FDA Approves First Non-opioid Treatment for Management of Opioid Withdrawal Symptoms in Adults

The FDA today approved lofexidine hydrochloride (Lucemyra) for the mitigation of opioid withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults, aged 18 and older. While lofexidine hydrochloride may lessen the severity of withdrawal symptoms, it may not completely prevent them, and is only approved for treatment for up to 14 days, according to a press release issued by the FDA. Lofexidine hydrochloride is not a treatment for opioid use disorder (OUD), but can be used as part of a broader, long-term treatment plan for managing the condition.

“As part of our commitment to support patients struggling with addiction, we’re dedicated to encouraging innovative approaches to help mitigate the physiological challenges presented when patients discontinue opioids,” said FDA Commissioner Scott Gottlieb, MD, in a statement. “We’re developing new guidance to help accelerate the development of better treatments, including those that help manage opioid withdrawal symptoms. We know that the physical symptoms of opioid withdrawal can be one of the biggest barriers for patients seeking help, and ultimately overcoming addiction. The fear of experiencing withdrawal symptoms often prevents those suffering from opioid addiction from seeking help. And those who seek assistance may relapse due to continued withdrawal symptoms. The FDA will continue to encourage the innovation, and development of therapies to help those suffering from opioid addiction transition to lives of sobriety, as well as address the unfortunate stigma that’s sometimes associated with the use of medication-assisted treatments.”

Physical dependence to opioids is an expected physiological response to opioid use. Withdrawal symptoms, such as anxiety, agitation, sleep problems, muscle aches, runny nose, sweating, nausea, vomiting, diarrhea and drug craving, can occur after stopping or reducing the use of opioids, in an individual with physical dependence. Symptoms of opioid withdrawal occur in patients who have been using opioids appropriately as prescribed, and in patients with OUD.

In patients using opioid analgesics appropriately, as prescribed, opioid withdrawal is typically managed by slow taper of the medication, which is intended to avoid or lessen the effects of withdrawal, while allowing the body to adapt to not having the opioid. In patients with OUD, withdrawal is typically managed by substitution of another opioid medicine, followed by gradual reduction or transition to maintenance therapy with FDA-approved medication-assisted treatment drugs, such as methadone, buprenorphine or naltrexone; or by various medications aimed at specific symptoms, such as OTC remedies for upset stomach or aches and pains. Other treatments may also be prescribed by a patient’s health care provider.

“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,” said Sharon Hertz, MD, director of the Division of Anesthesia, Analgesia and Addiction Products in the FDA’s Center for Drug Evaluation and Research, in a statement.

US WorldMeds’ Lucemyra is an oral, selective alpha 2-adrenergic receptor agonist that reduces the release of norepinephrine. The actions of norepinephrine in the autonomic nervous system are believed to play a role in many of the symptoms of opioid withdrawal. The safety, and efficacy of Lucemyra 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), which is a patient-reported outcome instrument that assesses opioid withdrawal symptoms. These symptoms include feeling sick, stomach cramps, muscle spasms/twitching, feeling of coldness, heart pounding, muscular tension, aches and pains, yawning, runny eyes and insomnia/problems sleeping.

The most common adverse effects from treatment with lofexidine hydrochloride include low blood pressure, slow heart rate, sleepiness, sedation, and dizziness. Lofexidine hydrochloride was also associated with a few cases of fainting, and can have an effect on the heart’s electrical activity, such as increasing the risk of abnormal heart rhythms. When lofexidine hydrochloride is stopped, patients can experience a marked increase in blood pressure.

Reference

FDA approves the first non-opioid treatment for management of opioid withdrawal symptoms in adults [news release]: Silver Spring, MD; May 16, 2018. FDA website. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm607884.htm. Accessed May 16, 2018.

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