Abstract
Background
More than 250,000 reports of adverse drug events were included in the database of the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan. However, these data have not been utilized sufficiently for analysis. While valacyclovir is the antiviral agent used worldwide, it is reported to induce nephrotoxicity. The aim of this study was to clarify the profiles of valacyclovir-induced adverse events using the PMDA database.
Methods
Case reports were screened in the PMDA adverse event database from 2004 to 2011. The profiles of patients with acute kidney injury (AKI) were analyzed by sex, age, diseases, concomitant suspected drugs, and outcomes.
Results
A total of 514 kidney-related adverse events were detected, and 344 were cases that included AKI. Of the AKI cases, 246 patients (71.5%) were female. There were 145 patients who were 70 to 79 years of age, which was the most affected of all age groups. Of the 344 patients, 183 patients had hypertension, and 65 had diabetes. Valacyclovir was the only drug used among 257 patients (74.1%).
Conclusions
There were many reports of AKI involving valacyclovir and females, particularly in the 70- to 79-year age group in Japan. The results suggest that these patients were most likely to develop AKI after valacyclovir treatment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Weller S, Blum MR, Doucette M, et al. Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers. Clin Pharmacol Ther. 1993;54:595–605.
Ganapathy ME, Huang W, Wang H, Ganapathy V, Leibach FH. Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998;246:470–475.
Sawada K, Terada T, Saito H, Hashimoto Y, Inui K. Recognition of L-amino acid ester compounds by rat peptide transporters PEPT1 and PEPT2. J Pharmacol Exp Ther. 1999;291:705–709.
Roberts DM, Smith MW, McMullan BJ, Sevastos J, Day RO. Acute kidney injury due to crystalluria following acute valacyclovir overdose. Kidney Int. 2011;79:574.
Fleischer R, Johnson M. Acyclovir nephrotoxicity: a case report highlighting the importance of prevention, detection, and treatment of acyclovir-induced nephropathy [article ID 602783]. Case Report Med. 2010;2010.
Sugimoto T, Yasuda M, Sakaguchi M, et al. Oliguric acute renal failure following oral valacyclovir therapy. QJM. 2008;101:164–166.
Izzedine H, Launay-Vacher V, Deray G. Antiviral drug-induced nephrotoxicity. Am J Kidney Dis. 2005;45:804–817.
Perazella MA. Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci. 2003;325:349–362.
Dos Santos Mde F, Dos Santos OF, Boim MA, et al. Nephrotoxicity of acyclovir and ganciclovir in rats: evaluation of glomerular hemodynamics. J Am Soc Nephrol. 1997;8:361–367.
Gunness P, Aleksa K, Bend J, Koren G. Acyclovir-induced nephrotoxicity: the role of the acyclovir aldehyde metabolite. Transl Res. 2011;158:290–301.
Takeda M, Khamdang S, Narikawa S, et al. Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002;300:918–924.
Motohashi H, Sakurai Y, Saito H, et al. Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J Am Soc Nephrol. 2002;13:866–874.
Sakurai Y, Motohashi H, Ogasawara K, et al. Pharmacokinetic significance of renal OAT3 (SLC22A8) for anionic drug elimination in patients with mesangial proliferative glomerulonephritis. Pharm Res. 2005;22:2016–2022.
Sakurai Y, Motohashi H, Ueo H, et al. Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res. 2004;21:61–67.
Ministry of Health, Labor and Welfare. [Resource page]. http://www.mhlw.go.jp/toukei/list/10-20.html. In Japanese.
Toyama N, Shiraki K. Epidemiology of herpes zoster and its relationship to varicella in Japan: a 10-year survey of 48,388 herpes zoster cases in Miyazaki prefecture. J Med Virol. 2009;81:2053–2058.
Wang LH, Schultz M, Weller S, Smiley ML, Blum MR. Pharmacokinetics and safety of multiple-dose valaciclovir in geriatric volunteers with and without concomitant diuretic therapy. Antimicrob Agents Chemother. 1996;40:80–85.
Bennett WM. Drug-related renal dysfunction in the elderly. Geriatr Nephrol Urol. 1999;9:21–25.
Jerkic M, Vojvodic S, Lopez-Novoa JM. The mechanism of increased renal susceptibility to toxic substances in the elderly: part I. The role of increased vasoconstriction. Int Urol Nephrol. 2001;32:539–547.
Gwak HS, Oh JH, Han HK. Effects of non-steroidal anti-inflammatory drugs on the pharmacokinetics and elimination of aciclovir in rats. J Pharm Pharmacol. 2005;57:393–398.
Uwai Y, Taniguchi R, Motohashi H, Saito H, Okuda M, Inui K. Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004;19:369–374.
Hata A, Kuniyoshi M, Ohkusa Y. Risk of Herpes zoster in patients with underlying diseases: a retrospective hospital-based cohort study. Infection. 2011;39:537–544.
Heymann AD, Chodick G, Karpati T, et al. Diabetes as a risk factor for herpes zoster infection: results of a population-based study in Israel. Infection. 2008;36:226–230.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kitano, A., Motohashi, H., Takayama, A. et al. Valacyclovir-Induced Acute Kidney Injury in Japanese Patients Based on the PMDA Adverse Drug Reactions Reporting Database. Ther Innov Regul Sci 49, 81–85 (2015). https://doi.org/10.1177/2168479014536897
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1177/2168479014536897