Lofexidine (Lucemyra) is an alpha-2A adrenergic receptor agonist that is used to help patients with symptoms of opioid withdrawal.
Lofexidine (Lucemyra) Uses:
-
Opioid withdrawal:
- It is indicated for the relief of opioid withdrawal symptoms to facilitate the abrupt discontinuation of opioids in adults.
Lofexidine (Lucemyra) Dose in Adults:
Lofexidine (Lucemyra) Dosing in the Opioid withdrawal:
- Initial: 0.54 mg orally four times a day administered every 5 to 6 hours) during peak withdrawal symptoms (generally for the first 5 to 7 days after last opioid use);
- Adjust the dose based on the patient's tolerability and withdrawal symptoms.
- The treatment may be continued for up to 14 days if needed.
- The maximum dose is 0.72 mg/dose or 2.88 mg/day.
Note: Lower doses may be more appropriate as opioid withdrawal symptoms reduce.
-
Discontinuation of therapy:
- Reduce the dose gradually over 2 - 4 days (eg, reduce by 0.18 mg per dose every 1 to 2 days).
Use in Children:
Not indicated.
Lofexidine (Lucemyra) Pregnancy Risk Category: N
- Its use in pregnancy is not known.
- It is not advised to abruptly stop opioid therapy for patients who are opioid dependent during pregnancy.
Lofexidine use during breastfeeding:
- It is unknown if the drug will be excreted into breastmilk.
- The manufacturer suggests that lactating mothers use the drug with caution. Consider the health benefits for the mother and infant, as well as the benefits to breastfeeding during treatment.
Lofexidine (Lucemyra) Dosing in Kidney Disease:
- eGFR ≥90 mL/minute/1.73 m²:
- No dose adjustment is necessary.
- eGFR 30 to 89.9 mL/minute/1.73 m²:
- 0.36 mg four times a day.
- eGFR <30 mL/minute/1.73 m²:
- 0.18 mg four times a day.
- ESRD or on hemodialysis:
- 0.18 mg four times a day.
- It is minimally dialyzable and may be administered without regard to the timing of dialysis
Lofexidine (Lucemyra) Dosing in Liver disease:
- Mild impairment (Child-Pugh class A):
- No dose adjustment is necessary.
- Moderate impairment (Child-Pugh class B):
- 0.36 mg four times a day.
- Severe impairment (Child-Pugh class C):
- 0.18 mg four times a day.
Common Side Effects of Lofexidine (Lucemyra):
-
Cardiovascular:
- Orthostatic hypotension
- Bradycardia
- Hypotension
-
Central nervous system:
- Insomnia
- Dizziness
- Sedation
- Drowsiness
-
Gastrointestinal:
- Xerostomia
Less Common Side Effects of Lofexidine (Lucemyra):
-
Cardiovascular:
- Syncope
-
Otic:
- Tinnitus
Contraindications to Lofexidine (Lucemyra):
The manufacturer's labeling does not contain any contraindications.
Warnings and precautions
-
Accidental opioid overdose:
- Not using lofexidine as a treatment for opioid abuse disorder is a mistake.
- It should only be used in conjunction with a comprehensive program for opioid use disorder management and treatment.
- Patients could become more sensitive to lower opioid doses, which could lead to a potentially fatal opioid overdose.
- Patients should be aware that they might be more sensitive to lower opioid doses if lofexidine treatment is stopped, missed or at the end of a dosing period.
-
Cardiovascular effects
- The drug can cause hypotension, syncope or bradycardia.
- Before taking the drug, it is important to monitor vital signs and look out for symptoms such as syncope or bradycardia.
- Patients with significant hypotension or bradycardia should stop receiving treatment.
- Patients with severe heart disease, recent myocardial injury, bradycardia, and patients with chronic kidney disease, as well as those with cerebrovascular disease, should not use the drug.
-
CNS depression:
- It can cause CNS depression, which may lead to impairment of mental or physical abilities.
- People who are required to be alert for tasks such as operating heavy machinery or performing other mental functions should be aware that the drug is not recommended.
-
Extension of QT
- QT interval prolongation has been linked to the use of this drug. Patients with congenital long QT syndrome should avoid it.
- ECG monitoring should be done for patients at high risk of QT interval prolongation. Patients at high risk include patients with heart disease, bradyarrhythmias and kidney disease.
- Pre-existing electrolyte imbalances should be addressed and monitored before the drug is initiated.
-
Hepatic impairment
- QTc prolongation is more likely in patients with severe hepatic impairment.
- Patients with hepatic impairment must be cautious when taking the drug.
-
Renal impairment
- QTc interval prolongation is more common in patients with severe renal impairment.
- Patients with severe renal impairment should use it with caution. Patients with chronic kidney failure should avoid using it.
