Lucemyra

Dosing Information

The usual Lucemyra 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 Lucemyra should not exceed 2.88 mg (16 tablets) and no single dose should exceed 0.72 mg (4 tablets).

Lucemyra treatment may be continued for up to 14 days with dosing guided by symptoms.

Discontinue Lucemyra with a gradual dose reduction over a 2- to 4-day period to mitigate Lucemyra withdrawal symptoms (e.g., reducing by 1 tablet per dose every 1 to 2 days) [see Warnings & Precautions (5.5)]. The Lucemyra dose should be reduced, held, or discontinued for individuals who demonstrate a greater sensitivity to Lucemyra side effects [see Adverse Reactions (6.1), Warnings and Precautions (5.1)]. Lower doses may be appropriate as opioid withdrawal symptoms wane.

Lucemyra can be administered in the presence or absence of food.

Dosage 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)].

Dosage Recommendations for Patients with Renal Impairment

Recommended dosage adjustments based on the degree of renal impairment are shown in Table 2. Lucemyra may be administered without regard to the timing of dialysis [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

Methadone

Lucemyra and methadone both prolong the QT interval. ECG monitoring is recommended in patients receiving methadone and Lucemyra [see Warnings and Precautions (5.2), Clinical Pharmacology (12.3)].

Oral Naltrexone

Coadministration of Lucemyra 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 Lucemyra. This interaction is not expected if naltrexone is administered by non-oral routes [see Clinical Pharmacology (12.3)].

CNS Depressant Drugs

Lucemyra 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)].

CYP2D6 Inhibitor - Paroxetine

Coadministration of Lucemyra and paroxetine resulted in 28% increase in the extent of absorption of Lucemyra. Monitor for orthostatic hypotension and bradycardia when an inhibitor of CYP2D6 is used concomitantly with Lucemyra [see Clinical Pharmacology (12.3)].

Pregnancy

Risk Summary

The safety of Lucemyra 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). 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.

Lactation

Risk Summary

There is no information regarding the presence of Lucemyra or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Caution should be exercised when Lucemyra is administered to a nursing woman.

The developmental and health benefits should be considered along with the mother's clinical need for Lucemyra and any other potential adverse effects on breastfed children from Lucemyra or from the underlying maternal condition.

Females 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)].

Pediatric Use

The safety and effectiveness of Lucemyra have not been established in pediatric patients.

Geriatric Use

No studies have been performed to characterize the pharmacokinetics of Lucemyra 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 (8.7)].

Hepatic Impairment

Hepatic impairment slows the elimination of Lucemyra but exhibits less effect on the peak plasma concentration than on AUC values following a single dose. Dosage adjustments are recommended based on the degree of hepatic impairment. [see Dosage and Administration (2.2), Clinical Pharmacology (12.2)].

Clinically relevant QT prolongation may occur in subjects with hepatic impairment [see Warnings and Precautions (5.2), Clinical Pharmacology (12.2)].

Renal Impairment

Renal impairment slows the elimination of Lucemyra but exhibits less effect on the peak plasma concentration than on AUC values following a single dose. Dosage adjustments are recommended based on the degree of renal impairment [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].

Only a negligible fraction of the Lucemyra dose is removed during a typical dialysis session, so no additional dose needs to be administered after a dialysis session; Lucemyra may be administered without regard to the timing of dialysis [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].

Clinically relevant QT prolongation may occur in subjects with renal impairment [see Warnings and Precautions (5.2), Clinical Pharmacology (12.2)].

CYP2D6 Poor Metabolizers

Although the pharmacokinetics of Lucemyra have not been systematically evaluated in patients who do not express the drug metabolizing enzyme CYP2D6, it is likely that the exposure to Lucemyra would be increased similarly to taking strong CYP2D6 inhibitors (approximately 28%). Monitor adverse events such as orthostatic hypotension and bradycardia in known CYP2D6 poor metabolizers. Approximately 8% of Caucasians and 3–8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM) [see Clinical Pharmacology (12.3)].

Overdose with Lucemyra 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

No adequate long-term animal studies have been completed to evaluate the carcinogenic potential of lofexidine.

Mutagenesis

Lofexidine tested positive in the in vitro mouse lymphoma assay. Lofexidine tested negative in the in vitro bacterial reverse mutation assay (Ames assay) and in the in vivo rat micronucleus assay.

