Adult: Initially, 0.8 mg daily in divided doses, may increase gradually by increments of 0.4-0.8 mg daily. Max: 2.4 mg daily (0.8 mg/single dose). After 7-10 days, withdraw gradually over at least 2-4 days.
Special Patient Group
Pharmacogenomics:
Lofexidine is metabolised by CYP2D6 and to a lesser extent by CYP1A2 and CYP2C19. Currently, there are no systematic evaluation of lofexidine in individuals with CYP2D6 genetic polymorphism. However, the possible influence of CYP2D6 polymorphism on the pharmacokinetics of lofexidine may be taken into consideration.
According to FDA-approved drug label for lofexidine, individuals with reduced CYP2D6 activity, known as CYP2D6 poor metabolisers, is likely to have an increased exposure to lofexidine similar to those taking strong CYP2D6 inhibitors. The prevalence of CYP2D6 poor metabolisers is approx 8% in Caucasians and 3-8% in African-Americans. Monitoring of adverse effects (e.g. orthostatic hypotension, bradycardia) in known CYP2D6 poor metabolisers is recommended.
Special Precautions
Patients with cerebrovascular disease, CV disease, severe coronary insufficiency, recent MI, bradycardia, hypotension, congenital long QT syndrome, electrolyte abnormalities (e.g. hypokalaemia, hypomagnesaemia), history of depression (prolonged therapy). CYP2D6 poor metabolisers. Renal and hepatic impairment. Pregnancy and lactation. Avoid abrupt withdrawal.
Adverse Reactions
Significant: QT prolongation, bradycardia, hypotension, syncope. Cardiac disorders: Torsades de pointes. Ear and labyrinth disorders: Tinnitus. General disorders and administration site conditions: Dry mouth, throat or nose. Nervous system disorders: Dizziness, drowsiness, sedation. Psychiatric disorders: Somnolence. Vascular disorders: Orthostatic hypotension.
Patient Counseling Information
This drug may cause sedation, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor blood pressure and heart rate.
Overdosage
Symptoms: Hypotension, bradycardia, sedation. Management: Supportive and symptomatic treatment. Perform gastric lavage if appropriate.
Drug Interactions
Additive effect with drugs which prolong QT interval (e.g. methadone). Enhanced CNS depressant effects of benzodiazepines, barbiturates and other sedatives. Enhanced effects of antihypertensive agents. Reduced efficacy with TCAs.
Food Interaction
Enhanced CNS depressant effects of alcohol.
Action
Description: Lofexidine, a central α-2 adrenergic agonist, binds to α-2A and α-2C adrenoreceptors thus reducing the release of norepinephrine and decreasing sympathetic tone. Pharmacokinetics: Absorption: Well-absorbed from the gastrointestinal tract. Bioavailability: 72%. Time to peak plasma concentration: 3-5 hours. Distribution: Extensively distributed into body tissue. Volume of distribution: 480 L. Plasma protein binding: Approx 55%. Metabolism: Extensively metabolised in the liver mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP2C19. Excretion: Via urine (93.5%; approx 15-20% as unchanged drug); faeces (0.92%). Elimination half-life: 11-13 hours.
Chemical Structure
Lofexidine Source: National Center for Biotechnology Information. PubChem Database. Lofexidine, CID=30668, https://pubchem.ncbi.nlm.nih.gov/compound/Lofexidine (accessed on Jan. 22, 2020)
Storage
Store at 25°C. Protect from excessive heat and moisture.
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