For Healthcare Professionals

Important Safety Information

Assessing Renal Function and Actively Managing Valcyte Dosing

To help optimize cytomegalovirus (CMV) disease prophylaxis in high-risk adult kidney transplant patients, actively manage Valcyte dosing based on renal function

Renal function affects Valcyte clearance and should be assessed regularly using the Cockcroft-Gault equation for accurate dosing consistent with pivotal trials.

  • The major elimination pathway for Valcyte is renal1
  • Impaired renal function is a common complication in the immediate posttransplantation period for both renal and nonrenal transplants2,3
  • Posttransplant renal impairment is usually temporary in kidney transplant patients4

Renal function should be assessed regularly posttransplant.*5

Because renal function in transplant patients can be variable, screening should be performed and dosage adjusted as necessary based on the Cockcroft-Gault formula for measuring CrCl.

KDIGO Recommended Minimum Posttransplant Serum Creatinine Screening Intervals for Kidney Transplant Patients*4,5

Posttransplant Time Period Screening Interval
1 week Daily
1 month 2-3 per week
Months 2-3 Weekly
Months 4-6 Every 2 weeks
* KDIGO=Kidney Disease Improves Global Outcomes.
* Adapted from KDIGO Clinical Practice Guideline, 2009. These recommendations are general and do not imply a specific protocol. More frequent monitoring may be required for specific patients.

Achieve balance using the appropriate Valcyte dose throughout prophylaxis

Valcyte dosing is based on renal function

  • Valcyte clinical trials were conducted using 900 mg daily dosing, adjusted for renal function based on the Cockcroft-Gault equation6,7
    • Since renal function may change posttransplant, it should be assessed throughout treatment using the Cockcroft-Gault equation, with dosage adjusted accordingly1,4

Valcyte dosage recommendations are only based on CrCl determined using the Cockcroft-Gault equation.6,7

Cockcroft-Gault Equation

Other methods of determining CrCl may provide different results, and doses of Valcyte may not be consistent with pivotal trials.6,7

In high-risk adult kidney transplantation...
Use Cockcroft-Gault to estimate renal function when making Valcyte dosing decisions

Valcyte Dosage Corresponding to the Patient’s Cockcroft-Gault Creatinine Clearance (CrCl)1

Crcl (mL/min) Maintenance/Prevention Dosage
≥60 900 mg once daily
40-59 450 mg once daily
25-39 450 mg every 2 days
10-24 450 mg twice weekly
<10
(on hemodialysis)		 Not recommended

When CrCI reaches ≥ 60 mL/min as determined using the Cockcroft-Gault equation, adjust Valcyte dosage to 900 mg once daily to help optimize CMV disease prevention.1

INDICATIONS

ADULT PATIENTS

Valcyte® (valganciclovir hydrochloride) tablets are indicated for the prevention of cytomegalovirus (CMV) disease in kidney, heart, or kidney-pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

PEDIATRIC PATIENTS

Valcyte (valganciclovir hydrochloride) for oral solution and tablets are indicated for the prevention of CMV disease in kidney or heart transplant patients (4 months to 16 years of age) at high risk.

LIMITATIONS OF USE

  • Valcyte is not indicated for use in either adult or pediatric liver transplant patients
  • The safety and efficacy of Valcyte have not been established for:
    • Prevention of CMV disease in solid organ transplants other than those indicated
    • Prevention of CMV disease in pediatric solid organ transplant patients <4 months of age
    • Treatment of congenital CMV disease

IMPORTANT DOSING INFORMATION

  • Adult patients should use Valcyte tablets, not Valcyte for oral solution
  • Valcyte should be taken with food
  • The bioavailability of ganciclovir from Valcyte is significantly higher than from ganciclovir capsules. Therefore, Valcyte tablets cannot be substituted for ganciclovir capsules on a one-to-one basis
  • Valcyte tablets should not be broken or crushed
  • Valcyte for oral solution must be prepared by the pharmacist prior to dispensing to patient

IMPORTANT SAFETY INFORMATION

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

CONTRAINDICATION

Valcyte is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (eg, anaphylaxis) to valganciclovir, ganciclovir, or any component of the formulation.

WARNINGS AND PRECAUTIONS:

  • Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been observed in patients treated with Valcyte or ganciclovir
  • Do not administer if the absolute neutrophil count is <500 cells/μL, the platelet count is <25,000/μL, or the hemoglobin is <8 g/dL
  • Use with caution in patients with pre-existing cytopenias, or who have received or who are receiving myelosuppressive drugs or irradiation. Cytopenia may occur at any time during treatment and may worsen with continued dosing. Cell counts usually begin to recover within 3 to 7 days after discontinuing drug
  • Advise women of childbearing potential to use effective contraception during treatment and for at least 30 days following treatment with Valcyte. Advise men to practice barrier contraception during and for at least 90 days following treatment with Valcyte
  • Acute renal failure may occur in:
    • Elderly patients with or without reduced renal function. Caution should be exercised when administering Valcyte to geriatric patients and dosage reduction is recommended for those with impaired renal function
    • Patients receiving potential nephrotoxic drugs. Caution should be exercised when administering Valcyte to patients receiving potential nephrotoxic drugs
    • Patients without adequate hydration. Adequate hydration should be maintained for all patients

ADVERSE REACTIONS

Adult Patients: The most common adverse events and laboratory abnormalities reported in at least one indication by ≥ 20% of patients treated with Valcyte tablets are diarrhea, pyrexia, nausea, tremor, neutropenia, anemia, graft rejection, thrombocytopenia, and vomiting.

