On October 25, 2017, intravenous (IV) rolapitant (Varubi) was approved for use 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.¹ Oral rolapitant was approved for this indication in September 2015.

Supporting Efficacy Data

Supporting efficacy data for rolapitant come from three phase III trials of oral rolapitant—two in patients receiving cisplatin-based highly emetogenic chemotherapy and one in patients receiving moderately emetogenic chemotherapy. Details are provided in the product labeling.

How It Works

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin (NK) 1 receptors. The drug does not have significant affinity for the NK2 or NK3 receptors or for a battery of other receptors, transporters, enzymes, and ion channels. It is active in animal models of chemotherapy-induced emesis.

How It Is Used

Rolapitant should be administered prior to the initiation of each chemotherapy cycle, but at no less than 2-week intervals. The recommended dosage of IV rolapitant in patients receiving cisplatin-based highly emetogenic chemotherapy is infusion of the injectable emulsion at 166.5 mg over 30 minutes on day 1 at least 2 hours prior to chemotherapy administration; the drug is given along with dexamethasone at 20 mg, 30 minutes prior to the initiation of chemotherapy on day 1 and at 8 mg twice daily on days 2 to 4 and with a 5-hydroxytryptamine (HT) 3 receptor antagonist on day 1. 

In patients receiving moderately emetogenic chemotherapy, the recommended dosage of IV rolapitant is infusion of the injectable emulsion at 166.5 mg over 30 minutes on day 1 at least 2 hours prior to chemotherapy administration; the drug is given along with dexamethasone at 20 mg, 30 minutes prior to initiation of chemotherapy on day 1 and a 5-HT3 receptor antagonist according to dosing instructions for the particular agent. 

Since there is no drug interaction between rolapitant and dexamethasone, no dosage adjustment for dexamethasone is required. Other instructions on the use of IV rolapitant are the same as those for the oral form, as specified in the product labeling.

Safety Profile

Since rolapitant injectable emulsion is the same active substance as rolapitant tablets, adverse reactions associated with the injectable emulsion are expected to be the same as those with tablets, with the exception of infusion-related reactions. In healthy subjects receiving the recommended therapeutic dose of rolapitant injectable emulsion, infusion-related adverse reactions were reported in 2 (2.6%) of 78 subjects during the infusion and included sensation of warmth, abdominal pain, dizziness, and paresthesia. 

Rolapitant carries warnings/precautions for use with CYP2D6 substrates. The drug is a moderate inhibitor of CYP2D6 and significantly increases plasma concentrations of CYP2D6 substrates (eg, dextromethorphan, thioridazine, pimozide) for at least 28 days following a single dose of rolapitant. Before starting rolapitant, it should be considered whether patients require thioridazine or pimozide; in such patients, an alternative antiemetic to rolapitant or an alternative to thioridazine or pimozide that is not metabolized by CYP2D6 should be used. If the use of other CYP2D6 substrates is considered, prescribing information for the substrate should be consulted for additional information about interactions with CYP2D6 inhibitors.

Rolapitant is contraindicated in patients taking CYP2D6 substrates with a narrow therapeutic index, such as thioridazine and pimozide. Rolapitant can significantly increase plasma concentrations of thioridazine and pimozide, which may result in QT interval prolongation and torsades de pointes. ■

REFERENCE

1. Varubi (rolapitant) injectable emulsion, for intravenous use, prescribing information, Tesaro, Inc, October 2017. Available at www.varubirx.com/en. Accessed November 21, 2017.