Do Children Have the Same Vulnerability to Metabolic Drug–Drug Interactions as Adults? A Critical Analysis of the Literature

Abstract

Many drug-drug interactions (DDIs) in the pediatric population are managed based on data generated in adults. However, due to developmental changes in elimination pathways from birth to adolesence, and variable weight-adjusted dose of interacting drugs, the assumption of DDIs being similar in adults and pediatrics might not be correct. This study compares the magnitude of reported DDIs in pediatric and adult populations. A systematic literature review was undertaken to identify reports of DDIs in pediatric subjects. A total of 145 reports of DDIs were identified over the age range of birth to 20 years. The magnitude of DDIs for 24 drug pairs from 31 different pediatric studies could be assessed and compared with those in adults where corresponding data existed. The magnitude of the DDI, as measured by a relevant parameter (e.g., AUC, CL) in the presence and absence of inhibitor, were higher (>1.25-fold), similar (0.8-to 1.25-fold) or lower (<0.8-fold) than the corresponding ratio in adults in 10, 15, and 8 cases respectively. An age-related trend in the magnitude of DDIs could not be established. However, the study highlighted the clear paucity of the data in children younger than 2 years. Care should be exercised when applying the knowledge of DDIs from adults to children younger than 2 years of age.

Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures: Update 2016

“…The practitioner should consult various sources (a pharmacist, textbooks, online services, or handheld databases) for specific information on drug interactions. [315][316][317][318][319] The US Food and Drug Administration issued a warning in February 2013 regarding the use of codeine for postoperative pain management in children undergoing tonsillectomy, particularly those with OSA. The safety issue is that some children have duplicated cytochromes that allow greater than expected conversion of the prodrug codeine to morphine, thus resulting in potential overdose; codeine should be avoided for postprocedure analgesia.…”

‘All those things together made me retire’: qualitative study on early retirement among Dutch employees

“…Despite this increase, many workers still retire before the official retirement age of 65 years. Currently, the general population is aging because of decreasing birth rates [2] and increasing longevity [3]. Moreover, the baby boom generation has started to leave work.…”

Influence of uridine diphosphate glucuronosyltransferase inducers and inhibitors on the plasma lamotrigine concentration in pediatric patients with refractory epilepsy

“…Several authors have reported that the combination of LTG with VPA achieves a significantly better response than combinations of LTG with other AEDs, and this differential response is associated with a strong pharmacodynamic interaction that leads to anticonvulsant synergy [16,24]. In routine clinical practice, most measured samples (58.7%) were from patients receiving combination therapy with LTG and VPA.…”

“…LTG þ multiple inducers or LTG þ VPA þ one or more inducers). Salem et al [16] reviewed 145 reports of drug interactions and suggested that interactions were more severe in children under 2 years old than in adults. Unfortunately, there have only been a few investigations of the pharmacokinetics of LTG in pediatric patients [1,3,6,7,10,14] and its plasma concentration profile in children less than 3 years old is unknown.…”