Identification

Name
Macitentan
Accession Number
DB08932
Type
Small Molecule
Groups
Approved
Description

Macitentan was approved in October 2013. It is indicated for patients with pulmonary arterial hypertension, and is marketed under the brand name Opsumit. Macitentan is an antagonist/blocker of endothelin receptors on blood vessels and smooth muscle, and, thus, blocks the stimulation of vasculature hypertrophy, inflammation, fibrosis, proliferation, and vasoconstriction. Similar to all drugs acting on the renin-angiotensin system, macitentan is associated with embryo and fetal toxicity, so it should not be used in pregnancy and has special precautions that must be followed for all females of child-bearing age.

Structure
Thumb
Synonyms
  • Macitentanum
External IDs
ACT 064992 / ACT-064992
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OpsumitTablet10 mgOralActelion2014-01-15Not applicableCanada
OpsumitTablet, film coated10 mg/1OralActelion2013-10-01Not applicableUs
Categories
UNII
Z9K9Y9WMVL
CAS number
441798-33-0
Weight
Average: 588.273
Monoisotopic: 585.963349142
Chemical Formula
C19H20Br2N6O4S
InChI Key
JGCMEBMXRHSZKX-UHFFFAOYSA-N
InChI
InChI=1S/C19H20Br2N6O4S/c1-2-7-26-32(28,29)27-17-16(13-3-5-14(20)6-4-13)18(25-12-24-17)30-8-9-31-19-22-10-15(21)11-23-19/h3-6,10-12,26H,2,7-9H2,1H3,(H,24,25,27)
IUPAC Name
{[5-(4-bromophenyl)-6-{2-[(5-bromopyrimidin-2-yl)oxy]ethoxy}pyrimidin-4-yl]sulfamoyl}(propyl)amine
SMILES
CCCNS(=O)(=O)NC1=C(C(OCCOC2=NC=C(Br)C=N2)=NC=N1)C1=CC=C(Br)C=C1

Pharmacology

Indication

Macitentan is indicated for patients with pulmonary arterial hypertension.

Structured Indications
Pharmacodynamics

Macitentan blocks simulators of hypertrophy, inflammation, fibrosis, proliferation, and vasoconstriction.

Mechanism of action

Macitentan is an antagonist/blocker of endothelin receptors. Endothelin receptors are found in the endothelial cells of blood vessels and smooth muscle. Macitentan binds to the receptors, endothelin A and B (ETA and ETB), which prevents the agonist endothelin -1 (ET-1) from binding and stimulating the ETA and ETB receptors.

TargetActionsOrganism
AEndothelin-1 receptor
antagonist
Human
AEndothelin B receptor
antagonist
Human
Absorption

Macitentan is administered orally, and it take about 8 hours for maximum plasma concentrations to be reached.

Volume of distribution

Macitentan has a volume of distribution of 50L.

Protein binding

Macitentan is >99% bound to plasma proteins, which are mainly albumin

Metabolism

Macitentan is metabolised to an active metabolite by CYP 3A4 (major) and CYP 2C19 (minor).

Route of elimination

Eliminated 50% through urine and 24% through feces.

Half life

The half life of macitentan is 16 hours, and the half life of it's active metabolite is 48 hours.

Clearance

Clearance data was not found.

