Valganciclovir hydrochloride warnings and precautions

Valganciclovir Hydrochloride
VALCYTE® FDA Package Insert
Description
Clinical Pharmacology
Microbiology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Overdosage
Clinical Studies
Dosage and Administration
Patient Counseling Information
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

Warnings and Precautions

WARNING: HEMATOLOGIC TOXICITY, CARCINOGENICITY, TERATOGENICITY, AND IMPAIRMENT OF FERTILITY Clinical toxicity of Valcyte, which is metabolized to ganciclovir, includes granulocytopenia, anemia, and thrombocytopenia [see Warnings and Precautions (5.1)]. In animal studies, ganciclovir was carcinogenic, teratogenic, and caused aspermatogenesis [see Warnings and Precautions (5.2, 5.3, 5.4)].

Hematologic Effects

Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been reported in patients treated with Valcyte or ganciclovir. Valcyte should not be administered if the absolute neutrophil count is less than 500 cells/µL, the platelet count is less than 25,000/µL, or the hemoglobin is less than 8 g/dL. Valcyte should also be used 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.

Due to the frequency of neutropenia, anemia, and thrombocytopenia in patients receiving Valcyte [see Adverse Reactions (6.1, 6.2)], complete blood counts with differential and platelet counts should be performed frequently, especially in patients in whom ganciclovir or other nucleoside analogues have previously resulted in leukopenia, or in whom neutrophil counts are less than 1000 cells/µL at the beginning of treatment. Increased monitoring for cytopenias may be warranted if therapy with oral ganciclovir is changed to Valcyte, because of increased plasma concentrations of ganciclovir after Valcyte administration [see Clinical Pharmacology (12.3)].

Impairment of Fertility

Animal data indicate administration of ganciclovir causes inhibition of spermatogenesis and subsequent infertility. These effects were reversible at lower doses but irreversible at higher doses [see Nonclinical Toxicology (13.1)]. In men, Valcyte at the recommended doses may cause temporary or permanent inhibition of spermatogenesis. Animal data also indicate suppression of fertility in females may occur.

Teratogenesis and Mutagenesis

Animal data indicate ganciclovir is teratogenic and mutagenic. Therefore, Valcyte should be considered to have the potential to cause birth defects and cancers in humans. Women of childbearing potential should be advised to use effective contraception during treatment and for at least 30 days following treatment with Valcyte. Similarly, men should be advised to practice barrier contraception during and for at least 90 days following treatment with Valcyte [see Dosage and Administration (2.6), Use in Specific Populations (8.1), Nonclinical Toxicology (13.1, 13.3)].

Carcinogenesis

Animal data indicate that administration of ganciclovir is carcinogenic. Valcyte should therefore be considered a potential carcinogen in humans [see Dosage and Administration (2.6), Nonclinical Toxicology (13.1)].

Acute Renal Failure

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 [see Dosage and Administration (2.5), Use in Specific Populations (8.5, 8.6)].

• 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.

References

Adapted from the FDA Package Insert.