to 18%)
Central nervous system: Headache (6% to 22%), insomnia (6% to 20%)
Gastrointestinal: Diarrhea (16% to 41%), nausea (8% to 30%), vomiting (3% to 21%), abdominal pain (15%)
Hematologic & oncologic: Anemia (≤31%), thrombocytopenia (≤22%), neutropenia (3% to 19%)
Immunologic: Graft rejection (24%)
Neuromuscular & skeletal: Tremor (12% to 28%)
Ophthalmic: Retinal detachment (15%)
Renal: Increased serum creatinine (Scr >1.5 to 2.5 mg/dL: 12% to 50%; Scr >2.5: 3% to 17%)
Miscellaneous: Fever (9% to 31%)
1% to 10%:
Cardiovascular: Hypotension (≥5%), peripheral edema (≥5%), cardiac arrhythmia (<5%)
Central nervous system: Peripheral neuropathy (9%), paresthesia (≤8%), anxiety (≥5%), chills (≥5%), depression (≥5%), dizziness (≥5%), fatigue (≥5%), malaise (≥5%), pain (≥5%), agitation (<5%), confusion (<5%), hallucination (<5%), psychosis (<5%), seizure (<5%)
Dermatologic: Dermatitis (≥5%), increased wound secretion (≥5%), night sweats (≥5%), pruritus (≥5%), cellulitis (<5%)
Endocrine & metabolic: Hyperkalemia (≥5%), hypophosphatemia (≥5%), weight loss (≥5%)
Gastrointestinal: Abdominal distention (≥5%), constipation (≥5%), decreased appetite (≥5%), dyspepsia (≥5%), oral mucosa ulcer (≥5%), dysgeusia (<5%), pancreatitis (<5%)
Genitourinary: Hematuria (≥5%), urinary tract infection (≥5%)
Hematologic & oncologic: Bone marrow depression (<5%; including aplastic anemia), febrile neutropenia (<5%), hemorrhage (<5%; associated with thrombocytopenia), pancytopenia (<5%)
Hepatic: Hepatic insufficiency (≥5%), increased serum ALT (<5%), increased serum AST (<5%)
Hypersensitivity: Hypersensitivity reaction (<5%)
Immunologic: Organ transplant rejection (6% to 9%)
Infection: Candidiasis (≥5%; including oral candidiasis), influenza (≥5%), wound infection (≥5%), sepsis (<5%)
Neuromuscular & skeletal: Arthralgia (≥5%), back pain (≥5%), muscle spasm (≥5%), myalgia (≥5%), weakness (≥5%), limb pain (<5%)
Ophthalmic: Eye pain (≥5%), macular edema (<5%)
Otic: Deafness (<5%)
Renal: Decreased creatinine clearance (≥5%), renal impairment (≥5%), renal failure (<5%)
Respiratory: Cough (≥5%), dyspnea (≥5%), pharyngitis (≥5%; including nasopharyngitis), upper respiratory tract infection (≥5%)
Miscellaneous: Postoperative complication (≥5%), postoperative pain (<5%), wound dehiscence (<5%)
Frequency not defined: Genitourinary: Reduced fertility
<1%, postmarketing and/or case reports: Agranulocytosis, anaphylaxis, granulocytopenia
Hypersensitivity (eg, anaphylaxis) to valganciclovir, ganciclovir, or any component of the formulation
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to acyclovir or valacyclovir
Concerns related to adverse effects:
• Acute renal failure: Acute renal failure may occur; ensure adequate hydration and use with caution in patients receiving concomitant nephrotoxic agents.
• Blood dyscrasias: [US Boxed Warning]: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, and bone marrow failure, including aplastic anemia have been reported. May occur at any time during treatment and worsen with continued use; cell counts usually begin to recover within 3 to 7 days of treatment discontinuation. Do not use in patients with an absolute neutrophil count <500 cells/mm3, platelet count <25,000/mm3, or hemoglobin <8 g/dL; use with caution in patients with preexisting bone marrow suppression, cytopenias, or in those receiving myelosuppressive drugs/irradiation. Monitor CBC and platelet count at baseline and frequently during therapy, especially in infants and in patients with renal impairment, those with previous drug-induced leukopenia, and those with neutrophil counts <1,000 cells/mm3 at treatment initiation.
• Carcinogenic/teratogenic: [US Boxed Warning]: May cause temporary or permanent inhibition of spermatogenesis and suppression of fertility; has the potential to cause birth defects and cancers in humans.
Disease-related concerns:
• Renal impairment: Use with caution in patients with impaired renal function; dosage adjustment required.
