Lucemyra
(lofexidine)Dosage & Administration
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Lucemyra Prescribing Information
LUCEMYRA is indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.
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 Warnings and Precautions (5.1), Adverse Reactions (6.1)]. 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)].
| 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) |
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)].
| Moderate Impairment | Severe Impairment, End-Stage Renal Disease, or on Dialysis | |
|---|---|---|
| Estimated GFR, mL/min/1.73 m2 | 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) |
LUCEMYRA is available as round, peach-colored, film-coated tablets, imprinted with "LFX" on one side and "18" on the other side. Each tablet contains 0.18 mg lofexidine (equivalent to 0.2 mg of lofexidine hydrochloride).
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). 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.
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 to establish its safety and effectiveness in geriatric patients. Caution should be exercised when LUCEMYRA 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 (12.3)].
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 to 8% of Black/African Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM) [see Clinical Pharmacology (12.3)].
None.
Risk of Hypotension, Bradycardia, and Syncope
LUCEMYRA 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 LUCEMYRA 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 LUCEMYRA should be reduced in amount, delayed, or skipped.
Inform patients that LUCEMYRA 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 LUCEMYRA doses when experiencing symptoms of hypotension or bradycardia and to contact their healthcare provider for guidance on how to adjust dosing.
Avoid using LUCEMYRA in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, and in patients with marked bradycardia.
Avoid using LUCEMYRA in combination with medications that decrease pulse or blood pressure to avoid the risk of excessive bradycardia and hypotension.
Risk of QT Prolongation
LUCEMYRA prolongs the QT interval.
Avoid using LUCEMYRA 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 LUCEMYRA [see Dosing and Administration (2.1), Adverse Reactions (6.1), Special Populations (8.6, 8.7), Clinical Pharmacology (12.2)].
Increased Risk of Central Nervous System Depression with Concomitant use of CNS Depressant Drugs
LUCEMYRA 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.
Advise patients using LUCEMYRA in an outpatient setting that, until they learn how they respond to LUCEMYRA, they should be careful or avoid doing activities such as driving or operating heavy machinery.
Increased Risk of Opioid Overdose after Opioid Discontinuation
LUCEMYRA 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 LUCEMYRA 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.
Risk of Discontinuation Symptoms
Stopping LUCEMYRA abruptly can cause a marked rise in blood pressure. Symptoms including diarrhea, insomnia, anxiety, chills, hyperhidrosis, and extremity pain have also been observed with LUCEMYRA discontinuation. Instruct patients not to discontinue therapy without consulting their healthcare provider. When discontinuing therapy with LUCEMYRA, gradually reduce the dose [see Dosing and Administration (2.1)].
Symptoms related to discontinuation can be managed by administration of the previous LUCEMYRA dose and subsequent taper.