Lofexidine: Drug Interaction
|
Alfuzosin |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). |
|
Benperidol |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Blood Pressure Lowering Agents |
May enhance the hypotensive effect of HypotensionAssociated Agents. |
|
Bradycardia-Causing Agents |
May enhance the bradycardic effect of other Bradycardia-Causing Agents. |
|
Brimonidine (Topical) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Chloroquine |
|
|
Clofazimine |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTcprolonging effect of Clofazimine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
CNS Depressants |
Lofexidine may enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Exceptions: Amisulpride; CloZAPine; Droperidol; Flupentixol; OLANZapine; QUEtiapine; RisperiDONE; Thioridazine. |
|
CYP2D6 Inhibitors (Strong) |
May increase the serum concentration of Lofexidine. |
|
Diazoxide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
DULoxetine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. |
|
Gadobenate Dimeglumine |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Halofantrine |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTcprolonging effect of Halofantrine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Haloperidol |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTcprolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Herbs (Hypotensive Properties) |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Hypotension-Associated Agents |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. |
|
Ivabradine |
Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. |
|
Lacosamide |
Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. |
|
Levodopa-Containing Products |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. |
|
Lormetazepam |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Midodrine |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Molsidomine |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Naftopidil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Naltrexone |
Lofexidine may decrease the serum concentration of Naltrexone. |
|
Nicergoline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nicorandil |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Nitroprusside |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. |
|
Ondansetron |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTcprolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Pentamidine (Systemic) |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Pentoxifylline |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Pholcodine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. |
|
Phosphodiesterase 5 Inhibitors |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
Prostacyclin Analogues |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
QT-prolonging Antidepressants (Moderate Risk) |
May enhance the QTc-prolonging effect of Lofexidine. Lofexidine may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Doxepin (Systemic); Doxepin (Topical). |
|
QT-prolonging Antipsychotics (Moderate Risk) |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Pimozide. |
|
QT-prolonging Class IC Antiarrhythmics (Moderate Risk) |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
QT-prolonging Kinase Inhibitors (Moderate Risk) |
May enhance the QTc-prolonging effect of QTprolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
QT-prolonging Miscellaneous Agents (Moderate Risk) |
May enhance the QTc-prolonging effect of Lofexidine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Chloroquine; Clofazimine; Domperidone; Gadobenate Dimeglumine; Halofantrine. |
|
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) |
May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
QT-prolonging Quinolone Antibiotics (Moderate Risk) |
QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
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Quinagolide |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. |
|
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. |
|
Serotonin/Norepinephrine Reuptake Inhibitors |
May diminish the antihypertensive effect of Alpha2-Agonists. |
|
Terlipressin |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Tofacitinib |
May enhance the bradycardic effect of Bradycardia-Causing Agents. |
|
Risk Factor D (Consider therapy modification) |
|
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Ajmaline |
Lofexidine may enhance the QTc-prolonging effect of Ajmaline. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
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. |
|
Amiodarone |
Lofexidine may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
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. |
|
Domperidone |
|
|
Doxepin-Containing Products |
May enhance the QTc-prolonging effect of Lofexidine. Lofexidine may enhance the QTc-prolonging effect of Doxepin-Containing Products. Doxepin-Containing Products may diminish the therapeutic effect of Lofexidine. Management: Consider avoiding this combination when possiblke. Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
Dronedarone |
Lofexidine may enhance the QTc-prolonging effect of Dronedarone. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Methadone |
Lofexidine may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. |
|
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. |
|
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. |
|
QT-prolonging Agents (Highest Risk) |
May enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Ajmaline; Amiodarone; Dronedarone; Methadone; Sotalol. |
|
Siponimod |
Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. |
|
Sotalol |
Lofexidine may enhance the QTc-prolonging effect of Sotalol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. |
|
Tricyclic Antidepressants |
May diminish the therapeutic effect of Lofexidine. Management: Consider avoiding this drug combination when possible. If concurrent administration is required, monitor blood pressure carefully at the beginning of the combined therapy and when either drug is stopped. Adjust the dosage accordingly. Exceptions: Doxepin (Systemic); Doxepin (Topical). |
|
Risk Factor X (Avoid combination) |
|
|
Bromperidol |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. |
|
Fexinidazole [INT] |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). |
|
Fexinidazole [INT] |
Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. |
|
Pimozide |
May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). |
|
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) |
May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). |
Monitoring parameters:
- Blood pressure;
- heart rate;
- Monitor electrolytes and ECG at baseline in at-risk populations;
- Observe for opioid withdrawal symptoms
How to administer Lofexidine (Lucemyra)?
It is administered orally with or without food.
Mechanism of action of Lofexidine (Lucemyra):
- Lofexidine (Lucemyra), a central alpha-2 adrenergic receptor agonist, decreases sympathetic tone.
- It binds alpha-2A (k=7.2nM), and alpha-2C (12 nM), adrenoreceptors.
- Because of its high selectivity to alpha-2A adrenergic receptors, it has less antihypertensive properties than Clonidine.
Absorption:
- Well-absorbed
Protein binding:
- About 55% of the drug is protein bound.
Metabolism:
- It undergoes first pass effect after it is absorbed from the gastrointestinal tract. About 30% of the drug is converted to inactive metabolites in the liver.
- It is metabolized in the liver primarily via CYP2D6 and also via CYP1A2 and CYP2C19.
Bioavailability:
- 72%
Half-life elimination:
- 11 to 13 hours (first dose);
- 17 to 22 hours (steady state)
Time to peak:
- 3 to 5 hours
Excretion:
- Urine (93.5%; 15% to 20% unchanged);
- feces (0.92%)
International Brand Names of Lofexidine:
- Lucemyra
- BritLofex
- Detoxydine
- Hopdetox
- Kai Er Ding
Lofexidine brand names in Pakistan:
No Brands Available in Pakistan.
