COMMENTARY

A Nonopioid Approach to Opioid Discontinuation

Charles E. Argoff, MD

Disclosures

February 08, 2019

This transcript has been edited for clarity.

This is Dr Charles Argoff, professor of neurology at Albany Medical Center and director of the Comprehensive Pain Center and Pain Management Fellowship at Albany Medical Center in Albany, New York.

Today I'd like to speak about opioid discontinuation, and specifically the availability of a new treatment. I'd like to frame this by looking at the numerous clinical scenarios in which opioid discontinuation—that is, stopping opioid therapy—may be warranted.

In this segment, I'm going to be focusing on clinical situations where people who are experiencing chronic pain are being taken off of opioids, not to exclude those who buy independently or otherwise suffer from substance abuse or heroin abuse, for example, but concentrating on those who are being treated with opioid therapy for chronic pain. That's not to say that the other areas are not important.

Let's broadly consider at least three areas where people might be in a position to be discontinued from opioid therapy. First, let's say you're involved in the care of a person with chronic pain who is requesting to be tapered from opioid therapy as quickly as possible, and you want to assist in doing so. In another scenario, you might be involved with a patient with chronic pain who has demonstrated that he or she cannot safely and/or appropriately use opioid therapy and is in need of a discontinuation for that person's safety.

Another condition or situation might be where you are involved in the care of a patient on a chronic opioid therapy for chronic pain who has been advised to undergo a procedure in which the surgeons have requested discontinuation or don't want to proceed—for wound healing or other purposes—until the patient has been tapered off of opioid therapy. Certainly, other scenarios can exist in which opioid discontinuation is important and key to the patient's care, but those are three examples.

I'd like to now concentrate on the relatively new availability of a medical treatment that has been approved by the US Food and Drug Administration (FDA) specifically to treat opioid withdrawal symptoms. Lofexidine, also known as Lucemyra, was FDA approved in May 2018.[1] It is a central alpha 2-adrenergic agonist. Clonidine is similar in that regard and has been commonly used for withdrawal symptoms; however, clonidine has never been specifically FDA approved. Lucemyra is the first nonopioid agent that has been indicated and approved by the FDA for the mitigation of withdrawal symptoms and to facilitate abrupt discontinuation of opioids in adults.

As I mentioned, this is the first nonopioid treatment for the management of opioid withdrawal symptoms that has been FDA approved. We know of medicines like clonidine—tizanidine is another alpha 2-adrenergic agonist that has been used—but these have been used in an off-label manner. Lucemyra was approved by the FDA with a priority review and Fast Track designation.

Before proceeding with other details of Lucemyra, let me briefly review key warnings and precautions. There's a risk for hypotension, bradycardia, syncope, and QT prolongation. There is an increased risk for central nervous system (CNS) depression with concomitant use of CNS depressants. There is actually an increased risk for opioid overdose after opioid discontinuation, should the person resume taking opioids. In general, there are other discontinuation symptoms as well, so if someone is using this medication, one should look very carefully at all of the prescribing information.[2]

The starting dose of Lucemyra is three 0.18-mg tablets taken orally four times daily during the period of peak withdrawal symptoms, which is 5-7 days following the last dose of the opioid. There should be 5-6 hours between each dose. Treatment can continue for up to 14 days, with dosing guidelines provided for how long the symptoms should be treated.

We would discontinue Lucemyra with a gradual dose reduction over a 2- to 4-day period. It is a one tablet per dose reduction every 1-2 days to help mitigate against worsening of withdrawal symptoms, and to do this in a way that would be acceptable to the person for whom it is being prescribed.

Needless to say, this medication would not have been approved without the completion of appropriate, positive studies. This approval was supported by three randomized, double-blind, placebo-controlled studies and an open-label study. Clinical pharmaceutical studies were conducted with concomitant administration of methadone, buprenorphine, or naltrexone.

The most common adverse events that occurred in at least 10% of people, and notably more frequently with Lucemyra than placebo, include orthostatic hypotension, bradycardia, hypotension, somnolence, sedation, and dry mouth. Lucemyra has been used all over the world. Specifically, it has been used extensively in certain areas of Europe, including the United Kingdom, for many years.

In summary, we face a set of circumstances all too often these days where there is a reason to try to appropriately discontinue or taper a person off of opioid therapy, and in some instances it's best to do this as rapidly as possible. Without concentrating on one specific treatment, multiple agents are available, including a newly FDA-approved treatment, Lucemyra, to mitigate withdrawal symptoms when acute opioid discontinuation is desired.

It is important for us to use these tools, realizing that other blogs have really emphasized how complicated opioid prescribing is. Opioid discontinuation is also quite complex and difficult. As we go forward, knowing that there are specific treatments available for the mitigation of withdrawal symptoms to facilitate abrupt disruption of opioids in adults is a good thing because there are individuals for whom this is the right path.

Lucemyra and other medicines that have been developed, perhaps not specifically for this, can be utilized, and perhaps should be proactively utilized to help accomplish the discontinuation of opioid therapy in those individuals for whom that is appropriate.

I'm Dr Charles Argoff. I hope that this has been instructive and helpful.

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