Details of Drug

Drug General Information (ID: D0966)
Drug Name	Macitentan
Drug Type	Small molecule
Drug Synonymous	Macitentan; 441798-33-0; Opsumit; ACT-064992; ACT 064992; UNII-Z9K9Y9WMVL; ACT064992; Z9K9Y9WMVL; N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide; N-(5-(4-Bromophenyl)-6-(2-((5-bromo-2-pyrimidinyl)oxy)ethoxy)-4-pyrimidinyl)-N'-propylsulfamide; CHEBI:76607; Actelion-1; Macitentan [USAN:INN]; macitentanum; zlchem 5; Opsumit (TN); Macitentan (JAN/USAN); (non-labelled)Macitentan-d7; MLS006011174; C19H20Br2N6O4S; SCHEMBL1445625; GTPL7352; CHEMBL2103873; ZLA0005; EX-A544; DTXSID50196063 Click to Show/Hide
Disease Class	BA00-BE2Z: Cardiovascular disease
Therapeutic Class	Agents For Pulmonary Hypertension
Structure
Structure	3D Structure		2D Structure
Formula	C19H20Br2N6O4S
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)
InChIKey	JGCMEBMXRHSZKX-UHFFFAOYSA-N
Canonical SMILES	CCCNS(=O)(=O)NC1=C(C(=NC=N1)OCCOC2=NC=C(C=N2)Br)C3=CC=C(C=C3)Br
External Link
	Pubchem ID	16004692
	CAS Number	441798-33-0
	CHEBI ID	76607
	TTD ID	D0S7JH
	INTEDE ID	DR0998

Drug-Drug Interaction Network
Sunburst Graph		Legend Information AM004 Affected intra/extra-hepatic metabolism AM006 Pharmacodynamic additive effects BM017 CYP450 enzyme inhibition BM022 CYP450 enzyme induction BM042 Additive hypotensive effects BM055 Increased risk of hepatotoxicity
Relation Graph

Full list of drugs interacting with Macitentan
Affected intra/extra-hepatic metabolism
	CYP450 enzyme inhibition					Drug Num: 71
Drug ID		Drug Name	Formula	Pubchem ID	Severity Level		Interaction Detail	REF
D0080		Amprenavir	C25H35N3O6S	65016	Major		Inter Info	[1]
D0192		Boceprevir	C27H45N5O5	10324367	Major		Inter Info	[1]
D0349		Clarithromycin	C38H69NO13	84029	Major		Inter Info	[1]
D0386		Conivaptan	C32H26N4O2	151171	Major		Inter Info	[1]
D0439		Delavirdine	C22H28N6O3S	5625	Major		Inter Info	[1]
D0597		Erythromycin	C37H67NO13	12560	Major		Inter Info	[1]
D0692		Fosamprenavir	C25H36N3O9PS	131536	Major		Inter Info	[1]
D0799		Indinavir	C36H47N5O4	5362440	Major		Inter Info	[1]
D0867		Itraconazole	C35H38Cl2N8O4	55283	Major		Inter Info	[1]
D0880		Ketoconazole	C26H28Cl2N4O4	456201	Major		Inter Info	[1]
D0946		Lonafarnib	C27H31Br2ClN4O2	148195	Major		Inter Info	[1]
D0302		Ceritinib	C28H36ClN5O3S	57379345	Major		Inter Info	[1]
D0375		Cobicistat	C40H53N7O5S2	25151504	Major		Inter Info	[1]
D0789		Idelalisib	C22H18FN7O	11625818	Major		Inter Info	[1]
D1653		Troleandomycin	C41H67NO15	202225	Major		Inter Info	[1]
D1660		Tucatinib	C26H24N8O2	51039094	Major		Inter Info	[1]
D1117		Nefazodone	C25H32ClN5O2	4449	Major		Inter Info	[1]
D1315		Posaconazole	C37H42F2N8O4	468595	Major		Inter Info	[1]
D1444		Saquinavir	C38H50N6O5	441243	Major		Inter Info	[1]
D1541		Telaprevir	C36H53N7O6	3010818	Major		Inter Info	[1]
D1544		Telithromycin	C43H65N5O10	3002190	Major		Inter Info	[1]
D1706		Voriconazole	C16H14F3N5O	71616	Major		Inter Info	[1]
D0066		Amiodarone	C25H29I2NO3	2157	Moderate		Inter Info	[1]
