How Lucemrya Reduces Opioid Withdrawal Symptoms


Information regarding the opioid crisis, lofexidine hydrochloride versus clonidine, and clinical pearls that pharmacists should know about.

In May 2018, the FDA approved lofexidine hydrochloride (Lucemyra) for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults.

Upon approval, lofexidine hydrochloride became the first non-opioid treatment for managing opioid withdrawal symptoms. Although many have welcomed a new medication to help curb the opioid epidemic in this country, others have questioned the cost-effectiveness of lofexidine hydrochloride compared with other therapies.

This article will highlight information regarding the opioid crisis, lofexidine hydrochloride versus clonidine, and key clinical pearls with which pharmacists should be familiar.


The United States is in the midst of a drug overdose epidemic, with both nonprescription and prescription opioids as the major driving factors. Overdose deaths involving prescription opioids were 5 times higher in 2016 than 1999, with more than 200,000 people dying from prescription opioid overdoses.1

Statistics suggest that more than 23 million people in the United States live with addiction, with only about 10% of them seeking and receiving help.2 Although the hesitancy of receiving treatment for opioid addiction can be multifactorial, a barrier for some involves the dread or fear of experiencing withdrawal symptoms.

Lofexidine Hydrochloride Overview

Lofexidine hydrochloride is a central alpha-2 adrenergic agonist FDA indicated for the mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.3 It works by binding to receptors on adrenergic neurons, which decreases sympathetic tone and reduces the release of norepinephrine.3 This is advantageous, because chronic opioid use suppresses noradrenergic outflow and thus norepinephrine release, and during acute opioid withdrawal, adrenergic outflow being restored causes many of the symptoms associated with withdrawal, including diaphoresis, hypertension, nausea, tachycardia, and vomiting. Notably, lofexidine does not suppress psychological cravings.4


The usual dosage is 3 0.18 mg tablets taken orally 4 times daily during the peak time of withdrawal symptoms, generally the first 5 to 7 days following last opioid use at 5-to-6-hour intervals, according to Lucemrya's product labeling.

The medication may be continued for up to 14 days with dosing guided by adverse effects and symptoms. The total daily dosage should not exceed 2.88 mg or 16 tablets, and no single dose should exceed 0.72 mg, or 4 tablets.

It should be discontinued via gradual dose reduction over 2 to 4 days to mitigate Lucemyra withdrawal symptoms. Product labeling suggests a dose reduction by 1 tablet per dose every 1 to 2 days. Lower doses may be appropriate as opioid withdrawal symptoms wane.3

Product Availability

The product is expected to be available starting in August. Once available, it will be supplied at bottles of 36 and 96 tablets. The cost of therapy has not yet been published on tertiary resources.

Safety Concerns

The most common adverse reactions of Lucemyra include bradycardia, dizziness, dry mouth, hypotension, orthostatic hypotension, sedation, somnolence, and sedation. Additionally, product labeling includes the following precautions and warnings:

  • Increased risk of central nervous system (CNS) depression with concurrent use of CNS depressants. Lucemyra can potentiate the CNS depressive effects of barbiturates, benzodiazepines, and other sedating drugs. Patients should avoid or be careful doing activities, such as driving or operating heavy machinery until the effects of Lucemyra are known.
  • Increased risk of opioid overdose after opioid discontinuation. Patients who complete opioid discontinuation are likely to have a reduced tolerance to opioids and are at increased risk of fatal overdose should they resume opioid use. Lucemyra should be used in conjunction with a comprehensive management program for the treatment of opioid use disorder.
  • Risk of discontinuation symptoms. Abrupt cessation of Lucemyra can cause a marked rise in blood pressure. Symptoms including anxiety, chills, diarrhea, extremity pain, hyperhidrosis, and insomnia have also been observed with sudden discontinuation. When discontinuing therapy, there should be a gradual dose reduction.3
  • Risk of bradycardia, hypotension, and syncope. Lucemyra can cause a decrease in blood pressure, pulse, and syncope. Therefore, patients should be instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. Additionally, instruct patients to stay hydrated, on how to recognize symptoms of low blood pressure, and how to reduce the risk of serious consequences should hypotension occur.
  • Risk of QT prolongation: Due to an increased risk of prolonging the QT interval, Lucemyra should be avoided in patients with congenital long QT prolongation and electrocardiographs should be monitored in higher risk patients.