Toxicity

Macitentan has a black box warning of embryo-fetal toxicity. Special precautions must be taken for all females of child-bearing age, and women who are pregnant must not be given macitentan.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Macitentan.Experimental
AbirateroneThe metabolism of Macitentan can be decreased when combined with Abiraterone.Approved
AcebutololAcebutolol may increase the hypotensive activities of Macitentan.Approved
AlfuzosinAlfuzosin may increase the hypotensive activities of Macitentan.Approved, Investigational
AliskirenAliskiren may increase the hypotensive activities of Macitentan.Approved, Investigational
AlprenololAlprenolol may increase the hypotensive activities of Macitentan.Approved, Withdrawn
AmbrisentanAmbrisentan may increase the hypotensive activities of Macitentan.Approved, Investigational
AmifostineMacitentan may increase the hypotensive activities of Amifostine.Approved, Investigational
AmiodaroneThe serum concentration of Macitentan can be increased when it is combined with Amiodarone.Approved, Investigational
AmlodipineAmlodipine may increase the hypotensive activities of Macitentan.Approved
AmphetamineAmphetamine may increase the hypotensive activities of Macitentan.Approved, Illicit
AprepitantThe serum concentration of Macitentan can be increased when it is combined with Aprepitant.Approved, Investigational
ArmodafinilThe metabolism of Macitentan can be decreased when combined with Armodafinil.Approved, Investigational
AtazanavirThe serum concentration of Macitentan can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololAtenolol may increase the hypotensive activities of Macitentan.Approved
AtomoxetineThe metabolism of Macitentan can be decreased when combined with Atomoxetine.Approved
AvanafilAvanafil may increase the antihypertensive activities of Macitentan.Approved
BenazeprilBenazepril may increase the hypotensive activities of Macitentan.Approved, Investigational
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Macitentan.Approved
BenmoxinBenmoxin may increase the hypotensive activities of Macitentan.Withdrawn
BepridilBepridil may increase the hypotensive activities of Macitentan.Approved, Withdrawn
BetaxololBetaxolol may increase the hypotensive activities of Macitentan.Approved
BethanidineBethanidine may increase the hypotensive activities of Macitentan.Approved
BietaserpineBietaserpine may increase the hypotensive activities of Macitentan.Experimental
BimatoprostBimatoprost may increase the hypotensive activities of Macitentan.Approved, Investigational
BisoprololBisoprolol may increase the hypotensive activities of Macitentan.Approved
BoceprevirThe serum concentration of Macitentan can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Macitentan can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Macitentan can be decreased when it is combined with Bosentan.Approved, Investigational
BQ-123BQ-123 may increase the hypotensive activities of Macitentan.Investigational
BretyliumBretylium may increase the hypotensive activities of Macitentan.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Macitentan.Approved
BrofaromineBrofaromine may increase the hypotensive activities of Macitentan.Experimental
BupranololBupranolol may increase the hypotensive activities of Macitentan.Approved
CadralazineCadralazine may increase the hypotensive activities of Macitentan.Experimental
CafedrineCafedrine may increase the hypotensive activities of Macitentan.Investigational
CandesartanCandesartan may increase the hypotensive activities of Macitentan.Experimental
Candesartan cilexetilCandesartan cilexetil may increase the hypotensive activities of Macitentan.Approved
CandoxatrilCandoxatril may increase the hypotensive activities of Macitentan.Experimental
CaptoprilCaptopril may increase the hypotensive activities of Macitentan.Approved
CarbamazepineThe serum concentration of Macitentan can be decreased when it is combined with Carbamazepine.Approved, Investigational
CaroxazoneCaroxazone may increase the hypotensive activities of Macitentan.Withdrawn
CarteololCarteolol may increase the hypotensive activities of Macitentan.Approved
CarvedilolCarvedilol may increase the hypotensive activities of Macitentan.Approved, Investigational
CeliprololCeliprolol may increase the hypotensive activities of Macitentan.Approved, Investigational
CeritinibThe serum concentration of Macitentan can be increased when it is combined with Ceritinib.Approved
ChloramphenicolThe metabolism of Macitentan can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChlorothiazideChlorothiazide may increase the hypotensive activities of Macitentan.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Macitentan.Approved
