LOFEXIDINE HYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H12Cl2N2O.ClH
Molecular Weight	295.593
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC(OC1=C(Cl)C=CC=C1Cl)C2=NCCN2

InChI

InChIKey=DWWHMKBNNNZGHF-UHFFFAOYSA-N

InChI=1S/C11H12Cl2N2O.ClH/c1-7(11-14-5-6-15-11)16-10-8(12)3-2-4-9(10)13;/h2-4,7H,5-6H2,1H3,(H,14,15);1H

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/30724094

Lofexidine is newly FDA approved in the United States under the brand name LUCEMYRA for the treatment of opioid withdrawal symptoms in adults. Lofexidine acts as an agonist to α2 adrenergic receptors. These receptors inhibit adenylyl cyclase activity, leading to the inhibition of the second messenger, cyclic adenosine monophosphate (cAMP). The inhibition of cAMP leads to potassium efflux through calcium-activated channels, blocking calcium ions from entering the nerve terminal, resulting in suppression of neural firing, inhibition of norepinephrine release. Lofexidine replaces the opioid-driven inhibition of cAMP production and moderating the symptoms of opioid withdrawal.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor alpha-2 114 Target ID: CHEMBL2095158 Sources: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM602419.pdf	Agonist 2752

Conditions

Condition	Modality	Targets	Highest Phase	Product
Opioid-Related Disorders 2 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf	Palliative		Approved 8583	LUCEMYRA Approved Use LUCEMYRA is a central alpha-2 adrenergic agonist indicated for mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults Launch Date 2018

C_max

Value	Dose	Analyte	Population
1755 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18393298/	1.2 mg single, oral dose: 1.2 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEXIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2795 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18393298/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEXIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.29 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	0.6 mg 4 times / day steady-state, oral dose: 0.6 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LOFEXIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
31652 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18393298/	1.2 mg single, oral dose: 1.2 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEXIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
54321 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18393298/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEXIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
25.8 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	0.6 mg 4 times / day steady-state, oral dose: 0.6 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LOFEXIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
11.16 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18393298/	1.2 mg single, oral dose: 1.2 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEXIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.44 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18393298/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	LOFEXIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	0.6 mg 4 times / day steady-state, oral dose: 0.6 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LOFEXIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
45% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	0.6 mg 4 times / day steady-state, oral dose: 0.6 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LOFEXIDINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.54 mg 4 times / day steady, oral Recommended Dose: 0.54 mg, 4 times / day Route: oral Route: steady Dose: 0.54 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	unhealthy, 34 years (range: 19-74 years) Health Status: unhealthy Age Group: 34 years (range: 19-74 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	Other AEs: Dizziness, Insomnia... Other AEs: Dizziness (3%) Insomnia (3%) Diarrhea (2%) Orthostatic hypotension (1%) Anxiety (2%) Myalgia (2%) Syncope (<1%) Somnolence (<1%) Restlessness (<1%) Nausea (2%) Vomiting (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf
