Lofexidine

Abstract Lofexidine is an agonist at the central alpha-2 adrenergic receptor and is indicated for relief of the symptoms of opioid withdrawal. Lofexidine has been marketed in the United Kingdom for opioid withdrawal management since 1992 and in the United States since 2018. This chapter outlines the pharmacodynamics and mechanisms of action of lofexidine with regard to its role in opioid withdrawal management, as well as its pharmacokinetic characteristics before outlining in detail the clinical use of lofexidine. This includes a discussion of safety considerations, drug interactions, and use in impaired populations. The authors conclude with a review of the evidence supporting lofexidine, spanning clinical trials to open label examinations, and a clinical vignette of a prototypical lofexidine experience.