Clinical pharmacology and dosing regimen optimization of neonatal opioid withdrawal syndrome treatments

Abstract In this paper, we review the management of neonatal opioid withdrawal syndrome (NOWS) and clinical pharmacology of primary treatment agents in NOWS, including morphine, methadone, buprenorphine, clonidine, and phenobarbital. Pharmacologic treatment strategies in NOWS have been mostly empirical, and heterogeneity in dosing regimens adds to the difficulty of extrapolating study results to broader patient populations. As population pharmacokinetics (PKs) of pharmacologic agents in NOWS become more well‐defined and knowledge of patient‐specific factors affecting treatment outcomes continue to accumulate, PK/pharmacodynamic modeling and simulation will be powerful tools to aid the design of optimal dosing regimens at the patient level. Although there is an increasing number of clinical trials on the comparative efficacy of treatment agents in NOWS, here, we also draw attention to the importance of optimizing the dosing regimen, which can be arguably equally important at identifying the optimal treatment agent.