lofexidine (Rx)

Brand and Other Names:Lucemyra
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 0.18mg

Opioid Withdrawal

Indicated for mitigation of withdrawal symptoms to facilitate abrupt opioid discontinuation in adults; for short-term use (see Dosing Considerations)

Starting dose: Three 0.18-mg tablets (0.54 mg) PO QID (5-6 hr between doses) during the period of peak withdrawal symptoms (generally the first 5-7 days after last opioid use)

Not to exceed a total daily dose of 2.88 mg (16 tablets)

No single dose should exceed 0.72 mg (4 tablets)

Treatment may be continued for up to 14 days with dosing guided by symptoms

Dose should be reduced, held, or discontinued for individuals who demonstrate a greater sensitivity

Lower doses may be appropriate as opioid withdrawal symptoms wane

Discontinue by gradually reducing dose over a 2- to 4-day period to mitigate lofexidine withdrawal symptoms (eg, reducing by 1 tablet per dose every 1-2 days) (see Cautions)

Dosage Modifications

Hepatic impairment

  • Mild (Child-Pugh score 5-6): 3 tablets QID (2.16 mg/day)
  • Moderate (Child-Pugh score 7-9): 2 tablets QID (1.44 mg/day)
  • Severe (Child-Pugh score >9): 1 tablet QID (0.72 mg/day)

Renal impairment

  • Mild or moderate (eGFR 30-89.9 mL/min/1.73 m²): 2 tablets QID (1.44 mg/day)
  • Severe (eGFR <30 mL/min/1.73 m²), ESRD, or dialysis: 1 tablet QID (0.72 mg/day)
  • May be administered without regard to timing of dialysis

Dosing Considerations

While lofexidine may lessen the severity of withdrawal symptoms, it may not completely prevent them and is only approved for treatment for up to 14 days

Not a treatment for opioid use disorder (OUD), but can be used as part of a broader, long-term treatment plan for managing OUD

Safety and efficacy not established

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Interactions

Interaction Checker

and lofexidine

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            Adverse Effects

            >10%

            Insomnia (51-55%)

            Orthostatic hypotension (29-42%)

            Bradycardia (24-32%)

            Hypotension (30%)

            Dizziness (19-23%)

            Somnolence (11-13%)

            Sedation (12-13%)

            Dry mouth (10-11%)

            1-10%

            Syncope: (0.9-1.4%)

            Tinnitus: (0.9-3.2%)

            Postmarketing Reports

            There has been one report of QT prolongation, bradycardia, torsades de pointes, and cardiac arrest with successful resuscitation in a patient who received lofexidine and three reports of clinically significant QT prolongation in subjects concurrently receiving methadone with lofexidine

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            Warnings

            Contraindications

            None

            Cautions

            May cause hypotension, bradycardia, and syncope; monitor vital signs before dosing and symptoms related to bradycardia and orthostasis; avoid use in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, and in patients with marked bradycardia

            Increased risk of QT prolongation; monitor ECG in congestive heart failure, bradyarrhythmias, hepatic impairment, renal impairment, or patients taking medications that lead to QT prolongation (eg, methadone); correct any electrolyte abnormalities (eg, hypokalemia, hypomagnesemia) prior to initiating treatment

            Patients administering therapy in outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms; instruct outpatients to withhold doses when experiencing symptoms of hypotension or bradycardia and to contact health care provider for guidance on how to adjust dosing; if clinically significant or symptomatic hypotension and/or bradycardia occur, next dose should be reduced in amount, delayed, or skipped

            Increased risk of opioid overdose after opioid discontinuation

            • 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 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

            Sudden discontinuation of treatment

            • Stopping abruptly can cause a marked rise in blood pressure; symptoms including diarrhea, insomnia, anxiety, chills, hyperhidrosis, and extremity pain have been observed with discontinuation
            • Instruct patients not to discontinue therapy without consulting their healthcare provider
            • When discontinuing therapy with tablets, gradually reduce the dose (see Dosing)
            • Manage symptoms related to discontinuation by administering the previous dose and subsequent taper

            Drug interaction overview

            • Avoid use in combination with medications that decrease pulse or blood pressure to avoid the risk of excessive bradycardia and hypotension
            • Methadone and lofexidine both prolong the QT interval; monitor ECG when used concomitantly
            • Coadministration with naltrexone may reduce efficacy of oral naltrexone
            • Coadministration with 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
            • Coadministration with CNS depressants
              • Lofexidine potentiates CNS depressive effects of benzodiazepines and is expected to potentiate CNS depressive effects of alcohol, barbiturates, and other sedating drugs
              • Advise patients to inform healthcare provider of other medications they are taking, including alcohol
              • In an outpatient setting, advise patients to be careful or to avoid doing activities such as driving or operating heavy machinery
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            Pregnancy

            Pregnancy

            There are no available data regarding use in pregnant women

            Animal data

            • In animal studies, lofexidine decreased breeding rate and increased resorptions at exposures below human exposure
            • Impact of lofexidine on male fertility has not be adequately characterized in animal studies

            Lactation

            No information is available regarding the presence of lofexidine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production

            Caution if administered to breastfeeding women

            The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Centrally acting alpha2-agonist that binds to receptors on adrenergic neurons; this reduces the release of norepinephrine and decreases sympathetic tone

            Absorption

            Absolute bioavailability: 72%

            Peak plasma time: 3-5 hr (single dose)

            Peak plasma concentration: 0.82 mg/mL (3 hr); 0.64 ng/mL (4 hr)

            AUC: 14.9 ng·hr/mL (3 hr); 12 ng·hr/mL (4 hr)

            Shows approximately dose-proportional pharmacokinetics

            Food does not alter pharmacokinetics

            Distribution

            Protein bound: 55%

            Vd: 480 L (PO); 297.9 L (IV); extensive distribution into body tissue

            Not preferentially taken up by blood cells

            Metabolism

            ~30% of administered dose is converted to inactive metabolites during first-pass effect associated with drug absorption from the gut

            Hepatic metabolized by CYP2D6 (major), CYP1A2 (minor), and CYP2C19 (minor)

            Elimination

            Half-life: ~12 hr

            Half-life, terminal: 11-13 hr (first dose); 17-22 hr (steady-state)

            Clearance: 17.6 L/hr

            Pharmacogenomics

            CYP2D6 poor metabolizers

            • Likely that lofexidine exposure would be increased similarly to taking strong CYP2D6 inhibitors (~28%) by CYP2D6 poor metabolizers
            • Monitor adverse events (eg, orthostatic hypotension, bradycardia) in known CYP2D6 poor metabolizers
            • ~8% of whites and 3-8% of blacks cannot metabolize CYP2D6 substrates and are classified as poor metabolizers
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            Administration

            Oral Administration

            May take with or without food

            Storage

            Store in original container at controlled room temperature 25°C (77°F); excursions permitted between 15-30°C (59-86°F)

            Keep 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

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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.