Xofluza Drug Interactions

No clinically significant drug-drug interactions are anticipated between baloxavir marboxil or its active metabolite baloxavir and substrates, inhibitors, or inducers of cytochrome P450 (CYP enzymes), inhibitors of UDP-glucuronosyltransferase (UGT) enzyme, or gut, renal, or hepatic transporters.
Polyvalent cation containing products may decrease plasma concentrations of baloxavir. XOFLUZA should not be taken with polyvalent cation containing laxatives or antacids, or oral supplements containing iron, zinc, selenium, calcium, magnesium.
Effects of Other Drugs on Baloxavir Marboxil or its Active Metabolite Baloxavir: Itraconazole, an inhibitor of P gp, increased the Cmax and AUC_0-inf of baloxavir 1.33 fold and 1.23 fold, respectively. These increases are not considered to be clinically meaningful.
Probenecid, an inhibitor of UGT enzyme, decreased the Cmax and AUC_0-inf of baloxavir by 21% and 25%, respectively. These decreases are not considered to be clinically meaningful.
Effects of Baloxavir Marboxil or its Active Metabolite Baloxavir on Other Drugs: In in vitro studies at clinically relevant concentrations, baloxavir marboxil and its active metabolite, baloxavir did not inhibit any of the following isozymes of CYP or UGT family: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, UGT1A1，UGT1A3，UGT1A4，UGT1A6，UGT1A9，UGT2B7, and UGT2B15 isozymes). In in vitro studies at clinically relevant concentrations, baloxavir marboxil and baloxavir did not cause significant induction of CYP1A2, CYP2B6, and CYP3A4 . In in vitro transporter studies at clinically relevant concentrations, baloxavir marboxil and baloxavir inhibited the efflux transporter (P-gp). Baloxavir but not baloxavir marboxil inhibited BCRP.
Based on in vitro transporter studies, despite a weak in vitro inhibitory potential, baloxavir is not expected to be an in vivo inhibitor of OATP1B1, OATP1B3, OCT1, OCT2, OAT1, OAT3, MATE1, or MATE2K, hence no relevant pharmacokinetic interaction is anticipated between baloxavir and medicines which are substrates of these transporters.
A single 40 mg dose of baloxavir marboxil did not affect the pharmacokinetics of midazolam, a substrate of CYP3A4, suggesting that baloxavir marboxil or baloxavir is not expected to affect the pharmacokinetics of co-administered drugs that are substrates of CYP3A.
A single 80 mg dose of baloxavir marboxil did not affect the pharmacokinetics of digoxin, a substrate of P-gp, suggesting that baloxavir marboxil or baloxavir is not expected to affect the pharmacokinetics of co-administered drugs that are substrates of P-gp.
A single 80 mg dose of baloxavir marboxil decreased C_max and AUC_0-inf of rosuvastatin, a substrate of BCRP, by 18% and 17%, respectively. These decreases are not considered to be clinically meaningful and indicate that baloxavir marboxil or baloxavir is not expected to affect the pharmacokinetics of co-administered drugs that are substrates of BCRP.