adrenergics (centrally acting)
Mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults.
Stimulates alpha2-adrenergic receptors in the CNS, which results in decreased sympathetic outflow.
Reduction in severity of opioid withdrawal symptoms.
Absorption: Well absorbed (72%) following oral administration.
Distribution: Extensively distributed to tissues, including CNS.
Metabolism and Excretion: Metabolized by the liver (primarily by CYP2D6, but also CYP1A2 and CYP2C19 to some extent) to inactive metabolites; primarily excreted in urine (15–20% as unchanged drug); ~7% of population may be poor metabolizers and may have significantly ↑ lofexidine concentrations and an ↑ risk of adverse effects.
Half-life: 17–22 hr.
TIME/ACTION PROFILE (plasma concentrations)
- Concurrent use with medications that lower blood pressure or heart rate
- Congenital long QT syndrome.
Use Cautiously in:
- Severe cardiac or cerebrovascular disease, recent MI, chronic renal failure, severe bradycardia;
- HF, bradyarrhythmias, hepatic impairment, renal impairment, hypokalemia, or hypomagnesemia
- Concurrent use of QT-interval prolonging medications
- CYP2D6 poor metabolizers;
- Geri: ↑ risk of orthostatic hypotension and adverse CNS effects in older adults (↓ dose recommended);
- OB: Safety not established
- Lactation: Use only if potential maternal benefit justifies potential risk to infant;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
CNS: drowsiness, dizziness, insomnia
CV: TORSADES DE POINTES, bradycardia, hypotension, palpitations, QT interval prolongation, syncope
GI: dry mouth
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Additive hypotension with other antihypertensives and nitrates; avoid concurrent use.
- Additive bradycardia with beta blockers, diltiazem, verapamil, digoxin, or ivabradine; avoid concurrent use.
- Additive sedation with CNS depressants, including alcohol, antihistamines, opioid analgesics, and sedative/hypnotics.
- Concurrent use with QT interval-prolonging medications, including methadone, may ↑ risk of QT interval prolongation and torsades de pointes.
- May ↓ naltrexone (PO) levels; separate administration by >2 hr.
- CYP2D6 inhibitors, including paroxetine may ↑ levels.
PO (Adults) 0.54 mg 4 times daily (with 5–6 hr between each dose) during the period of peak withdrawal symptoms (usually the first 5–7 days after the last opioid dose); may adjust dose based on symptoms (max dose = 2.88 mg/day or 0.72 mg/dose); may be continued for up to 14 days. Must taper therapy upon discontinuation (gradually ↓ dose over 2–4–day period).
PO (Adults) Moderate hepatic impairment (Child-Pugh B)–0.36 mg 4 times daily (with 5–6 hr between each dose) during the period of peak withdrawal symptoms (usually the first 5–7 days after the last opioid dose); Severe hepatic impairment (Child-Pugh C)–0.18 mg 4 times daily (with 5–6 hr between each dose) during the period of peak withdrawal symptoms (usually the first 5–7 days after the last opioid dose).
PO (Adults) CCr 30–<90 mL/min–0.36 mg 4 times daily (with 5–6 hr between each dose) during the period of peak withdrawal symptoms (usually the first 5–7 days after the last opioid dose); CCr <30 mL/min–0.18 mg 4 times daily (with 5–6 hr between each dose) during the period of peak withdrawal symptoms (usually the first 5–7 days after the last opioid dose).
Tablets: 0.18 mg
- Assess vital signs and symptoms of bradycardia and orthostatic hypotension (low blood pressure, slow heartbeat, dizziness, lightheadedness, feeling faint at rest or when standing up) before dose and as needed during therapy.
- Monitor ECG when starting therapy and in patients with HF, bradyarrhythmias, hepatic impairment, renal impairment, or those taking medications (methadone) that lead to QT prolongation.
Lab Test Considerations:
Monitor electrolytes before starting and during therapy. Correct electrolyte abnormalities (hypokalemia, hypomagnesemia) before starting therapy.
- PO Administer 3 tablets four times daily without regard to food, with 5–6 hrs between doses.
- Instruct patient to take lofexidine as directed and not to stop without consulting health care professional. Abrupt discontinuation can cause diarrhea, insomnia, anxiety, chills, hyperhidrosis, and extremity pain. Reduce dose gradually.
- Caution patients that after a period of not using opioids, they may be more sensitive to the effects of opioids and at greater risk of overdosing.
- May cause dizziness and sedation. Caution patient to avoid driving and activities requiring alertness until response to medication is known.
- Caution patient to avoid sudden changes in position to decrease orthostatic hypotension. Use of alcohol, standing for long periods, exercising, dehydration, and hot weather may increase orthostatic hypotension.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products, especially benzodiazepines, barbiturates, tranquilizers, or sleeping pills.
- Caution patient to avoid concurrent use of alcohol or other CNS depressants with lofexidine.
- Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Reduction in severity of opioid withdrawal symptoms.
is a sample topic from the Davis's Drug Guide
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