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Identification
NameMacitentan
Accession NumberDB08932
TypeSmall Molecule
GroupsApproved
DescriptionMacitentan 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 Identifiers
  • ACT 064992
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OpsumitTablet10 mgOralActelion Pharmaceuticals Ltd2014-01-15Not applicableCanada
OpsumitTablet, film coated10 mg/1OralActelion Pharmaceuticals US, Inc.2013-10-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIZ9K9Y9WMVL
CAS number441798-33-0
WeightAverage: 588.273
Monoisotopic: 585.963349142
Chemical FormulaC19H20Br2N6O4S
InChI KeyJGCMEBMXRHSZKX-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
IndicationMacitentan is indicated for patients with pulmonary arterial hypertension.
Structured Indications
PharmacodynamicsMacitentan blocks simulators of hypertrophy, inflammation, fibrosis, proliferation, and vasoconstriction.
Mechanism of actionMacitentan 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Endothelin-1 receptorProteinyes
antagonist
HumanP25101 details
Endothelin B receptorProteinyes
antagonist
HumanP24530 details
Related Articles
AbsorptionMacitentan 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 bindingMacitentan 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 eliminationEliminated 50% through urine and 24% through feces.
Half lifeThe 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.

ToxicityMacitentan 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot 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
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
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
BexaroteneThe serum concentration of Macitentan can be decreased when it is combined with Bexarotene.Approved, Investigational
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
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
BretyliumBretylium may increase the hypotensive activities of Macitentan.Approved
BrimonidineBrimonidine may increase the hypotensive activities of Macitentan.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Macitentan.Approved
BupranololBupranolol may increase the hypotensive activities of Macitentan.Approved
CandesartanCandesartan 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
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
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
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
DeferasiroxThe serum concentration of Macitentan can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Macitentan can be decreased when combined with Delavirdine.Approved
DeserpidineDeserpidine may increase the hypotensive activities of Macitentan.Approved
DexamethasoneThe serum concentration of Macitentan can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DiazoxideDiazoxide may increase the hypotensive activities of Macitentan.Approved
DihydralazineMacitentan may increase the hypotensive activities of Dihydralazine.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 serum concentration of Macitentan can be decreased when it is combined with Efavirenz.Approved, Investigational
EfonidipineEfonidipine may increase the hypotensive activities of Macitentan.Approved
EnalaprilEnalapril may increase the hypotensive activities of Macitentan.Approved, Vet Approved
EnalaprilatEnalaprilat may increase the hypotensive activities of Macitentan.Approved
EnzalutamideThe serum concentration of Macitentan can be decreased when it is combined with Enzalutamide.Approved
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 serum concentration of Macitentan can be decreased when it is combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Macitentan can be decreased when combined with Esomeprazole.Approved, Investigational
EtravirineThe serum concentration of Macitentan can be decreased when it is combined with Etravirine.Approved
FelodipineFelodipine may increase the hypotensive activities of Macitentan.Approved, Investigational
FenoldopamFenoldopam may increase the hypotensive activities of Macitentan.Approved
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, 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
GuanadrelGuanadrel may increase the hypotensive activities of Macitentan.Approved
GuanethidineGuanethidine may increase the hypotensive activities of Macitentan.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Macitentan.Approved, Investigational
HexamethoniumHexamethonium may increase the hypotensive activities of Macitentan.Experimental
HydracarbazineHydracarbazine may increase the hypotensive activities of Macitentan.Approved
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
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
ImidaprilMacitentan may increase the hypotensive activities of Imidapril.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
KetanserinMacitentan may increase the hypotensive activities of Ketanserin.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
LatanoprostLatanoprost may increase the hypotensive activities of Macitentan.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Macitentan.Approved, Investigational
LisinoprilLisinopril may increase the hypotensive activities of Macitentan.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
MebanazineMebanazine may increase the hypotensive activities of Macitentan.Withdrawn
MecamylamineMecamylamine may increase the hypotensive activities of Macitentan.Approved
MethyldopaMethyldopa may increase the hypotensive activities of Macitentan.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Macitentan.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
MetyrosineMacitentan may increase the hypotensive activities of Metyrosine.Approved
MibefradilMibefradil may increase the hypotensive activities of Macitentan.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
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 serum concentration of Macitentan can be decreased when it is combined with Modafinil.Approved, Investigational
MoexiprilMoexipril may increase the hypotensive activities of Macitentan.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Macitentan.Approved
MoxonidineMoxonidine may increase the hypotensive activities of Macitentan.Approved
NadololNadolol may increase the hypotensive activities of Macitentan.Approved
NafcillinThe serum concentration of Macitentan can be decreased when it is combined with Nafcillin.Approved
NaftopidilMacitentan may increase the hypotensive activities of Naftopidil.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
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
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
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
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
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
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
RilmenidineMacitentan may increase the hypotensive activities of Rilmenidine.Investigational
RiociguatRiociguat may increase the hypotensive activities of Macitentan.Approved
RitonavirThe serum concentration of Macitentan can be increased when it is combined with Ritonavir.Approved, Investigational
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.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
TelaprevirThe serum concentration of Macitentan can be increased when it is combined with Telaprevir.Approved
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
TiboloneTibolone may increase the hypotensive activities of Macitentan.Approved
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
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
UdenafilUdenafil may increase the antihypertensive activities of Macitentan.Approved, Investigational
UnoprostoneUnoprostone may increase the hypotensive activities of Macitentan.Approved
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
VinpocetineMacitentan may increase the hypotensive activities of Vinpocetine.Investigational
VoriconazoleThe serum concentration of Macitentan can be increased when it is combined with Voriconazole.Approved, Investigational
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
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
ATC CodesC02KX04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (836 KB)
MSDSDownload (105 KB)
ADMET
Predicted ADMET featuresNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral10 mg
Tablet, film coatedOral10 mg/1
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7094781 No2002-10-122022-10-12Us
US8268847 No2009-04-182029-04-18Us
US8367685 No2008-10-042028-10-04Us
US9265762 No2007-05-292027-05-29Us
Properties
StateSolid
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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPhenylpyrimidines
Alternative Parents
Substituents
  • 5-phenylpyrimidine
  • Halopyrimidine
  • Halobenzene
  • Bromobenzene
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Sulfuric acid diamide
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl bromide
  • Heteroaromatic compound
  • Organic sulfuric acid or derivatives
  • Azacycle
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organobromide
  • Organohalogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors

Targets

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: ET1 > ET2 >> ET3.
Gene Name:
EDNRA
Uniprot ID:
P25101
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 ]
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
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
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Drug created on December 29, 2013 11:30 / Updated on December 08, 2016 02:48