New Drug for Opioid Withdrawal

 

 

 

Last week the Food and Drug Administration (FDA) approved lofexidine for the treatment of opioid withdrawal symptoms, under the brand name Lucemyra.

This medication is an alpha 2a adrenergic receptor agonist, which means it acts on the same receptors as epinephrine and norepinephrine. However, when the specific alpha 2a receptors are activated, less norepinephrine is released, and so the actions of epinephrine and norepinephrine are reduced.

Lofexidine is not an opioid, and has no effect on the opioid receptors. It doesn’t cause euphoria or intoxication and thus is not a controlled substance.

So, you may be wondering, how does this medication help with opioid withdrawal?

Among many other places in the central nervous system, opioids act on a part of the brain called the locus ceruleus. The locus ceruleus, which in Latin means the “blue place,” is part of the system that controls the autonomic nervous system. When locus ceruleus neurons are stimulated, norepinephrine is released into the brain, and this causes overall stimulation of the brain.

Opioids slow the firing of these neurons in the locus ceruleus, reducing the release of norepinephrine. When the body gets opioids regularly from an outside source, the locus ceruleus gradually adjusts, to make up for the extra opioids. Then if the supply of opioids is suddenly stopped, the locus ceruleus becomes unbalanced, and releases an overabundance of norepinephrine. The heart rate and blood pressure increase, along with other symptoms: runny nose, yawning, tearing of the eyes, diarrhea, and nausea.

Alpha a2 agonists reduce this storm of norepinephrine, thus reducing the autonomic nervous system effects of too much norepinephrine, which cause many of the extremely distressing signs and symptoms of opioid withdrawal.

Lofexidine is in the same family of medications as clonidine, a blood pressure medication used for many years, which is also an apha 2a adrenergic agonist. Lofexidine also can cause low blood pressure, and physicians must monitor patients for this side effect.

Lofexidine has been sold in Great Britain since 1992 for management of opioid withdrawal symptoms. There’s some data to suggest it may work a bit better than clonidine and have fewer side effects, but it’s significantly more expensive than clonidine.

In the UK, lofexidine has been used to get patients through opioid withdrawal in preparation to administer naltrexone, an opioid antagonist that blocks opioids. Before initiating naltrexone, the patient must be through the withdrawal phase. Though naltrexone in tablet form hasn’t been too successful, due to problems getting patients to take this medication daily, the monthly depot injection has better compliance, for obvious reasons. The depot formulation works much better than the tablet form for this reason.

Please note that lofexidine isn’t a treatment for opioid use disorder, but only for opioid withdrawal symptoms. Many times, people assume that once the withdrawal is treated, to the problem goes away. We’ve seen since the 1950’s that keeping people with opioid use disorder away from opioids doesn’t treat the opioid use disorder, but it can be a prelude to treatment.

According to GoodRx.com, lofexidine will be available in pharmacies by August of this year, but the manufacturer hasn’t released pricing information yet.

So how big a deal is this medication? Not so big, in my opinion. I’ve never prescribed it, obviously, but from what I read, it works perhaps minimally better than the far cheaper clonidine which we’ve used for decades.

I suspect with the big price attached to this medication, we can expect to see brand name Lucemyra promoted heavily in the next year.

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2 responses to this post.

  1. It may be helpful for our patients who are motivated to taper their meds (hopefully after counseling agrees with the plan) and just need some assistance with managing the withdrawal symptoms. But, I totally agree that, for most of our patients the addiction is more than just physical. Nevertheless, if they have insurance, it will add another tool to our pharmacopoeia.

    Reply

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