LAS VEGAS -- Lofexidine (Lucemyra), an alpha-2 adrenergic agonist, reduced the severity of opioid withdrawal and retained more people through the withdrawal process, researchers reported here.
A pooled analysis of two phase III, randomized, placebo-controlled trials showed that lofexidine at either 2.88 mg/day or 2.16 mg/day bested placebo in reducing symptoms like nausea, diarrhea, anxiety, insomnia, pain, and muscle spasms in patients who had abruptly discontinued short-acting opioids, said Mark Pirner, MD, PhD, of US WorldMeds in Louisville, Kentucky, in a at the 2018 PAINWeek conference.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Patients with opioid use disorder often cite withdrawal symptoms as the primary reason for continuing opioid use, Pirner said in an interview with 鶹ý. "If you can keep a patient through withdrawal, you give them a chance to move on to whatever's next."
The studies were used to support lofexidine's recent FDA approval as the first non-opioid medication to treat abrupt withdrawal in adults.
The trials enrolled people with moderate to severe opioid use disorder who showed signs of active withdrawal. Participants had an average age of 35; 72% were male and 79% used heroin. They were randomized to 2.88 mg (n=229) or 2.16 mg (n=356) of lofexidine or placebo (n=281).
About 41% of people in the lofexidine groups completed the treatment period, compared with 28% of the placebo group. Scores on the Short Opiate Withdrawal Scale of Gossop, a subject-rated assessment, indicated a greater reduction in withdrawal symptoms in both lofexidine groups compared with placebo (P<0.05). Most adverse events were mild or moderate in severity.
Lofexidine is similar to clonidine, which is used off-label to treat opioid withdrawal symptoms. "Clonidine is not FDA-approved and lacks evidence-based, standardized dosing guidelines for opioid withdrawal management," Pirner said. Lofexidine has clearly defined prescribing and safety information supported by FDA review and approval, which has the "potential to change how patients and clinicians address" withdrawal, he added.
While clonidine is generic and inexpensive, "lofexidine may be superior in terms of a better side effect profile and less low blood pressure, which is the main limitation of the short-term use of clonidine," noted Joshua Lee, MD, of New York University Langone Health in New York City.
But "the biggest issue is if payers and providers will use, or feel they need to use, a new and relatively expensive alpha-2 agonist now FDA-labeled for the non-opioid treatment of opioid withdrawal," Lee, who was not involved in the study, told 鶹ý.
Lofexidine can be used to treat withdrawal in either opioid use disorder or opioid dependence, Pirner noted. "If withdrawal is the major barrier to keeping patients and their providers from getting off opioids, but they don't really need methadone or buprenorphine, this can help them manage," he said.
The FDA has mandated 15 post-marketing studies of lofexidine, mostly in pediatric patients including adolescents in acute opioid withdrawal and infants with neo-natal abstinence syndrome. In addition, the FDA has required an adult study to assess lofexidine in the context of opioid tapering instead of abrupt withdrawal.
Disclosures
The studies were funded by US WorldMeds and the National Institute on Drug Abuse. Pirner and a co-author are employees of US WorldMeds.
A co-author disclosed relevant relationships with Indivior and Alkermes.
Primary Source
PAINWeek
Pirner M, et al "Efficacy and safety of lofexidine for opioid withdrawal syndrome: Pooled analysis of phase 3 studies" Pain Week 2018; Abstract 80.