Lofexidine .18 mg Tablet, 96-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Drugs used in opioid dependence class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Lofexidine is used to manage opioid withdrawal symptoms (e.g., sick feeling, stomach cramps, muscle spasms or twitching, cold sensation, heart pounding, muscle tension, aches and pains, yawning, runny eyes, or difficulty falling asleep or staying asleep) that may occur after an opioid medication is suddenly stopped. Lofexidine is in a class of medications called central alpha adrenergic agonists. It works by relaxing blood vessels so that blood can flow more easily through the body.
Read the full MedlinePlus article ↗- No, lofexidine is not an opioid at all. It works completely differently. It targets receptors in your brain that control the stress response, reducing the release of a chemical cal...
- What exactly does lofexidine do — is it an opioid?
- It's not designed to treat addiction on its own — it's specifically for managing the physical symptoms that happen when you stop opioids suddenly. Think of it as a tool to get thro...
- Will lofexidine cure my opioid addiction?
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII XF417D3PSL
Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
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UNII 3SY5LH9PMK
Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
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UNII 776XM7047L
Calcium stearate is a white powder derived from stearic acid and calcium. It works as a lubricant and glidant to help the medicine flow smoothly during manufacturing and prevent ingredients from sticking to equipment.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII L06K8R7DQK
A synthetic blue dye approved by the FDA for use in medications and foods. It serves as a colorant to make pills and liquids visually distinct and easier to identify.
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UNII H77VEI93A8
A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
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UNII 9XZ8H6N6OH
A plant-based cellulose derivative used as a binder to hold tablet ingredients together, a thickener in liquids, and a coating agent to control how fast the medicine dissolves.
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UNII U725QWY32X
Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
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UNII 6DC9Q167V3
Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
11 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $8.656 | $831.00 / 96 tablets |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $10.36 | $994.46 / 96 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Lofexidine hydrochloride .2 mg 66993-0345-37 | Prasco | 36 tablets | $8.656 | AB | Availability likely | — |
| Lofexidine .18 mgthis 70954-0909-20 | ANI | 96 tablets | $8.656 | AB | Availability likely | — |
| Lofexidine .18 mg 71921-0250-36 | Florida | 36 tablets | $8.656 | AB | Availability likely | — |
| lofexidine hydrochloride .2 mg 72205-0246-42 | Novadoz | 36 tablets | $8.656 | AB | Availability likely | — |
| Lofexidine .18 mg 14445-0146-36 | Indoco | 36 tablets | — | AB | FDA listed | — |
| Lucemyra .2 mg 78670-0050-03 | USWM, | 36 tablets | — | AB | Discontinued | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 70954-0909-10 | 36 TABLET in 1 BOTTLE (70954-909-10) | $8.66 / ea | $311.63 | 2025-10-22 | Active |
| 70954-0909-20 You're viewing this | 96 TABLET in 1 BOTTLE (70954-909-20) | $8.66 / ea | $831.00 | 2025-10-22 | Active |
You're viewing the largest of 2 pack sizes for this product.
This pack effectively ties for the lowest per-ea cost of the 2 priced pack sizes ($8.66 NADAC).
Pack size FAQ
What quantity is in NDC 70954-0909-20?
What is the difference between NDC 70954-0909-20 and NDC 70954-0909-10?
What NDC number is used to bill for this package of Lofexidine .18 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS & USAGE 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. (1)
⏱️ Dosage and Administration ▾
2 DOSAGE & ADMINISTRATION 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)
2.1Dosing 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.
