FDA Approves Lofexidine Hydrochloride, First Non-Opioid Treatment for Management of Opioid Withdrawal Symptoms in Adults

The US Food and Drug Administration (FDA) approved lofexidine hydrochloride (Lucemyra) for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults, announced US WorldMeds.

Lucemyra, not a treatment for opioid use disorder, can be used as a long-term treatment plan, however while it may lessen the severity of withdrawal symptoms, it may not completely prevent them and is only approved for treatment for up to 14 days.

“Today’s approval represents the first FDA-approved non-opioid treatment for the management of opioid withdrawal symptoms and provides a new option that allows providers to work with patients to select the treatment best suited to an individual’s needs,” Sharon Hertz, MD, director, division of the anesthesia, analgesia and addiction products, in the FDA’s Center for Drug and Evaluation and Research, said in a statement.

The safety and efficacy was supported by 2 randomized, double-blind, placebo-controlled clinical trials of 866 adults meeting Diagnostic and Statistical Manual-IV criteria for opioid dependence who were physically dependent on opioids and undergoing abrupt opioid discontinuation.

The studies evaluated benefit using the Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) to assess opioid withdrawal symptoms that included feeling sick, stomach cramps, muscle spasms/twitching, feeling of coldness, heart pounding, muscular tension, aches and pains, yawning, runny eyes and insomnia.

For each withdrawal symptom, patients were asked to rate the severity using 4 response options (none, mild, moderate and severe) with the SOWS-Gossop total score ranging from 0—30—a higher score indicated a greater withdrawal symptom severity.

SOWS-Gossop scores were lower for patients treated with Lucemyra versus placebo and more patients in the Lucemyra group completed the treatment period.

The most common side effects from treatment include hypotension, bradycardia, somnolence, sedation and dizziness, and was also associated with a few cases of syncope. Lucemyra can also effect the heart’s electrical activity, which can increase risk of abnormal heart rhythms. When treatment is stopped, patients can experience a marked increase in blood pressure.

The safety and efficacy have not been established in children or adolescents 17 years of age and younger.

"A better understanding of opioid withdrawal represents an opportunity in the prevention, treatment and recovery process for physical opioid dependence and opioid use disorder,” co-author, Mark Pirner, MD, PhD, Senior Medical Director, Clinical Research and Medical Affairs, US WorldMeds, previously told MD Magazine. “The lofexidine data demonstrate that, compared with placebo, study participants treated with LUCEMYRA experienced less severe withdrawal symptoms and were significantly more likely to complete opioid withdrawal treatment."

The FDA is requiring the completion of 15 postmarketing animal and human studies; and additional animal safety studies will be required to support longer-term use and use in children.

Clinical studies will be required to evaluate the safety in situations where use could be expected to exceed the maximum 14-day treatment period for which Lucemyra is currently approved; to gather additional safety data on the effects of lofexidine on the liver; and to further characterize the effects on blood pressure after treatment is stopped.

Studies in pediatric patients will be conducted on newborns with neonatal opioid withdrawal and studies of various age groups of children with opioid withdrawal related to stopping medical-prescribed opioid drugs.

Lucemyra is an oral, selective alpha 2-adrenergic receptor agonist that reduces the release of norepinephrine and its actions are believed to play a role in the symptoms of withdrawal.

The FDA granted this application both priority review and fast track designations. Additionally, an independent FDA advisory committee supported the approval at a meeting in March.