Overview
11 DESCRIPTION Lofexidine tablets contain lofexidine, a central alpha-2 adrenergic agonist, as the hydrochloride salt. Lofexidine hydrochloride is chemically designated as 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5 dihydro-1 H -imidazole monohydrochloride with a molecular formula of C 11 H 12 Cl 2 N 2 O•HCl. Its molecular weight is 295.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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. 12.2 Pharmacodynamics Cardiac Electrophysiology Single lofexidine doses of 1.44 mg to 1.8 mg produced maximum mean change from baseline in QTcF (ΔQTcF) of 14.4 msec (upper two-sided 90% CI: 22.3 msec) and 13.6 msec (17.4 msec) for 1.44 mg and 1.8 mg respectively in healthy normal volunteers. In a Phase 3 placebo-controlled, dose response study in opioid dependent subjects, lofexidine was associated with a maximum mean prolongation of the QTcF interval 7.3 (8.8) msec and 9.3 (10.9) msec at doses of 2.16 mg/day and 2.88 mg/day, respectively.
Indications
- 1 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 )
Common Doses
- 0.18 mg
- 2.88 mg
- 0.72 mg
- 2.16 mg
Dosage
2 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.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in labeling: Hypotension, Bradycardia, and Syncope [see Warnings and Precautions (5.1)] QT Prolongation [see Warnings and Precautions (5.2)] Central Nervous System Depression [see Warnings and Precautions (5.3)] Opioid Overdose [see Warnings and Precautions (5.4)] Discontinuation Symptoms [see Warnings and Precautions (5.5)] Most common adverse reactions (incidence ≥ 10% and notably more frequent than placebo) are orthostatic hypotension, bradycardia, hypotension, dizziness, somnolence, sedation, and dry mouth.
Interactions
- 7 DRUG INTERACTIONS Methadone: Methadone and lofexidine both prolong the QT interval. ECG monitoring is recommended when used concomitantly. ( 7.1 ) Oral Naltrexone: Concomitant use may reduce efficacy of oral naltrexone. ( 7.2 ) 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. ( 7.4 ) 7.1 Methadone Lofexidine and methadone both prolong the QT interval.