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Lofexidine

Medically reviewed on Sep 10, 2018

Pronunciation

(loe FEX i deen)

Index Terms

  • Lofexidine Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Lucemyra: 0.18 mg [contains fd&c blue #2 (indigotine), fd&c yellow #6 (sunset yellow)]

Brand Names: U.S.

  • Lucemyra

Pharmacologic Category

  • Alpha2-Adrenergic Agonist

Pharmacology

Lofexidine is a central alpha-2 adrenergic agonist that reduces the release of norepinephrine and decreases sympathetic tone. It binds to alpha-2A (ki=7.2 nM) and alpha-2C (ki=12 nM) adrenoreceptors. Due to its high selectivity for the alpha-2A receptor, lofexidine is thought to be associated with less anti-hypertensive activity than clonidine (Gish 2010).

Absorption

Well-absorbed

Distribution

Oral: Vd apparent = 480 L; IV: Vd = 297.9 L

Metabolism

First pass effect associated with gut absorption (~30% of the dose is converted to inactive metabolites); hepatic via CYP2D6 (primary), CYP1A2 and CYP2C19

Excretion

Urine (93.5%; 15% to 20% unchanged); feces (0.92%)

Time to Peak

3 to 5 hours

Half-Life Elimination

11 to 13 hours (first dose); 17 to 22 hours (steady state)

Protein Binding

~55%

Special Populations: Renal Function Impairment

Cmax, AUC and half-life increased slightly with the severity of renal impairment.

Special Populations: Hepatic Function Impairment

Half-life was prolonged in patients with hepatic impairment.

Use: Labeled Indications

Opioid withdrawal: Mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Opioid withdrawal: Oral: Initial: 0.54 mg 4 times daily (every 5 to 6 hours) during peak withdrawal symptoms (generally the first 5 to 7 days after last opioid use); adjust dosing based on tolerability and withdrawal symptoms and may continue for up to 14 days if needed; maximum dose: 0.72 mg/dose or 2.88 mg/day. Note: Lower doses may be appropriate as opioid withdrawal symptoms wane.

Discontinuation of therapy: Decrease dose gradually over 2 to 4 days (eg, reduce by 0.18 mg per dose every 1 to 2 days).

Dosing: Geriatric

Refer to adult dosing; use with caution; consider lower doses

Administration

Oral: Administer with or without food.

Storage

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from excess heat and moisture.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Beta-Blockers: Alpha2-Agonists may enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Levobunolol; Metipranolol. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Avoid combination

CNS Depressants: Lofexidine may enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Lofexidine. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

FLUoxetine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hydroxychloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Macimorelin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Methadone: Lofexidine may enhance the QTc-prolonging effect of Methadone. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Mirtazapine: May diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding concurrent use. If the combination cannot be avoided, monitor for decreased effects of alpha2-agonists if mirtazapine is initiated/dose increased, or increased effects if mirtazapine is discontinued/dose decreased. Consider therapy modification

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naltrexone: Lofexidine may decrease the serum concentration of Naltrexone. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Probucol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Promazine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

QTc-Prolonging Agents (Highest Risk): QTc-Prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Avoid combination

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

QTc-Prolonging Agents (Moderate Risk): May enhance the QTc-prolonging effect of other QTc-Prolonging Agents (Moderate Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May diminish the antihypertensive effect of Alpha2-Agonists. Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Tricyclic Antidepressants: May diminish the antihypertensive effect of Alpha2-Agonists. Consider therapy modification

Vinflunine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Xipamide: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Orthostatic hypotension (29% to 42%), bradycardia (24% to 32%), hypotension (30%)

Central nervous system: Insomnia (51% to 55%), dizziness (19% to 23%), sedation (12% to 13%), drowsiness (11% to 13%)

Gastrointestinal: Xerostomia (10% to 11%)

1% to 10%

Cardiovascular: Syncope (≤1%)

Otic: Tinnitus (≤3%)

<1%, postmarketing, and/or case reports: Prolonged QT interval on ECG, torsades de pointes

Warnings/Precautions

Concerns related to adverse effects:

• Accidental opioid overdose: Lofexidine is not a treatment for opioid use disorder, and it should be used only in conjunction with a comprehensive management program for the treatment of opioid use disorder. Patients who had been treated with lofexidine may respond to lower opioid doses than previously used. This could result in potentially life-threatening opioid overdose. Patients should be aware that they may be more sensitive to lower doses of opioids after lofexidine treatment is discontinued, after a missed dose, or near the end of the dosing interval.

• Cardiovascular effects: May cause syncope or a decrease in blood pressure or heart rate; monitor vital signs before dosing and observe for symptoms of bradycardia and syncope. Reduce dose or interrupt therapy if clinically significant bradycardia and/or hypotension occur. Avoid use in patients with severe coronary insufficiency, recent myocardial infarction, significant bradycardia, cerebrovascular disease, and chronic renal failure.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• QT prolongation: May cause QT prolongation; avoid use in patients with congenital long QT syndrome. Monitor ECG in at-risk patients (heart failure, bradyarrhythmias, hepatic impairment, renal impairment, concomitant QT-prolonging medications). In patients with electrolyte abnormalities, correct abnormality first, then monitor ECG before initiating lofexidine.

Disease-related concerns:

• Hepatic impairment: Prolongation of the QTc interval is more pronounced in patients with severe hepatic impairment. Use caution in patients with hepatic impairment.

• Renal impairment: Prolongation of the QTc interval is more pronounced in patients with severe renal impairment. Use caution in patients with renal impairment; avoid use in patients with chronic renal failure.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• CYP2D6 poor metabolizers: Exposure to lofexidine may be increased; monitor for orthostasis and bradycardia.

Other warnings/precautions:

• Discontinuation of therapy: Discontinuing lofexidine abruptly may result in a marked rise in blood pressure, anxiety, chills, diarrhea, extremity pain, hyperhidrosis and insomnia. When discontinuing therapy, treatment should be gradually reduced to avoid these symptoms. Do not abruptly discontinue.

Monitoring Parameters

Blood pressure; heart rate; electrolytes and ECG at baseline in at-risk populations; opioid withdrawal symptoms

Pregnancy Considerations

Information related to the use of lofexidine in pregnancy is limited (Akhurst 2000). Abrupt discontinuation of opioid therapy in dependent females is generally not recommended during pregnancy (Kampman 2015).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience insomnia, fatigue, or dry mouth. Have patient report immediately to prescriber dizziness, passing out, bradycardia, abnormal heartbeat, or tachycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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