D0313		Chloramphenicol	C11H12Cl2N2O5	5959	Moderate		Inter Info	[1]
D0337		Cimetidine	C10H16N6S	2756	Moderate		Inter Info	[1]
D0341		Ciprofloxacin	C17H18FN3O3	2764	Moderate		Inter Info	[1]
D0367		Clotrimazole	C22H17ClN2	2812	Moderate		Inter Info	[1]
D0393		Crizotinib	C21H22Cl2FN5O	11626560	Moderate		Inter Info	[1]
D0413		Dalfopristin	C34H50N4O9S	6323289	Moderate		Inter Info	[1]
D0416		Danazol	C22H27NO2	28417	Moderate		Inter Info	[1]
D0426		Darunavir	C27H37N3O7S	213039	Moderate		Inter Info	[1]
D0428		Dasatinib	C22H26ClN7O2S	3062316	Moderate		Inter Info	[1]
D0497		Diltiazem	C22H26N2O4S	39186	Moderate		Inter Info	[1]
D0534		Dronedarone	C31H44N2O5S	208898	Moderate		Inter Info	[1]
D0667		Fluconazole	C13H12F2N6O	3365	Moderate		Inter Info	[1]
D0687		Fluvoxamine	C15H21F3N2O2	5324346	Moderate		Inter Info	[1]
D0693		Fosaprepitant	C23H22F7N4O6P	135413538	Moderate		Inter Info	[1]
D0740		Grepafloxacin	C19H22FN3O3	72474	Moderate		Inter Info	[1]
D0793		Imatinib	C29H31N7O	5291	Moderate		Inter Info	[1]
D0852		Isavuconazonium	C35H35F2N8O5S+	6918606	Moderate		Inter Info	[1]
D0858		Isoniazid	C6H7N3O	3767	Moderate		Inter Info	[1]
D0869		Ivacaftor	C24H28N2O3	16220172	Moderate		Inter Info	[1]
D0894		Lapatinib	C29H26ClFN4O4S	208908	Moderate		Inter Info	[1]
D0002		Abametapir (topical)	C12H12N2	15664	Moderate		Inter Info	[32]
D0171		Berotralstat	C30H26F4N6O	137528262	Moderate		Inter Info	[1]
D0543		Duvelisib	C22H17ClN6O	50905713	Moderate		Inter Info	[1]
D0638		Fedratinib	C27H36N6O3S	16722836	Moderate		Inter Info	[1]
D0696		Fosnetupitant	C31H35F6N4O5P	71544786	Moderate		Inter Info	[1]
D0699		Fostamatinib	C23H26FN6O9P	11671467	Moderate		Inter Info	[35]
D0735		Goldenseal	NA	NA	Moderate		Inter Info	[1]
D0896		Larotrectinib	C21H22F2N6O2	46188928	Moderate		Inter Info	[1]
D0899		Lefamulin	C28H45NO5S	25185057	Moderate		Inter Info	[36]
D0901		Lemborexant	C22H20F2N4O2	56944144	Moderate		Inter Info	[1]
D0906		Letermovir	C29H28F4N4O4	45138674	Moderate		Inter Info	[1]
D1127		Netupitant	C30H32F6N4O	6451149	Moderate		Inter Info	[1]
D1214		Palbociclib	C24H29N7O2	5330286	Moderate		Inter Info	[1]
D1398		Ribociclib	C23H30N8O	44631912	Moderate		Inter Info	[1]
D1432		Rucaparib	C19H18FN3O	9931954	Moderate		Inter Info	[1]
D1459		Selpercatinib	C29H31N7O3	134436906	Moderate		Inter Info	[1]
D1505		Stiripentol	C14H18O3	5311454	Moderate		Inter Info	[1]
D1524		Suvorexant	C23H23ClN6O2	24965990	Moderate		Inter Info	[1]
D1709		Voxelotor	C19H19N3O3	71602803	Moderate		Inter Info	[1]
D1057		Miconazole	C18H14Cl4N2O	4189	Moderate		Inter Info	[1]
D1063		Mifepristone	C29H35NO2	55245	Moderate		Inter Info	[1]
D1134		Nifedipine	C17H18N2O6	4485	Moderate		Inter Info	[1]
D1136		Nilotinib	C28H22F3N7O	644241	Moderate		Inter Info	[1]
D1232		Pazopanib	C21H23N7O2S	10113978	Moderate		Inter Info	[1]
D1383		Ranolazine	C24H33N3O4	56959	Moderate		Inter Info	[1]
D1579		Ticagrelor	C23H28F2N6O4S	9871419	Moderate		Inter Info	[1]
D1690		Verapamil	C27H38N2O4	2520	Moderate		Inter Info	[1]
