Lofexidine (Lucemyra)

What it treats

Lofexidine is approved by the U.S. Food and Drug Administration for the mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.

It's used most often as part of a short medically supervised withdrawal (sometimes called detox), often as a bridge to extended-release naltrexone or to abstinence-based treatment. It's not a maintenance treatment for opioid use disorder, and using it alone without connecting the person to ongoing treatment tends to end in relapse.

How it works

When someone dependent on opioids stops using, the brain's noradrenaline system, which had been suppressed by the opioid, comes roaring back. That overactivation is what drives most of the physical misery of withdrawal: sweating, tearing, runny nose, GI cramping, goosebumps, restlessness, high heart rate. Lofexidine stimulates the α2-adrenergic autoreceptor in the brainstem, which acts as a brake on noradrenaline release. The brake dampens the surge and the physical symptoms ease.

It's similar to clonidine but was developed to be more selective and slightly less sedating and less hypotensive, though it still lowers blood pressure meaningfully. Lofexidine doesn't touch cravings much because cravings live in a different circuit. That's the piece to understand: withdrawal and craving are separate problems, and lofexidine only addresses the first one.

Receptor mechanism (detail)

Lofexidine is an agonist at the α2-adrenergic receptor, with modest selectivity for α2 over α1 subtypes. Its main action is at the α2A autoreceptor in the locus coeruleus and other noradrenergic areas, which reduces the release of norepinephrine. It's structurally and mechanistically very similar to clonidine, and both do the same job of dampening noradrenergic overactivity in opioid withdrawal.

Potency and typical dosing pattern

Ranges are typical framework only, not a prescription for any individual.

The standard dose is 0.54 mg (three 0.18 mg tablets) four times daily during the peak withdrawal period. That's 2.16 mg per day total, given roughly every 5 to 6 hours while awake. Doses can be adjusted down for tolerability. Maximum single dose is 0.72 mg (four tablets), and maximum daily dose is 2.88 mg.

Duration is up to 14 days at full dose, then a taper of 2 to 4 days to reduce the risk of rebound blood pressure elevation.

Safety monitoring

• Baseline blood pressure, heart rate, and ECG including QTc.
• Blood pressure and heart rate before each dose during the first days, then daily. Hold or reduce for hypotension or bradycardia.
• Signs of oversedation, especially with any other sedating medications on board.
• Renal and hepatic function. Dose adjustment is needed in significant impairment.
• Withdrawal severity using something like the COWS scale to track symptoms.

What to expect

Lofexidine tends to take the edge off physical withdrawal symptoms starting within an hour or two of the first dose. It doesn't erase withdrawal, and people typically still feel unwell for several days. Peak physical symptoms from short-acting opioids are usually days 2 to 4; from long-acting opioids like methadone, they can peak later and last longer.

The mental piece (low mood, low energy, disturbed sleep, and cravings) tends to linger longer than the physical symptoms. That's why connecting the person to ongoing treatment (naltrexone, buprenorphine started after a washout, or a residential program) before the lofexidine course ends is what matters for outcomes.

Common side effects

Most people get some side effects. The common ones include:

• Dizziness or lightheadedness on standing.
• Sedation and drowsiness.
• Low blood pressure.
• Dry mouth.
• Slow heart rate.
• Tinnitus (ringing in the ears).

The dizziness and hypotension are usually the ones that need attention. Standing up slowly, staying hydrated, and holding a dose if blood pressure is low are the standard responses.

Serious side effects and warnings

Serious problems are uncommon, but a few are worth knowing.

• Symptomatic hypotension and syncope. This is the most common serious issue. Blood pressure and heart rate should be checked before each dose in the first days.
• Bradycardia, especially in people already on rate-slowing medications.
• QTc prolongation. Modest, but relevant in people with other QTc risk factors or on other QTc-prolonging drugs.
• Rebound hypertension if stopped abruptly, especially at higher doses. Taper is standard.
• Increased opioid overdose risk after any withdrawal management, because tolerance drops fast. If the person goes back to their prior dose of opioids, that dose can be lethal. This is why naloxone and follow-up treatment are essential.

Sexual and relational effects

Lofexidine is used for a short course during withdrawal, so long-term sexual effects aren't really the frame. During the course, low blood pressure and fatigue can dampen sexual interest, which usually recovers as the medication is stopped. On the relational side, the value of lofexidine is that it makes a hard week more tolerable, which can be the difference between finishing a withdrawal plan and walking out on day two.

