Dosing and uses of Valcyte (valganciclovir)
Adult dosage forms and strengths
tablet
- 450mg
powder for oral solution
- 50mg/mL when reconstituted
Cytomegalovirus Retinitis
Indicated for treatment of CMV retinitis in patients with AIDs
Induction dose: 900 mg PO q12hr for 21 days
Maintenance dose: 900 mg PO qDay
CMV Prevention in Solid Organ Transplant
Indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk (donor CMV seropositive/recipient CMV seronegative [D+/R-])
Kidney transplantation
- 900 mg PO qDay
- Begin within 10 days of transplant until 200 days post-transplant
Kidney-pancreas transplantation
- 900 mg PO qDay
- Begin within 10 days of transplant until 100 days posttransplant
Heart transplantation
- 900 mg PO qDay
- Begin within 10 days of transplant until 100 days posttransplant
Renal Impairment
CrCl 40-59 mL/min: 450 mg PO q12hr (induction), THEN 450 mg qDay
CrCl 25-39 mL/min: 450 mg PO qDay (induction), THEN 450 mg q2days
CrCl 10-24 mL/min: 450 mg PO q2days (induction), THEN 450 mg 2 times/week
<10 mL/min (on hemodialysis): Not recommended
Pediatric dosage forms and strengths
tablet
- 450mg
powder for oral solution
- 50mg/mL when reconstituted
CMV Prevention in Kidney & Heart Transplant
Kidney transplantation
- <4 months: Safety and efficacy not established
- 4 months to16 years: Daily dose (mg) = 7 x BSA x CrCl; not to exceed 900 mg/day
- Begin within 10 days of transplant and continue until 200 days post-transplant
Heart transplantation
- <1 month: Safety and efficacy not established
- 1 month to16 years: Daily dose (mg) = 7 x BSA x CrCl; not to exceed 900 mg/day
- Begin within 10 days of transplant and continue until 100 days post-transplant
Dosing Considerations
Calculation of creatinine clearance for the dose in children is by a modified Schwartz formula
The oral solution is the preferred formulation for children since it provides the ability to administer a dose calculated according to the Schwartz formula
Tablets may be used if the calculated doses are within 10% of available tablet strength (450 mg)
For example, if the calculated dose is between 405 mg and 495 mg, one 450 mg tablet may be taken
Assess children for the ability to swallow tablets
Calculate BSA by Mosteller equation
- BSA (m²) = height (cm) X weight (kg) divided by 3600
Calculate CrCl by Schwartz equation
- CrCl (mL/min/1.73 m²) = K x height (cm) divided by serum Cr (mg/dL)
- If CrCl exceeds 150 mL/min/1.73 m², then use maximum value of 150 mL/min/1.73 m²; an upper limit of 150 mL/min/1.73 m² helps prevent the potential for over dosing
- If the calculated pediatric dose exceeds 900 mg, a dose of 900 mg should be given to the child
- Where K =
- 0.33 for infants aged <1 yr with low birth weight for gestational age
- 0.45 for infants aged <1 yr with birth weight appropriate for gestational age
- 0.45 for aged 4 months to <1-2 yr
- 0.55 for boys aged 2 to <13 yr and girls aged 2 to <16 yr
- 0.7 for boys aged 13-16 yr
Valcyte (valganciclovir) adverse (side) effects
>10%
Abdominal pain (15%)
Anemia (8-26%)
Diarrhea (16-41%)
Fever (31%)
Granulocytopenia (11-27%)
Headache (9-22%)
Insomnia (16%)
Nausea (8-30%)
Retinal detachment (15%)
Vomiting (21%)
1-10%
Peripheral neuropathy (9%)
Paresthesia (8%)
Seizures (<5%)
Psychosis, hallucinations (<5%)
Confusion (<5%)
Agitation (<5%)
Thrombocytopenia (8%)
Pancytopenia (<5%)
Bone marrow depression (<5%)
Aplastic anemia (<5%)
Bleeding, potentially life-threatening due to thrombocytopenia (<5%)
Decr renal function (<5%),
Local & systemic infections, incl sepsis (<5%)
Allergic reaction (<5%)
Warnings
Black box warnings
Valganciclovir metabolized to ganciclovir
Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia reported
Animal studies showed cidofovir was carcinogenic, teratogenic, and caused hypospermia
Contraindications
Hypersensitivity to valganciclovir, ganciclovir
Hemodialysis patients (use ganciclovir instead)
ANC <500/cu.mm, Patients <25,000/cu.mm, Hgb <8 g/dL
Liver transplant patients
Concomitant zidovudine: increases hematological toxicity
Cautions
Preexisting cytopenias
May be teratogenic or embryotoxic, avoid pregnancy; male patients advised to use barrier method during and for 90 days after treatment
Risk of: hematologic toxicity, female infertility; aspermatogenesis
Maintain adequate hydration
Concomitant nephrotoxic drugs
Pregnancy and lactation
Pregnancy category: C
Lactation: not known if distributed in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Valcyte (valganciclovir)
Mechanism of action
Prodrug, converted to ganciclovir in intestine and liver
Inhibits viral DNA polymerases resulting in chain termination
Pharmacokinetics
Absorption: Well absorbed; high-fat meal increases AUC by 30%
Vdss: ; 0.7 L/kg (gancyclovir); widely to all tissues including CSF and ocular tissue
Metabolism: converted to ganciclovir by intestinal mucosal cells and hepatocytes
Vd: Ganciclovir: 15.26 L/1.73 sq.meter
Protein Bound: Ganciclovir 1-2%
Half-life, elimination: ganciclovir: 4 hr in nontransplant patients; 6-7 hr in transplant patients; prolonged with renal impairment; severe renal impairment: up to 68 hr
Bioavailability: With food: 60%
Excretion: urine (primarily as ganciclovir)
Administration
Instructions
Take with food (improved bioavailability)
Handle and dispose according to guidelines for antineoplastic drugs because ganciclovir (active metabolite) shares some of the properties of antitumor agents (ie, carcinogenicity and mutagenicity)