CholecalciferolThe metabolism of Macitentan can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CicletanineCicletanine may increase the hypotensive activities of Macitentan.Investigational
CilazaprilCilazapril may increase the hypotensive activities of Macitentan.Approved
CimetidineThe metabolism of Macitentan can be decreased when combined with Cimetidine.Approved
CitalopramThe metabolism of Macitentan can be decreased when combined with Citalopram.Approved
ClarithromycinThe serum concentration of Macitentan can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Macitentan can be decreased when combined with Clemastine.Approved
ClonidineClonidine may increase the hypotensive activities of Macitentan.Approved
CloranololCloranolol may increase the hypotensive activities of Macitentan.Experimental
ClotrimazoleThe metabolism of Macitentan can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Macitentan can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Macitentan can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Macitentan can be decreased when combined with Crizotinib.Approved
CryptenamineCryptenamine may increase the hypotensive activities of Macitentan.Approved
CyclopenthiazideCyclopenthiazide may increase the hypotensive activities of Macitentan.Experimental
CyclosporineThe metabolism of Macitentan can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CyclothiazideCyclothiazide may increase the hypotensive activities of Macitentan.Approved
DabrafenibThe serum concentration of Macitentan can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Macitentan can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Macitentan can be increased when it is combined with Dasatinib.Approved, Investigational
DebrisoquinDebrisoquin may increase the hypotensive activities of Macitentan.Approved, Investigational
DeferasiroxThe serum concentration of Macitentan can be decreased when it is combined with Deferasirox.Approved, Investigational
DelaprilDelapril may increase the hypotensive activities of Macitentan.Experimental
DelavirdineThe metabolism of Macitentan can be decreased when combined with Delavirdine.Approved
DeserpidineDeserpidine may increase the hypotensive activities of Macitentan.Approved
DiazoxideDiazoxide may increase the hypotensive activities of Macitentan.Approved
diethylnorsperminediethylnorspermine may increase the hypotensive activities of Macitentan.Investigational
DihydralazineDihydralazine may increase the hypotensive activities of Macitentan.Investigational
DihydroergotamineThe metabolism of Macitentan can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Macitentan can be decreased when combined with Diltiazem.Approved
DorzolamideDorzolamide may increase the hypotensive activities of Macitentan.Approved
DoxazosinDoxazosin may increase the hypotensive activities of Macitentan.Approved
DoxycyclineThe metabolism of Macitentan can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Macitentan can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Macitentan can be decreased when combined with Efavirenz.Approved, Investigational
EfonidipineEfonidipine may increase the hypotensive activities of Macitentan.Approved, Investigational
EnalaprilEnalapril may increase the hypotensive activities of Macitentan.Approved, Vet Approved
EnalaprilatEnalaprilat may increase the hypotensive activities of Macitentan.Approved
EndralazineEndralazine may increase the hypotensive activities of Macitentan.Experimental
EnzalutamideThe serum concentration of Macitentan can be decreased when it is combined with Enzalutamide.Approved
EpanololEpanolol may increase the hypotensive activities of Macitentan.Experimental
EpoprostenolEpoprostenol may increase the hypotensive activities of Macitentan.Approved
EprosartanEprosartan may increase the hypotensive activities of Macitentan.Approved
ErythromycinThe metabolism of Macitentan can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe metabolism of Macitentan can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Macitentan can be decreased when combined with Esomeprazole.Approved, Investigational
EtravirineThe metabolism of Macitentan can be decreased when combined with Etravirine.Approved
FelodipineFelodipine may increase the hypotensive activities of Macitentan.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Macitentan.Approved
Ferulic acidFerulic acid may increase the hypotensive activities of Macitentan.Experimental
