Details of the Drug

General Information of Drug (ID: DM8RFNJ)

Drug Name

Pitolisant

Synonyms

Pitolisant; 362665-56-3; TIPROLISANT; BF2.649; UNII-4BC83L4PIY; 1-[3-[3-(4-chlorophenyl)propoxy]propyl]piperidine; Pitolisant (BF2.649); 1-(3-(3-(4-Chlorophenyl)propoxy)propyl)piperidine; 4BC83L4PIY; Piperidine, 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-; CHEMBL462605; wakix; 1-[3-[3-(4-Chlorophenyl)propoxy]propyl]-piperidinehydrochloride; 1-{3-[3-(4-chlorophenyl)propoxy]propyl}piperidine; Tirolisant; Pitolisant (INN); tiprolisant [USAN]; Wakix (TN); Pitolisant [USAN:INN]; SCHEMBL117648; GTPL8924; CTK1B6404; HBS-101

Indication

Disease Entry	ICD 11	Status	REF
Excessive daytime sleepiness	MG42	Approved	[1]
Schizophrenia	6A20	Phase 3	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

295.8

Topological Polar Surface Area (xlogp)

4.3

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 812 mcgh/L [3]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 73 mcg/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3 h [3]
Clearance: The apparent oral clearance of drug is 43.9 L/h [3]
Elimination: Following hepatic metabolism, about 63% of total elimination occurs via renal excretion into the urine as an inactive non-conjugated metabolite BP2.951 and a glycine conjugated metabolite [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 10 - 12 hours [4]
Metabolism: The drug is metabolized via the CYP2D6 and to a lesser extent by CYP3A4 in the liver [4]
Vd: The volume of distribution (Vd) of drug is 1100-2825 L [5]

Chemical Identifiers

Formula: C17H26ClNO
IUPAC Name: 1-[3-[3-(4-chlorophenyl)propoxy]propyl]piperidine
Canonical SMILES: C1CCN(CC1)CCCOCCCC2=CC=C(C=C2)Cl
InChI: InChI=1S/C17H26ClNO/c18-17-9-7-16(8-10-17)6-4-14-20-15-5-13-19-11-2-1-3-12-19/h7-10H,1-6,11-15H2
InChIKey: NNACHAUCXXVJSP-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 9948102
ChEBI ID: CHEBI:134709
CAS Number: 362665-56-3
DrugBank ID: DB11642
TTD ID: D01UUD
ACDINA ID: D01345

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histamine H3 receptor (H3R)	TT9JNIC	HRH3_HUMAN	Agonist	[1]

