VARUBI

AbsorptionFollowing a single oral dose administration of 180 mg VARUBI under fasting conditions to healthy subjects, rolapitant was measurable in plasma within 30 minutes and the peak plasma concentration (C max ) for rolapitant which was reached in about 4 hours and mean C max was 968 ng/mL (%CV:28%). Following multiple oral doses of 9 to 45 mg once daily of rolapitant (5% to 25% of the recommended dose) for 10 days, accumulation of rolapitant (ratio of AUC 0-24hr ) ranged from 5.0 to 5.3 fold...

Cisplatin-Based Highly Emetogenic Chemotherapy (HEC) In two multicenter, randomized, double-blind, parallel group, controlled clinical studies (Study 1 and Study 2), the VARUBI regimen (VARUBI, granisetron and dexamethasone) was compared with control therapy (placebo, granisetron and dexamethasone) in patients receiving a chemotherapy regimen that included cisplatin >60 mg/m 2 . See Table 7 for the treatment regimens.

Table 7Treatment Regimens in Studies 1 and 2 a VARUBI was administered 1 to 2 hours prior to chemotherapy treatment on Day 1. b Dexamethasone was administered 30 minutes prior ...

The following adverse reactions are discussed in greater detail in other sections of the labeling: Interaction with CYP2D6 Substrates [see Contraindications (4) , Warnings and Precautions (5.1) ] Most common adverse reactions (≥3%) are: Cisplatin Based Highly Emetogenic Chemotherapy: neutropenia, hiccups and abdominal pain. ( 6.1 ) Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide: decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infect...

VARUBI is contraindicated in patients taking CYP2D6 substrates with a narrow therapeutic index, such as thioridazine and pimozide. VARUBI can significantly increase the plasma concentrations of thioridazine and pimozide, which may result in QT prolongation and Torsades de Pointes [see Warnings and Precautions (5.1) ] . VARUBI is contraindicated in pediatric patients less than 2 years of age becaus...

CYP2D6 Substrates : Rolapitant is a moderate inhibitor of CYP2D6 and significantly increases the plasma concentrations of CYP2D6 substrates for at least 28 days following single dose administration of VARUBI. Before starting VARUBI, consider if patients require: thioridazine or pimozide; if so, use an alternative antiemetic to VARUBI or an alternative to thioridazine or pimozide that is not metabolized by CYP2D6. other CYP2D6 substrates; if so, consult the prescribing information for the CYP2D6 ...

7 DRUG INTERACTIONS Rolapitant is a moderate CYP2D6 inhibitor. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in dextromethorphan concentrations, the last time point measured. The inhibitory effect of rolapitant on CYP2D6 is expected to persist beyond 28 days for an unknown duration following administration of VARUBI [see Clinical Pharmacology (12.3) ] . Oral rolapitant is a...