Lofexidine

Lofexidine is a central alpha-2 adrenergic agonist that binds to receptors on adrenergic neurons. This reduces the release of norepinephrine and decreases sympathetic tone.

• Lofexidine tablets are indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults. Lofexidine tablets are a central alpha-2 adrenergic agonist indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.

• None. None.contraindicated

The usual lofexidine tablet dosage is three 0.18 mg tablets taken orally 4 times daily at 5- to 6-hour intervals. Lofexidine tablet treatment may be continued for up to 14 days with dosing guided by symptoms. ( 2.1 ) Discontinue lofexidine tablets with a gradual dose reduction over 2 to 4 days. ( 2.1 ) Hepatic or Renal Impairment: Dosage adjustments are recommended based on degree of impairment. ( 2.2 , 2.3 ) 2.1 Dosing Information The usual lofexidine tablet starting dosage is three 0.18 mg tablets taken orally 4 times daily during the period of peak withdrawal symptoms (generally the first 5 to 7 days following last use of opioid) with dosing guided by symptoms and side effects. There should be 5 to 6 hours between each dose. The total daily dosage of lofexidine tablets should not exceed 2.88 mg (16 tablets) and no single dose should exceed 0.72 mg (4 tablets). Lofexidine tablet treatment may be continued for up to 14 days with dosing guided by symptoms. Discontinue lofexidine tablets with a gradual dose reduction over a 2- to 4-day period to mitigate lofexidine tablet withdrawal symptoms (e.g., reducing by 1 tablet per dose every 1 to 2 days) [see Warnings & Precautions (5.5)] .The lofexidine tablet dose should be reduced, held, or discontinued for individuals who demonstrate a greater sensitivity to lofexidine tablets side effects [see Warnings and Precautions (5.1) , Adverse Reactions (6.1) ] . Lower doses may be appropriate as opioid withdrawal symptoms wane. Lofexidine tablets can be administered in the presence or absence of food.

Risk of Hypotension, Bradycardia, and Syncope : May cause a decrease in blood pressure, a decrease in pulse, and syncope. Monitor vital signs before dosing and advise patients on how to minimize the risk of these cardiovascular effects and manage symptoms, should they occur. Monitor symptoms related to bradycardia and orthostasis. When using in outpatients, ensure that patients are capable of self-monitoring for signs and symptoms. Avoid use in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, or chronic renal failure, as well as in patients with marked bradycardia. ( 5.1 ) Ri sk of QT Prolongation: Lofexidine prolong the QT interval. Avoid use in patients with congenital long QT syndrome. Monitor ECG in patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias, hepatic or renal impairment, or in patients taking other medicinal products that lead to QT prolongation. ( 5.2 ) Increased Risk of CNS Depression with Concomitant use of CNS Depressant Drugs: Lofexidine potentiate the CNS depressant effects of benzodiazepines and may potentiate the CNS depressant effects of alcohol, barbiturates, and other sedating drugs. ( 5.3 ) Increased Risk of Opioid Overdose after Opioid Discontinuation: Patients who complete opioid discontinuation are at an increased risk of fatal overdose should they resume opioid use. Use in conjunction with a comprehensive management program for treatment of opioid use disorder and inform patients and caregivers of increased risk of overdose.

The following serious adverse reactions are described elsewhere in labeling: Hypotension, Bradycardia, and Syncope [see Warnings and Precautions (5.1)] QT Prolongation [see Warnings and Precautions (5.2)] Central Nervous System Depression [see Warnings and Precautions (5.3)] Opioid Overdose [see Warnings and Precautions (5.4)] Discontinuation Symptoms [see Warnings and Precautions (5.5)] Most common adverse reactions (incidence ≥ 10% and notably more frequent than placebo) are orthostatic hypotension, bradycardia, hypotension, dizziness, somnolence, sedation, and dry mouth. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to adverse reaction rates observed for another drug and may not reflect the rates observed in practice. The safety of lofexidine was supported by three randomized, double-blind, placebo-controlled clinical trials, an open-label study, and clinical pharmacology studies with concomitant administration of either methadone, buprenorphine, or naltrexone. The three randomized, double-blind, placebo-controlled clinical trials enrolled 935 subjects dependent on short-acting opioids undergoing abrupt opioid withdrawal. Patients were monitored before each dose in an inpatient setting.

