lofexidine

General Information

Lofexidine (brand Lucemyra) is an α2-adrenergic agonist indicated to mitigate opioid withdrawal symptoms during abrupt opioid discontinuation (label).

It does not treat opioid use disorder (OUD) itself and does not reduce relapse risk without follow-on care; it is typically used as a short-term bridge within a broader treatment plan (guideline/clinical).

Key safety considerations include hypotension, bradycardia/syncope, and QT prolongation. Labeling recommends vital sign monitoring and ECG monitoring when QT risk factors are present (label).

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Used for short-term symptom control during opioid withdrawal when opioid agonist treatment is not used or as a bridge during transitions. Practical constraints include frequent dosing and monitoring for hypotension and QT prolongation (label/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Lofexidine is an α2-adrenergic receptor agonist that reduces sympathetic outflow. In opioid withdrawal, this can reduce autonomic hyperactivity symptoms such as tachycardia, sweating, and GI distress (label/review).

It does not address opioid receptor-dependent craving/relapse biology, so it is typically paired with follow-on treatment strategies for OUD (guideline/clinical).

• Central α2-adrenergic agonism (label).

Metabolism and Pharmacokinetics

• Lofexidine is well absorbed with peak plasma concentrations ~3 to 5 hours after a single dose; food does not meaningfully alter pharmacokinetics (label).
• Hepatic metabolism is mediated primarily by CYP2D6, with CYP1A2 and CYP2C19 also capable of metabolism (label).
• Renal excretion is the primary elimination route. Mass balance data showed most radiolabel recovery in urine (~93.5%), with a smaller fraction in feces (~0.92%); ~15–20% is eliminated unchanged in urine (label).
• Terminal half-life is ~11–13 hours after the first dose and ~17–22 hours at steady state with repeated dosing (label).
• Hepatic or renal impairment slows elimination and can increase QT prolongation risk; labeling recommends dose reductions and ECG monitoring when risk factors are present (label).

Dosing and Administration

• The usual starting dosage is three 0.18 mg tablets (0.54 mg) four times daily during peak withdrawal symptoms, with 5 to 6 hours between doses (label).
• The total daily dose should not exceed 2.88 mg (16 tablets) and no single dose should exceed 0.72 mg (4 tablets) (label).
• Treatment may be continued for up to 14 days guided by symptoms and side effects (label).
• Labeling recommends tapering over 2 to 4 days to mitigate rebound lofexidine withdrawal symptoms (label).
• Dose reductions are recommended in hepatic impairment (Child-Pugh based) and in moderate-to-severe renal impairment (eGFR based) (label).

Monitoring & Labs

• Monitor blood pressure and pulse before dosing and in symptomatic patients; adjust/hold dosing for clinically significant hypotension or bradycardia (label/clinical).
• Consider ECG monitoring when QT risk factors are present (electrolyte abnormalities, heart failure, bradyarrhythmias, hepatic/renal impairment, or concurrent QT-prolonging drugs such as methadone) (label).
• Review sedation, dizziness, and fall risk; reinforce a taper plan to reduce rebound symptoms at discontinuation (label/clinical).

Because opioid withdrawal is a high-relapse-risk period, follow-up planning typically includes linkage to longer-term OUD treatment options (guideline/clinical).

Adverse Effects

Interactions

• Other hypotensive or bradycardic agents can increase hypotension/syncope risk; regimen review is important in medically complex patients (label/clinical).
• Methadone and lofexidine both prolong QT interval; ECG monitoring is recommended when used together (label).
• Strong CYP2D6 inhibitors can increase lofexidine exposure; monitoring for orthostasis and bradycardia is recommended in those scenarios (label).
• Additive sedation can occur with CNS depressants (alcohol, sedatives); clinicians often reassess sedative stacking during withdrawal management (clinical).

Other Useful Information

• Lofexidine can reduce opioid withdrawal symptom severity and improve tolerability of detoxification. Reviews describe it as a useful option when opioid agonist-based withdrawal management is not used or as a bridge into longer-term OUD treatment (review/clinical).
• Guidelines emphasize that withdrawal management alone does not treat OUD; linkage to evidence-based OUD pharmacotherapy and psychosocial supports is typically part of the care plan (guideline).

References

1. LUCEMYRA (lofexidine hydrochloride) tablets prescribing information — DailyMed (2026)
2. The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update — Journal of Addiction Medicine (2020)
3. TIP 63: Medications for Opioid Use Disorder — SAMHSA (2021)
4. The Role of Lofexidine in Management of Opioid Withdrawal — Pain Therapy (2019)