Lofexidine .18 mg Tablet, Coated, 96-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Drugs used in opioid dependence class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- 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?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Lofexidine Hydrochloride — tap one for details:
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
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.
-
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.
-
UNII 2968PHW8QP
A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
-
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.
-
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.
-
UNII U72Q2I8C85
A mixture of fats derived from coconut oil that acts as an emulsifier and solubilizer. It helps blend oil and water-based ingredients together and improves how the body absorbs certain drugs.
-
UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
-
UNII 532B59J990
Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
-
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.
-
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.
-
UNII H8AV0SQX4D
A modified starch derived from potato or corn starch. It absorbs water quickly and helps tablets or capsules break apart and dissolve in the stomach, acting as a disintegrant to ensure the medicine releases its active ingredients properly.
-
UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
-
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.
13 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
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
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| 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 |
Where does this data come from?
🔁 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 mg 70954-0909-10 | ANI | 36 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 mgthis 14445-0146-96 | Indoco | 96 tablets | — | AB | FDA listed | — |
| Lucemyra .2 mg 78670-0050-03 | USWM, | 36 tablets | — | AB | Discontinued | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 14445-0146-36 | 1 BOTTLE in 1 CARTON (14445-146-36) / 36 TABLET, COATED in 1 BOTTLE | 2024-08-21 | Active |
| 14445-0146-96 You're viewing this | 1 BOTTLE in 1 CARTON (14445-146-96) / 96 TABLET, COATED in 1 BOTTLE | 2024-08-21 | Active |
Pack size FAQ
What quantity is in NDC 14445-0146-96?
What is the difference between NDC 14445-0146-96 and NDC 14445-0146-36?
What NDC number is used to bill for this package of Lofexidine .18 mg Tablet, Coated?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Does this product come in other package sizes?
Who lists this product with the FDA?
Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND 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.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • The usual lofexidine tablets dosage are three 0.18 mg tablets taken orally 4 times daily at 5-to 6-hour intervals lofexidine tablets treatment may be continued for up to14 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 tablets 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 tablets 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 tablets withdrawal symptoms (e.g., reducing by 1 tablet per dose every 1 to 2 days). [see Warnings & Precautions (5.5) ]. The lofexidine tablets dose should be reduced, held, or discontinued for individuals who demonstrate a greater sensitivity to lofexidine tablets side effects [see Adverse Reactions (6.1), Warnings and Precautions (5.1) ].
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 (8.5), 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 (8.6), Clinical Pharmacology (12.3) ]. Table 2: Dosage Recommendations in Patients with Renal Impairment Mild or 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 AND STRENGTHS Lofexidine tablet is available as round, concave-shaped, peach-colored, film-coated tablets, debossed with “C” on one side and “71” on other side. Each tablet contains 0.18 mg lofexidine (equivalent to 0.2 mg of lofexidine hydrochloride). Tablets: 0.18 mg.
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None.
⚠️ 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 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 prolongs 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 potentiates 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 comprehensive management program for treatment of opioid use disorder and inform patients and caregivers of increased risk of overdose. ( 5.4 ) • Risk of Discontiuation 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 tablet 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 tablet 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 tablet should be reduced in amount, delayed, or skipped. Inform patients that lofexidine tablet 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 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 tablet doses when experiencing symptoms of hypotension or bradycardia and to contact their health care provider for guidance on how to adjust dosing. Avoid use lofexidine tablets in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, and in patients with marked bradycardia.
Avoid use 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 tablet prolongs the QT interval. Avoid using lofexidine tablet 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 tablet [see Dosing and Administration (2.1) Adverse Reactions (6.1…
🤒 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 Lambda Therapeutics Research Ltd. at +1-855-642-2594 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 was supported by 3 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 3 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 and for which the incidence in patients treated with lofexidine was greater than the incidence in subjects treated with placebo in a study that tested two doses of lofexidine, 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 tablet 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 tablet 2.16 mg 1 (%)N=229 Lofexidine tablet 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 * 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 tablet but reported in <10% of patients in the lofexidine tablet group included: • Syncope: 0.9%, 1.4% and 0% for lofexidine tablet 2.16 mg/day and 2.88 mg/day and placebo,respectively • Tinnitus: 0.9%, 3.2% and 0% for lofexidine tablet 2.16 mg/day and 2.88 mg/day and placebo,respectively Blood pressure changes and adverse reactions after lofexidine tablet cessation Elevations in blood pressure above normal values (≥ 140 mmHg systolic) and above a subject’s pre-treatment baseline are associated with discontinuing lofexidine tablet, 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 tablet 2.88mg/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 ≥ 170 mmHg and ≥ 20 mmHg increase from baseline 58 23(39.7) 58 5(8.6) 37 6 (16.2) 37 0 Blood pressure elevations of a similar magnitude and incidence were observed in a small number of patients (N=10) that had a one-day, 50% dose redu…
🔄 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 : Comcomitant use may reduce efficacy of oral naltrexone. ( 7.2 ) • CYP2D6 Inhibitors : Concomitant use of paroxetine resulted in increased plasma levels of lofexidine tablets. Monitor for symptoms of orthostasis and bradycardia with concomitant use of a CYP2D6 inhibitor. ( 7.4 )
7.1Methadone Lofexidine tablet and methadone both prolong the QT interval. ECG monitoring is recommended in patients receiving methadone and lofexidine tablet [see Warnings and Precautions (5.2), Clinical Pharmacology (12.3) ].