8.1 Pregnancy Risk Summary The safety of lofexidine in pregnant women has not been established. In animal reproduction studies, oral administration of lofexidine during organogenesis to pregnant rats and rabbits caused a reduction in fetal weights, increases in fetal resorptions, and litter loss at exposures below that in humans. When oral lofexidine was administered from the beginning of organogenesis through lactation, increased stillbirths and litter loss were noted along with decreased viability and lactation indices. The offspring exhibited delays in sexual maturation, auditory startle, and surface righting. These effects occurred at exposures below that in humans [see Animal Data]. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects in the U.S. general population is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Metabolism

Absorption Lofexidine is well absorbed and achieves peak plasma concentration 3 to 5 hours after administration of a single dose. Lofexidine shows approximately dose-proportional pharmacokinetics.

Overdose with lofexidine may manifest as hypotension, bradycardia, and sedation. In the event of acute overdose, perform gastric lavage where appropriate. Dialysis will not remove a substantial portion of the drug. Initiate general symptomatic and supportive measures in cases of overdosage.

• May 16, 2018NDANDA209229Biocorrx Pharms
• Aug 20, 2024ANDAANDA218613Regcon Holdings
• Feb 24, 2025ANDAANDA218699Msn
• Oct 22, 2025ANDAANDA219917Novitium Pharma

1. 1Dizziness2415%
2. 2Hypotension1711%
3. 3Somnolence159.4%
4. 4Dyspnoea148.8%
5. 5Diarrhoea127.5%
6. 6Dry Mouth116.9%
7. 7Fatigue106.3%
8. 8Insomnia106.3%
9. 9Malaise106.3%
10. 10Vomiting106.3%
11. 11Withdrawal Syndrome106.3%
12. 12Loss Of Consciousness95.7%
13. 13Nausea95.7%
14. 14Fall85.0%
15. 15Syncope85.0%

The 10 most recently updated of 40 ClinicalTrials.gov registrations naming Lofexidine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• An Innovative Intervention for OUD Treatment
  Completed · Phase 2 · Phase 3 · Interventional · 36 enrolled · Johns Hopkins University
  NCT04325659updated 2026-06-09
• Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans
  Completed · Phase 2 · Interventional · 84 enrolled · Pharmacotherapies for Alcohol and Substance Use Disorders Alliance
  NCT04360681updated 2026-05-08
• Evaluating Buspirone to Treat Opioid Withdrawal
  Recruiting · Phase 2 · Interventional · 100 enrolled · University of Maryland, Baltimore
  NCT05511909updated 2026-05-01
• Sublingual Dexmedetomidine for Treating Opioid Withdrawal
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 160 enrolled · New York State Psychiatric Institute
  NCT05712707updated 2026-04-14
• Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal
  Recruiting · Phase 2 · Interventional · 150 enrolled · University of Pennsylvania
  NCT05995535updated 2026-02-13
• Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids
  Active not recruiting · Phase 2 · Interventional · 24 enrolled · BioCorRx Pharmaceuticals Inc
  NCT06047834updated 2025-10-01
• Assessing a Clinically-meaningful Opioid Withdrawal Phenotype
  Recruiting · Phase 2 · Interventional · 60 enrolled · University of Maryland, Baltimore
  NCT05027919updated 2025-09-12
• A Pharmacokinetic, Safety, and Tolerability Study of LUCEMYRA in the Treatment of Opioid Withdrawal Management in Adolescent Subjects
  Withdrawn · Phase 1 · Interventional · 0 enrolled · USWM, LLC (dba US WorldMeds)
  NCT06711640updated 2025-08-01
• Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder
  Completed · Interventional · 108 enrolled · Spark Biomedical, Inc.
  NCT05053503updated 2025-07-04
• Impact of Lofexidine on Stress, Craving and Opioid Use
  Completed · Phase 2 · Interventional · 112 enrolled · Medical University of South Carolina
  NCT03718065updated 2025-02-07

CPIC-curated drug–gene pairs for Lofexidine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• CYP2D6CPIC B/C (provisional)FDA label: Actionable PGx

Frequently asked questions

How does Lofexidine work?

Lofexidine is a central alpha-2 adrenergic agonist that binds to receptors on adrenergic neurons. This reduces the release of norepinephrine and decreases sympathetic tone.

What is Lofexidine used for?

According to FDA labeling, Lofexidine carries indications including: Lofexidine tablets are indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults. Lofexidine tablets are a central alpha-2 adrenergic agonist indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Lofexidine?

Lofexidine is classified as Drugs used in opioid dependence, Adrenergic alpha1-Agonists, Adrenergic alpha2-Agonists, ATP-Binding Cassette (ABC) Transporter Interactions, Multidrug and Toxin Extrusion Transporter 1 Inhibitors, Decreased Norepinephrine Activity.

What are the brand names for Lofexidine?

Lofexidine is marketed under brand names including Lucemyra.

What are the contraindications for Lofexidine?

Lofexidine labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.