Lofexidine


Concise Prescribing Info
Indications/Uses
Opioid withdrawal.
Dosage/Direction for Use
Adult : PO Initial: 0.8 mg daily in divided doses, may increase gradually by increments of 0.4-0.8 mg daily. Max: 2.4 mg/day (0.8 mg/single dose). After 7-10 days, withdraw gradually over at least 2-4 days.
Dosage Details
Oral
Opioid withdrawal
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.
MonitoringParameters
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

Chemical Structure Image
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.
ATC Classification
N07BC04 - lofexidine ; Belongs to the class of drugs used in the management of opioid dependence.
References
Annotation of FDA Label for Lofexidine and CYP2D6. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/ . Accessed 22/10/2019.

Anon. CYP2D6 - Lofexidine (Pharmacogenomics). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 25/10/2019.

Anon. Lofexidine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 22/10/2019.

Buckingham R (ed). Lofexidine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 22/10/2019.

Lucemyra (US WorldMeds, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 22/10/2019.

Disclaimer: This information is independently developed by MIMS based on Lofexidine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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