Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIH045MJQ)
Drug Name			Rifapentine		Drug Info		Cabotegravir		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antituberculosis Agents				Antiviral Agents
Structure

Mechanism of Rifapentine-Cabotegravir Interaction (Severity Level: Major)
UGT induction Click to Show/Hide Mechanism Graph

Drug Name		Rifapentine				Cabotegravir
Mechanism		UGT1A1 inducer				UGT1A1 substrate
Key Mechanism Factor 1
		Factor Name		UDP-glucuronosyltransferase 1A1				× Structure Sequence MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVLAPDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDSAMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLEFEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQREVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEHGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
		Gene Name		UGT1A1
		Uniprot ID		UD11_HUMAN
		KEGG Pathway		hsa:54658
		Protein Family		UDP-glycosyltransferase family
		Protein Function		[Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558). Click to Show/Hide
Mechanism Description		Increased metabolism of Cabotegravir caused by Rifapentine mediated induction of UGT

Recommended Action
Management		Per the manufacturer, concomitant use of cabotegravir with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, or rifapentine is considered contraindicated.

References
1	Cerner Multum, Inc. "Canadian Product Information.".
2	Product Information. Cabenuva (cabotegravir-rilpivirine). ViiV Healthcare ULC, Laval, QU.
3	Product Information. Vocabria (cabotegravir). ViiV Healthcare, Research Triangle Park, NC.