7.2Oral Naltrexone Coadministration of lofexidine tablet 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 tablet.This interaction is not expected if naltrexone is administered by non-oral routes [see Clinical Pharmacology (12.3) ] .
7.3CNS Depressant Drugs Lofexidine tablet potentiates 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 tablet and paroxetine resulted in 28% increase in the extent of absorption of lofexidine tablet. Monitor for orthostatic hypotension and bradycardia when an inhibitor of CYP2D6 is used concomitantly with lofexidine tablet [see Clinical Pharmacology (12.3) ].
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary The safety of lofexidine tablet 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 indicies.
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).
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 tablet or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Caution should be exercised when lofexidine tablet is administered to a nursing woman. The developmental and health benefits should be considered along with the mother’s clinical need for lofexidine tablet and any other potential adverse effects on breast-fed children from lofexidine tablet 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 be adequately characterized in animal studies [see Impariment of Fertility (13.1) ].
8.4 Pediatric Use The safety and effect…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary The safety of lofexidine tablet 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 indicies.
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).
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 tablet have not been established in pediatric patients.
🧓 Geriatric Use ▾
8.5Geriatric Use No studies have been performed to characterize the pharmacokinetics of lofexidine tablet or establish its safety and effectiveness in geriatric patients. Caution should be exercised when it is 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 (8.6) ].
🆘 Overdosage ▾
10 OVERDOSAGE Overdose with lofexidine tablet 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 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 and 1.8 mg respectively in healthy normal volunteers. In a Phase 3 placebo-controlled, dose-response study in opioid-dependent subjects, lofexidine tablet was associated with a maximum mean prolongation of the QTcF interval 7.3 (8.8) and 9.3 (10.9) msec at doses of 2.16 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 tablet 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 tablet (2.88 mg/day) coadministered with methadone in 18 methadone-maintained patients (80-120 mg/day) resulted in a maximum mean increase from methadone-alone baseline in QTcF of 9.1 (14.2) msec.
Lofexidine tablet coadministered with buprenorphine Lofexidine tablet (2.88 mg/day) coadministered with buprenorphine in 21 buprenorphine-maintained patients (16-24 mg/day) resulted in a maximum mean QTcF increase in QTcF of 15 (5.6) msec compared to a buprenorphine-alone baseline. In Vitro Binding Lofexidine tablet 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 tablet is well absorbed and achieves peak plasma concentration 3 to 5 hours after administration of a single dose. Lofexidine tablet shows approximately dose-proportional pharmacokinetics. Administration of lofexidine tablet with food does not alter its pharmacokinetics.
The absolute bioavailability of a single oral lofexidine tablet dose ( 0.36 mg in solution) compared with an intravenous infusion (0.2 mg infused for 200 minutes) was 72%. Mean lofexidine tablet 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 (AUC inf ) were 14.9 ng•h/mL and 12.0 ng•h/mL, respectively.
Distribution Mean lofexidine tablet 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 tablet distribution into body tissue. Lofexidine tablet protein binding is approximately 55%. Lofexidine tablet is not preferentially taken up by blood cells.
In a study comparing lofexidine tablet concentrations in plasma and whole blood at the time of peak lofexidine tablet concentrations in human volunteers, it was determined that red blood cells contain approximately 27% the lofexidine tablet concentration of the plasma. Elimination Metabolism From absolute bioavailability results, approximately 30% of the administered lofexidine tablet dose is converted to inactive metabolites during the first pass effect associated with drug absorption from the gut. Lofexidine tablet and its major metabolites did not induce or inhibit any CYP450 isoforms, with the exception of a slight inhibition of CYP2D6 by lofe…
🧬 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, concave-shaped, peach colored, film-coated tablets, debossed with “C” on one side and “71” on other side; approximately 7 mm in diameter. Bottle of 36 tablets……………………NDC 14445-146-36 Bottle of 96 tablets……………………NDC 14445-146-96 Storage Store in original container at controlled room temperature, 25°C (77°F); with excursions permitted between 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 tablet is available as round, concave-shaped, peach-colored, film-coated tablets, debossed with “C” on one side and “71” on other side for oral administration. Each tablet contains 0.18 lofexidine, equivalent to 0.2 mg of lofexidine hydrochloride and the following inactive ingredients: 87 mg lactose monohydrate, 12.3 mg citric acid monohydrate, 5.7 mg microcrystalline cellulose, 1.1 mg povidone K-30, 0.70 mg sodium lauryl sulphate, 5.0 mg sodium starch glycolate, 2.0 mg calcium stearate and Opadry AMB II orange 88A530003 (contains polyvinyl alcohol, talc, titanium dioxide, Glyceryl mono and dicaprylocaprate, sodium lauryl sulfate, FD&C yellow #6/sunset yellow FCF aluminum lake and FD&C blue #2/indigo carmine aluminium lake). lofexidine-structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient 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 on 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 tablet 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 the patient all concomitant medications being taken and request that the patient 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 tablet in an outpatient setting that, until they learn how they respond to lofexidine tablet, they should be careful or avoid doing activities such as driving or operating heavy machinery. [see Warnings and Precautions (5.3) ]. Sudden Discontinuation of lofexidine tablet Inform patients not to discontinue lofexidine tablet 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) ].
Manufactured by: INDOCO REMEDIES LTD. L-14, Verna Industrial Area, Verna Goa. 403 722, India.
Revised: 08/2024