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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 Pitolisant (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Pitolisant and Ivosidenib.	Acute myeloid leukaemia [2A60]	[15]
Arn-509	DMT81LZ	Major	Increased metabolism of Pitolisant caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[16]
Oliceridine	DM6MDCF	Major	Increased metabolism of Pitolisant caused by Oliceridine mediated induction of CYP450 enzyme.	Acute pain [MG31]	[17]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of Pitolisant and Levalbuterol.	Asthma [CA23]	[18]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Pitolisant caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[19]
Tucatinib	DMBESUA	Moderate	Decreased metabolism of Pitolisant caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[20]
Osilodrostat	DMIJC9X	Moderate	Increased risk of prolong QT interval by the combination of Pitolisant and Osilodrostat.	Cushing syndrome [5A70]	[16]
Deutetrabenazine	DMUPFLI	Moderate	Increased risk of prolong QT interval by the combination of Pitolisant and Deutetrabenazine.	Dystonic disorder [8A02]	[21]
Ingrezza	DMVPLNC	Moderate	Increased risk of prolong QT interval by the combination of Pitolisant and Ingrezza.	Dystonic disorder [8A02]	[16]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Pitolisant caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[22]
Ripretinib	DM958QB	Moderate	Increased metabolism of Pitolisant caused by Ripretinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[23]
Avapritinib	DMK2GZX	Moderate	Increased metabolism of Pitolisant caused by Avapritinib mediated induction of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[16]
Fostemsavir	DM50ILT	Moderate	Increased risk of prolong QT interval by the combination of Pitolisant and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Givosiran	DM5PFIJ	Moderate	Decreased metabolism of Pitolisant caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[16]
Pemigatinib	DM819JF	Moderate	Increased metabolism of Pitolisant caused by Pemigatinib mediated induction of CYP450 enzyme.	Liver cancer [2C12]	[16]
Lurbinectedin	DMEFRTZ	Moderate	Increased metabolism of Pitolisant caused by Lurbinectedin mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[24]
PF-06463922	DMKM7EW	Major	Increased metabolism of Pitolisant caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[25]
Dacomitinib	DMOH8VY	Major	Decreased metabolism of Pitolisant caused by Dacomitinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[16]
Capmatinib	DMYCXKL	Moderate	Increased metabolism of Pitolisant caused by Capmatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[26]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Pitolisant and Selpercatinib.	Lung cancer [2C25]	[16]
IPI-145	DMWA24P	Moderate	Increased metabolism of Pitolisant caused by IPI-145 mediated induction of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[27]
Acalabrutinib	DM7GCVW	Moderate	Increased metabolism of Pitolisant caused by Acalabrutinib mediated induction of CYP450 enzyme.	Mature B-cell lymphoma [2A85]	[28]
Selumetinib	DMC7W6R	Moderate	Increased metabolism of Pitolisant caused by Selumetinib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[29]
LGX818	DMNQXV8	Moderate	Increased risk of prolong QT interval by the combination of Pitolisant and LGX818.	Melanoma [2C30]	[30]
Ubrogepant	DM749I3	Moderate	Increased metabolism of Pitolisant caused by Ubrogepant mediated induction of CYP450 enzyme.	Migraine [8A80]	[31]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Pitolisant and Ozanimod.	Multiple sclerosis [8A40]	[32]
Deflazacort	DMV0RNS	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Pitolisant and Deflazacort.	Muscular dystrophy [8C70]	[16]
Entrectinib	DMMPTLH	Moderate	Increased metabolism of Pitolisant caused by Entrectinib mediated induction of CYP450 enzyme.	Non-small cell lung cancer [2C25]	[33]
S-297995	DM26IH8	Moderate	Increased metabolism of Pitolisant caused by S-297995 mediated induction of CYP450 enzyme.	Opioid use disorder [6C43]	[16]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Pitolisant and Rucaparib.	Ovarian cancer [2C73]	[16]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Pitolisant and Triclabendazole.	Parasitic worm infestation [1F90]	[17]
Istradefylline	DM20VSK	Moderate	Increased metabolism of Pitolisant caused by Istradefylline mediated induction of CYP450 enzyme.	Parkinsonism [8A00]	[16]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Pitolisant and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[34]
Lefamulin	DME6G97	Major	Increased risk of prolong QT interval by the combination of Pitolisant and Lefamulin.	Pneumonia [CA40]	[35]
Relugolix	DMK7IWL	Moderate	Increased risk of prolong QT interval by the combination of Pitolisant and Relugolix.	Prostate cancer [2C82]	[16]
Upadacitinib	DM32B5U	Moderate	Increased metabolism of Pitolisant caused by Upadacitinib mediated induction of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[36]
Larotrectinib	DM26CQR	Moderate	Increased metabolism of Pitolisant caused by Larotrectinib mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[16]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Pitolisant and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[17]
Betrixaban	DM2C4RF	Moderate	Accelerated clearance of Pitolisant due to the transporter induction by Betrixaban.	Venous thromboembolism [BD72]	[37]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Crospovidone	E00626	Not Available	Disintegrant
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling 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
Pitolisant 17.8 mg tablet	17.8 mg	Tablet	Oral
Pitolisant 4.45 mg tablet	4.45 mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
2	ClinicalTrials.gov (NCT01800045) Pitolisant to Assess Weekly Frequency of Cataplexy Attacks and EDS in Narcoleptic Patients (HARMONY CTP). U.S. National Institutes of Health.
3	WAKIX? (pitolisant) tablets, for oral use - FDA Label
4	Wakix, INN-Pitolisant - European Medicines Agency - Europa EU
5	Wakix, INN-pitolisant - European Medicines Agency - Europa EU: Assessment report
6	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7	Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist. Br J Pharmacol. 2004 Nov;143(5):649-61.
8	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
9	JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the abuse-related effects of alcohol in rats. Psychopharmacology (Berl). 2011 Apr;214(4):829-41.
10	SAR110894, a potent histamine H receptor antagonist, displays procognitive effects in rodents. Pharmacol Biochem Behav. 2012 Aug;102(2):203-14.
11	Randomized clinical study of a histamine H3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs. 2012 May 1;26(5):421-34.
12	A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.J Alzheimers Dis.2014;42(3):959-71.
13	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032225)
14	Histamine H3 Receptors and Sleep-Wake Regulation. JPET January 2011 vol. 336 no. 1 17-23.
15	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
16	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
17	Canadian Pharmacists Association.
18	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
19	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
20	Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
21	Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
22	Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
23	Cerner Multum, Inc. "Australian Product Information.".
24	Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
25	Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
26	Product Information. Tabrecta (capmatinib). Novartis Pharmaceuticals, East Hanover, NJ.
27	Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
28	Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
29	Product Information. Koselugo (selumetinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
30	Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
31	Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
32	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
33	Product Information. Rozlytrek (entrectinib). Genentech, South San Francisco, CA.
34	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
35	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
36	Product Information. Rinvoq (upadacitinib). AbbVie US LLC, North Chicago, IL.
37	Gelosa P, Castiglioni L, Tenconi M, et.al "Pharmacokinetic drug interactions of the non-vitamin K antagonist oral anticoagulants (NOACs)" Pharmacol Res 135 (2018): 60-79. [PMID: 30040996]