LOFEXIDINE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOFEXIDINE HYDROCHLORIDE (LOFEXIDINE HYDROCHLORIDE).

How it works

Alpha-2 adrenergic receptor agonist; reduces central sympathetic outflow by binding to presynaptic alpha-2 receptors in the brainstem, decreasing norepinephrine release.

What the body does with it

Metabolism	Hepatic; primarily via glucuronidation (UGT2B7) and partial CYP2D6 oxidation.
Excretion	Primarily renal (approximately 80-90% as unchanged drug and metabolites, with 20-30% unchanged); minor fecal excretion (<5%).
Half-life	Terminal elimination half-life is 11-13 hours in patients with normal renal function; prolonged to up to 40 hours in renal impairment.
Protein binding	Approximately 49% bound to plasma proteins (mainly albumin).
Volume of Distribution	Vd is 3.1-4.5 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 72% (range 50-80%) due to first-pass metabolism; transdermal: approximately 96% relative to oral.
Onset of Action	Oral: 1-3 hours; transdermal: 2-3 days (steady state).
Duration of Action	Oral: 8-12 hours after single dose; transdermal: 7 days (patch replacement interval).

Classification & Brands

Dosing & administration

0.2 mg orally twice daily, titrate by 0.2-0.4 mg/day every 1-2 days to maximum 2.4 mg/day in divided doses.

Dosage form	TABLET
Renal impairment	GFR 30-60 mL/min: reduce dose by 25-50%. GFR <30 mL/min: reduce dose by 50-75% or extend dosing interval.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated.
Pediatric use	Not approved for pediatric use; safety and efficacy not established.
Geriatric use	Initiate at lower dose (0.1 mg twice daily); titrate cautiously due to increased risk of hypotension and bradycardia.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LOFEXIDINE HYDROCHLORIDE (LOFEXIDINE HYDROCHLORIDE).

Breastfeeding	Excreted into breast milk in low amounts; M/P ratio not established. Use with caution, monitor infant for sedation, bradycardia, hypotension.
Teratogenic Risk	Insufficient human data; animal studies show no teratogenicity at clinically relevant doses. First trimester: limited data, cannot rule out risk. Second and third trimesters: no specific fetal risks identified, but potential for neonatal withdrawal or bradycardia if used near term.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to lofexidine","Severe coronary insufficiency","Bradycardia (<55 bpm) or prolonged QT interval (QTc >450 ms)","Concurrent use with clonidine or other alpha-2 agonists"]

Clinical Precautions

Precautions

["Risk of hypotension, bradycardia, QT prolongation","May cause CNS depression","Avoid abrupt discontinuation (may cause rebound hypertension)","Use cautiously in renal impairment","Concomitant use with CNS depressants may potentiate effects"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

LOFEXIDINE HYDROCHLORIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LOFEXIDINE HYDROCHLORIDE (LOFEXIDINE HYDROCHLORIDE).

How it works

Alpha-2 adrenergic receptor agonist; reduces central sympathetic outflow by binding to presynaptic alpha-2 receptors in the brainstem, decreasing norepinephrine release.

What the body does with it

Metabolism	Hepatic; primarily via glucuronidation (UGT2B7) and partial CYP2D6 oxidation.
Excretion	Primarily renal (approximately 80-90% as unchanged drug and metabolites, with 20-30% unchanged); minor fecal excretion (<5%).
Half-life	Terminal elimination half-life is 11-13 hours in patients with normal renal function; prolonged to up to 40 hours in renal impairment.
Protein binding	Approximately 49% bound to plasma proteins (mainly albumin).
Volume of Distribution	Vd is 3.1-4.5 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 72% (range 50-80%) due to first-pass metabolism; transdermal: approximately 96% relative to oral.
Onset of Action	Oral: 1-3 hours; transdermal: 2-3 days (steady state).
Duration of Action	Oral: 8-12 hours after single dose; transdermal: 7 days (patch replacement interval).

Classification & Brands

Dosing & administration

0.2 mg orally twice daily, titrate by 0.2-0.4 mg/day every 1-2 days to maximum 2.4 mg/day in divided doses.

Dosage form	TABLET
Renal impairment	GFR 30-60 mL/min: reduce dose by 25-50%. GFR <30 mL/min: reduce dose by 50-75% or extend dosing interval.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated.
Pediatric use	Not approved for pediatric use; safety and efficacy not established.
Geriatric use	Initiate at lower dose (0.1 mg twice daily); titrate cautiously due to increased risk of hypotension and bradycardia.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LOFEXIDINE HYDROCHLORIDE (LOFEXIDINE HYDROCHLORIDE).

Breastfeeding	Excreted into breast milk in low amounts; M/P ratio not established. Use with caution, monitor infant for sedation, bradycardia, hypotension.
Teratogenic Risk	Insufficient human data; animal studies show no teratogenicity at clinically relevant doses. First trimester: limited data, cannot rule out risk. Second and third trimesters: no specific fetal risks identified, but potential for neonatal withdrawal or bradycardia if used near term.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to lofexidine","Severe coronary insufficiency","Bradycardia (<55 bpm) or prolonged QT interval (QTc >450 ms)","Concurrent use with clonidine or other alpha-2 agonists"]