FluconazoleThe metabolism of Macitentan can be decreased when combined with Fluconazole.Approved
FluoxetineThe metabolism of Macitentan can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvoxamineThe metabolism of Macitentan can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Macitentan can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Macitentan can be increased when it is combined with Fosaprepitant.Approved
FosinoprilFosinopril may increase the hypotensive activities of Macitentan.Approved
FosphenytoinThe serum concentration of Macitentan can be decreased when it is combined with Fosphenytoin.Approved
FurazolidoneFurazolidone may increase the hypotensive activities of Macitentan.Approved, Investigational, Vet Approved
Fusidic AcidThe serum concentration of Macitentan can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe metabolism of Macitentan can be decreased when combined with Gemfibrozil.Approved
GuanabenzGuanabenz may increase the hypotensive activities of Macitentan.Approved, Investigational
GuanadrelGuanadrel may increase the hypotensive activities of Macitentan.Approved
GuanazodineMacitentan may increase the hypotensive activities of Guanazodine.Experimental
GuanethidineGuanethidine may increase the hypotensive activities of Macitentan.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Macitentan.Approved, Investigational
GuanoclorMacitentan may increase the hypotensive activities of Guanoclor.Experimental
GuanoxabenzMacitentan may increase the hypotensive activities of Guanoxabenz.Experimental
GuanoxanMacitentan may increase the hypotensive activities of Guanoxan.Experimental
HarmalineHarmaline may increase the hypotensive activities of Macitentan.Experimental
HexamethoniumHexamethonium may increase the hypotensive activities of Macitentan.Experimental
HydracarbazineHydracarbazine may increase the hypotensive activities of Macitentan.Experimental
HydralazineHydralazine may increase the hypotensive activities of Macitentan.Approved
HydrochlorothiazideHydrochlorothiazide may increase the hypotensive activities of Macitentan.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypotensive activities of Macitentan.Approved, Investigational
IdelalisibThe serum concentration of Macitentan can be increased when it is combined with Idelalisib.Approved
IloprostIloprost may increase the hypotensive activities of Macitentan.Approved, Investigational
ImatinibThe metabolism of Macitentan can be decreased when combined with Imatinib.Approved
ImidaprilImidapril may increase the hypotensive activities of Macitentan.Investigational
IndapamideIndapamide may increase the hypotensive activities of Macitentan.Approved
IndenololIndenolol may increase the hypotensive activities of Macitentan.Withdrawn
IndinavirThe serum concentration of Macitentan can be increased when it is combined with Indinavir.Approved
IndoraminIndoramin may increase the hypotensive activities of Macitentan.Withdrawn
IproclozideIproclozide may increase the hypotensive activities of Macitentan.Withdrawn
IproniazidIproniazid may increase the hypotensive activities of Macitentan.Withdrawn
IrbesartanIrbesartan may increase the hypotensive activities of Macitentan.Approved, Investigational
IsavuconazoniumThe metabolism of Macitentan can be decreased when combined with Isavuconazonium.Approved, Investigational
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Macitentan.Approved
IsoniazidThe metabolism of Macitentan can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Macitentan can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Macitentan can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Macitentan can be increased when it is combined with Ivacaftor.Approved
KetanserinKetanserin may increase the hypotensive activities of Macitentan.Investigational
KetoconazoleThe serum concentration of Macitentan can be increased when it is combined with Ketoconazole.Approved, Investigational
LabetalolLabetalol may increase the hypotensive activities of Macitentan.Approved
LacidipineLacidipine may increase the hypotensive activities of Macitentan.Approved, Investigational
LatanoprostLatanoprost may increase the hypotensive activities of Macitentan.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Macitentan.Approved, Investigational
LinsidomineLinsidomine may increase the hypotensive activities of Macitentan.Experimental
LisinoprilLisinopril may increase the hypotensive activities of Macitentan.Approved, Investigational
LobeglitazoneThe metabolism of Macitentan can be decreased when combined with Lobeglitazone.Approved, Investigational
