Drug-drug interactions in Neonatal Intensive Care Units: how to overcome a challenge

INTRODUCTION: Critically ill patients in neonatal intensive-care units (NICU) are exposed to a large number of drugs. Clinical trials for safety, dosing and efficacy are lacking although age-dependent alterations of pharmacokinetics (PK), drug-drug-interactions (DDIs), as well as intravenous admixture incompatibilities (IAI) may impact drug efficacy and trigger side-effects in this vulnerable population. Consequently, implementation of a routinely used DDIs checking regimen may help guide in decision making and will assist clinicians to avoid serious and preventable events. Therefore, the goal of the present work is to identify and assess the risk of relevant DDIs of drugs commonly used in the NICU. EVIDENCE ACQUISITION: A literature review study was performed to identify and further assess the risk of relevant DDIs of 48 drugs frequently used in the tertiary care NICU of the University Hospital of Cologne. DDIs were categorized into five different classes according to their severity (contraindicated, minor, moderate, and major DDI, IAI), based on the classification used in the Micromedex database. In the database a major interaction is defined as any interaction that can be life threatening and/or demands medical intervention to avoid severe adverse effects. Moderate interactions can lead to a degradation of the patient's status and demand an adjustment in the therapy, and minor interactions only have a limited clinical effect. All identified DDIs in the present study are presented as a Visual Interaction Triangle (VIT) and recommendations on the management of clinically significant DDIs are provided. EVIDENCE SYNTHESIS: According to the classification used in the Micromedex database: a total of 160 (13.2%) possible interactions (DDI, IAI) were found. Fifty-five (4.9%) cases were categorized as serious interactions (DDI-major), 48 (4.2%) were less severe (DDI-moderate/minor) and in 52 (4.6%) cases an intravenous admixture drug interaction was found. Five (0.4%) drug-combinations were contraindicated. CONCLUSIONS: In this web-based study, a total of 160 DDIs were identified. Although only 4.9% were classified as clinically relevant, practitioners can use the presented VIT as a unique clinical reference to avoid possible predictable adverse effects and to uncover possible drug-interaction potential.