D0402		Cyclosporine	C62H111N11O12	5284373	Minor		Inter Info	[2], [1]
	CYP450 enzyme induction					Drug Num: 50
Drug ID		Drug Name	Formula	Pubchem ID	Severity Level		Interaction Detail	REF
D0255		Carbamazepine	C15H12N2O	2554	Major		Inter Info	[2], [1]
D0578		Enzalutamide	C21H16F4N4O2S	15951529	Major		Inter Info	[2], [1]
D0697		Fosphenytoin	C16H15N2O6P	56339	Major		Inter Info	[2], [1]
D0095		Apalutamide	C21H15F4N5O2S	24872560	Major		Inter Info	[2], [1]
D0958		Lumacaftor	C24H18F2N2O5	16678941	Major		Inter Info	[2], [7], [1]
D1078		Mitotane	C14H10Cl4	4211	Major		Inter Info	[2], [1]
D1265		Phenobarbital	C12H12N2O3	4763	Major		Inter Info	[2], [1]
D1283		Phenytoin	C15H12N2O2	1775	Major		Inter Info	[2], [1]
D1340		Primidone	C12H14N2O2	4909	Major		Inter Info	[2], [1]
D1399		Rifabutin	C46H62N4O11	135398743	Major		Inter Info	[2], [1]
D1400		Rifampicin	C43H58N4O12	135398735	Major		Inter Info	[2], [7], [1]
D1401		Rifapentine	C47H64N4O12	135403821	Major		Inter Info	[2], [1]
D1502		St. John's Wort	NA	NA	Major		Inter Info	[2], [1]
D0061		Aminoglutethimide	C13H16N2O2	2145	Moderate		Inter Info	[2], [1]
D0071		Amobarbital	C11H18N2O3	2164	Moderate		Inter Info	[2], [1]
D0178		Bexarotene	C24H28O2	82146	Moderate		Inter Info	[2], [1]
D0194		Bosentan	C27H29N5O6S	104865	Moderate		Inter Info	[2], [1]
D0224		Butabarbital	C10H16N2O3	2479	Moderate		Inter Info	[2], [1]
D0225		Butalbital	C11H16N2O3	2481	Moderate		Inter Info	[2], [1]
D0300		Cenobamate	C10H10ClN5O2	11962412	Moderate		Inter Info	[2], [1]
D0432		Deferasirox	C21H15N3O4	214348	Moderate		Inter Info	[2], [1]
D0453		Dexamethasone	C22H29FO5	5743	Moderate		Inter Info	[2], [1]
D0554		Efavirenz	C14H9ClF3NO2	64139	Moderate		Inter Info	[2], [1]
D0628		Etravirine	C20H15BrN6O	193962	Moderate		Inter Info	[2], [1]
D0639		Felbamate	C11H14N2O4	3331	Moderate		Inter Info	[2], [1]
D0741		Griseofulvin	C17H17ClO6	441140	Moderate		Inter Info	[2], [1]
D0545		Echinacea	NA	NA	Moderate		Inter Info	[13], [34]
D0555		Elagolix	C32H30F5N3O5	11250647	Moderate		Inter Info	[2], [1]
D0601		Eslicarbazepine	C15H14N2O2	9881504	Moderate		Inter Info	[2], [1]
D0872		Ivosidenib	C28H22ClF3N6O3	71657455	Moderate		Inter Info	[2], [1]
D0953		Lorlatinib	C21H19FN6O2	71731823	Moderate		Inter Info	[2], [1]
D1302		Pitolisant	C17H26ClNO	9948102	Moderate		Inter Info	[14], [37]
D1493		Somapacitan	C54H95N13O20S2	129894493	Moderate		Inter Info	[2], [1]
D1495		Somatrem	C43H72N14O14	5487805	Moderate		Inter Info	[2], [1]
D1538		Tazemetostat	C34H44N4O4	66558664	Moderate		Inter Info	[2], [1]
D1546		Telotristat ethyl	C27H26ClF3N6O3	25181577	Moderate		Inter Info	[14], [41]
D1040		Methylphenobarbital	C13H14N2O3	8271	Moderate		Inter Info	[2], [1]
D1099		Nafcillin	C21H22N2O5S	8982	Moderate		Inter Info	[2], [1]
D1128		Nevirapine	C15H14N4O	4463	Moderate		Inter Info	[2], [1]
D1198		Oxcarbazepine	C15H12N2O2	34312	Moderate		Inter Info	[2], [1]
D1248		Pentobarbital	C11H18N2O3	4737	Moderate		Inter Info	[2], [1]