LofexidineLofexidine may increase the hypotensive activities of Macitentan.Approved, Investigational
LopinavirThe serum concentration of Macitentan can be increased when it is combined with Lopinavir.Approved
LosartanLosartan may increase the hypotensive activities of Macitentan.Approved
LovastatinThe metabolism of Macitentan can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Macitentan can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Macitentan can be decreased when it is combined with Lumacaftor.Approved
ManidipineManidipine may increase the hypotensive activities of Macitentan.Approved, Investigational
MebanazineMebanazine may increase the hypotensive activities of Macitentan.Withdrawn
MecamylamineMecamylamine may increase the hypotensive activities of Macitentan.Approved
MethoserpidineMacitentan may increase the hypotensive activities of Methoserpidine.Experimental
MethyldopaMethyldopa may increase the hypotensive activities of Macitentan.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Macitentan.Approved, Investigational
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Macitentan.Approved, Investigational
MetipranololMetipranolol may increase the hypotensive activities of Macitentan.Approved
MetolazoneMetolazone may increase the hypotensive activities of Macitentan.Approved
MetoprololMetoprolol may increase the hypotensive activities of Macitentan.Approved, Investigational
MetyrosineMetyrosine may increase the hypotensive activities of Macitentan.Approved
MibefradilMibefradil may increase the hypotensive activities of Macitentan.Investigational, Withdrawn
MifepristoneThe serum concentration of Macitentan can be increased when it is combined with Mifepristone.Approved, Investigational
MinaprineMinaprine may increase the hypotensive activities of Macitentan.Approved
MinoxidilMinoxidil may increase the hypotensive activities of Macitentan.Approved
MirodenafilMirodenafil may increase the antihypertensive activities of Macitentan.Investigational
MitotaneThe serum concentration of Macitentan can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Macitentan can be decreased when combined with Moclobemide.Approved
ModafinilThe metabolism of Macitentan can be decreased when combined with Modafinil.Approved, Investigational
MoexiprilMoexipril may increase the hypotensive activities of Macitentan.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Macitentan.Approved, Investigational
MoxonidineMoxonidine may increase the hypotensive activities of Macitentan.Approved, Investigational
MuzolimineMuzolimine may increase the hypotensive activities of Macitentan.Experimental
NadololNadolol may increase the hypotensive activities of Macitentan.Approved
NaftopidilNaftopidil may increase the hypotensive activities of Macitentan.Investigational
NebivololNebivolol may increase the hypotensive activities of Macitentan.Approved, Investigational
NefazodoneThe serum concentration of Macitentan can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Macitentan can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Macitentan can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Macitentan can be decreased when it is combined with Nevirapine.Approved
NialamideNialamide may increase the hypotensive activities of Macitentan.Withdrawn
NicardipineThe metabolism of Macitentan can be decreased when combined with Nicardipine.Approved
NicorandilNicorandil may increase the hypotensive activities of Macitentan.Approved, Investigational
NiguldipineNiguldipine may increase the hypotensive activities of Macitentan.Experimental
NilotinibThe metabolism of Macitentan can be decreased when combined with Nilotinib.Approved, Investigational
NilvadipineNilvadipine may increase the hypotensive activities of Macitentan.Approved, Investigational
NimodipineNimodipine may increase the hypotensive activities of Macitentan.Approved
NisoldipineNisoldipine may increase the hypotensive activities of Macitentan.Approved
NitrendipineNitrendipine may increase the hypotensive activities of Macitentan.Approved, Investigational
NitroprussideNitroprusside may increase the hypotensive activities of Macitentan.Approved
ObinutuzumabMacitentan may increase the hypotensive activities of Obinutuzumab.Approved
OctamoxinOctamoxin may increase the hypotensive activities of Macitentan.Withdrawn
OlaparibThe metabolism of Macitentan can be decreased when combined with Olaparib.Approved
OlmesartanOlmesartan may increase the hypotensive activities of Macitentan.Approved, Investigational
OmapatrilatOmapatrilat may increase the hypotensive activities of Macitentan.Investigational
