The FDA has approved an intravenous (IV) formulation of rolapitant (Varubi, Tesaro, Inc.) to help prevent the nausea and vomiting that can occur hours or even days after chemotherapy.
Rolapitant IV 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. Delayed nausea and vomiting can occur anytime between 25 and 120 hours following chemotherapy and is often extremely debilitating.
Rolapitant is a highly selective and competitive antagonist of human substance P/neurokinin 1 (NK-1) receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV). With a long plasma half-life of approximately seven days, a single dose of rolapitant, as part of an antiemetic regimen, significantly improved complete response rates in the delayed phase of CINV.
Rolapitant may be particularly effective for patients receiving cisplatin, carboplatin, or anthracycline/cyclophosphamide-based chemotherapy
Results from three phase 3 trials of rolapitant oral tablets demonstrated a significant reduction in episodes of vomiting or use of rescue medication during the 25- to 120-hour period following administration of highly emetogenic and moderately emetogenic chemotherapy regimens. In addition, patients who received rolapitant reported experiencing less nausea that interfered with normal daily life and fewer episodes of vomiting or retching over multiple cycles of chemotherapy. Results from a bioequivalence trial demonstrated comparability of the IV and oral formulations of rolapitant.
The new IV formulation is supplied in ready-to-use vials and does not require refrigerated storage or mixing. It is to be administered up to two hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone, a CYP3A4 substrate, and rolapitant is the first IV NK-1 receptor antagonist approved by the FDA that does not contain polysorbate 80.
The majority of NK-1 receptor antagonist doses are administered intravenously in the U.S.
More than half of patients treated with emetogenic chemotherapy experience delayed CINV, even when prescribed standard preventive therapies.
Source: Tesaro; October 25, 2017.