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

Molecular Formula	C11H12Cl2N2O
Molecular Weight	259.132
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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-2 113 Target ID: CHEMBL2095158 Sources: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM602419.pdf	Agonist 2662

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 8360	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 1.52634235E12

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 (max) 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) n = 229 Health Status: unhealthy Condition: facilitation of abruption opioid discontinuation Age Group: 34 years (range: 19-74 years) Sex: M+F Population Size: 229 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 (max) 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) n = 229 Health Status: unhealthy Condition: facilitation of abruption opioid discontinuation Age Group: 34 years (range: 19-74 years) Sex: M+F Population Size: 229 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 (starting) 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) n = 229 Health Status: unhealthy Condition: facilitation of abruption opioid discontinuation Age Group: 34 years (range: 19-74 years) Sex: M+F Population Size: 229 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 (max) 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) n = 390 Health Status: unhealthy Condition: facilitation of abruption opioid discontinuation Age Group: 34 years (range: 19-74 years) Sex: M+F Population Size: 390 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 (starting) 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) n = 390 Health Status: unhealthy Condition: facilitation of abruption opioid discontinuation Age Group: 34 years (range: 19-74 years) Sex: M+F Population Size: 390 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 (max) 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 n = 229 Health Status: unhealthy Condition: facilitation of abruption opioid discontinuation Population Size: 229 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 (max) 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 n = 222 Health Status: unhealthy Condition: facilitation of abruption opioid discontinuation Population Size: 222 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 1752 inducer 383	substrate 1193 inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437 BCRP 691 OAT1 595 OAT3 636 OCT1 506 OCT2 638 OATP1B1 781 OATP1B3 700 MATE2 261 BSEP 401 CYP1A2 1509 CYP2A6 704 CYP2B6 799 CYP2C8 901 CYP2C19 1463 CYP2E1 876 CYP3A4/5 273 MATE1 304	CYP1A2 1032 CYP2C19 985 P-gp 1527	CYP1A2 689 CYP2A6 79 CYP2B6 538 CYP2C8 168 CYP2C19 290 CYP2E1 126 CYP3A4/5 120

Drug as perpetrator

Target	Modality	Activity	Metabolite
BCRP 765	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
BSEP 402	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2A6 736	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C19 1537	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C8 955	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C9 1803	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2E1 964	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP3A4/5 330	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP3A4/5 330	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP3A4/5 330	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP3A4/5 330	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP3A4/5 330	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
MATE2 261	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OAT1 599	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OAT3 638	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OATP1B1 796	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OATP1B3 709	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OCT1 523	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OCT2 639	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
P-gp 1626	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0	yes [IC50 4551 uM]
MATE1 306	inhibitor 3240 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 1193	substrate 3326 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 1527	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0	yes
CYP2C19 985	substrate 3326 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 1632	inhibitor 1613 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
MolPort	MolPort-003-848-405	https://www.molport.com/shop/molecule-link/MolPort-003-848-405
eMolecules	36552991	https://www.emolecules.com/cgi-bin/more?vid=36552991

PubMed

Title	Date	PubMed
Animal experiments on the safety pharmacology of lofexidine.	1982	6890367
Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal.	1997 Nov 25	9363412
Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in-patient opiate detoxification.	1998 May 1	9649976
[Therapy of tic disorders apparently of organic origin in a multi-morbid 5-year-old patient with lofexidine (Britlofex) and clonidine (Catapressan)].	2001	11582998
Alpha2 adrenergic agonists for the management of opioid withdrawal.	2001	11279747
Randomized placebo controlled trial of lofexidine hydrochloride for chronic pelvic pain in women.	2001 Aug	11473971
Two methods of community detoxification from opiates: an open-label comparison of lofexidine and buprenorphine.	2001 Dec 1	11714592
Lofexidine versus clonidine in rapid opiate detoxification.	2001 Jul	11516922
Repeated lofexidine treatment attenuates stress-induced, but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats.	2001 Sep	11522461
A double-blind randomized placebo-controlled trial of lofexidine in alcohol withdrawal: lofexidine is not a useful adjunct to chlordiazepoxide.	2001 Sep-Oct	11524309
Lofexidine in hyperactive and impulsive children with autistic disorder.	2002 Dec	12447025
Acceptability and availability of pharmacological interventions for substance misuse by British NHS treatment services.	2002 Jan	11895271
Prescribing to drug misusers in practice--often effective, but rarely straightforward.	2002 Jul	12126485
[125I]2-(2-chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911), a high-affinity radioligand selective for I1 imidazoline receptors.	2002 Jul	12065769
Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone.	2002 Jul 1	12095666
A review of chemical agents in the pharmacotherapy of addiction.	2002 Oct	12369879
Alpha2 adrenergic agonists for the management of opioid withdrawal.	2003	12804419
Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans.	2003 Apr	12653813
The effectiveness of combined naloxone/lofexidine in opiate detoxification: results from a double-blind randomized and placebo-controlled trial.	2003 Jul-Sep	14504022
Major disruptions of sleep during treatment of the opiate withdrawal syndrome: differences between methadone and lofexidine detoxification treatments.	2003 Mar	12745416
A placebo-controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.	2003 Mar	12680748
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: an open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728].	2004 Apr 29	15117415
A placebo-controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.	2004 Jun	15260900
[Clinical observation on effect of modified banxia houpu decoction in treating patients with protracted heroin abstinence syndrome].	2004 Mar	15074088
Evidence-based addiction medicine: the use of lofexidine for opioid detoxification.	2004 Nov	21191525
Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls.	2006 Feb 24	16504127
Opiate addiction in China: current situation and treatments.	2006 May	16669899
The place of detoxification in treatment of opioid dependence.	2006 May	16612211
Pharmacologic treatments for opioid dependence: detoxification and maintenance options.	2007	18286804
In-patient detoxification procedures, treatment retention, and post-treatment opiate use: comparison of lofexidine + naloxone, lofexidine + placebo, and methadone.	2007 Apr 17	17064857
Hemodynamic and cognitive effects of lofexidine and methadone coadministration: a pilot study.	2007 Aug	17655511
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 Jan 8	17210080
Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial.	2007 Jan 8	17210079
Opioid dependence.	2007 Jun 1	19454085
Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings.	2007 Mar	17136399
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
Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse.	2008 Mar	18161012
A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.	2008 Sep 1	18508207
Urine and plasma pharmacokinetics of lofexidine after oral delivery in opiate-dependent patients.	2009	19637105
Norepinephrine and stimulant addiction.	2009 Apr	18811678
Alpha2-adrenergic agonists for the management of opioid withdrawal.	2009 Apr 15	19370574
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project: a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification.	2009 Feb 5	19196468
Pharmacokinetics of lofexidine hydrochloride in healthy volunteers.	2009 Jan	18393298
Electrocardiographic effects of lofexidine and methadone coadministration: secondary findings from a safety study.	2009 May	19397459
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 Sep	19686525
A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence.	2010	20798544
The pharmacological treatment of opioid addiction--a clinical perspective.	2010 Jun	20169438

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

Substance Class	Chemical Created by `admin` on `Wed Jul 05 22:55:08 UTC 2023` Edited by `admin` on `Wed Jul 05 22:55:08 UTC 2023`
Record UNII	V47G1SDI1B
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LOFEXIDINE HYDROCHLORIDE

Official 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

LUCEMYRA

Brand 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