Clinical Efficacy

The approval for Lucemyra was based on 2 randomized, double-blind, placebo-controlled clinical trials in people who were physically dependent on short-acting opioids.

In the first study, the main endpoint to support efficacy was the mean Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) total score on days 1 to 7 of treatment. This measure evaluates a variety of opioid withdrawal symptoms. Study results showed the mean SOWS-Gossop scores for days 1 to 7 were 8.8, 6.5, and 6.1 for the placebo, Lucemyra 2.16 mg, and Lucemyra 2.88 mg. The mean difference between both doses of Lucemyra and the placebo were significant.

In the second study, the main endpoint was the SOWS-Gossop total score on days 1 to 5 of treatment. The mean SOWS-Gossop scores were 8.9 and 7 for the placebo and Lucemyra 2.88 mg, demonstrating a statistically significant difference.3

History of Lofexidine and Comparison Versus Clonidine

Lofexidine was initially approved in Germany more than 25 years ago as an antihypertensive agent but was withdrawn because of a lack of clinical efficacy. In 1992, ;;ofexidine was approved for use in the United Kingdom to treatment opioid withdrawal.4

Lofexidine is a structural analog of clonidine. Clinical trials comparing the 2 medications have demonstrable comparable efficacy, though the severity of adverse events may be less than those with clonidine, likely because of the differences in alpha 2a receptor selectivity.4,5 This decreased risk for adverse effects could potentially make lofexidine a safer option for detoxification.

The UK NICE guidelines recommend that lofexidine be considered as a second-line agent in the management of opioid use disorder after buprenorphine or methadone use. Lofexidine may also be considered for those with mild or uncertain dependence. The guidelines note that clonidine should not be used routinely in opioid detoxification and that detoxification using lofexidine is much faster than using either buprenorphine or methadone, which typically require several weeks and 3 months reduction, respectively.5

Although tertiary resources do not yet list the price of Lucemyra, it will undoubtedly be significantly more expensive than generic clonidine.

Clinical Pearls and Counseling Considerations3

Here are some key points to keep in mind:

  • Counsel patients on the risk of hypotension and to be alert for any symptoms of low blood pressure or pulse.
  • Lucemyra can be taken with or without food.
  • Patients should be aware that “Lucemyra may mitigate, but not completely prevent, the symptoms associated with opioid withdrawal syndrome, which may include feeling sick, stomach cramps, muscle spasms or twitching, feeling of cold, heart pounding, muscular tension, aches and pains, yawning, runny eyes and sleep problems [insomnia],” according to the prescribing information. Therefore, additional supportive measures, such as psychosocial support, should be advised, and adjunctive medications should be considered based on symptoms.
  • The total daily dosage of Lucemyra should not exceed 2.88 mg or 16 tablets, and no single dose should exceed 0.72 mg or 4 tablets.


1. CDC. Prescription opioid overdose data. Updated August 1, 2017. Accessed June 22, 2018.

2. Meadows B. The 3 biggest reasons people don’t seek help for addiction. Addiction Campuses. Published June 27, 2016. Accessed June 22, 2018.

3. Lucemyra [prescribing Information]. Louisville, KY: US World Meds; 2018. Accessed June 22, 2018.

4. Gish EC, Miller JL, Honey BL, Johnson PN. Lofexidine, an {alpha}2-receptor agonist for opioid detoxification. Ann Pharmacother. 2010;44(2):343-51. doi: 10.1345/aph.1M347.

5. British Psychological Society. Drug misuse: opioid detoxification: the NICE Guideline. Published 2008. Accessed June 22, 2018.

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