Details of the Drug

General Information of Drug (ID: DM1WXA6)

Drug Name

Lofexidine

Synonyms

Britlofex; Lofexidina; Lofexidinum; Britlofex (TN); Lofexidina [INN-Spanish]; Lofexidine (INN); Lofexidine [INN:BAN]; Lofexidinum [INN-Latin]; 1H-Imidazole, 2-(1-(2,6-dichlorophenoxy)ethyl)-4,5-dihydro-(9CI); 2-(1-(2,6-Dichlorophenoxy)ethyl)-4,5-dihydro-1H-imidazole; 2-(a-(2,6-dichlorophenoxy)ethyl)2-imidazoline; 2-(alpha-(2,6-Dichlorophenoxy)ethyl)2-imidazoline; 2-(alpha-(2,6-dichlorophenoxy)ethyl) delta-2-imidazoline; 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole; 2-{1-[(2,6-dichlorophenyl)oxy]ethyl}-4,5-dihydro-1H-imidazole

Indication

Disease Entry	ICD 11	Status	REF
Heroin and opiate withdrawal	6C43	Approved	[1]
Opioid dependence	6C43.2Z	Approved	[2]
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Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

259.13

Logarithm of the Partition Coefficient (xlogp)

2.6

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 46 mcgh/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 0.5 h [3]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Bioavailability: The bioavailability of drug is 85% [3]
Clearance: The clearance of drug is 17.6 L/h [5]
Elimination: The elimination of lofexidine is primarily through the renal system and it represents 94% of the administered dose while elimination in feces corresponds to only 0.93% []
Half-life: The concentration or amount of drug in body reduced by one-half in 11 hours [6]
Metabolism: The drug is metabolized via the CYP2D6 and in a minor degree by CYP1A2 and CYP2C19 []
Vd: The volume of distribution (Vd) of drug is 300 L [5]

Chemical Identifiers

Formula: C11H12Cl2N2O
IUPAC Name: 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole
Canonical SMILES: CC(C1=NCCN1)OC2=C(C=CC=C2Cl)Cl
InChI: InChI=1S/C11H12Cl2N2O/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)
InChIKey: KSMAGQUYOIHWFS-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 30668
ChEBI ID: CHEBI:51368
CAS Number: 31036-80-3
DrugBank ID: DB04948
TTD ID: D0K0MW
INTEDE ID: DR0967
ACDINA ID: D01217

