Lofexidine: 7 things you should know

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Oct 31, 2023.

1. How it works

• Lofexidine works by binding to alpha-2 receptors in the brain and reduces the release of the chemical norepinephrine. It causes your muscles to relax, blood vessels to widen, and blood pressure to reduce to help lower an overactive nervous system.
• It is used to help ease opioid (narcotic) withdrawal symptoms when opioids need to be stopped right away. These symptoms can include: insomnia, chills, feeling sick to your stomach, runny eyes, yawning, muscles spasms or stomach cramps. Lofexidine does not treat opioid addiction (opioid use disorder).
• Belongs to the group of medicines known as centrally acting antiadrenergic agents (also called alpha-2 adrenergic agonists).

2. Upsides

• May be used in adults to reduce withdrawal symptoms so that opioids can be quickly discontinued. It is not an opioid and is not addictive.
• Taken orally (by mouth) with or without food. May be administered for up to 14 days. Dosing is guided by symptoms and side effects that may occur.
• There are no contraindications (reasons why you could not receive this treatment) listed by the manufacturer to lofexidine; however, it should be used with caution in people with certain medical conditions, especially certain heart or kidney problems (see below in downsides).
• Slows down nervous system activity which typically occurs during opioid withdrawal. Helps relieve symptoms such as nausea, stomach cramps, muscle spasms, twitching, feeling cold, a pounding heart, muscle tension, aches and pains, yawning, runny eyes, and sleep problems due to opioid withdrawal.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Sleeplessness, low blood pressure, low blood pressure upon standing (which may lead to fainting or injury), a slow heart rate, dizziness, drowsiness, and a dry mouth. This may affect your ability to drive or operate machinery, particularly during the first few days of dosing, during hot weather, or after activity. Do not drive or operate machinery until you know how lofexidine affects you.
• Fainting and tinnitus (ringing in the ears) have also been reported at higher dosages.
• Can cause withdrawal symptoms so needs to be withdrawn slowly over a 2 to 4 day period (reduce by 1 tablet per dose every 1 to 2 days). High blood pressure on withdrawal has been reported, this usually peaks on day two. Other withdrawal symptoms include diarrhea, insomnia, anxiety, chills, and increased sweating.
• The dosage may need to be reduced in people with liver or kidney disease. Lofexidine may also cause abnormal heart rhythms.
• This medicine may not be suitable for people with certain heart or kidney disorders. Females are more likely to experience a serious cardiovascular (heart/blood vessel) side effect while taking lofexidine.
• May interact with many drugs, including those that also lower blood pressure, prolong the QT interval, or cause sedation.
• Safety in pregnancy has not been established but animal studies show a possible risk. There is no information about using lofexidine during breastfeeding but caution should be used. Talk to your doctor about use in pregnancy / breastfeeding.
• May affect female fertility, but the effect on male fertility is unknown.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Lofexidine is used to ease the symptoms due to abruptly stopping opioids in people with opioid addiction (opioid use disorder). It is given for up to 14 days, based on symptoms and peak withdrawal, but must be slowly discontinued. Peak withdrawal typically occurs the first 5 to 7 days following last use of opioid. The main side effects are low blood pressure, a slow heartbeat (bradycardia), sleepiness, dizziness, and dry mouth.

5. Tips

• Lofexidine is not a treatment for opioid use disorder (OUD), but it helps to ease the symptoms of opioid withdrawal. You will have a reduced tolerance to opioids once you have gone through opioid discontinuation. You will be at an increased risk for a fatal overdose if you resume opioid use.
• It is initially given four times a day. Doses may decrease as your withdrawal symptoms improve. The dosage you are prescribed depends on your kidney or liver function and other additional medical conditions or medications you take.
• Do not drink alcohol, drive or operate machinery, or perform hazardous activities while you are taking this medicine.
• Withdrawing from the effects of opioids is not easy. Lofexidine will help relieve some of the symptoms associated with opioid withdrawal such as feeling sick, aches and pains, sweating, and a pounding heart but should be used in addition to a comprehensive treatment program for opioid use disorder. Make sure you follow all recommendations from your healthcare provider.
• This medicine can drop your blood pressure and slow your heartbeat which may make you feel dizzy or pass out. If you are feeling like you might faint all the time, talk to your doctor right away. Be careful when moving from lying down to sitting up or standing position. If you feel yourself beginning to faint or feeling dizzy or lightheaded while on lofexidine, lie down until the feeling passes.
• Keep hydrated by drinking plenty of water. Do not allow yourself to become dehydrated or overheated while taking lofexidine because it may make the side effects worse.
• Do not stop taking lofexidine suddenly. This may cause a marked increase in blood pressure and symptoms may include diarrhea, insomnia (trouble sleeping), anxiety, chills, increased sweating, and pain in your fingers and toes. Lofexidine needs to be slowly stopped over time and you should talk to your doctor about this.
• This medicine may interact with several other medications that also lower blood pressure, cause sleepiness, or slow your heart rate. Tell your doctor about all the medications you take before starting lofexidine treatment.
• Tell your doctor if you are breastfeeding or pregnant because lofexidine may not be suitable for you.

