Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4, P-glycoprotein (P-gp), and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of larotrectinib. According to the prescribing information, larotrectinib is metabolized primarily by the CYP450 3A4 isoenzyme and is a substrate of the P-gp and BCRP efflux transporters in vitro. When a single 100 mg dose of larotrectinib was coadministered with itraconazole (200 mg once daily for 7 days), a potent CYP450 3A4 inhibitor and P-gp/BCRP inhibitor, larotrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.8- and 4.3-fold, respectively, compared to administration of larotrectinib alone. When a single 100 mg dose of larotrectinib was administered in healthy adult subjects with a single 600 mg dose of rifampin (a P-gp and BCRP inhibitor during initial use, but an inducer of CYP450 3A4 and P-gp following chronic use), larotrectinib Cmax and AUC increased by 1.8- and 1.7-fold, respectively. Coadministration with fluconazole, a moderate CYP450 3A4 inhibitor, is predicted to increase larotrectinib steady-state Cmax by 1.9-fold and AUC by 2.7-fold.

MANAGEMENT: Caution is advised when larotrectinib is used with CYP450 3A4, P-gp, and/or BCRP inhibitors. Patients should be monitored more frequently for adverse effects such as neurotoxicity (delirium, dysarthria, dizziness, gait disturbance, paraesthesia, encephalopathy, memory impairment, tremor) and hepatotoxicity (elevations in liver transaminases), and the larotrectinib dosage adjusted based on severity of emergent adverse reactions in accordance with the product labeling.

Grapefruit juice can increase the blood levels of larotrectinib. This may increase the risk and/or severity of side effects such as dizziness, confusion, coordination problems, memory problems, liver problems, and tingling, numbness or burning in the hands and feet. You should avoid the consumption of grapefruit and grapefruit juice during treatment with larotrectinib. Talk to your doctor or pharmacist if you have questions on this or other medications you are prescribed. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Consumer information for this interaction is not currently available.

MONITOR: Smoking and alcohol consumption during therapy with vadadustat may increase the risk of gastrointestinal erosions. Serious erosions, including gastrointestinal bleeding and the need for red blood cell transfusions, have been reported during vadadustat clinical trials. Patients with a history of gastrointestinal erosion, peptic ulcer disease, and current tobacco smokers and alcohol drinkers may be at higher risk of gastrointestinal injury.

MANAGEMENT: Caution is advised if vadadustat is prescribed to current tobacco smokers or alcohol drinkers. Patients should be advised to contact their physician if they develop potential signs and symptoms of gastrointestinal injury such as abdominal pain, hematemesis, trouble swallowing, chest or throat pain, and/or black, tarry stools.