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor Alpha-2 (ADRA2)	TTQ8AFT	NOUNIPROTAC	Agonist	[7]
Adrenergic receptor alpha-2A (ADRA2A)	TTWG9A4	ADA2A_HUMAN	Agonist	[2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Lofexidine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Ivosidenib.	Acute myeloid leukaemia [2A60]	[10]
Midostaurin	DMI6E0R	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Midostaurin.	Acute myeloid leukaemia [2A60]	[11]
Arn-509	DMT81LZ	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Arn-509.	Acute myeloid leukaemia [2A60]	[12]
Gilteritinib	DMTI0ZO	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Gilteritinib.	Acute myeloid leukaemia [2A60]	[13]
Ivabradine	DM0L594	Major	Increased risk of ventricular arrhythmias by the combination of Lofexidine and Ivabradine.	Angina pectoris [BA40]	[12]
Bedaquiline	DM3906J	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[14]
Levalbuterol	DM5YBO1	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Levalbuterol.	Asthma [CA23]	[15]
Retigabine	DMGNYIH	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Retigabine.	Behcet disease [4A62]	[11]
Eribulin	DM1DX4Q	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Eribulin.	Breast cancer [2C60-2C6Y]	[11]
Bosutinib	DMTI8YE	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Bosutinib.	Breast cancer [2C60-2C6Y]	[11]
PF-04449913	DMSB068	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[16]
Olodaterol	DM62B78	Moderate	Increased risk of ventricular arrhythmias by the combination of Lofexidine and Olodaterol.	Chronic obstructive pulmonary disease [CA22]	[17]
Vilanterol	DMF5EK1	Moderate	Increased risk of ventricular arrhythmias by the combination of Lofexidine and Vilanterol.	Chronic obstructive pulmonary disease [CA22]	[15]
Indacaterol	DMQJHR7	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Indacaterol.	Chronic obstructive pulmonary disease [CA22]	[17]
Pasireotide	DMHM7JS	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Pasireotide.	Cushing syndrome [5A70]	[11]
Osilodrostat	DMIJC9X	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Osilodrostat.	Cushing syndrome [5A70]	[12]
OPC-34712	DMHG57U	Moderate	Additive hypotensive effects by the combination of Lofexidine and OPC-34712.	Depression [6A70-6A7Z]	[18]
Esketamine	DMVU687	Moderate	Additive CNS depression effects by the combination of Lofexidine and Esketamine.	Depression [6A70-6A7Z]	[19]
Ingrezza	DMVPLNC	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Ingrezza.	Dystonic disorder [8A02]	[11]
Fostemsavir	DM50ILT	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[20]
Rilpivirine	DMJ0QOW	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Rilpivirine.	Human immunodeficiency virus disease [1C60-1C62]	[11]
ITI-007	DMUQ1DO	Moderate	Additive hypotensive effects by the combination of Lofexidine and ITI-007.	Insomnia [7A00-7A0Z]	[18]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of ventricular arrhythmias by the combination of Lofexidine and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[12]
Crizotinib	DM4F29C	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Crizotinib.	Lung cancer [2C25]	[21]
Ceritinib	DMB920Z	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Ceritinib.	Lung cancer [2C25]	[11]
Osimertinib	DMRJLAT	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Osimertinib.	Lung cancer [2C25]	[22]
Lumefantrine	DM29GAD	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Lumefantrine.	Malaria [1F40-1F45]	[19]
Inotuzumab ozogamicin	DMAC130	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Inotuzumab ozogamicin.	Malignant haematopoietic neoplasm [2B33]	[12]
Vemurafenib	DM62UG5	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Vemurafenib.	Melanoma [2C30]	[11]
Allopregnanolone	DMNLHAC	Moderate	Additive CNS depression effects by the combination of Lofexidine and Allopregnanolone.	Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z]	[23]
Lasmiditan	DMXLVDT	Moderate	Additive CNS depression effects by the combination of Lofexidine and Lasmiditan.	Migraine [8A80]	[24]
Panobinostat	DM58WKG	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Panobinostat.	Multiple myeloma [2A83]	[25]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of Lofexidine and Siponimod.	Multiple sclerosis [8A40]	[19]
Fingolimod	DM5JVAN	Major	Increased risk of ventricular arrhythmias by the combination of Lofexidine and Fingolimod.	Multiple sclerosis [8A40]	[11]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Lofexidine and Ozanimod.	Multiple sclerosis [8A40]	[26]
Romidepsin	DMT5GNL	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Romidepsin.	Mycosis fungoides [2B01]	[11]
Entrectinib	DMMPTLH	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Entrectinib.	Non-small cell lung cancer [2C25]	[19]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Rucaparib.	Ovarian cancer [2C73]	[11]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Triclabendazole.	Parasitic worm infestation [1F90]	[11]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Lofexidine and Safinamide.	Parkinsonism [8A00]	[27]
Pimavanserin	DMR7IVC	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Pimavanserin.	Parkinsonism [8A00]	[28]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[29]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Lefamulin.	Pneumonia [CA40]	[30]
Degarelix	DM3O8QY	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Degarelix.	Prostate cancer [2C82]	[12]
ABIRATERONE	DM8V75C	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and ABIRATERONE.	Prostate cancer [2C82]	[12]
Enzalutamide	DMGL19D	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Enzalutamide.	Prostate cancer [2C82]	[12]
Relugolix	DMK7IWL	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Relugolix.	Prostate cancer [2C82]	[12]
Asenapine	DMSQZE2	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Asenapine.	Schizophrenia [6A20]	[11]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Lofexidine and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[11]
Vandetanib	DMRICNP	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Vandetanib.	Solid tumour/cancer [2A00-2F9Z]	[11]
Triptorelin	DMTK4LS	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Triptorelin.	Solid tumour/cancer [2A00-2F9Z]	[12]
Pitolisant	DM8RFNJ	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Pitolisant.	Somnolence [MG42]	[12]
Telavancin	DM58VQX	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Telavancin.	Staphylococcal/streptococcal disease [1B5Y]	[11]
Lenvatinib	DMB1IU4	Moderate	Increased risk of prolong QT interval by the combination of Lofexidine and Lenvatinib.	Thyroid cancer [2D10]	[11]
Cabozantinib	DMIYDT4	Major	Increased risk of prolong QT interval by the combination of Lofexidine and Cabozantinib.	Thyroid cancer [2D10]	[12]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
FD&C blue no. 2	E00446	2723854	Colorant
Kyselina citronova	E00014	311	Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Sunset yellow FCF	E00255	17730	Colorant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Calcium stearate	E00244	15324	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Lofexidine 0.18 mg tablet	0.18 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Drug Alcohol Depend. 2008 Sep 1;97(1-2):158-68.
2	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
3	EMA Public Assessment Report: Hepcludex (bulevirtide) powder for injectable solution
4	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
5	FDA reports
6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	Clinical pharmacokinetics of lofexidine, the alpha 2-adrenergic receptor agonist, in opiate addicts plasma using a highly sensitive liquid chromatography tandem mass spectrometric analysis. Am J DrugAlcohol Abuse. 2008;34(5):611-6.
8	Advisory committee lofexidine hydrochloride (lucemyratm) briefing document.
9	The Drugs.com International Drug Name Database: Lofexidine
10	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
11	Canadian Pharmacists Association.
12	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
13	Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
14	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
15	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
16	Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
17	Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
18	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
19	Cerner Multum, Inc. "Australian Product Information.".
20	Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
21	Product Information. Xalkori (crizotinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
22	Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
23	Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
24	Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
25	Product Information. Farydak (panobinostat). Novartis Pharmaceuticals, East Hanover, NJ.
26	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
27	Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
28	Product Information. Nuplazid (pimavanserin). Accelis Pharma, East Windsor, NJ.
29	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
30	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.