• 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.
• Belongs to the group of medicines known as centrally acting antiadrenergic agents (also called alpha-2 adrenergic agonists).

• May be used to reduce withdrawal symptoms in adults 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.

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, a slow heart rate, dizziness, drowsiness, and a dry mouth. Dizziness or drowsiness may occur. This may affect your ability to drive or operate machinery, particularly during the first few days of dosing, when going from lying down to a standing position, 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• Can cause withdrawal symptoms so needs to be withdrawn slowly over a 2 to 4 day period (reduce by 1 tablet per dose every 1 to 2 days).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.
• Some individuals are sensitive to the side effects of lofexidine and a lower dosage may be needed.
• Not for use in children under the age of 18 years.
• The dosage may need to be reduced in people with liver or kidney disease.
• This medicine may not be suitable for people with severe coronary insufficiency, recent myocardial infarction (heart attack), cerebrovascular disease, chronic renal (kidney) failure, congenital QT syndrome, or marked bradycardia (slow heart rate).
• Prolongs the QT interval. ECG monitoring may be required in people at risk of QT prolongation. Correct any electrolyte abnormalities first (such as low potassium or low magnesium levels) before administering lofexidine. Review for drug interactions that may prolong QT interval.
• Females are more likely to experience a serious cardiovascular (heart/blood vessel) side effect while taking lofexidine. Thirty-one percent of females had to have their dose held or discontinued due to side effects compared to 18% of males.
• May interact with many drugs, including those that also lower blood pressure, prolong the QT interval, or cause sedation.
• The absorption and effects of lofexidine may be increased in people who are poor CYP2D6 metabolizers. Monitor for side effects.
• Safety in pregnancy has not been established but animal studies show an increased risk of fetal resorption, reduced birth weights, and miscarriages.
• There is no information about using lofexidine during breastfeeding but caution should be administered.
• May affect female fertility, 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

• Lofexidine is not a treatment for opioid use disorder (OUD), it just helps ease the symptoms of opioid withdrawal. You will have a reduced tolerance to opioids once you have gone through opioid discontinuation and will be at an increased risk for fatal overdose if you resume opioid use.
• It is usually given four times a day. 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 or drive or operate machinery 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. Keep hydrated. If you feel yourself beginning to faint or feeling dizzy or lightheaded while on lofexidine, lie down until the feeling passes.
• 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, anxiety, chills, increased sweating, and pain in your fingers and toes. Lofexidine needs to be slowly tapered off and you should talk to your doctor about this.
• This medicine may interact with several other medications that also lower blood pressure, cause sedation, or slow your heart rate. Tell your doctor about all the medications you take before starting lofexidine.
• Tell your doctor if you are breastfeeding or pregnant because lofexidine may not be suitable for you.

• Blood levels of lofexidine reach a peak within three to five hours after a single dose. Accumulation of lofexidine occurs with repeat dosing.
• About 40% to 41% of patients using lofexidine completed 7 days of treatment, compared to only 28% of patients given a placebo (an inactive medication).
• 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.

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 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. It may increase your risk for dizziness, drowsiness, confusion, and difficulty concentrating.

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 CNS depression or sedation.

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.