Risk of Acute Kidney Injury From Oral Acyclovir: A Population-Based Study

BACKGROUND: Intravenous acyclovir-induced acute kidney injury (AKI) from drug crystallization in the renal tubules is described in case reports, review articles, and drug prescribing manuals. Similarly, AKI from oral acyclovir is described in case reports, but the risk in routine practice is unknown. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: We studied a large cohort of older patients in Ontario, Canada, receiving new outpatient prescriptions from 1997 to 2011 for oral acyclovir or valacyclovir (which is metabolized to acyclovir). The comparison drug was famciclovir, an antiviral used for indications similar to acyclovir, but with no known renal toxicity. PREDICTOR: Outpatient prescription for oral acyclovir, valacyclovir, or famciclovir. OUTCOMES: The primary outcome was hospital admission with AKI in the 30 days after the initial prescription. MEASUREMENTS: We assessed the primary outcome with health care diagnostic codes. In a subpopulation, we assessed AKI using available laboratory serum creatinine measurements. RESULTS: 76,269 patients received acyclovir or valacyclovir and 84,646 received famciclovir. On average, patients were aged 76 [IQR, 71-81] years and prescription duration was 7 days. Acyclovir or valacyclovir use was not associated with a higher risk of hospital admission with AKI (209 [0.27%] events with acyclovir or valacyclovir vs 238 [0.28%] events with famciclovir [relative risk, 0.97; 95% CI, 0.81-1.17]). Results were consistent in adjusted analyses, in all subgroups, and in the subpopulation with laboratory measurements. LIMITATIONS: Diagnostic codes had high specificity but low sensitivity and underestimated the incidence of AKI. Only a limited number of patients (n = 2,729) had serum creatinine values available. CONCLUSIONS: In this population-based study of older adults, oral acyclovir use was not associated with a higher risk of AKI compared to famciclovir.