Vitrakvi Drug Interactions

Drug Interactions Overview: Larotrectinib is a substrate of cytochrome P450 (CYP) 3A, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Coadministration of VITRAKVI with strong CYP3A inhibitors, P-gp and BCRP inhibitors may increase larotrectinib plasma concentrations.
Coadministration of VITRAKVI with strong CYP3A and P-gp inducers may decrease larotrectinib plasma concentrations.
In vitro, larotrectinib is not a substrate for the transporters OAT1, OAT3, OCT1, OCT2, OATP1B1, or OATP1B3.
In vitro studies indicate that larotrectinib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6 at clinically relevant concentrations. In vitro, larotrectinib is a metabolism-dependent irreversible inhibitor of CYP3A4/5 (contributing to weak inhibition clinically) (see Drug-Drug Interactions as follows).
In vitro studies indicate that larotrectinib induces CYP2B6, but does not induce CYP1A2.
In vitro studies indicate that larotrectinib does not inhibit the transporters BCRP, P-gp, OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, BSEP, MATE1 and MATE2-K at clinically relevant concentrations.
Drug-Drug Interactions: See Table 10.

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Effects of Other Agents on Larotrectinib: P-gp and BCRP Inhibitors: Clinical data in healthy adult subjects indicate that coadministration of a single 100 mg VITRAKVI dose with a single dose of rifampin (a P-gp and BCRP inhibitor) increased larotrectinib C_max and AUC by 1.8-fold and 1.7-fold, respectively.
Gastric pH-elevating Agents: Larotrectinib has pH-dependent solubility. In vitro studies show that in liquid volumes relevant to the gastrointestinal tract (GI) larotrectinib at the recommended dose is fully soluble over entire pH range of the GI tract. Therefore, larotrectinib is unlikely to be affected by pH-modifying agents.
Drug-Food Interactions: Larotrectinib may be administered with or without food (see Pharmacology: Pharmacokinetics: Absorption under Actions). Avoid grapefruit or grapefruit juice as these may also increase plasma concentrations of larotrectinib.
Drug-Herb Interactions: Avoid Hypericum perforatum (a CYP3A4 inducer), also known as St. John's wort, as it may decrease plasma concentrations of larotrectinib.