D1274		Phenylbutazone	C19H20N2O2	4781	Moderate		Inter Info	[2], [1]
D1433		Rufinamide	C10H8F2N4O	129228	Moderate		Inter Info	[2], [1]
D1453		Secobarbital	C12H18N2O3	5193	Moderate		Inter Info	[2], [1]
D1494		Somatotropin	NA	NA	Moderate		Inter Info	[2], [1]
D1518		Sulfinpyrazone	C23H20N2O3S	5342	Moderate		Inter Info	[2], [1]
D1652		Troglitazone	C24H27NO5S	5591	Moderate		Inter Info	[2], [1]
D1687		Vemurafenib	C23H18ClF2N3O3S	42611257	Moderate		Inter Info	[2], [1]
D0106		Armodafinil	C15H15NO2S	9690109	Minor		Inter Info	[47], [48], [49], [50], [51]
D1081		Modafinil	C15H15NO2S	4236	Minor		Inter Info	[47], [48], [49], [50], [51]
Pharmacodynamic additive effects
	Additive hypotensive effects					Drug Num: 1
Drug ID		Drug Name	Formula	Pubchem ID	Severity Level		Interaction Detail	REF
D0942		Lofexidine	C11H12Cl2N2O	30668	Moderate		Inter Info	[14], [30], [31]
	Increased risk of hepatotoxicity					Drug Num: 21
Drug ID		Drug Name	Formula	Pubchem ID	Severity Level		Interaction Detail	REF
D0900		Leflunomide	C12H9F3N2O2	3899	Major		Inter Info	[3], [4], [5]
D0944		Lomitapide	C39H37F6N3O2	9853053	Major		Inter Info	[6]
D1258		Pexidartinib	C20H15ClF3N5	25151352	Major		Inter Info	[8]
D1073		Mipomersen	C230H324N67O122P19S19	118984467	Major		Inter Info	[9]
D1556		Teriflunomide	C12H9F3N2O2	54684141	Major		Inter Info	[3], [4], [5]
D0113		Asparaginase Erwinia chrysanthemi	NA	NA	Moderate		Inter Info	[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]
D0114		Asparaginase Escherichia coli	NA	NA	Moderate		Inter Info	[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]
D0149		Bedaquiline	C32H31BrN2O2	5388906	Moderate		Inter Info	[23]
D0199		Brentuximab vedotin	NA	NA	Moderate		Inter Info	[24]
D0357		Clofarabine	C10H11ClFN5O3	119182	Moderate		Inter Info	[25]
D0826		Interferon beta-1a	NA	NA	Moderate		Inter Info	[26], [27], [28], [29]
D0827		Interferon beta-1b	NA	NA	Moderate		Inter Info	[26], [27], [28], [29]
D0232		Calaspargase pegol	NA	NA	Moderate		Inter Info	[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]
D0248		Cannabidiol	C21H30O2	644019	Moderate		Inter Info	[14], [33]
D1239		Peginterferon beta-1a	NA	NA	Moderate		Inter Info	[26], [27], [28], [29]
D1389		Remdesivir	C27H35N6O8P	121304016	Moderate		Inter Info	[13], [14], [38], [39], [40]
D1025		Methotrexate	C20H22N8O5	126941	Moderate		Inter Info	[14], [42]
D1106		Naltrexone	C20H23NO4	5360515	Moderate		Inter Info	[43]
D1234		Pegaspargase	C14H19NO	436058	Moderate		Inter Info	[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]
D1589		Tioguanine	C5H5N5S	2723601	Moderate		Inter Info	[44], [45]
D1615		Trabectedin	C39H43N3O11S	108150	Moderate		Inter Info	[14], [46]

References
1	Product Information. Opsumit (macitentan). Actelion Pharmaceuticals US Inc, South San Francisco, CA.
2	Bruderer S, Aanismaa P, Homery MC, et al. "Effect of cyclosporine and rifampin on the pharmacokinetics of macitentan, a tissue-targeting dual endothelin receptor antagonist." AAPS J 14 (2012): 68-78. [PMID: 22189899]
