Lofexidine Outperforms Placebo in Taming Opioid Withdrawal Symptoms

May 11, 2018

NEW YORK CITY—A non-narcotic medication currently in clinical development reduced opioid withdrawal symptoms in a pair of phase 3 studies involving more than 800 patients, according to research presented at a poster session at the American Psychiatric Association’s annual meeting.

Poster presenter Carlos Francisco Tirado, MD, MPH, and colleagues analyzed data to see how the alpha-2 adrenergic agonist lofexidine performed compared with placebo in adults with opioid dependence. One study randomized participants to 3.2 mg of daily lofexidine or placebo for 5 days. The other randomized participants to 2.4 mg or 3.2 mg of daily lofexidine or placebo for 7 days. In all, 586 participants received lofexidine and 281 received placebo.

Some 41.3% of patients receiving lofexidine and 27.4% of those receiving placebo finished the double-blind treatment, researchers reported. Participants receiving lofexidine stayed in the trials longer.

lofexidine poster

Pooled data showed Short Opioid Withdrawal Scale–Gossop scores were lower in patients treated with lofexidine compared with placebo, “indicating greater reduction in withdrawal symptoms with lofexidine,” researchers reported. Peak opioid withdrawal scale scores over the first 5 days of treatment were significantly lower with lofexidine, and other secondary and exploratory endpoints favored the drug over placebo.

Most adverse events associated with lofexidine were mild or moderate in severity and included hypotension, orthostatic hypotension, bradycardia, dizziness, somnolence, dry mouth, and sedation.

Adults With Chronic Pain, Psych Disorders at Highest Risk of Opioid Death

“These data suggest that lofexidine can be safely administered at 3.2 and 2.4 mg/day, lofexidine reduces opioid withdrawal symptoms to a clinically meaningful extent, and lofexidine facilitates opioid discontinuation treatment,” concluded Dr. Tirado and coauthors Mark Pirner, MD, PhD; Thomas Clinch, BS; and Charles W. Gorodetzky, MD, PhD.

In March, the Psychopharmacologic Drugs Advisory Committee of the US Food and Drug Administration (FDA) voted 11 to 1 to recommend approval of lofexidine for mitigating opioid withdrawal symptoms. The recommendation is not binding. The application for the drug was granted Priority Review by the FDA in November 2017.

—Jolynn Tumolo and Terri Airov


“Lofexidine efficacy and safety in opioid withdrawal: pooled analysis of phase 3 studies.” Abstract presented at: the American Psychiatric Association Annual Meeting; May 7, 2018; New York, NY.