Special populations:
• Older patients: Acute renal failure may occur in older patients with or without preexisting renal impairment; use with caution and adjust dose as needed based on renal function.
• Liver transplant recipients: Not indicated for use in liver transplant recipients (higher incidence of tissue-invasive cytomegalovirus [CMV] relative to oral ganciclovir was observed in trials).
• Pediatric: The preferred dosage form for pediatric patients is the oral solution; however, valganciclovir tablets may be used so long as the calculated dose is within 10% of the available tablet strength (450 mg). Use of valganciclovir for the treatment of congenital CMV disease has not been evaluated.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
The rates of certain adverse events and laboratory abnormalities, such as upper respiratory tract infection, pyrexia, nasopharyngitis, anemia, and neutropenia, were reported more frequently in pediatric patients than in adults in clinical trials. In a 6-month trial evaluating congenital cytomegalovirus treatment in neonates and infants, the reported incidence of grade 3 or 4 neutropenia was similar between valganciclovir and placebo (21% vs 27%) (Kimberlin 2015).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Oral:
Valcyte: 50 mg/mL (88 mL) [contains saccharin sodium, sodium benzoate; tutti-frutti flavor]
Generic: 50 mg/mL (88 mL)
Tablet, Oral:
Valcyte: 450 mg
Generic: 450 mg
Yes
Solution (reconstituted) (Valcyte Oral)
50 mg/mL (per mL): $14.59
Solution (reconstituted) (valGANciclovir HCl Oral)
50 mg/mL (per mL): $6.12 - $11.37
Tablets (Valcyte Oral)
450 mg (per each): $106.08
Tablets (valGANciclovir HCl Oral)
450 mg (per each): $64.40 - $68.78
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Oral:
Valcyte: 50 mg/mL (100 mL) [contains propylene glycol, saccharin sodium, sodium benzoate]
Generic: 50 mg/mL (100 mL)
Tablet, Oral:
Valcyte: 450 mg
Generic: 450 mg
Oral: Valganciclovir should be administered with meals. Do not break or crush tablets.
Due to the carcinogenic and mutagenic potential, avoid direct contact with broken or crushed tablets, powder for oral solution, and oral solution. Handle and dispose of valganciclovir according to guidelines issued for antineoplastic drugs.
Oral: Administer with meals. The preferred dosage form for pediatric patients is the oral solution; however, valganciclovir tablets may be used as long as the calculated dose is within 10% of the available tablet strength (450 mg). Do not break or crush tablets.
Oral solution: Shake well prior to use. Use provided reusable oral syringe to measure and administer dose; do not use a household teaspoon, tablespoon, or other measuring device to measure dose (overdosage may occur).
Hazardous agent (NIOSH 2016 [group 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Cytomegalovirus, prophylaxis in solid organ transplant recipients:
Prevention of cytomegalovirus (CMV) in high-risk adult patients (donor CMV seropositive/recipient CMV seronegative) undergoing kidney, heart, or kidney/pancreas transplantation.
Prevention of CMV in high-risk pediatric patients undergoing kidney transplant (age 4 months to 16 years) or heart transplant (age 1 month to 16 years).
Cytomegalovirus, treatment, retinitis: Treatment of CMV retinitis in patients with AIDS.
Cytomegalovirus, mild to moderate, treatment in solid organ transplant recipients; Cytomegalovirus, preemptive therapy in hematopoietic cell transplant recipients; Cytomegalovirus, treatment, esophagitis or colitis in patients with HIV
Valcyte may be confused with Valium, Valtrex
ValGANciclovir may be confused with acyclovir, valACYclovir, ganciclovir
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Amphotericin B: Ganciclovir-Valganciclovir may enhance the nephrotoxic effect of Amphotericin B. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
CycloSPORINE (Systemic): Ganciclovir-Valganciclovir may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Risk C: Monitor therapy
Didanosine: Ganciclovir-Valganciclovir may increase the serum concentration of Didanosine. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification
Imipenem: Ganciclovir-Valganciclovir may enhance the adverse/toxic effect of Imipenem. Specifically, the risk of seizures may be increased. Management: Avoid concomitant use of these agents unless the prospective benefits of therapy outweigh the risks. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Maribavir: May diminish the therapeutic effect of Ganciclovir-Valganciclovir. Risk X: Avoid combination
Mycophenolate: May enhance the adverse/toxic effect of Ganciclovir-Valganciclovir. Specifically, the risk for leukopenia or neutropenia may be increased with this combination. Mycophenolate may increase the serum concentration of Ganciclovir-Valganciclovir. Risk C: Monitor therapy
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Ganciclovir-Valganciclovir. Risk C: Monitor therapy
Taurursodiol: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk X: Avoid combination
Tenofovir Products: May increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Vaborbactam: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Vadadustat: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
Zidovudine: Ganciclovir-Valganciclovir may enhance the adverse/toxic effect of Zidovudine. Specifically, hematologic toxicity may be enhanced. Risk C: Monitor therapy
Coadministration with a high-fat meal increased AUC by 30%. Management: Valganciclovir should be taken with meals.