2.2Dosage Recommendations for Patients with Hepatic Impairment Recommended dosage adjustments based on the degree of hepatic impairment are shown in Table 1. [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)] . Table 1: Dosage Recommendations in Patients with Hepatic Impairment Mild Impairment Moderate Impairment Severe Impairment Child-Pugh score 5-6 7-9 >9 Recommended dose 3 tablets 4 times daily (2.16 mg per day) 2 tablets 4 times daily (1.44 mg per day) 1 tablet 4 times daily (0.72 mg per day)
2.3Dosage Recommendations for Patients with Renal Impairment Recommended dosage adjustments based on the degree of renal impairment are shown in Table 2. Lofexidine tablets may be administered without regard to the timing of dialysis [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)] . Table 2: Dosage Recommendations in Patients with Renal Impairment Moderate Impairment Severe Impairment, End-Stage Renal Disease, or on Dialysis Estimated GFR, mL/min/1.73 m 2 30 - 89.9 < 30 Recommended dose 2 tablets 4 times daily (1.44 mg per day) 1 tablet 4 times daily (0.72 mg per day)
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS & STRENGTHS Lofexidine tablets are available as round, convex-shaped, peach colored, film-coated tablets, debossed with “909” on one side and “N” on other side, free from physical defects. Each tablet contains 0.18 mg lofexidine (equivalent to 0.2 mg of lofexidine hydrochloride). Tablets: 0.18 mg. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS 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) Risk of QT Prolongation : Lofexidine tablets 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 tablets 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. (5.4) Risk of Discontinuation Symptoms : Instruct patients not to discontinue therapy without consulting their healthcare provider.
When discontinuing therapy, reduce dose gradually. (5.5)
5.1Risk of Hypotension, Bradycardia, and Syncope Lofexidine tablets can cause a decrease in blood pressure, a decrease in pulse, and syncope [see Adverse Reactions (6.1), Clinical Pharmacology (12.2)] . Monitor vital signs before dosing. Monitor symptoms related to bradycardia and orthostasis.
Patients being given lofexidine tablets in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms. If clinically significant or symptomatic hypotension and/or bradycardia occur, the next dose of lofexidine tablets should be reduced in amount, delayed, or skipped. Inform patients that lofexidine tablets may cause hypotension and that patients moving from a supine to an upright position may be at increased risk for hypotension and orthostatic effects.
Instruct patients to stay hydrated, on how to recognize symptoms of low blood pressure, and on how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position). Instruct outpatients to withhold lofexidine tablets doses when experiencing symptoms of hypotension or bradycardia and to contact their healthcare provider for guidance on how to adjust dosing. Avoid using lofexidine tablets in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, and in patients with marked bradycardia.
Avoid using lofexidine tablets in combination with medications that decrease pulse or blood pressure to avoid the risk of excessive bradycardia and hypotension.
5.2Risk of QT Prolongation Lofexidine tablets prolong the QT interval. Avoid using lofexidine tablets in patients with congenital long QT syndrome. Monitor ECG in patients with congestive heart failure, bradyarrhythmias, hepatic impairment, renal impairment, or patients taking other medicinal products that lead to QT prolongation (e.g. methadone).
In patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), correct these abnormalities first, and monitor ECG upon initiation of lofexidine tablets [see Dosing and Administration (2.1), Adverse Reactions…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS 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 ANI Pharmaceuticals, Inc. at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical 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 tablets 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. Table 3 presents the incidence, rounded to the nearest percent, of adverse events that occurred in at least 10% of subjects treated with lofexidine tablets and for which the incidence in patients treated with lofexidine tablets were greater than the incidence in subjects treated with placebo in a study that tested two doses of lofexidine tablets, 2.16 mg per day and 2.88 mg per day, and placebo.
The overall safety profile in the combined dataset was similar. Orthostatic hypotension, bradycardia, hypotension, dizziness, somnolence, sedation, and dry mouth were notably more common in subjects treated with lofexidine tablets than subjects treated with placebo. Table 3: Adverse Reactions Reported by ≥ 10% of Lofexidine Tablet-Treated Patients and More Frequently than Placebo Adverse Reaction Lofexidine Tablets 2.16 mg 1 (%) N=229 Lofexidine Tablets 2.88 mg 1 (%) N=222 Placebo (%) N=151 Insomnia 51 55 48 Orthostatic Hypotension 29 42 5 Bradycardia 24 32 5 Hypotension 30 30 1 Dizziness 19 23 3 Somnolence 11 13 5 Sedation 13 12 5 Dry Mouth 10 11 0 1 Assigned dose; mean average daily dose received was 79% of assigned dose due to dose-holds for out-of-range vital signs.