Pediatric Patients: The most common adverse events and laboratory abnormalities reported in >10% of solid organ transplant recipients treated with Valcyte for oral solution or tablets are diarrhea, pyrexia, hypertension, upper respiratory tract infection, vomiting, anemia, neutropenia, constipation, nausea, and cough.

Please see full Prescribing Information, including Boxed WARNING, for additional Important Safety Information.

References:
1.
Valcyte® [package insert]. South San Francisco, CA: Genentech USA, Inc.; 2010.
2.
Wilkinson AH, Cohen DJ. Renal failure in the recipients of nonrenal solid organ transplants. J Am Soc Nephrol. 1999;10(5):1136-1144.
3.
Yarlagadda SG, Klein CL, Jani A. Long-term renal outcomes after delayed graft function. Adv Chronic Kidney Dis. 2008;15(3):248-256.
4.
Rodrigo E, Ruiz JC, Pinera C, et al. Creatinine reduction ratio on post-transplant day two as criterion in defining delayed graft function. Am J Transplant. 2004;4:1163-1169.
5.
Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients. Am J Transplant. 2009;9(suppl 3):S1-S155.
6.
Humar A, Lebranchu Y, Vincenti F, et al. The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Am J Transplant. 2010;10:1228-1237.
7.
Paya C, Humar A, Dominguez E, et al. Efficacy and safety of valganciclovir vs oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2004;4:611-620.
8.
Guidance for Industry: Pharmacokinetics in Patients with Impaired Renal Function–Study Design, Data Analysis, and Impact on Dosing and Labeling. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). 2010; Clinical Pharmacology: Revision 1.

Important Safety Informationclose

INDICATIONS

ADULT PATIENTS

Valcyte® (valganciclovir hydrochloride) tablets are indicated for the prevention of cytomegalovirus (CMV) disease in kidney, heart, or kidney-pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

PEDIATRIC PATIENTS

Valcyte (valganciclovir hydrochloride) for oral solution and tablets are indicated for the prevention of CMV disease in kidney or heart transplant patients (4 months to 16 years of age) at high risk.

LIMITATIONS OF USE

  • Valcyte is not indicated for use in either adult or pediatric liver transplant patients
  • The safety and efficacy of Valcyte have not been established for:
    • Prevention of CMV disease in solid organ transplants other than those indicated
    • Prevention of CMV disease in pediatric solid organ transplant patients <4 months of age
    • Treatment of congenital CMV disease

IMPORTANT DOSING INFORMATION

  • Adult patients should use Valcyte tablets, not Valcyte for oral solution
  • Valcyte should be taken with food
  • The bioavailability of ganciclovir from Valcyte is significantly higher than from ganciclovir capsules. Therefore, Valcyte tablets cannot be substituted for ganciclovir capsules on a one-to-one basis
  • Valcyte tablets should not be broken or crushed
  • Valcyte for oral solution must be prepared by the pharmacist prior to dispensing to patient

IMPORTANT SAFETY INFORMATION

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

CONTRAINDICATION

Valcyte is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (eg, anaphylaxis) to valganciclovir, ganciclovir, or any component of the formulation.

WARNINGS AND PRECAUTIONS:

  • Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been observed in patients treated with Valcyte or ganciclovir
  • Do not administer if the absolute neutrophil count is <500 cells/μL, the platelet count is <25,000/μL, or the hemoglobin is <8 g/dL
  • Use with caution in patients with pre-existing cytopenias, or who have received or who are receiving myelosuppressive drugs or irradiation. Cytopenia may occur at any time during treatment and may worsen with continued dosing. Cell counts usually begin to recover within 3 to 7 days after discontinuing drug
  • Advise women of childbearing potential to use effective contraception during treatment and for at least 30 days following treatment with Valcyte. Advise men to practice barrier contraception during and for at least 90 days following treatment with Valcyte
  • Acute renal failure may occur in:
    • Elderly patients with or without reduced renal function. Caution should be exercised when administering Valcyte to geriatric patients and dosage reduction is recommended for those with impaired renal function
    • Patients receiving potential nephrotoxic drugs. Caution should be exercised when administering Valcyte to patients receiving potential nephrotoxic drugs
    • Patients without adequate hydration. Adequate hydration should be maintained for all patients

ADVERSE REACTIONS

Adult Patients: The most common adverse events and laboratory abnormalities reported in at least one indication by ≥ 20% of patients treated with Valcyte tablets are diarrhea, pyrexia, nausea, tremor, neutropenia, anemia, graft rejection, thrombocytopenia, and vomiting.

Pediatric Patients: The most common adverse events and laboratory abnormalities reported in >10% of solid organ transplant recipients treated with Valcyte for oral solution or tablets are diarrhea, pyrexia, hypertension, upper respiratory tract infection, vomiting, anemia, neutropenia, constipation, nausea, and cough.

Please see full Prescribing Information, including Boxed WARNING, for additional Important Safety Information.