OmeprazoleThe metabolism of Macitentan can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Macitentan can be increased when it is combined with Osimertinib.Approved
OxprenololOxprenolol may increase the hypotensive activities of Macitentan.Approved
PalbociclibThe serum concentration of Macitentan can be increased when it is combined with Palbociclib.Approved
PantoprazoleThe metabolism of Macitentan can be decreased when combined with Pantoprazole.Approved
PargylinePargyline may increase the hypotensive activities of Macitentan.Approved
PenbutololPenbutolol may increase the hypotensive activities of Macitentan.Approved, Investigational
PentobarbitalThe serum concentration of Macitentan can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PentoliniumPentolinium may increase the hypotensive activities of Macitentan.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Macitentan.Approved, Investigational
PerindoprilPerindopril may increase the hypotensive activities of Macitentan.Approved
PhenelzinePhenelzine may increase the hypotensive activities of Macitentan.Approved
PheniprazinePheniprazine may increase the hypotensive activities of Macitentan.Withdrawn
PhenobarbitalThe serum concentration of Macitentan can be decreased when it is combined with Phenobarbital.Approved
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Macitentan.Approved
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Macitentan.Withdrawn
PhentolaminePhentolamine may increase the hypotensive activities of Macitentan.Approved
PhenytoinThe serum concentration of Macitentan can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PinacidilPinacidil may increase the hypotensive activities of Macitentan.Withdrawn
PindololPindolol may increase the hypotensive activities of Macitentan.Approved
PirlindolePirlindole may increase the hypotensive activities of Macitentan.Approved
PivhydrazinePivhydrazine may increase the hypotensive activities of Macitentan.Withdrawn
Platelet Activating FactorPlatelet Activating Factor may increase the hypotensive activities of Macitentan.Experimental
PolythiazidePolythiazide may increase the hypotensive activities of Macitentan.Approved
PosaconazoleThe serum concentration of Macitentan can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrazosinPrazosin may increase the hypotensive activities of Macitentan.Approved
PrimidoneThe serum concentration of Macitentan can be decreased when it is combined with Primidone.Approved, Vet Approved
ProcarbazineProcarbazine may increase the hypotensive activities of Macitentan.Approved
PropranololPropranolol may increase the hypotensive activities of Macitentan.Approved, Investigational
QuinaprilQuinapril may increase the hypotensive activities of Macitentan.Approved, Investigational
QuinineQuinine may increase the hypotensive activities of Macitentan.Approved
RamiprilRamipril may increase the hypotensive activities of Macitentan.Approved
RanolazineThe metabolism of Macitentan can be decreased when combined with Ranolazine.Approved, Investigational
RasagilineRasagiline may increase the hypotensive activities of Macitentan.Approved
RemikirenRemikiren may increase the hypotensive activities of Macitentan.Approved
RescinnamineRescinnamine may increase the hypotensive activities of Macitentan.Approved
ReserpineReserpine may increase the hypotensive activities of Macitentan.Approved, Investigational
RifabutinThe serum concentration of Macitentan can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Macitentan can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Macitentan can be decreased when it is combined with Rifapentine.Approved
RilmenidineRilmenidine may increase the hypotensive activities of Macitentan.Investigational
RiociguatRiociguat may increase the hypotensive activities of Macitentan.Approved
RituximabMacitentan may increase the hypotensive activities of Rituximab.Approved
SafrazineSafrazine may increase the hypotensive activities of Macitentan.Withdrawn
SaprisartanSaprisartan may increase the hypotensive activities of Macitentan.Experimental
SaquinavirThe serum concentration of Macitentan can be increased when it is combined with Saquinavir.Approved, Investigational
SelegilineSelegiline may increase the hypotensive activities of Macitentan.Approved, Investigational, Vet Approved
SelexipagSelexipag may increase the hypotensive activities of Macitentan.Approved
SertralineThe metabolism of Macitentan can be decreased when combined with Sertraline.Approved
SildenafilSildenafil may increase the antihypertensive activities of Macitentan.Approved, Investigational
