Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIUSRTZXN)
Drug Name			Erlotinib		Drug Info		Riociguat		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antineoplastics				Vasodilator Agents
Structure

Mechanism of Erlotinib-Riociguat Interaction (Severity Level: Moderate)
CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph

Drug Name		Erlotinib				Riociguat
Mechanism		CYP450 1A1 inhibitor				CYP450 1A1 substrate
Key Mechanism Factor 1
		Factor Name		Cytochrome P450 1A1				× Structure Sequence MLFPISMSATEFLLASVIFCLVFWVIRASRPQVPKGLKNPPGPWGWPLIGHMLTLGKNPHLALSRMSQQYGDVLQIRIGSTPVVVLSGLDTIRQALVRQGDDFKGRPDLYTFTLISNGQSMSFSPDSGPVWAARRRLAQNGLKSFSIASDPASSTSCYLEEHVSKEAEVLISTLQELMAGPGHFNPYRYVVVSVTNVICAICFGRRYDHNHQELLSLVNLNNNFGEVVGSGNPADFIPILRYLPNPSLNAFKDLNEKFYSFMQKMVKEHYKTFEKGHIRDITDSLIEHCQEKQLDENANVQLSDEKIINIVLDLFGAGFDTVTTAISWSLMYLVMNPRVQRKIQEELDTVIGRSRRPRLSDRSHLPYMEAFILETFRHSSFVPFTIPHSTTRDTSLKGFYIPKGRCVFVNQWQINHDQKLWVNPSEFLPERFLTPDGAIDKVLSEKVIIFGMGKRKCIGETIARWEVFLFLAILLQRVEFSVPLGVKVDMTPIYGLTMKHACCEHFQMQLRS
		Gene Name		CYP1A1
		Uniprot ID		CP1A1_HUMAN
		KEGG Pathway		hsa:1543
		Protein Family		Cytochrome P450 family
		Protein Function		A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15805301, PubMed:15041462, PubMed:18577768, PubMed:19965576, PubMed:20972997, PubMed:10681376). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15805301, PubMed:15041462, PubMed:18577768, PubMed:19965576, PubMed:20972997, PubMed:10681376). Catalyzes the hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Click to Show/Hide
Mechanism Description		Decreased metabolism of Riociguat caused by Erlotinib mediated inhibition of CYP450 enzyme

Recommended Action
Management		Caution is advised if riociguat is prescribed in combination with an inhibitor of CYP450 1A1. Blood pressure should be monitored, and a dose reduction of riociguat should be considered if necessary.

References
1	Canadian Pharmacists Association.
2	Cerner Multum, Inc. "Australian Product Information.".
3	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4	Product Information. Ziagen (abacavir). Glaxo Wellcome, Research Triangle Pk, NC.