FDA Approves Intravenous Rolapitant for Prevention of Delayed Chemotherapy-Induced Nausea and Vomiting

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ON OCTOBER 25, the U.S. Food and Drug Administration (FDA) approved intravenous (IV) rolapitant (Varubi) 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 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 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting. With a plasma half-life of approximately 7 days, a single dose of rolapitant, as part of an antiemetic regimen, significantly improved complete response rates in the delayed phase of chemotherapy-induced nausea and vomiting. 

Safety and Efficacy 

THE EFFICACY of oral rolapitant was established in multiple global randomized, well-controlled, double-blinded clinical trials that enrolled more than 2,500 patients. Rolapitant, when administered in combination with a 5-HT3 receptor antagonist and dexamethasone, was superior to a 5-HT3 receptor antagonist and dexamethasone alone in preventing delayed chemotherapy-induced nausea and vomiting in patients receiving either moderately or highly emetogenic chemotherapy. The oral formulation of rolapitant received FDA approval in 2015. 

In addition to the phase III program, a bioequivalence study was conducted in healthy volunteers to compare the exposure of the 166.5-mg dose of IV rolapitant to the exposure of a 180-mg dose of oral rolapitant. Study participants were randomized to receive a single dose of either 166.5 mg of IV rolapitant administered over 30 minutes (n = 61) or 180 mg of oral rolapitant (n = 62). The primary endpoint of this pivotal study was bioequivalence. Safety and tolerability were also assessed for both formulations. Results demonstrated comparability of the IV and oral formulations of rolapitant. Further, the safety 

profile of the IV formulation was consistent with that in previous clinical trials with oral rolapitant, except for infusion-site reactions observed with the IV formulation. 

IV rolapitant is supplied in ready-to-use vials and does not require refrigerated storage or mixing. IV rolapitant is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone. No dosage adjustment is required for dexamethasone, a CYP3A4 substrate. 

“Many health-care providers tend to believe that chemotherapy-induced nausea and vomiting is no longer an unmet need, but the reality is that more than half of patients treated with emetogenic chemotherapy experience delayed chemotherapy-induced nausea and vomiting, even when prescribed standard preventative therapies, such as a 5-HT3 receptor antagonist and dexamethasone,” said Lee Schwartzberg, MD, Professor of Medicine at the University of Tennessee Health Science Center. “The FDA approval of rolapitant IV gives doctors and nurses a new option to help protect their patients from these often preventable side effects.” ■




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