Other notable adverse reactions associated with the use of lofexidine tablets but reported in <10% of patients in the lofexidine tablets group included: Syncope: 0.9%, 1.4% and 0% for lofexidine tablets 2.16 mg/day and 2.88 mg/day and placebo, respectively Tinnitus: 0.9%, 3.2% and 0% for lofexidine tablets 2.16 mg/day and 2.88 mg/day and placebo, respectively Blood pressure changes and adverse reactions after lofexidine tablets cessation Elevations in blood pressure above normal values (≥ 140 mmHg systolic) and above a subject’s pre-treatment baseline are associated with discontinuing lofexidine tablets, and peaked on the second day after discontinuation, as shown in Table 4.
Blood pressure values were evaluated for 3 days following the last dose of a 5-day course of lofexidine tablets 2.88 mg/day. Table 4: Blood Pressure Elevations after Stopping Treatment Abrupt Lofexidine Tablet Discontinuation 2.88 mg (N = 134) Placebo (N = 129) N at risk n (%) N at risk n (%) Systolic Blood Pressure on Day 2 after Discontinuation ≥ 140 mmHg and ≥ 20 mmHg increase from baseline 58 23 (39.7) 37 6 (16.2) ≥ 170 mmHg and ≥ 20 mmHg increase from baseline 58 5 (8.6) 37 0 Blood pressure elevations of a similar magnitude and incidence were observed in a small number of patients (N=10) tha…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Methadone : Methadone and lofexidine tablets both prolong the QT interval. ECG monitoring is recommended when used concomitantly. (7.1) Oral Naltrexone : Concomitant use may reduce efficacy of oral naltrexone. (7.2) CYP2D6 Inhibitors : Concomitant use of paroxetine resulted in increased plasma levels of lofexidine. Monitor for symptoms of orthostasis and bradycardia with concomitant use of a CYP2D6 inhibitor. (7.4)
7.1Methadone Lofexidine tablets and methadone both prolong the QT interval. ECG monitoring is recommended in patients receiving methadone and lofexidine tablets concomitantly [see Warnings and Precautions (5.2), Clinical Pharmacology (12.3)] .
7.2Oral Naltrexone Coadministration of lofexidine tablets and oral naltrexone resulted in statistically significant differences in the steady-state pharmacokinetics of naltrexone. It is possible that oral naltrexone efficacy may be reduced if used concomitantly within 2 hours of lofexidine tablets. This interaction is not expected if naltrexone is administered by non-oral routes [see Clinical Pharmacology (12.3)] .
7.3CNS Depressant Drugs Lofexidine tablets potentiate the CNS depressant effects of benzodiazepines and may potentiate the CNS depressant effects of alcohol, barbiturates, and other sedating drugs. Advise patients to inform their healthcare provider of other medications they are taking, including alcohol [see Warnings and Precautions (5.3)] .
7.4CYP2D6 Inhibitor – Paroxetine Coadministration of lofexidine tablets and paroxetine resulted in a 28% increase in the extent of absorption of lofexidine. Monitor for orthostatic hypotension and bradycardia when an inhibitor of CYP2D6 is used concomitantly with lofexidine tablets [see Clinical Pharmacology (12.3)] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary The safety of lofexidine tablets 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. Data Animal Data Increased incidence of resorptions, decreased number of implantations, and a concomitant reduction in the number of fetuses were observed when pregnant rabbits were orally administered lofexidine hydrochloride during organogenesis (from gestation day [GD] 7 to 19) at a daily dose of 5.0 mg/kg/day (approximately 0.08 times the maximum recommended human dose [MRHD] of 2.88 mg lofexidine base on an AUC basis).