6. Response and effectiveness

• Blood levels of lofexidine reach a peak within 3 to 5 hours after a single dose. Accumulation of lofexidine occurs with repeat dosing.
• About 40% of patients using lofexidine completed 7 days of treatment, compared to only 28% of patients given a placebo (an inactive medication), a significant difference. Patients in the placebo group were more likely to drop out of studies early due to lack of effectiveness compared to those taking lofexidine.
• The Short Opiate Withdrawal Scale (SOWS)-Gossop is a 10-item questionnaire developed to evaluate opioid withdrawal symptom severity. It measures symptoms such as anxiety, yawning, and perspiration. People taking lofexidine reported a significantly lower score in the SOWS-Gossop than people taking a placebo.

7. Interactions

Medicines that interact with lofexidine may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with doxazosin. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor and pharmacist about how drug interactions should be managed.

Lofexidine interacts with over 500 medications, most of these interactions are considered moderate or major. Common medications or substances that may interact with lofexidine include:

• alcohol (ethanol)
• amisulpride
• antiarrhythmic medications such as disopyramide
• antibiotics such as norfloxacin
• antidepressants such as escitalopram
• antinausea medications such as dolasetron
• antipsychotics such as clozapine, haloperidol, or ziprasidone
• any medication that causes sedation, such as sedating antihistamines or barbiturates
• benzodiazepines such as clonazepam, diazepam, or lorazepam
• bisacodyl
• bromocriptine
• bupropion
• buspirone
• cannabis (marijuana)
• erectile dysfunction medications (eg, alprostadil, sildenafil, tadalafil, or vardenafil)
• HIV medications such as efavirenz or saquinavir
• hydroxychloroquine
• lithium
• methadone (also prolongs the QT interval)
• mifepristone
• monoamine oxidase inhibitor antidepressants, such as phenelzine or tranylcypromine
• multiple sclerosis medications such as fingolimod or siponimod
• other heart medications that may also lower blood pressure, such as atenolol, carvedilol, clonidine, diltiazem, labetalol, metoprolol, nadolol, propranolol, sotalol, trandolapril, or verapamil
• paroxetine (inhibits CYP2D6 and may cause a 28% increase in the absorption of lofexidine)
• papaverine
• quinidine
• QT-prolonging medicines such as buprenorphine, amiodarone, or cisapride
• sedating antihistamines such as diphenhydramine or azelastin
• tamoxifen
• targeted treatments such as ceritinib or cabozantinib
• valerian
• valproic acid

Avoid drinking alcohol while taking lofexidine, as it may increase your risk for dizziness, drowsiness, confusion, and difficulty concentrating.

Lofexidine may reduce the efficacy of oral naltrexone if used together. Administer naltrexone by other routes.

Avoid using lofexidine with any other medications that decrease pulse or blood pressure to avoid the risk of excessively slowed heart rate and low blood pressure.

Avoid other medications that also cause nervous system (CNS) depression or sedation. Especially tell your healthcare provider if you take benzodiazepines, barbiturates, tranquilizers, or sleeping pills. Taking lofexidine with these medicines can cause serious side effects.

Note that this list is not all-inclusive and includes only common medications that may interact with lofexidine. You should refer to the prescribing information for lofexidine for a complete list of interactions, and discuss drug interactions with your healthcare provider.

References

• Lucemyra (lofexidine). Prescribing information. Revised 10/5/2023. US World Meds, Louisville, KY. Accessed 10/31/2023 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b748f308-ba71-4fd9-84ec-ec7e0f210885

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use lofexidine only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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