On May 16, 2018, the FDA granted to US WorldMeds LLC the approval of Lucemyra (lofexidine hydrochloride) for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults. While Lucemyra may lessen the severity of withdrawal symptoms, it may not completely prevent them. Lucemyra is only approved for treatment for up to 14 days. Lucemyra is not a treatment for opioid use disorder (OUD), physical and psychological reliance on opioids, but can be used as part of a broader, long-term treatment plan for managing OUD.
“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, M.D. “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.”
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.
Opioid withdrawal includes symptoms such as anxiety, agitation, sleep problems, muscle aches, runny nose, sweating, nausea, vomiting, diarrhea, and drug craving, which occur after stopping or reducing the use of opioids in anyone with a physical dependence on opioids. Physical dependence to opioids is an expected physiological response to opioid use. These symptoms of opioid withdrawal occur both 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 over-the-counter remedies for upset stomach or aches and pains.
“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, M.D., director of the Division of Anesthesia, Analgesia and Addiction Products in the FDA’s Center for Drug Evaluation and Research.
The most common side effects from Lucemyra include hypotension (low blood pressure), bradycardia (slow heart rate), somnolence (sleepiness), sedation, and dizziness. Lucemyra was also associated with a few cases of syncope (fainting). Lucemyra affects the heart’s electrical activity, which can increase the risk of abnormal heart rhythms. When Lucemyra is stopped, patients can experience a marked increase in blood pressure. After a period of not using opioid drugs, patients may be more sensitive to the effects of lower amounts of opioids if relapse does occur, and taking opioids in amounts that were used before withdrawing from opioids can lead to overdose and death. The safety and efficacy of Lucemyra have not been established in children or adolescents less than 17 years of age.
The FDA is requiring postmarketing studies, including both animal and human studies. Additional animal safety studies will be required to support longer-term use (such as during a gradual opioid taper in pain patients discontinuing opioid analgesics) and use in children. Clinical studies will be required to evaluate the safety of Lucemyra in clinical situations where use could be expected to exceed the maximum 14-day treatment period for which the product is currently approved, such as gradual opioid taper; to gather additional safety data on the effects of Lucemyra on the liver; and to further characterize the effects on blood pressure after Lucemyra is stopped. Studies in pediatric patients will include studies of newborns with neonatal opioid withdrawal and studies of different age groups of children who have opioid withdrawal related to stopping medically-prescribed opioid drugs.
See the FDA Announcement
See also Medical Risk Law Report: Prescription Painkillers: Risks for Patients, Pharmacists, and Physicians
See also Medical Risk Law Report: Drugs, Dosage, and Damage: Physician Liability for Prescribing or Administering Medication
See the Medical Risk Law Blog: Risks of Prescription and OTC Pain Medicines During Pregnancy
See the Medical Risk Law Blog: Pharmacy Owes Duty To Patient Not To Fill Excessive Prescriptions for Opioids