QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Peyrière, H. Articles by Hillaire-Buys, D. Search for Related Content PubMed PubMed Citation Articles by Peyrière, H. Articles by Hillaire-Buys, D.

Neurotoxicity Related to Valganciclovir in a Child with Impaired Renal Function: Usefulness of Therapeutic Drug Monitoring

Lecturer in Clinical Pharmacy, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital, Montpellier, France

Eric Jeziorsky, MD

Physician, Department of Pediatric Oncology, Arnaud de Villeneuve Hospital, Montpellier

Anne Jalabert, PharmD

Assistant Professor, Department of Pharmacy, Lapeyronie Hospital

Marylène Cociglio, PharmD PhD

Lecturer in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

Abdelkader Benketira, MD

Physician, Department of Pediatric Oncology, Arnaud de Villeneuve Hospital

Jean-Pierre Blayac, MD PhD

Professor in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

Sylvie Hansel, PharmD PhD

Professor in Clinical Pharmacy, Department of Pharmacy, Lapeyronie Hospital

Geneviève Margueritte, MD

Physician, Department of Pediatric Oncology, Arnaud de Villeneuve Hospital

Dominique Hillaire-Buys, MD PhD

Lecturer in Clinical Pharmacology, Department of Medical Pharmacology and Toxicology, Lapeyronie Hospital

Reprints: Dr. Peyrière, Service de Pharmacologie Médicale, Hôpital Lapeyronie, 371 avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France, fax 33-4-67-33-67-51, h-peyriere{at}chumontpellier.fr

OBJECTIVE: To report a case of neurotoxicity related to antiviral drugs, discuss the involvement of concomitant medications, and document the pharmacokinetics of ganciclovir (administered as valganciclovir) in a child with impaired renal function.

CASE SUMMARY: A 13-year-old boy with acute lymphoblastic leukemia was treated for cytomegalovirus retinitis with valganciclovir 450 mg every 2 days in the course of hematopoietic stem cell transplantation. Concomitant medication included omeprazole, furosemide, and acetaminophen. During treatment, when creatinine clearance decreased to 20 mL/min, the child presented with acute neurotoxicity, consisting of mental confusion and hallucinations, which resolved when all medications were stopped. Valganciclovir therapeutic monitoring showed high ganciclovir concentrations in the plasma (3.85 µg/mL) and cerebrospinal fluid (2.6 µg/mL) 48 hours after the last valganciclovir dose. After recovery of neurologic function, valganciclovir was resumed at a lower dosage (225 mg twice a week) with therapeutic drug monitoring and was well tolerated. However, the cytomegalovirus infection was not resolved. The leukemia relapsed, and the patient had terminal renal failure and died. The Naranjo probability scale indicated a probable relationship between valganciclovir and neurotoxicity.

DISCUSSION: Drugs taken by this child (acyclovir, valganciclovir, omeprazole) have been reported to induce neurotoxicity, with the pharmacokinetics of the first 2 being altered by renal failure. At the time when acyclovir was first administered, symptoms of neurotoxicity were already apparent. Moreover, plasma concentrations of ganciclovir were very high during the course of the neurotoxicity. Thus, the adverse effects seemed related to an overdosage of valganciclovir and were worsened by the addition of acyclovir.

CONCLUSIONS: This case is informative because few clinical and pharmacokinetic data are available concerning the use of valganciclovir in children. A study should be performed to determine the proper pediatric dose of valganciclovir with and without renal impairment to prevent the occurrence of adverse effects.

Key Words: acyclovir, neurotoxicity, renal failure, valganciclovir

Published Online, December 20, 2005. www.theannals.com, DOI 10.1345/aph.1G214