Weight, appetite, and sleep

Appetite is often poor during withdrawal itself. Lofexidine doesn't drive weight change over such a short course. Sleep during opioid withdrawal is famously bad. Lofexidine can help a little through sedation, but it doesn't fix insomnia. Some clinicians add a short course of a non-habit-forming sleep aid.

Starting and dosing basics

This section is general background, not a dosing instruction for any individual. The right dose is a decision for a prescriber.

Lofexidine comes as 0.18 mg tablets. The standard starting dose is three tablets (0.54 mg) four times daily on the first day of withdrawal. Doses are held or reduced for hypotension, bradycardia, or excessive sedation. In renal or hepatic impairment, doses are cut.

Lofexidine is not a replacement for methadone or buprenorphine as maintenance treatment. It's a bridge across the withdrawal window, and the plan for what comes next (naltrexone, residential care, or something else) should be in place before the course starts.

Missed doses and interactions

If a dose is missed, take it as soon as you remember unless it's close to the next scheduled dose. Don't double up.

The most important interactions are with other drugs that lower blood pressure or heart rate: beta blockers, other α2 agonists like clonidine, and some antihypertensives. Combining lofexidine with methadone is a QTc concern and generally avoided. Alcohol adds to sedation. Any medication that prolongs the QTc interval (some antipsychotics, some antibiotics, some antiarrhythmics) should be reviewed. Give every prescriber and pharmacist a full list of your medications and supplements, including over-the-counter ones.

Stopping and tapering

Don't stop lofexidine abruptly. Rebound elevation in blood pressure and heart rate can happen. Taper over 2 to 4 days at the end of the course. If a course is cut short, the taper still applies.

Pregnancy and breastfeeding

Data on lofexidine in pregnancy is limited. Untreated opioid withdrawal in pregnancy is dangerous for both parent and fetus, so decisions about how to manage opioid dependence in pregnancy usually center on methadone or buprenorphine, not lofexidine. It's not known whether lofexidine passes into breast milk in humans in significant amounts.

Anyone who is pregnant, planning a pregnancy, or breastfeeding should talk it through with their prescriber so the specific risks and benefits can be weighed.

Cost and generic availability

Lofexidine is more expensive than generic clonidine, which does a similar job and is often used off-label for the same purpose. Some insurance plans cover Lucemyra with prior authorization. A generic version of lofexidine has been approved but availability varies. Many programs use clonidine for cost reasons, and outcomes appear broadly similar.

Common questions

Is this the same as clonidine? Very close. Same mechanism, same job. Lofexidine is marketed as somewhat more selective and slightly less hypotensive, but in practice they're used interchangeably in many programs.

Will this cure my withdrawal? No. It softens the physical symptoms. You'll still feel bad for several days. It also doesn't treat cravings, so what happens after the withdrawal course is what really determines whether the effort was worth it.

Why not just use buprenorphine? Buprenorphine treats both withdrawal and cravings and prevents overdose, which is why for most people it's the better first choice. Lofexidine is for people who want to be fully off opioids (usually as a bridge to naltrexone) or who can't or won't use buprenorphine.

How long does it take to work? Physical symptoms start to ease within an hour or two of a dose. Full effect on withdrawal severity builds over the first day.

Can I drive on it? Not at the start. Sedation and low blood pressure are common. Don't drive until you know how you respond.

Questions to ask your prescriber

• What's the plan for what happens after the 14 days?
• Should I be on naloxone at home during and after this?
• What blood pressure or heart rate reading should make me hold a dose?
• Are any of my other medications a problem with this?
• If I decide to try buprenorphine instead, how would we transition?

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes, and current as of June 8, 2026.

• U.S. Food and Drug Administration. Lofexidine (Lucemyra) prescribing information.
• DailyMed, U.S. National Library of Medicine. Lofexidine hydrochloride label.
• MedlinePlus, U.S. National Library of Medicine. Lofexidine.
• Substance Abuse and Mental Health Services Administration. Medications for opioid use disorder.
• American Society of Addiction Medicine. National Practice Guideline for the Treatment of Opioid Use Disorder.
• National Institute of Mental Health. Mental health medications.