0.54 mg 4 times / day steady, oral Recommended Dose: 0.54 mg, 4 times / day Route: oral Route: steady Dose: 0.54 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	unhealthy, 34 years (range: 19-74 years) Health Status: unhealthy Age Group: 34 years (range: 19-74 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	Other AEs: Hypotension... Other AEs: Hypotension (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf
0.54 mg 4 times / day steady, oral Recommended Dose: 0.54 mg, 4 times / day Route: oral Route: steady Dose: 0.54 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	unhealthy, 34 years (range: 19-74 years) Health Status: unhealthy Age Group: 34 years (range: 19-74 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	Disc. AE: Hypotension, Dizziness... AEs leading to discontinuation/dose reduction: Hypotension (1%) Dizziness (3%) Insomnia (3%) Diarrhea (2%) Orthostatic hypotension (1%) Anxiety (2%) Myalgia (2%) Syncope (<1%) Somnolence (<1%) Restlessness (<1%) Nausea (2%) Vomiting (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf
0.72 mg 4 times / day steady, oral Studied dose Dose: 0.72 mg, 4 times / day Route: oral Route: steady Dose: 0.72 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	unhealthy, 34 years (range: 19-74 years) Health Status: unhealthy Age Group: 34 years (range: 19-74 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	Other AEs: Hypotension, Dizziness... Other AEs: Hypotension (3%) Dizziness (2%) Insomnia (2%) Diarrhea (2%) Orthostatic hypotension (2%) Anxiety (1%) Myalgia (1%) Syncope (1%) Somnolence (1%) Restlessness (1%) Nausea (<1%) Vomiting (<1%) Bradycardia (3%) Pain (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf
0.72 mg 4 times / day steady, oral Studied dose Dose: 0.72 mg, 4 times / day Route: oral Route: steady Dose: 0.72 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	unhealthy, 34 years (range: 19-74 years) Health Status: unhealthy Age Group: 34 years (range: 19-74 years) Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf	Disc. AE: Hypotension, Dizziness... AEs leading to discontinuation/dose reduction: Hypotension (3%) Dizziness (2%) Insomnia (2%) Diarrhea (2%) Orthostatic hypotension (2%) Anxiety (1%) Myalgia (1%) Syncope (1%) Somnolence (1%) Restlessness (1%) Nausea (<1%) Vomiting (<1%) Bradycardia (3%) Pain (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf
0.54 mg 4 times / day steady, oral Recommended Dose: 0.54 mg, 4 times / day Route: oral Route: steady Dose: 0.54 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf	Disc. AE: Bradycardia, Orthostatic hypotension... Other AEs: Insomnia, Orthostatic hypotension... AEs leading to discontinuation/dose reduction: Bradycardia (13.5%) Orthostatic hypotension (13.5%) Other AEs: Insomnia (51%) Orthostatic hypotension (29%) Bradycardia (24%) Hypotension (30%) Dizziness (19%) Somnolence (11%) Sedation (13%) Dry mouth (10%) Syncope (0.9%) Tinnitus (0.9%) Bradycardia (13.5%) Orthostatic hypotension (13.5%) Insomnia (51%) Orthostatic hypotension (29%) Bradycardia (24%) Hypotension (30%) Dizziness (19%) Somnolence (11%) Sedation (13%) Dry mouth (10%) Syncope (0.9%) Tinnitus (0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf
0.72 mg 4 times / day steady, oral Studied dose Dose: 0.72 mg, 4 times / day Route: oral Route: steady Dose: 0.72 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf	Disc. AE: Hypertension, Bradycardia... Other AEs: Insomnia, Orthostatic hypotension... AEs leading to discontinuation/dose reduction: Hypertension (21%) Bradycardia (22%) Orthostatic hypotension (22%) Other AEs: Insomnia (55%) Orthostatic hypotension (42%) Bradycardia (32%) Hypotension (30%) Dizziness (23%) Somnolence (12%) Sedation (13%) Dry mouth (11%) Syncope (1.4%) Tinnitus (3.2%) Hypertension (21%) Bradycardia (22%) Orthostatic hypotension (22%) Insomnia (55%) Orthostatic hypotension (42%) Bradycardia (32%) Hypotension (30%) Dizziness (23%) Somnolence (12%) Sedation (13%) Dry mouth (11%) Syncope (1.4%) Tinnitus (3.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209229s000lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 2438 inducer 440	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 BCRP 910 OAT1 725 OAT3 747 OCT1 620 OCT2 779 OATP1B1 1079 OATP1B3 961 MATE2 267 BSEP 550 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296 MATE1 415	CYP1A2 1197 CYP2C19 1119 P-gp 2052	CYP1A2 832 CYP2A6 86 CYP2B6 669 CYP2C8 198 CYP2C19 329 CYP2E1 131 CYP3A4/5 133