Maternal toxicity evidenced by increased mortality was noted at the highest tested dose of 15 mg/kg/day (approximately 0.4 times the MRHD on an AUC basis). Decreased implantations per dam and decreased mean fetal weights were noted in a study in which pregnant rats were treated with oral lofexidine hydrochloride during organogenesis (from GD 7 to 16) at a daily dose of 3.0 mg/kg/day (approximately 0.9 times the MRHD on an AUC basis). This dose was associated with maternal toxicity (decreased body weight gain and mortality).
No malformations or evidence of developmental toxicity were evident at 1.0 mg/kg/day (approximately 0.2 times the MRHD on an AUC basis). A dose-dependent increase in pup mortality was noted in all doses of lofexidine hydrochloride administered orally to pregnant rats from GD 6 through lactation at an exposure less than the human exposure based on AUC comparisons. Doses higher than 1.0 mg/kg/day (approximately 0.2 times the MRHD on an AUC basis) resulted in incidences of total litter loss and maternal toxicity (piloerection and decreased body weight gain).
At the highest dose tested of 2.0 mg/kg/day (approximately 0.6 times the MRHD on an AUC basis), increased stillbirths as well as decreased viability and lactation indices were reported. Surviving offspring exhibited lower body weights, developmental delays, and increased delays in auditory startle at doses of 1.0 mg/kg/day or higher. Sexual maturation was delayed in male offspring (preputial separation) at 2.0 mg/kg/day and in female offspring (vaginal opening) at 1.0 mg/kg/day or higher.
8.2Lactation Risk Summary There is no information regarding the presence of lofexidine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Caution should be exercised when lofexidine tablets are administered to a nursing woman. The developmental and health benefits should be considered along with the mother’s clinical need for lofexidine tablets and any other potential adverse effects on breastfed children from lofexidine tablets or from the underlying maternal condition.
8.3Females and Males of Reproductive Potential In animal studies that included some fertility endpoints, lofexidine decreased breeding rate and increased resorptions at exposures below human exposures. The impact of lofexidine on male fertility has not been adequately characterized in animal studies [see Impairment of Fertility (13.1)] .
8.4 Pediatric Use The safety and effec…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary The safety of lofexidine tablets 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. Data Animal Data Increased incidence of resorptions, decreased number of implantations, and a concomitant reduction in the number of fetuses were observed when pregnant rabbits were orally administered lofexidine hydrochloride during organogenesis (from gestation day [GD] 7 to 19) at a daily dose of 5.0 mg/kg/day (approximately 0.08 times the maximum recommended human dose [MRHD] of 2.88 mg lofexidine base on an AUC basis).
Maternal toxicity evidenced by increased mortality was noted at the highest tested dose of 15 mg/kg/day (approximately 0.4 times the MRHD on an AUC basis). Decreased implantations per dam and decreased mean fetal weights were noted in a study in which pregnant rats were treated with oral lofexidine hydrochloride during organogenesis (from GD 7 to 16) at a daily dose of 3.0 mg/kg/day (approximately 0.9 times the MRHD on an AUC basis). This dose was associated with maternal toxicity (decreased body weight gain and mortality).
No malformations or evidence of developmental toxicity were evident at 1.0 mg/kg/day (approximately 0.2 times the MRHD on an AUC basis). A dose-dependent increase in pup mortality was noted in all doses of lofexidine hydrochloride administered orally to pregnant rats from GD 6 through lactation at an exposure less than the human exposure based on AUC comparisons. Doses higher than 1.0 mg/kg/day (approximately 0.2 times the MRHD on an AUC basis) resulted in incidences of total litter loss and maternal toxicity (piloerection and decreased body weight gain).
At the highest dose tested of 2.0 mg/kg/day (approximately 0.6 times the MRHD on an AUC basis), increased stillbirths as well as decreased viability and lactation indices were reported. Surviving offspring exhibited lower body weights, developmental delays, and increased delays in auditory startle at doses of 1.0 mg/kg/day or higher. Sexual maturation was delayed in male offspring (preputial separation) at 2.0 mg/kg/day and in female offspring (vaginal opening) at 1.0 mg/kg/day or higher.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of lofexidine tablets have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use No studies have been performed to characterize the pharmacokinetics of lofexidine tablets or to establish its safety and effectiveness in geriatric patients. Caution should be exercised when lofexidine tablets are administered to patients over 65 years of age. Dosing adjustments similar to those recommended in patients with renal impairment should be considered [see Dosage and Administration (2.3), Use in Specific Populations (8.7)] .