Impairment of Fertility

In a female fertility study in rabbits, fertility was not adversely impacted by administration of lofexidine hydrochloride up to 6.4 mg/kg/day (approximately 0.1 times the MRHD of 2.88 mg on an AUC basis) when administered orally to female rabbits starting 2 weeks prior to mating and through gestation and lactation. However, decreased breeding rate and higher post-implantation loss was observed at this dose, which correlated with higher resorptions and reduced litter size. Maternal toxicity, which included increased mortality rate, reduced body weight gain, and moderate sedation was observed at 6.4 mg/kg/day. The NOAEL for female fertility was 6.4 mg/kg/day and the NOAEL for female-mediated developmental parameters was 0.4 mg/kg/day (approximately 0.005 times the MRHD on an AUC basis).

In a fertility study in rats, fertility was unaffected by administration of lofexidine up to 0.88 mg/kg/day (approximately 0.2 times the MRHD on an AUC basis) via diet to male and female rats prior to mating and to the dams through gestation and lactation. No evidence of maternal toxicity was observed. However, no assessment of sperm or reproductive organs were performed in this study.

Reduced testes, epididymis, and seminiferous tubule weights, as well as delayed sexual maturation of males and females and decreases in the number of corpora lutea and implantations after mating, were noted in offspring of pregnant rats administered lofexidine hydrochloride orally from GD 6 through lactation at exposures less than the human exposure based on AUC comparisons.

Rx only
NDC 27505-050-96

Lucemyra™
(lofexidine) tablets

0.18 mg

Store and dispense
in original container.

Protect from heat and moisture.
Do not remove desiccants.
Keep the bottle tightly closed.

Keep out of reach of children.
96 tablets

US WorldMeds™

Medical Disclaimer

Lofexidine hydrochloride is an alpha-adrenergic agonist.1

Contraindications

None.1

Warnings/Precautions

Risk of Hypotension, Bradycardia, and Syncope

Lofexidine hydrochloride can cause a decrease in blood pressure, a decrease in pulse, and syncope. Monitor vital signs before dosing. Monitor symptoms related to bradycardia and orthostasis.1

Patients being given lofexidine hydrochloride 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 hydrochloride should be reduced in amount, delayed, or skipped.1

Inform patients that lofexidine hydrochloride 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 hydrochloride doses when experiencing symptoms of hypotension or bradycardia and to contact their healthcare provider for guidance on how to adjust dosing.1

Avoid using lofexidine hydrochloride in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, and in patients with marked bradycardia.1

Avoid using lofexidine hydrochloride in combination with medications that decrease pulse or blood pressure to avoid the risk of excessive bradycardia and hypotension.1

Risk of QT Prolongation

Lofexidine hydrochloride prolongs the QT interval.1

Avoid using lofexidine hydrochloride in patients with congenital long QT syndrome.1

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 hydrochloride.1

Increased Risk of Central Nervous System Depression with Concomitant Use of CNS Depressant Drugs

Lofexidine hydrochloride potentiates the CNS depressive effects of benzodiazepines and can also be expected to potentiate the CNS depressive effects of alcohol, barbiturates, and other sedating drugs. Advise patients to inform their healthcare provider of other medications they are taking, including alcohol.1

Advise patients using lofexidine hydrochloride in an outpatient setting that, until they learn how they respond to lofexidine hydrochloride, they should be careful or avoid doing activities such as driving or operating heavy machinery.1

Increased Risk of Opioid Overdose After Opioid Discontinuation

Lofexidine hydrochloride is not a treatment for opioid use disorder. Patients who complete opioid discontinuation are likely to have a reduced tolerance to opioids and are at increased risk of fatal overdose should they resume opioid use. Use lofexidine hydrochloride in patients with opioid use disorder only in conjunction with a comprehensive management program for the treatment of opioid use disorder and inform patients and caregivers of this increased risk of overdose.1

Risk of Discontinuation Symptoms

Stopping lofexidine hydrochloride abruptly can cause a marked rise in blood pressure. Symptoms including diarrhea, insomnia, anxiety, chills, hyperhidrosis, and extremity pain have also been observed with lofexidine hydrochloride discontinuation. Instruct patients not to discontinue therapy without consulting their healthcare provider. When discontinuing therapy with lofexidine hydrochloride tablets, gradually reduce the dose.1