Patients who may become pregnant should undergo pregnancy testing prior to treatment with valganciclovir.
Patients who may become pregnant should use effective contraception during treatment and for at least 30 days after therapy with valganciclovir. Patients with partners who could become pregnant should use condoms during treatment and for at least 90 days after valganciclovir therapy.
Based on animal data and limited human data, valganciclovir may cause temporary or permanent inhibition of spermatogenesis. Sperm density was decreased following 200 days of treatment with valganciclovir in patients following a renal transplant. Six months after treatment was discontinued, sperm density was comparable to transplant recipients who did not receive valganciclovir. Suppression of fertility may also occur in females.
Following maternal use of valganciclovir, ganciclovir can be detected in umbilical cord blood (Seidel 2017).
Valganciclovir is converted to ganciclovir and shares its reproductive toxicity. Based on animal data, valganciclovir has the potential to cause birth defects in humans.
Outcome data following maternal use of valganciclovir for cytomegalovirus (CMV) infection during pregnancy are limited (Bergin 2014; DeNoble 2020; Seidel 2017).
CMV infection in immunocompromised patients is associated with significant maternal morbidity and mortality. Congenital CMV infection may also occur; hearing loss, intellectual disability, microcephaly, seizures, and other medical problems have been observed in infants with congenital CMV infection.
Until additional data are available, use of antivirals for the treatment of congenital CMV outside of a clinical trial is not currently recommended (SMFM 2016).
The indications for treating maternal CMV retinitis during pregnancy are the same as in non-pregnant HIV infected people. In general, intravitreous injections for local therapy are preferred for retinal disease to limit systemic exposure during the first trimester when possible. Valganciclovir is the preferred systemic therapy in pregnant patients (limited data). Close fetal monitoring is recommended. Use of valganciclovir is recommended to treat maternal infection, but not recommended for the treatment of asymptomatic maternal disease for the sole purpose of preventing infant infection (HHS [OI adult] 2021).
It is not known if ganciclovir or valganciclovir are present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer. In addition, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients in the United States with HIV when safer infant feeding options are available (HHS [perinatal] 2023).
Cytomegalovirus can also be transferred from mother to infant via breast milk; the risk of adverse outcomes if infection occurs is more likely in infants born <32 weeks' gestation and <1,500 g (Osterholm 2020).
Should be taken with meals.
CBC, platelet count, serum creatinine at baseline and periodically during therapy; monitor CBC and platelet count more frequently during therapy in infants and in patients with renal impairment, those with previous drug-induced leukopenia, and those with neutrophil counts <1,000 cells/mm3 at treatment initiation; pregnancy test prior to initiation in females of reproductive potential.
Valganciclovir is rapidly converted to ganciclovir in the body. Ganciclovir is phosphorylated to a substrate which competitively inhibits the binding of deoxyguanosine triphosphate to DNA polymerase resulting in inhibition of viral DNA synthesis.
Absorption: Well absorbed; high-fat meal increases AUC by 30%.
Distribution: Vdss: Ganciclovir: 0.7 L/kg; widely to all tissue including CSF and ocular tissue.
Protein binding: Ganciclovir: 1% to 2%.
Metabolism: Converted to ganciclovir by intestinal mucosal cells and hepatocytes.
Bioavailability: With food: 60%; similar in pediatric patients 4 months to 16 years; neonates: Initial data: 54% (Acosta 2007).
Half-life elimination:
Pediatric patients (heart, kidney, or liver transplant): Ganciclovir: Mean range:
1 to <4 months: 3.5 hours (heart transplant only).
4 months to 2 years: Mean range: 2.8 to 4.5 hours.
2 to 12 years: Mean range: 2.8 to 4.8 hours.
12 to 16 years: Mean range: 4.4 to 6 hours.
Adults:
Ganciclovir: 4.08 hours; prolonged with renal impairment; Severe renal impairment: Up to 68 hours.
Heart, kidney, kidney-pancreas, or liver transplant recipients: Mean range: 6.18 to 6.77 hours.
Time to peak: Ganciclovir: 1.7 to 3 hours.
Excretion: Urine (80% to 90%; primarily as ganciclovir).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
