lofexidine

Contraindicated in:

Congenital long QT syndrome.

Use Cautiously in:

Severe cardiac or cerebrovascular disease, recent MI, chronic kidney disease, or severe bradycardia (↑ risk of hypotension, bradycardia, and/or syncope);
HF, bradyarrhythmias, hepatic impairment, renal impairment, hypokalemia, hypomagnesemia, or concurrent use of QT-interval prolonging medications (↑ risk of QT interval prolongation);
CYP2D6 poor metabolizers;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children;
Geri: ↑risk of orthostatic hypotension and adverse CNS effects in older adults (↓ dose recommended).

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, hypotension, palpitations, QT interval prolongation, syncope, TORSADES DE POINTES

EENT: tinnitus

GI: dry mouth

Neuro: dizziness, drowsiness, insomnia

Interactions ⬆ ⬇

Drug-drug:

Additive hypotension with other antihypertensives and nitrates; avoid concurrent use.
Additive bradycardia with beta blockers, diltiazem, verapamil, digoxin, clonidine, 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 and effectiveness; separate administration by >2 hr.
CYP2D6 inhibitors, including paroxetine, may ↑ levels and risk of toxicity.

Availability ⬆ ⬇

(Generic available)

Tablets: 0.18 mg

Route/Dosage ⬆ ⬇

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 on discontinuation (gradually ↓ dose over 2–4-day period).

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 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: 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).

Renal Impairment

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).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Stimulates alpha₂-adrenergic receptors in the CNS, which results in decreased sympathetic outflow.

Therapeutic effects:

Reduction in severity of opioid withdrawal symptoms.

Classifications ⬆ ⬇

Therapeutic Classification: none assigned

Pharmacologic Classification: adrenergics (centrally acting)

Pharmacokinetics ⬆ ⬇

Absorption: 72% absorbed following oral administration.

Distribution: Extensively distributed to tissues, including CNS.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP2D6 isoenzyme and to a lesser extent by the CYP1A2 and CYP2C19 isoenzymes to inactive metabolites; primarily excreted in urine (15–20% as unchanged drug); the CYP2D6 isoenzyme exhibits genetic polymorphism; ∼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)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3–5 hr	unknown

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of lofexidine to patient. Instruct patient to take lofexidine as directed and not to stop without consulting health care professional. Take missed doses as soon as remembered unless almost time for next dose. Abrupt discontinuation can cause diarrhea, insomnia, anxiety, chills, hyperhidrosis, and extremity pain. ↓ dose gradually. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
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 ↓ orthostatic hypotension. Use of alcohol, standing for long periods, exercising, dehydration, and hot weather may ↑ 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.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Indications ⬇

Contraind./Precautions ⬆ ⬇