Drug as perpetrator

Target	Modality	Activity	Metabolite
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
BSEP 554	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2A6 911	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C19 2141	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C8 1117	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C9 2497	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2E1 1146	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP3A4/5 357	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
MATE2 267	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OCT1 656	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0	yes [IC50 4551 uM]
MATE1 416	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	yes [Inhibition 1.1 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0	major	no (co-administration study) Comment: Paroxetine did not affect mean lofexidine Cmax values and slightly increased mean AUC values by approximately 30%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0	yes
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=156 Page: 156.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:51368	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:51368
ChemicalBook	CB3731949	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3731949
eMolecules	36552991	https://www.emolecules.com/cgi-bin/more?vid=36552991
MolPort	MolPort-003-848-405	https://www.molport.com/shop/molecule-link/MolPort-003-848-405

PubMed

Title	Date	PubMed
Clonidine in adults as a sedative agent in the intensive care unit.	2010-10	21547166
The pharmacological treatment of opioid addiction--a clinical perspective.	2010-06	20169438
A comparison of methadone, buprenorphine and alpha(2) adrenergic agonists for opioid detoxification: a mixed treatment comparison meta-analysis.	2010-04-01	20074867
Lofexidine, an {alpha}2-receptor agonist for opioid detoxification.	2010-02	20040696
A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence.	2010	20798544
Opioid antagonists with minimal sedation for opioid withdrawal.	2009-10-07	19821290
Alpha2-receptor agonists for treatment and prevention of iatrogenic opioid abstinence syndrome in critically ill patients.	2009-09	19690220
A double-blind, randomized, parallel group study to compare the efficacy, safety and tolerability of slow-release oral morphine versus methadone in opioid-dependent in-patients willing to undergo detoxification.	2009-09	19686525
Opioid dependence.	2009-07-24	21696648
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Project Study: protocol for a randomised controlled trial comparing methadone and buprenorphine for opiate detoxification.	2009-07-14	19602218
Buprenorphine for the management of opioid withdrawal.	2009-07-08	19588330
Electrocardiographic effects of lofexidine and methadone coadministration: secondary findings from a safety study.	2009-05	19397459
Alpha2-adrenergic agonists for the management of opioid withdrawal.	2009-04-15	19370574
Norepinephrine and stimulant addiction.	2009-04	18811678
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project: a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification.	2009-02-05	19196468
Pharmacokinetics of lofexidine hydrochloride in healthy volunteers.	2009-01	18393298
A study on Fu-Yuan Pellet, a traditional chinese medicine formula for detoxification of heroin addictions.	2009	20014908
Urine and plasma pharmacokinetics of lofexidine after oral delivery in opiate-dependent patients.	2009	19637105
Pharmacotherapy for cannabis dependence: how close are we?	2009	19552483
Agenda for specialty section in addiction medicine.	2008-10	19823604
A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.	2008-09-01	18508207
Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans.	2008-09	19506724
Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse.	2008-03	18161012
A comparative clinical study of the effects of the traditional Chinese medicine Jinniu capsules and lofexidine on acute heroin withdrawal symptoms.	2008	19016185
Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis.	2008	18821454
Tai-Kang-Ning, a Chinese herbal medicine formula, alleviates acute heroin withdrawal.	2008	18428069
Hemodynamic and cognitive effects of lofexidine and methadone coadministration: a pilot study.	2007-08	17655511
Opioid dependence.	2007-06-01	19454085
In-patient detoxification procedures, treatment retention, and post-treatment opiate use: comparison of lofexidine + naloxone, lofexidine + placebo, and methadone.	2007-04-17	17064857
Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings.	2007-03	17136399
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification.	2007-01-08	17210080
Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial.	2007-01-08	17210079
Pharmacologic treatments for opioid dependence: detoxification and maintenance options.	2007	18286804
Opiate addiction in China: current situation and treatments.	2006-05	16669899
The place of detoxification in treatment of opioid dependence.	2006-05	16612211
Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls.	2006-02-24	16504127
Opioid antagonists with minimal sedation for opioid withdrawal.	2006-01-25	16437438
A comparison of buprenorphine and lofexidine for community opiate detoxification: results from a randomized controlled trial.	2005-12	16367987
Is clonidine useful for treatment of clozapine-induced sialorrhea?	2005-07	15983000
Induction of patients with moderately severe methadone dependence onto buprenorphine.	2005-06	16191667
Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats.	2005-05	15551068
Lofexidine for opioid detoxification.	2005-01	21179638
QT interval increased after single dose of lofexidine.	2004-11-06	15528619
Evidence-based addiction medicine: the use of lofexidine for opioid detoxification.	2004-11	21191525
Alpha2 adrenergic agonists for the management of opioid withdrawal.	2004-10-18	15495025
A placebo-controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.	2004-06	15260900
Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in-patient opiate detoxification.	1998-05-01	9649976
Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal.	1997-11-25	9363412
Alcohol withdrawal syndromes: clinical management with lofexidine.	1985-03-01	3890587
Animal experiments on the safety pharmacology of lofexidine.	1982	6890367

Patents

Sample Use Guides

In Vivo Use Guide

The usual LUCEMYRA starting dosage is three 0.18 mg tablets taken orally 4 times daily during the period of peak withdrawal symptoms (generally the first 5 to 7 days following last use of opioid) with dosing guided by symptoms and side effects. There should be 5 to 6 hours between each dose. The total daily dosage of LUCEMYRA should not exceed 2.88 mg (16 tablets) and no single dose should exceed 0.72 mg (4 tablets).

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

LOFEXIDINE HYDROCHLORIDE

Official Name

English

LUCEMYRA

Preferred Name

English

2-(1-(2,6-DICHLOROPHENOXY)ETHYL)-4,5-DIHYDRO-1H-IMIDAZOLE HYDROCHLORIDE

Systematic Name

English

LOFEXIDINE HYDROCHLORIDE [USAN]

Common Name

English

MDL-14042

Code

English

2-[1-(2,6-Dichlorophenoxy)ethyl]-2-imidazoline monohydrochloride

Systematic Name

English

LOFEXIDINE HYDROCHLORIDE [VANDF]

Common Name

English

Lofexidine hydrochloride [WHO-DD]

Common Name

English

MDL 14,042

Code

English

1H-IMIDAZOLE, 2-(1-(2,6-DICHLOROPHENOXY)ETHYL)-4,5-DIHYDRO-, MONOHYDROCHLORIDE

Common Name

English

NSC-759654

Code

English

LOFEXIDINE HCL

Common Name

English

LOFEXIDINE HYDROCHLORIDE [MART.]

Common Name

English

LOFEXIDINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

LOFEXIDINE HYDROCHLORIDE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29709