Use of High-Dose Oral Valacyclovir During an Intravenous Acyclovir Shortage: A Retrospective Analysis of Tolerability and Drug Shortage Management

INTRODUCTION: In late 2011, a shortage of IV acyclovir led to the need to empirically substitute high-dose oral valacyclovir (HDVA) to conserve IV acyclovir for patients with confirmed herpes simplex virus (HSV) meningitis or encephalitis. This report describes the management of the most recent national IV acyclovir shortage by the Antimicrobial Stewardship Program (ASP) at Northwestern Memorial Hospital (NMH), Chicago, IL, USA, and the use of HDVA. Secondarily, we assessed the safety and tolerability of HDVA as an alternate to IV acyclovir during this shortage. METHODS: We report the step-wise management, restrictions, and guidelines implemented at NMH during a protracted IV acyclovir shortage. The assessment of HDVA was a retrospective, observational cohort study of hospitalized patients receiving HDVA between 1 January 2012 and 31 December 2013. Appropriate demographic and treatment variables were collected. The primary outcome was percentage of patients experiencing an adverse event. RESULTS: There were 15 adult patients included in the study on a median daily dose of HDVA of 3 g (IQR 2–8). There were four patients with microbiologically confirmed viral CNS infections (n = 1 HSV-1, n = 2 HSV-2, n = 1 VZV encephalitis) and eleven patients with unknown causative pathogens. Six (40%) patients experienced at least one adverse drug reaction (ADR) to HDVA (thrombocytopenia, 33.3%, n = 5; headache, 6.7%, n = 1; nausea, 6.7%, n = 1; rash, 6.7%, n = 1). One patient (6.7%) was readmitted within 30 days with a suspected non-CNS infection. There were no treatment discontinuations or symptomatic therapy necessary to treat any of the ADRs. CONCLUSIONS: The shortage of IV acyclovir was successfully managed by the ASP and HDVA appeared to be well tolerated when used as an alternative to IV acyclovir.