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-2 113 Target ID: CHEMBL2095158 Sources: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM602419.pdf	Agonist 2678

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 8429	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 (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 1767 inducer 389	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 OAT1 599 OAT3 642 OCT1 512 OCT2 647 OATP1B1 788 OATP1B3 706 MATE2 263 BSEP 402 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 MATE1 306	CYP1A2 1054 CYP2C19 991 P-gp 1537	CYP1A2 701 CYP2A6 79 CYP2B6 547 CYP2C8 168 CYP2C19 293 CYP2E1 128 CYP3A4/5 124

Drug as perpetrator

Target	Modality	Activity	Metabolite
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2A6 739	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP2E1 970	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	2, 6-DC 2
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LADP 2
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=340 Page: 340.0	no	LDPA 2
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0	yes [IC50 4551 uM]
MATE1 308	inhibitor 3277 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 1217	substrate 3367 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 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=330 Page: 330.0	no
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000MultidisciplineR.pdf#page=28 Page: 28.0	yes
CYP2C19 991	substrate 3367 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 1647	inhibitor 1626 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
Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking.	2000 Aug	10882840
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
Repeated lofexidine treatment attenuates stress-induced, but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats.	2001 Sep	11522461
[125I]2-(2-chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911), a high-affinity radioligand selective for I1 imidazoline receptors.	2002 Jul	12065769
Alpha2 adrenergic agonists for the management of opioid withdrawal.	2003	12804419
The effectiveness of combined naloxone/lofexidine in opiate detoxification: results from a double-blind randomized and placebo-controlled trial.	2003 Jul-Sep	14504022
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
QT interval increased after single dose of lofexidine.	2004 Nov 6	15528619
Alpha2 adrenergic agonists for the management of opioid withdrawal.	2004 Oct 18	15495025
Is clonidine useful for treatment of clozapine-induced sialorrhea?	2005 Jul	15983000
Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats.	2005 May	15551068
Cognitive function during early abstinence from opioid dependence: a comparison to age, gender, and verbal intelligence matched controls.	2006 Feb 24	16504127
Pharmacologic treatments for opioid dependence: detoxification and maintenance options.	2007	18286804
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
Agenda for specialty section in addiction medicine.	2008 Oct	19823604
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 Sep	19506724
A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.	2008 Sep 1	18508207
A study on Fu-Yuan Pellet, a traditional chinese medicine formula for detoxification of heroin addictions.	2009	20014908
Pharmacotherapy for cannabis dependence: how close are we?	2009	19552483
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 Study: protocol for a randomised controlled trial comparing methadone and buprenorphine for opiate detoxification.	2009 Jul 14	19602218
Opioid dependence.	2009 Jul 24	21696648
Buprenorphine for the management of opioid withdrawal.	2009 Jul 8	19588330
Electrocardiographic effects of lofexidine and methadone coadministration: secondary findings from a safety study.	2009 May	19397459
Opioid antagonists with minimal sedation for opioid withdrawal.	2009 Oct 7	19821290
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

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

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