lofexidine 0.18 MG Oral Tablet [Lucemyra]

INDICATIONS AND USAGE Lofexidine tablets are indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults. Lofexidine tablets are a central alpha-2 adrenergic agonist indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults. ( 1 )

DOSAGE AND ADMINISTRATION The usual lofexidine tablet dosage is three 0.18 mg tablets taken orally 4 times daily at 5- to 6-hour intervals. Lofexidine tablet treatment may be continued for up to 14 days with dosing guided by symptoms. ( 2.1 ) Discontinue lofexidine tablets with a gradual dose reduction over 2 to 4 days. ( 2.1 ) Hepatic or Renal Impairment: Dosage adjustments are recommended based on degree of impairment. ( 2.2 , 2.3 ) 2.1 Dosing Information The usual lofexidine tablet 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 lofexidine tablets should not exceed 2.88 mg (16 tablets) and no single dose should exceed 0.72 mg (4 tablets). Lofexidine tablet treatment may be continued for up to 14 days with dosing guided by symptoms. Discontinue lofexidine tablets with a gradual dose reduction over a 2- to 4-day period to mitigate lofexidine tablet withdrawal symptoms (e.g., reducing by 1 tablet per dose every 1 to 2 days) [see Warnings & Precautions (5.5)] .The lofexidine tablet dose should be reduced, held, or discontinued for individuals who demonstrate a greater sensitivity to lofexidine tablets side effects [see Warnings and Precautions (5.1) , Adverse Reactions (6.1) ] . Lower doses may be appropriate as opioid withdrawal symptoms wane. Lofexidine tablets can be administered in the presence or absence of food. 2.2 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)] . Table 1: Dosage Recommendations in Patients with Hepatic Impairment Mild Impairment Moderate Impairment Severe Impairment Child-Pugh score 5 to 6 7 to 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) 2.3 Dosage Recommendations for Patients with Renal Impairment Recommended dosage adjustments based on the degree of renal impairment are shown in Table 2. Lofexidine tablets may be administered without regard to the timing of dialysis [see Use in Specific Populations (8.7) , Clinical Pharmacology (12.3)]. Table 2: Dosage Recommendations in Patients with Renal Impairment Moderate Impairment Severe Impairment, End- Stage Renal Disease, or on Dialysis Estimated GFR, mL/min/1.73 m 2 30 to 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)

WARNINGS AND PRECAUTIONS Risk of Hypotension, Bradycardia, and Syncope : May cause a decrease in blood pressure, a decrease in pulse, and syncope. Monitor vital signs before dosing and advise patients on how to minimize the risk of these cardiovascular effects and manage symptoms, should they occur. Monitor symptoms related to bradycardia and orthostasis. When using in outpatients, ensure that patients are capable of self-monitoring for signs and symptoms. Avoid use in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, or chronic renal failure, as well as in patients with marked bradycardia. ( 5.1 ) Risk of QT Prolongation : Lofexidine tablets prolong the QT interval. Avoid use in patients with congenital long QT syndrome. Monitor ECG in patients with electrolyte abnormalities, congestive heart failure, bradyarrhythmias, hepatic or renal impairment, or in patients taking other medicinal products that lead to QT prolongation. ( 5.2 ) Increased Risk of CNS Depression with Concomitant use of CNS Depressant Drugs : Lofexidine tablets potentiate the CNS depressant effects of benzodiazepines and may potentiate the CNS depressant effects of alcohol, barbiturates, and other sedating drugs. ( 5.3 ) Increased Risk of Opioid Overdose after Opioid Discontinuation : Patients who complete opioid discontinuation are at an increased risk of fatal overdose should they resume opioid use. Use in conjunction with a comprehensive management program for treatment of opioid use disorder and inform patients and caregivers of increased risk of overdose. ( 5.4 ) Risk of Discontinuation Symptoms : Instruct patients not to discontinue therapy without consulting their healthcare provider. When discontinuing therapy, reduce dose gradually. ( 5.5 ) 5.1 Risk of Hypotension, Bradycardia, and Syncope Lofexidine tablets 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 Lofexidine tablets 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 tablets should be reduced in amount, delayed, or skipped. Inform patients that Lofexidine tablets 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 Lofexidine tablets doses when experiencing symptoms of hypotension or bradycardia and to contact their healthcare provider for guidance on how to adjust dosing. Avoid using Lofexidine tablets in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, and in patients with marked bradycardia. Avoid using Lofexidine tablets in combination with medications that decrease pulse or blood pressure to avoid the risk of excessive bradycardia and hypotension. 5.2 Risk of QT Prolongation Lofexidine tablets prolong the QT interval. Avoid using Lofexidine tablets 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 Lofexidine tablets [see Dosing and Administration (2.1) , Adverse Reactions (6.1) , Special Populations (8.6 , 8.7) , Clinical Pharmacology (12.2) ] . 5.3 Increased Risk of Central Nervous System Depression with Concomitant use of CNS Depressant Drugs Lofexidine tablets potentiate 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 Lofexidine tablets in an outpatient setting that, until they learn how they respond to Lofexidine tablets, they should be careful or avoid doing activities such as driving or operating heavy machinery. 5.4 Increased Risk of Opioid Overdose after Opioid Discontinuation Lofexidine tablets are 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 tablets 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. 5.5 Risk of Discontinuation Symptoms Stopping Lofexidine tablets 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 tablets discontinuation. Instruct patients not to discontinue therapy without consulting their healthcare provider. When discontinuing therapy with Lofexidine tablets, gradually reduce the dose [see Dosing and Administration (2.1) ] . Symptoms related to discontinuation can be managed by administration of the previous Lofexidine tablet dose and subsequent taper.

CONTRAINDICATIONS None. None. ( 4 )

Mechanism of Action Lofexidine is a central alpha-2 adrenergic agonist that binds to receptors on adrenergic neurons. This reduces the release of norepinephrine and decreases sympathetic tone.