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Abstract
Valganciclovir is an l-valyl ester pro-drug of ganciclovir that was initially used
to treat cytomegalovirus (CMV)-associated retinitis in patients with human immunodeficiency
virus. Currently, it is also indicated for the prevention of CMV disease in solid-organ
transplantation. It is primarily eliminated via the kidneys through glomerular filtration
and tubular secretion. Decreased renal function results in decreased drug clearance.
Valganciclovir has been reported to cause usually mild to moderate hematologic adverse
effects such as leukopenia, neutropenia, anemia, thrombocytopenia, and pancytopenia.
Severe and fatal bone marrow depression has been described in 1 adult patient. Herein,
we describe the cases of 4 patients with end-stage renal disease who underwent cadaveric
renal transplantation and received valganciclovir prophylaxis for CMV at a standard
dose of 900 mg/d despite persistant renal failure. This therapy resulted in severe
bone marrow failure after 18 to 20 days in all 4 patients, with fatal infections in
2 patients. This report demonstrates the in vivo pharmacodynamics of valganciclovir
overdose in terms of hematotoxicity in the setting of renal impairment. Valganciclovir,
as its derivative ganciclovir, should be used cautiously in patients with renal impairment.