3	Canadian Pharmacists Association.
4	EMEA "EMEA public statement on leflunomide (ARAVA) - severe and serious hepatic reactions.".
5	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
6	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
7	Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
8	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
9	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
10	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
11	Bodmer M, Sulz M, Stadlmann S, Droll A, Terracciano L, Krahenbuhl S "Fatal liver failure in an adult patient with acute lymphoblastic leukemia following treatment with L-asparaginase." Digestion 74 (2006): epub. [PMID: 16988508]
12	Cerner Multum, Inc "ANVISA Bulario Eletrnico.".
13	Cerner Multum, Inc. "Australian Product Information.".
14	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
15	Christ TN, Stock W, Knoebel RW "Incidence of asparaginase-related hepatotoxicity, pancreatitis, and thrombotic events in adults with acute lymphoblastic leukemia treated with a pediatric-inspired regimen." J Oncol Pharm Pract 24 (2018): 299-308. [PMID: 28355969]
16	Jenkins R, Perlin E "Severe hepatotoxicity from Escherichia coli L-asparaginase." J Natl Med Assoc 79 (1987): 775-9. [PMID: 3305969]
17	Lu G, Karur V, Herrington JD, Walker MG "Successful treatment of pegaspargase-induced acute hepatotoxicity with vitamin B complex and L-carnitine" Proc (Bayl Univ Med Cent) 29 (2016): 46-7. [PMID: 26722167]
18	Product Information. Asparlas (calaspargase pegol). Servier, Boston, MA.
19	Product Information. Elspar (asparaginase). Merck & Co, Inc, West Point, PA.
20	Product Information. Erwinaze (asparaginase Erwinia chrysanthemi). EUSA Pharma, Newtown, PA.
21	Product Information. Oncaspar (pegaspargase). Rhone-Poulenc Rorer, Collegeville, PA.
22	Burke PW, Aldoss I, Lunning MA, et.al "High-grade PEGylated asparaginase-related hepatotoxicity occurrence in a pediatric-inspired adult acute lymphoblastic leukemia regimen does not necessarily predict recurrent hepatotoxicity in subsequent cycles." Blood 122 (2013): 2671. [PMID: 29407583]
23	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
24	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
25	Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
26	Product Information. Avonex (interferon beta-1a). Biogen, Cambridge, MA.
27	Product Information. Betaseron (interferon beta-1b). Berlex, Richmond, CA.
28	Product Information. Plegridy (peginterferon beta-1a). Biogen Idec Inc, Cambridge, MA.
29	Product Information. Rebif (interferon beta-1a). Serono Laboratories Inc, Norwell, MA.
30	Product Information. Lucemyra (lofexidine). US WorldMeds LLC, Louisville , KY.
31	Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7. [PMID: 3725002]
32	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
33	Product Information. Epidiolex (cannabidiol). Greenwich Biosciences Inc, Carlsbad, CA.
34	Gorski JC, Huang SM, Pinto A, et al. "The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo." Clin Pharmacol Ther 75 (2004): 89-100. [PMID: 14749695]
35	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
36	Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
37	Product Information. Wakix (pitolisant). Harmony Biosciences, LLC, Plymouth Meeting, PA.
38	European Medicines Agency "Summary on compassionate use. Remdesivir Gilead.".
39	Gilead Sciences, Inc "About Remdesivir.".
40	US Food and Drug Administration "Fact sheet for health care providers emergency use authorization (EUA) of remdesivir (GS-5734TM)".
41	Product Information. Xermelo (telotristat ethyl). Lexicon Pharmaceuticals, Inc., The Woodlands, TX.
42	Product Information. Methotrexate (methotrexate). Lederle Laboratories, Wayne, NJ.
43	Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.
44	Product Information. Aubagio (teriflunomide). Genzyme Corporation, Cambridge, MA.
45	Product Information. Tabloid (thioguanine). Prasco Laboratories, Cincinnati, OH.
46	Product Information. Yondelis (trabectedin). Janssen Pharmaceuticals, Titusville, NJ.
47	Doherty MM, Charman WN "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet 41 (2002): 235-53. [PMID: 11978143]
48	Product Information. Nuvigil (armodafinil). Cephalon Inc, West Chester, PA.
49	Product Information. Provigil (modafinil). Cephalon, Inc, West Chester, PA.
50	Robertson P Jr, Hellriegel ET, Arora S, Nelson M "Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers." Clin Pharmacol Ther 71 (2002): 46-56. [PMID: 11823757]
51	Robertson P, Decory HH, Madan A, Parkinson A "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil." Drug Metab Dispos 28 (2000): 664-71. [PMID: 10820139]

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