Opioid Antagonists: Clinical Utility, Pharmacology, and Safety and Tolerability

This work was sponsored by Alkermes, Inc. INTRODUCTION: Opioid antagonists block opioid receptors; several are available for therapeutic use. We review the pharmacology, indications, and safety/tolerability profiles of existing opioid antagonists. METHODS AND DESIGN: PubMed was searched for information on US FDA-approved opioid antagonists; findings are presented descriptively. RESULTS: Available opioid antagonists differ in their relative pharmacokinetics, pharmacodynamics, bioavailability, and binding affinities, leading to unique clinical attributes and uses. Centrally acting opioid antagonists treat acute opioid overdose and are used for treatment of opioid and alcohol use disorders. Given the opioid system’s effect on weight and metabolism, one opioid antagonist combination product is available for chronic weight management; another combination product indicated for treating adults with schizophrenia or bipolar I disorder mitigates the weight gain associated with olanzapine use. Three peripherally acting opioid antagonists are used to treat opioid-induced constipation; another accelerates gastrointestinal recovery after bowel surgery. Opioid antagonists are well tolerated and not associated with physiological dependence or abuse. Adverse effects may include nausea, vomiting, and abdominal pain. Opioid antagonists can precipitate acute opioid withdrawal in patients using or undergoing withdrawal from opioid agonists. There is a risk of opioid overdose if opioid agonists are taken to overcome antagonist blockade or after stopping an opioid antagonist and resuming previously tolerated opioid use. CONCLUSION: Opioid receptor antagonists, either alone or in combination with other medications, have efficacy in a range of clinical indications, including the treatment of opioid overdose, alcohol and opioid use disorders, and opioid-induced constipation and for weight management.