SiltuximabThe serum concentration of Macitentan can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Macitentan can be increased when it is combined with Simeprevir.Approved
SitaxentanSitaxentan may increase the hypotensive activities of Macitentan.Approved, Investigational, Withdrawn
SpiraprilSpirapril may increase the hypotensive activities of Macitentan.Approved
St. John's WortThe serum concentration of Macitentan can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Macitentan can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Macitentan can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TadalafilTadalafil may increase the antihypertensive activities of Macitentan.Approved, Investigational
TalinololTalinolol may increase the hypotensive activities of Macitentan.Investigational
TelaprevirThe serum concentration of Macitentan can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Macitentan can be increased when it is combined with Telithromycin.Approved
TelmisartanTelmisartan may increase the hypotensive activities of Macitentan.Approved, Investigational
TemocaprilTemocapril may increase the hypotensive activities of Macitentan.Experimental, Investigational
TerlipressinTerlipressin may increase the hypotensive activities of Macitentan.Approved, Investigational
TetrahydropalmatineTetrahydropalmatine may increase the hypotensive activities of Macitentan.Investigational
TheodrenalineTheodrenaline may increase the hypotensive activities of Macitentan.Investigational
TiboloneTibolone may increase the hypotensive activities of Macitentan.Approved, Investigational
TiclopidineThe metabolism of Macitentan can be decreased when combined with Ticlopidine.Approved
TicrynafenTicrynafen may increase the hypotensive activities of Macitentan.Withdrawn
TimololTimolol may increase the hypotensive activities of Macitentan.Approved
TocilizumabThe serum concentration of Macitentan can be decreased when it is combined with Tocilizumab.Approved
TolazolineTolazoline may increase the hypotensive activities of Macitentan.Approved, Vet Approved
TolonidineMacitentan may increase the hypotensive activities of Tolonidine.Experimental
ToloxatoneToloxatone may increase the hypotensive activities of Macitentan.Approved
TopiramateThe metabolism of Macitentan can be decreased when combined with Topiramate.Approved
TorasemideTorasemide may increase the hypotensive activities of Macitentan.Approved
TrandolaprilTrandolapril may increase the hypotensive activities of Macitentan.Approved
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Macitentan.Experimental
TranylcypromineThe metabolism of Macitentan can be decreased when combined with Tranylcypromine.Approved
TravoprostTravoprost may increase the hypotensive activities of Macitentan.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Macitentan.Approved, Investigational
TrichlormethiazideTrichlormethiazide may increase the hypotensive activities of Macitentan.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Macitentan.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Macitentan.Approved, Investigational
UdenafilUdenafil may increase the antihypertensive activities of Macitentan.Approved, Investigational
UnoprostoneUnoprostone may increase the hypotensive activities of Macitentan.Approved
UrapidilUrapidil may increase the hypotensive activities of Macitentan.Investigational
ValsartanValsartan may increase the hypotensive activities of Macitentan.Approved, Investigational
VardenafilVardenafil may increase the antihypertensive activities of Macitentan.Approved
VenlafaxineThe metabolism of Macitentan can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Macitentan can be decreased when combined with Verapamil.Approved
VincamineVincamine may increase the hypotensive activities of Macitentan.Experimental
VinpocetineVinpocetine may increase the hypotensive activities of Macitentan.Investigational
VoriconazoleThe serum concentration of Macitentan can be increased when it is combined with Voriconazole.Approved, Investigational
XipamideXipamide may increase the hypotensive activities of Macitentan.Experimental
XylometazolineXylometazoline may increase the hypotensive activities of Macitentan.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Macitentan.Approved, Vet Approved
ZiprasidoneThe metabolism of Macitentan can be decreased when combined with Ziprasidone.Approved
ZofenoprilZofenopril may increase the hypotensive activities of Macitentan.Experimental
ZucapsaicinThe metabolism of Macitentan can be decreased when combined with Zucapsaicin.Approved
Food Interactions
  • Can be taken with or without food.