🆘 Overdosage ▾
10 OVERDOSAGE Overdose with lofexidine tablets 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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.
12.2Pharmacodynamics Cardiac Electrophysiology Single lofexidine doses of 1.44 mg to 1.8 mg produced maximum mean change from baseline in QTcF (ΔQTcF) of 14.4 msec (upper two-sided 90% CI: 22.3 msec) and 13.6 msec (17.4 msec) for 1.44 mg and 1.8 mg respectively in healthy normal volunteers. In a Phase 3 placebo-controlled, dose-response study in opioid-dependent subjects, lofexidine was associated with a maximum mean prolongation of the QTcF interval 7.3 (8.8) msec and 9.3 (10.9) msec at doses of 2.16 mg/day and 2.88 mg/day, respectively.
Patients with hepatic impairment Administration of lofexidine to subjects with hepatic impairment was associated with prolongation of the QTc interval, which was more pronounced in subjects with severe hepatic impairment [see Use in Specific Populations (8.6)] . Patients with renal impairment Administration of lofexidine to subjects with renal impairment was associated with prolongation of the QTc interval, which was more pronounced in subjects with severe renal impairment [see Use in Specific Populations (8.7). Lofexidine coadministered with methadone Lofexidine (2.88 mg/day) coadministered with methadone in 18 methadone-maintained patients (80 to 120 mg/day) resulted in a maximum mean increase from methadone-alone baseline in QTcF of 9.1 (14.2) msec.
Lofexidine coadministered with buprenorphine Lofexidine (2.88 mg/day) coadministered with buprenorphine in 21 buprenorphine-maintained patients (16 to 24 mg/day) resulted in a maximum mean QTcF increase of 1.5 (5.6) msec compared to a buprenorphine-alone baseline. In Vitro Binding Lofexidine exhibits in vitro binding affinity and functional agonist activity with alpha-2A and alpha-2C adrenoreceptors at concentrations within clinical exposure plasma levels (K i values of approximately 7.2 nM and 12 nM, and EC 50 values of 4.9 nM and 0.9 nM, respectively).
12.3Pharmacokinetics 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. Administration of lofexidine with food does not alter its pharmacokinetics.
The absolute bioavailability of a single oral lofexidine dose (0.36 mg in solution) compared with an intravenous infusion (0.2 mg infused for 200 minutes) was 72%. Mean lofexidine C max after the oral dose and intravenous infusion was 0.82 ng/mL (at median T max of 3 hours) and 0.64 ng/mL (at median T max of 4 hours), respectively. Mean estimates of overall systemic exposure (AUCinf) were 14.9 ng•h/mL and 12.0 ng•h/mL, respectively.
Distribution Mean lofexidine apparent volume of distribution and volume of distribution values following the administration of an oral dose and an intravenous dose were 480.0 L and 297.9 L, respectively, which are appreciably greater than total body volume, suggesting extensive lofexidine distribution into body tissue. Lofexidine protein binding is approximately 55%. Lofexidine is not preferentially taken up by blood cells.
In a study comparing lofexidine concentrations in plasma and whole blood at the time of peak lofexidine concentrations in human volunteers, it was determined that red blood cells contain approximately 27% the lofexidine concentration of the plasma. Elimination Metabolism From absolute bioavailability results, approximately 30% of the administered lofexidine dose is converted to inactive metabolites during the first pass effect associated with drug absorption from the gut. Lofexidine and its major metabolites did not induce or inhibit any CYP450 isoforms, with the exception of a slight inhibition of CYP2D6 by lofexidine, with an IC50 of 4551 nM (approximately 225 times the steady-state C max for lofexidine with 0.72 mg 4 times daily dosin…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Available as 0.18 mg round, convex-shaped, peach colored, film-coated tablets, debossed with “909” on one side and “N” on other side, free from physical defects. Bottle of 36 tablets NDC 70954-909-10 Bottle of 96 tablets NDC 70954-909-20 Storage Store in original container at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Keep lofexidine tablets away from excess heat and moisture both in the pharmacy and after dispensing.
