For Healthcare Professionals

Important Safety Information

A Retrospective Analysis of the IMPACT Study: Poster Presentation

Evaluation of the Modification of Diet in Renal Disease (MDRD) Equation Versus the Cockcroft-Gault (CG) Equation as a Measure of Renal Function for Valganciclovir Dose Calculations

Limaye AP, Blumberg E, Mu Y, et al.

Findings

  • Posttransplant renal function recovered rapidly* in the majority of patients in the IMPACT trial (N=320)1
    • – 56% had a CrCl (CG) of ≥ 60 mL/min by week 4
    • – 61% had a CrCl (CG) of ≥ 60 mL/min by week 8
  • Use of MDRD instead of CG to estimate renal function would have resulted in many patients receiving a Valcyte dose inconsistent with pivotal trials1
    • – 35% to 51% of patients would have received a dose lower than recommended
    • – 3% to 6% of patients would have received a dose higher than recommended

* Renal function recovery is not a direct or indirect effect of Valcyte.

In high-risk adult kidney transplantation...
Peak renal function was reached by week 8 and stabilized for the remainder of the pivotal trial

Percentage of patients with Cockcroft-Gault estimated CrCl ≥60 mL/min grew rapidly.1

  • 56% by week 4
  • 61% by week 8

66% of the patients had received deceased-donor allografts.1

For full patient characteristics, please see IMPACT Study Design.

Proportions of Patients in Each CrCl (CG) Category over time
Renal function recovery may vary from patient to patient.
Study results may not reflect your patient population.

Renal function should be assessed regularly posttransplant

In high-risk adult kidney transplantation...
Use of the MDRD equation could lead to Valcyte dosing inconsistent with pivotal trials based on Cockcroft-Gault

Valcyte dose adjustments are only based on the CG equation for estimated CrCl as an assessment of renal function.2

Proportions of Patients in Each CrCl (CG) Category over time
The MDRD equation was substituted for the CG equation in the dosing algorithm to simulate Valcyte dosage based on MDRD, and then Valcyte dosages were compared with those dosages determined using the CG equation.5
  • 35% to 51% of patients would have received a dose lower than recommended1
  • 3% to 6% of patients would have received a dose higher than recommended1

Use the CG equation to ensure that the Valcyte dose is consistent with pivotal trials

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.
Limaye AP, Blumberg E, Mu Y, et al. Evaluation of the modification of diet in renal disease (MDRD) equation versus the Cockcroft-Gault (CG) equation as a measure of renal function for valganciclover dose calculations. Poster presented at 2011 American Transplant Congress-11th Joint Annual Meeting of the American Society of Transplant Surgeons and the American Society of Transplantation; April 30–May 4, 2011; Philadelphia, PA.
2.
Valcyte® [package insert]. South San Francisco, CA: Genentech USA, Inc.; 2010.

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.