Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI6SN3G14)
Drug Name			Anisindione		Drug Info		Rucaparib		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anticoagulants				Poly (Adp-Ribose) Polymerase Inhibitors
Structure

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

Drug Name		Anisindione				Rucaparib
Mechanism		CYP450 2C9 substrate				CYP450 2C9 inhibitor
Key Mechanism Factor 1
		Factor Name		Cytochrome P450 2C9				× Structure Sequence MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPV
		Gene Name		CYP2C9
		Uniprot ID		CP2C9_HUMAN
		KEGG Pathway		hsa:1559
		Protein Family		Cytochrome P450 family
		Protein Function		A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). 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:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:7574697, PubMed:15766564, PubMed:19965576, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9866708, PubMed:9435160). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031). Click to Show/Hide
Mechanism Description		Decreased metabolism of Anisindione caused by Rucaparib mediated inhibition of CYP450 enzyme

Recommended Action
Management		Concomitant administration of rucaparib with warfarin should generally be avoided however, if coadministration cannot be avoided caution and close monitoring are advised. The INR should be checked more frequently and warfarin dosage adjusted accordingly, particularly following initiation, change of dosage, or discontinuation of rucaparib therapy. The same precaution may be applicable during therapy with other coumarin anticoagulants, although clinical data are lacking. Patients should be advised to promptly report any signs of bleeding to their doctor, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

References
1	EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".