Safety of Enalapril in Infants Admitted to the Neonatal Intensive Care Unit.
Enalapril is used to treat hypertension and congestive heart failure in infants. However, enalapril is not labeled for neonates, and safety data in infants are sparse. To evaluate the safety of enalapril in young infants, we conducted a retrospective cohort study of infants who were exposed to enalapril in the first 120 days of life and were cared for in 348 neonatal intensive care units from 1997 to 2012. We determined the proportion of exposed infants who developed adverse events, including death, hypotension requiring pressors, hyperkalemia, and elevated serum creatinine. Using multivariable logistic regression, we examined risk factors for adverse events, including postnatal age at first exposure, exposure duration, gestational age group, small for gestational age status, race, sex, 5-min Apgar score, and inborn status. Of a cohort of 887,910 infants, 662 infants (0.07%) were exposed to enalapril. Among exposed infants, 142 infants (21%) suffered an adverse event. The most common adverse event was hyperkalemia (13%), followed by elevated serum creatinine (5%), hypotension (4%), and death (0.5%). Significant risk factors for adverse events included postnatal age <30 days at first exposure and longer exposure duration. This study is the largest to date examining the safety of enalapril in young term and preterm infants without significant structural cardiac disease.
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.|Duke Clinical Research Institute, Duke University School of Medicine, Box 17969, Durham, NC, 27715, USA.
Lawrence C
LC
Ku
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.|Duke Clinical Research Institute, Duke University School of Medicine, Box 17969, Durham, NC, 27715, USA.
Kanecia
K
Zimmerman
Clemson University, Clemson, SC, USA.
Daniel K
DK
Benjamin
Pediatrix-Obstetrix Center for Research and Education, Sunrise, FL, USA.
Reese H
RH
Clark
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.|Duke Clinical Research Institute, Duke University School of Medicine, Box 17969, Durham, NC, 27715, USA.
Christoph P
CP
Hornik
Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA. brian.smith@duke.edu.|Duke Clinical Research Institute, Duke University School of Medicine, Box 17969, Durham, NC, 27715, USA. brian.smith@duke.edu.
P Brian
PB
Smith
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D004656:Enalapril / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005865:Gestational Age; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced / Q000453:epidemiology; D007022:Hypotension / Q000139:chemically induced / Q000453:epidemiology; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D016015:Logistic Models; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D003404:Creatinine
Drug safety; Enalapril; Infant pharmacology; Pharmacoepidemiology