Food and Drug Administration approves lofexidine (LucemyraTM): the first non-addictive opioid withdrawal therapy in the United States

By: Evanthia Siozios, PharmD Candidate c/o 2020

           Anxiety, nausea, muscle pain, insomnia are some of the most common withdrawal symptoms experienced when users stop taking opioids. According to a randomized controlled trial entitled Prescription Opioid Addiction Treatment Study (POATS) conducted in outpatient treatment settings across the United States including Mclean Hospital in Massachusetts and University of California, Los Angeles, researchers found that the avoidance of withdrawal was the most important reason for continued opioid use.¹ In May 2018, the Food and Drug Administration (FDA) approved lofexidine (Lucemyra^TM), the first and only non-opioid, non-addictive treatment for symptoms of opioid withdrawal, in attempt to help extenuate continued opioid use.² The novel medication is manufactured by Salix Pharmaceuticals, Inc. and US WorldMeds, LLC and is indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults aged 18 years and older. It works by acting as an alpha 2-adrenergic agonist, decreasing the release of norepinephrine, which in turn, reduces the severity of withdrawal symptoms.³

To demonstrate lofexidine’s efficacy, a randomized, double-blind, double-dummy clinical trial was performed by Dr. Song Guo, consultant psychiatrist and head of research at the Singapore National Addictions Management Service. The clinical trial was a collaboration between Singapore’s National Addictions Management Service and the Singapore Clinical Research Institute and looked to explore the effectiveness of non-addictive medications in an inpatient detoxification program. The study was ultimately published in the Journal of Substance Abuse Treatment in August 2018. In the trial, opioid dependent patients were given a ten-day course of lofexidine or diazepam to treat opioid withdrawal. Results found that lofexidine was at least as effective as diazepam in reducing opioid withdrawal syndrome while simultaneously increasing treatment retention.⁴ Lofexidine proved to be an attractive drug in this study because, unlike diazepam, it is non-addictive. Patients given lofexidine had fewer withdrawal symptoms, less opioid cravings, smaller changes in pupil size, and were more likely to finish treatment and complete detoxification. The aforementioned results indicate lofexidine’s superiority over diazepam.

The opioid epidemic has affected communities across the United States including the greater New York City area. In 2017, the New York City Department of Health found that, one hundred and one Staten Island residents died of a drug overdose and that nearly all of these fatal drug overdoses involved opioids. Lofexidine could play a key role in decreasing fatalities without posing the risk of new addictions being caused by other classes of medications which have abuse potential, such as benzodiazepines.

A noteworthy characteristic of lofexidine, which is only available as 0.18 mg tablets, is its heavy pill burden – patients who are prescribed the medication must take twelve tablets per day as the standard starting dosage. FDA approved prescribing information dictates that lofexidine should be taken as such: three 0.18 mg tablets taken orally four times daily during peak withdrawal symptoms, which are generally the first five to seven days following last use of an opioid, with dosing guided by symptoms and side effects. A gradual dose reduction should be implemented over a two to four day period, such as reducing one tablet per dose every one to two days or administering lower doses as opioid withdrawal symptoms wane.⁶ Lofexidine may be continued for up to fourteen days depending on patient symptoms or risk of fainting due to hypotension.⁶ When compared to buprenorphine and naloxone sublingual films, which are available in a variety of different strengths that can be adjusted such that a patient is only required to take one or two films per day, the aforementioned pill burden may seem to be a significant barrier to adherence. However, the benefits of a non-addictive withdrawal treatment far outweigh the potential barriers associated with a twelve tablet per day regimen.

Lofexidine is a new medication that we as pharmacists and health care providers should be informed about given the current climate surrounding opioid use and misuse. Although lofexidine’s pill burden and increased risk of hypotension could be interpreted as deterrents, the benefit of a non-addictive withdrawal treatment is one that is unique and unparalleled by any of the other treatment options that are currently on the market.

SOURCES:

1. Rx Product News. Pharmacy Times. https://www.pharmacytimes.com/publications/issue/2018/december2018/rx-product-news-december-2018-. Published 12/20/2018. Accessed 01/15/2019.
2. Introducing LUCEMYRA (lofexidine). LUCEMYRA (lofexidine). https://lucemyra.com/. Accessed 01/15/2019.
3. Lucemyra (lofexidine) for the Management of Opioid Withdrawal Symptoms. Drug Development Technology. https://www.drugdevelopment-technology.com/projects/lucemyra-lofexidine-management-opioid-withdrawal-symptoms/. Accessed 01/31/ 2019.
4. Guo S, Manning V, Yang Y, et al. Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore. Journal Of Substance Abuse Treatment. 2018;91:1-11. doi:10.1016/j.jsat.2018.04.012.
5. Health Department Announces Funding for Substance Use Prevention Program for At-Risk Youth in Staten Island. NYC. https://www1.nyc.gov/site/doh/about/press/pr2018/pr060-18.page. Published 07/26/2018. Accessed 01/15/2019.
6. Lucemyra (Lofexidine) [package insert]. Louisville, K.Y. and Bridgewater, N.J; US WorldMeds, LLC, and Salix Pharmaceuticals; Revised 05/2018.