Rolapitant

VARUBI ® is indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. VARUBI is a substance P/neurokinin 1 (NK1) receptor antagonist indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

Rolapitant is a selective and competitive antagonist of human substance P/NK1 receptors. Rolapitant does not have significant affinity for the NK2 or NK3 receptors or for a battery of other receptors, transporters, enzymes and ion channels. Rolapitant is also active in animal models of chemotherapy-induced emesis.

The recommended dosage of VARUBI in adults in combination with a 5-HT 3 receptor antagonist and dexamethasone for the prevention of nausea and vomiting with emetogenic cancer chemotherapy is shown in Table 1. There is no drug interaction between rolapitant and dexamethasone, so no dosage adjustment for dexamethasone is required. Administer a dexamethasone dose of 20 mg on Day 1. Administer VARUBI prior to the initiation of each chemotherapy cycle, but at no less than 2 week intervals. Administer VARUBI without regards to meals.

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. VARUBI is contraindicated in pediatric patients less than 2 years of age because of irreversible impairment of sexual development and fertility observed in juvenile rats at clinically relevant dosages. CYP2D6 substrates with a narrow therapeutic index (e.g., thioridazine and pimozide). Pediatric patients less than 2 years of age because of irreversible impairment of sexual development and fertility in juvenile rats

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 substrate for additional information about interactions with CYP2D6 inhibitors.

The following adverse reactions are discussed in greater detail in other sections of the labeling: Interaction with CYP2D6 Substrates Most common adverse reactions (≥3%) are: Cisplatin Based Highly Emetogenic Chemotherapy: neutropenia, hiccups and abdominal pain. Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide: decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infection, stomatitis and anemia.

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. Oral rolapitant is an inhibitor of Breast-Cancer-Resistance Protein (BCRP) and p-glycoprotein (P-gp). Rolapitant, given as a single oral dose, is not an inhibitor or inducer of CYP3A4. Therefore, no dosage adjustment for dexamethasone (CYP3A4 substrate) is needed when co-administered with VARUBI. Table 4 and Table 5 include drugs with clinically important drug interactions when administered concomitantly with VARUBI and instructions for preventing or managing them.

Store at 20ºC to 25ºC (68ºF to 77ºF), excursions permitted to 15°C to 30°C (59°F to 86°F).