Adult: Initially, 0.8 mg daily in divided doses, may be increased in increments of 0.4-0.8 mg daily. Max: 2.4 mg daily (0.8 mg per single dose). After 7-10 days, gradually withdraw over at least 2-4 days. Alternative dose: Initially, 0.54 mg 4 times daily (every 5-6 hours) during peak withdrawal symptoms up to 14 days. Max: 0.72 mg per dose or 2.88 mg daily. Gradually reduce over 2-4 days by 0.18 mg per dose every 1-2 days. Dose is adjusted according to patient's response and tolerability. Dosage recommendations may vary among individual products and between countries (refer to specific product guidelines).
Special Patient Group
Pharmacogenomics:
Lofexidine is metabolised by CYP2D6 and to a lesser extent by CYP1A2 and CYP2C19. Currently, limited data are available on the association between CYP2D6 phenotype and lofexidine. However, lofexidine exposure is expected to increase in CYP2D6 poor metabolizers, similarly to when administered with CYP2D6 inhibitors. The prevalence of poor metabolisers of CYP2D6 substrates is approximately 8% in Caucasians and 3-8% in Black/African Americans.
US Food and Drug Administration (FDA) drug label states that although the pharmacokinetics of lofexidine have not been systematically studied in patients who do not express CYP2D6, drug exposure is likely to increase in these patients. Monitoring for adverse effects (e.g. orthostatic hypotension, bradycardia) is recommended in patients identified as CYP2D6 poor metabolisers.
Renal Impairment
ESRD or on dialysis: 0.18 mg 4 times daily.
eGFR (mL/min/1.73 m2)
Dosage
<30
0.18 mg 4 times daily.
30-89.9
0.36 mg 4 times daily.
Dosage recommendations may vary among individual products and between countries (refer to specific product guidelines).
Hepatic Impairment
Moderate: 0.36 mg 4 times daily. Severe: 0.18 mg 4 times daily. Dosage recommendations may vary among individual products and between countries (refer to specific product guidelines).
Administration
Lofexidine May be taken with or without food.
Special Precautions
Patient with severe coronary insufficiency, recent MI, significant bradycardia, congenital long QT syndrome, cerebrovascular disease, depression. Avoid abrupt withdrawal. Not indicated for treatment of opioid use disorder. CYP2D6 poor metabolisers. Renal and hepatic impairment. Elderly. Pregnancy and lactation.
This drug may impair physical or mental abilities, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor blood pressure, heart rate, electrolytes, ECG (at baseline). Assess for signs of withdrawal symptoms.
Overdosage
Symptoms: Hypotension, bradycardia, and sedation.
Management: Symptomatic and supportive treatment. May perform gastric lavage if necessary.
Drug Interactions
May decrease serum concentration of oral naltrexone. Increased peak serum concentration and systemic exposure with paroxetine. Enhanced QT-prolonging effect with methadone and buprenorphine. May potentiate the CNS depressant effects of benzodiazepines, barbiturates, and other sedating drugs.
Food Interaction
May potentiate the CNS depressant effects of alcohol.
Action
Description: Mechanism of Action: Lofexidine is a central α2-adrenoceptor agonist. It decreases the norepinephrine release and reduces 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%; 15-20% as unchanged drug); faeces (0.92%). Elimination half-life: 11-13 hours.
Chemical Structure
Lofexidine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 30668, Lofexidine. https://pubchem.ncbi.nlm.nih.gov/compound/Lofexidine. Accessed Sept. 25, 2025.
Storage
Store between 15-30°C. Protect from excess heat and moisture.
N07BC04 - lofexidine ; Belongs to the class of drugs used in the management of opioid dependence.
References
Whirl-Carillo M, Huddart R, Gong L et al. An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine. Clin Pharmacol Ther. 2021 Sep;110(3):563-572. doi: 10.1002/cpt.2350. Accessed 05/09/2025. PMID: 34216021Annotation of FDA Label for Lofexidine and CYP2D6. ClinPGx. https://www.clinpgx.org. Accessed 05/09/2025.Brayfield A, Cadart C (eds). Lofexidine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/09/2025.CYP2D6 - Lofexidine. UpToDate Lexidrug, Pharmacogenomics Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/09/2025.Joint Formulary Committee. Lofexidine Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/09/2025.Lofexidine Hydrochloride Tablet, Film Coated (Novadoz Pharmaceuticals LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/09/2025.Lofexidine Hydrochloride. UpToDate Lexidrug, AHFS DI (Adult and Pediatric) Online. American Society of Health-System Pharmacists, Inc. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/09/2025.Lofexidine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/09/2025.
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