Symptoms related to discontinuation can be managed by administration of the previous lofexidine hydrochloride dose and subsequent taper.1

Specific Populations

Risk Summary: The safety of lofexidine hydrochloride 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.1

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.1

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 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).1

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 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 mg/kg/day (approximately 0.2 times the MRHD on an AUC basis).1

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 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 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 mg/kg/day or higher. Sexual maturation was delayed in male offspring (preputial separation) at 2 mg/kg/day and in female offspring (vaginal opening) at 1 mg/kg/day or higher.1

There is no information regarding the presence of lofexidine hydrochloride or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Caution should be exercised when lofexidine hydrochloride is administered to a nursing woman.1

The developmental and health benefits should be considered along with the mother's clinical need for lofexidine hydrochloride and any other potential adverse effects on breastfed children from lofexidine hydrochloride or from the underlying maternal condition.1

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.1

The safety and effectiveness of lofexidine hydrochloride have not been established in pediatric patients.1

No studies have been performed to characterize the pharmacokinetics of lofexidine hydrochloride 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.1

Hepatic impairment slows the elimination of lofexidine hydrochloride but exhibits less effect on the peak plasma concentration than on AUC values following a single dose. Dosage adjustments are recommended based on the degree of hepatic impairment.1

Clinically relevant QT prolongation may occur in subjects with hepatic impairment.1

Renal impairment slows the elimination of lofexidine hydrochloride but exhibits less effect on the peak plasma concentration than on AUC values following a single dose. Dosage adjustments are recommended based on the degree of renal impairment.1

Only a negligible fraction of the lofexidine hydrochloride dose is removed during a typical dialysis session, so no additional dose needs to be administered after a dialysis session; lofexidine hydrochloride may be administered without regard to the timing of dialysis.1

Clinically relevant QT prolongation may occur in subjects with renal impairment.1

Although the pharmacokinetics of lofexidine hydrochloride have not been systematically evaluated in patients who do not express the drug metabolizing enzyme CYP2D6, it is likely that the exposure to lofexidine hydrochloride would be increased similarly to taking strong CYP2D6 inhibitors (approximately 28%). Monitor adverse events such as orthostatic hypotension and bradycardia in known CYP2D6 poor metabolizers. Approximately 8% of Caucasians and 3–8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM).1

Common Adverse Effects

Most common adverse reactions (incidence ≥10% and notably more frequent than placebo) are orthostatic hypotension, bradycardia, hypotension, dizziness, somnolence, sedation, and dry mouth.1

Use Lucemyra (lofexidine) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• Do not take naltrexone within 2 hours before or 2 hours after Lucemyra (lofexidine).

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Dizziness or passing out.
• Slow heartbeat.
• A type of abnormal heartbeat (prolonged QT interval) can happen with Lucemyra (lofexidine). Call your doctor right away if you have a fast heartbeat, a heartbeat that does not feel normal, or if you pass out.

• Store at room temperature.
• Protect from heat.
• Store in a dry place. Do not store in a bathroom.
• Store in the original container. Do not take out the antimoisture cube or packet.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Lucemyra (lofexidine), please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

You may take lofexidine with or without food.

You may need to take lofexidine for up to 14 days. Your doctor will change your dose or stop this treatment based on your opioid withdrawal symptoms. Follow all dosing instructions very carefully.

Lofexidine may not completely prevent all symptoms of opioid withdrawal, which may include yawning, pounding heartbeats, watery eyes, feeling cold, stomach pain, feeling sick, body aches, muscle tightness, or trouble sleeping.

You may need additional forms of counseling, support, and/or monitoring as you go through opioid withdrawal.

Lofexidine can cause serious side effects on your heart or blood vessels. Call your doctor at once if you have slow heartbeats, severe dizziness, or a light-headed feeling (like you might pass out). If you have these side effects, do not take your next lofexidine dose until you talk with your doctor.

You should not stop using lofexidine suddenly, or you could have a rapid increase in blood pressure and unpleasant symptoms. Follow your doctor's instructions about tapering your dose.

Store at room temperature away from moisture and heat. Keep the tablets in their original container, along with the packet or canister of moisture- absorbing preservative.

If you start using opioid medication after a long period of not using it, you will be more sensitive to opioid effects. This could increase your risk of overdose and death.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Use the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not use two doses at one time.