References

Synthesis Reference

Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T: The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012 Sep 13;55(17):7849-61. doi: 10.1021/jm3009103. Epub 2012 Aug 16. Pubmed

General References
  1. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T: The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012 Sep 13;55(17):7849-61. doi: 10.1021/jm3009103. Epub 2012 Aug 16. [PubMed:22862294]
External Links
KEGG Drug
D10135
PubChem Compound
16004692
PubChem Substance
175427162
ChemSpider
13134960
BindingDB
50395626
ChEBI
76607
ChEMBL
CHEMBL2103873
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Macitentan
ATC Codes
C02KX04 — Macitentan
AHFS Codes
  • 48:48.00 — Vasodilating Agents
FDA label
Download (836 KB)
MSDS
Download (105 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentGlioblastomas1
1RecruitingOtherPulmonary Hypertension (PH) / Sickle Cell Disorders1
1TerminatedTreatmentGlioblastomas1
2Active Not RecruitingTreatmentChronic Thromboembolic Pulmonary Hypertension / Chronic Thromboembolic Pulmonary Hypertension (CTEPH)1
2CompletedTreatmentChronic Thromboembolic Pulmonary Hypertension / Chronic Thromboembolic Pulmonary Hypertension (CTEPH)1
2CompletedTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2CompletedTreatmentPulmonary Hypertension (PH)1
2RecruitingTreatmentHeart Failure With Preserved Ejection Fraction (HFpEF)1
2RecruitingTreatmentPulmonary Hypertension (PH)1
2WithdrawnTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
3Active Not RecruitingTreatmentPulmonary Arterial Hypertension (PAH)4
3CompletedTreatmentPulmonary Arterial Hypertension (PAH)2
3CompletedTreatmentSclerosis, Progressive Systemic / Ulcers1
3RecruitingTreatmentCongenital Heart Disease (CHD)1
3RecruitingTreatmentPulmonary Arterial Hypertension (PAH)2
3TerminatedTreatmentDigital Ulcers / Sclerosis, Progressive Systemic / Ulcers1
3TerminatedTreatmentPulmonary Arterial Hypertension (PAH)2
4Active Not RecruitingTreatmentPortopulmonary Hypertension1
4Active Not RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
4Not Yet RecruitingTreatmentLung Transplant Rejection1
4RecruitingTreatmentPulmonary Arterial Hypertension (PAH)2
Not AvailableRecruitingNot AvailablePulmonary Arterial Hypertension (PAH)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral10 mg
Tablet, film coatedOral10 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8268847No2009-04-182029-04-18Us
US8367685No2008-10-042028-10-04Us
US9265762No2007-05-292027-05-29Us
US7094781No2002-10-122022-10-12Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityNot water solubleNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00668 mg/mLALOGPS
logP3.05ALOGPS
logP3.69ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)7.76ChemAxon
pKa (Strongest Basic)2.26ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area128.22 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity126.98 m3·mol-1ChemAxon
Polarizability50.55 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as halopyrimidines. These are aromatic compounds containing a halogen atom linked to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Halopyrimidines
Alternative Parents
Bromobenzenes / Alkyl aryl ethers / Sulfuric acid diamides / Imidolactams / Aryl bromides / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organobromides
show 2 more
Substituents
Alkyl aryl ether / Bromobenzene / Halobenzene / Halopyrimidine / Aryl bromide / Aryl halide / Monocyclic benzene moiety / Imidolactam / Benzenoid / Sulfuric acid diamide
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organobromine compound, aromatic ether, pyrimidines, ring assembly, sulfamides (CHEBI:76607)

Targets

Details
1. Endothelin-1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is:...
Gene Name
EDNRA
Uniprot ID
P25101
Uniprot Name
Endothelin-1 receptor
Molecular Weight
48721.76 Da
References
  1. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T: The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012 Sep 13;55(17):7849-61. doi: 10.1021/jm3009103. Epub 2012 Aug 16. [PubMed:22862294]
  2. Bruderer S, Hopfgartner G, Seiberling M, Wank J, Sidharta PN, Treiber A, Dingemanse J: Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans. Xenobiotica. 2012 Sep;42(9):901-10. doi: 10.3109/00498254.2012.664665. Epub 2012 Mar 30. [PubMed:22458347]
  3. Dingemanse J, Sidharta PN, Maddrey WC, Rubin LJ, Mickail H: Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. Expert Opin Drug Saf. 2014 Mar;13(3):391-405. doi: 10.1517/14740338.2014.859674. Epub 2013 Nov 22. [PubMed:24261583]
Details
2. Endothelin B receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Peptide hormone binding
Specific Function
Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name
EDNRB
Uniprot ID
P24530
Uniprot Name
Endothelin B receptor
Molecular Weight
49643.255 Da
References
  1. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T: The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-p ropylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem. 2012 Sep 13;55(17):7849-61. doi: 10.1021/jm3009103. Epub 2012 Aug 16. [PubMed:22862294]
  2. Bruderer S, Hopfgartner G, Seiberling M, Wank J, Sidharta PN, Treiber A, Dingemanse J: Absorption, distribution, metabolism, and excretion of macitentan, a dual endothelin receptor antagonist, in humans. Xenobiotica. 2012 Sep;42(9):901-10. doi: 10.3109/00498254.2012.664665. Epub 2012 Mar 30. [PubMed:22458347]
  3. Dingemanse J, Sidharta PN, Maddrey WC, Rubin LJ, Mickail H: Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. Expert Opin Drug Saf. 2014 Mar;13(3):391-405. doi: 10.1517/14740338.2014.859674. Epub 2013 Nov 22. [PubMed:24261583]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da

Drug created on December 29, 2013 11:30 / Updated on November 22, 2017 12:37