Phenobarbital — Phenobarbital is eliminated by the liver and kidney; thus, infants with impaired hepatic or renal function, such as those with hypoxic-ischemic encephalopathy (HIE), will have a reduced rate of elimination and potential for toxicity with standard dosing. Although therapeutic hypothermia treatment may reduce clearance of phenobarbital marginally, no a priori change in loading or initial maintenance dosing is required [23,39]. The half-life of phenobarbital is greater in premature compared with term infants, and longer in the first month of life compared with older ages in term infants.