Do not remove desiccant packs from bottles until all tablets are used. Keep lofexidine tablets and all medicines out of the reach of children.
📋 Description ▾
11 DESCRIPTION Lofexidine tablets contain lofexidine, a central alpha-2 adrenergic agonist, as the hydrochloride salt. Lofexidine hydrochloride is chemically designated as 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5 dihydro-1 H - imidazole monohydrochloride with a molecular formula of C 11 H 12 Cl 2 N 2 O•HCl. Its molecular weight is 295.6 g/mole and its structural formula is: Lofexidine hydrochloride is a white to off-white crystalline powder freely soluble in water, methanol, and ethanol.
It is slightly soluble in chloroform and practically insoluble in n-hexane and benzene. Lofexidine tablets are available as round, convex-shaped, peach colored, film-coated tablets, debossed with “909” on one side and “N” on other side, free from physical defects for oral administration. Each tablet contains 0.18 mg lofexidine, equivalent to 0.2 mg of lofexidine hydrochloride and the following inactive ingredients: lactose, citric acid, povidone, microcrystalline cellulose, calcium stearate, sodium lauryl sulphate, hydroxypropyl cellulose, titanium dioxide, propylene glycol, FD&C yellow No.
6 and FD&C blue No. 2. structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Patient Information). Lofexidine tablets may mitigate, but not completely prevent, the symptoms associated with opioid withdrawal syndrome, which may include feeling sick, stomach cramps, muscle spasms or twitching, feeling of cold, heart pounding, muscular tension, aches and pains, yawning, runny eyes and sleep problems (insomnia). Patients should be advised that withdrawal will not be easy.
Additional supportive measures should be clearly advised, as needed. Hypotension and Bradycardia Inform patients to be alert for any symptoms of low blood pressure or pulse (e.g., dizziness, lightheadedness, or feelings of faintness at rest or upon abruptly standing). Advise patients on how to reduce the risk of serious consequences should hypotension occur (sit or lie down, carefully rise from a sitting or lying position).
Patients being given lofexidine tablets in an outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis and bradycardia and advised to withhold lofexidine tablet doses and contact their healthcare provider for instructions if they experience these signs or related symptoms [see Warnings and Precautions (5.1)] . Advise patients to avoid becoming dehydrated or overheated, which may potentially increase the risks of hypotension and syncope [see Warnings and Precautions (5.1)] .
Concomitant Medications Review with patients all concomitant medications being taken and request that they immediately inform their healthcare provider of any changes in concomitant medications, including any other medications that may be used to treat individual symptoms of withdrawal. Increased Risk of CNS Depression with Concomitant use of CNS Depressant Drugs Inform patients of the increased risk of CNS depression with concomitant use of benzodiazepines, alcohol, barbiturates, or other sedating drugs [see Warnings and Precautions (5.3)] .
Advise patients using lofexidine tablets in an outpatient setting that, until they learn how they respond to lofexidine tablets, they should be careful or avoid doing activities such as driving or operating heavy machinery. Sudden Discontinuation of Lofexidine Tablets Inform patients not to discontinue lofexidine tablets without consulting their healthcare provider [see Warnings and Precautions (5.5)]. Risk of Opioid Overdose After Discontinuation of Opioids Advise patients that after a period of not using opioid drugs, they may be more sensitive to the effects of opioids and at greater risk of overdosing [see Warnings and Precautions (5.4)] .
All trademarks are the property of their respective owners. Distributed by: ANI Pharmaceuticals, Inc. Baudette, MN 56623 Issued: 10/2025 LB4774-02