FDA Expands Approval of Nausea/Vomiting Agent

Fosaprepitant dimeglumine is now approved as a single intravenous dose

The US Food and Drug Administration has approved the first single-dose intravenous NK1 receptor antagonist, fosaprepitant dimeglumine (Emend), for the treatment of nausea and vomiting that can accompany the use of moderately and highly emetogenic chemotherapy. The drug is approved in combination with other antiemetics.

“Despite significant advances in supportive care, nausea and vomiting has remained a challenge for many cancer patients undergoing moderately emetogenic chemotherapy-and has historically required multi-day antiemetic therapy,” said Stuart Green, vice president, clinical research, Merck Research Laboratories, in a statement. “Today’s approval of an expanded indication for Emend for injection means that physicians now have a new single-dose intravenous option, combined with other anti-vomiting medicines, for the prevention of delayed nausea and vomiting in these patients.”

The intravenous injection version of Emend is a pro-drug version of the oral Emend formulation, known as aprepitant. Upon injection, fosaprepitant dimeglumine is rapidly converted to aprepitant in the body. The drug is a selective high-affinity antagonist of human substance P/neurokinin-1 (NK1) receptors and has little affinity for serotonin, dopamine, and corticosteroid receptors, which are the targets of existing therapies for chemotherapy-induced nausea and vomiting.

In a randomized, double-blind trial, a single 150 mg injection of fosaprepitant dimeglumine in combination with ondansetron and dexamethasone (n = 502) was compared to a regimen of ondansetron and dexamethasone alone (n = 498) in patients receiving moderately emetogenic chemotherapy. Seventy-nine percent of patients in the experimental arm had a complete response compared with 68.5% of patients in the control arm (P < .001). A complete response was defined as no vomiting or use of rescue therapy during the delayed phase of chemotherapy-25 to 120 hours following administration of chemotherapy.

Adverse events were similar across both arms of the trial. Among the most common adverse reactions were fatigue, 15% vs 13% in the experimental and control arms, respectively; diarrhea, 13% vs 11%; and neutropenia, 8% vs 7%.

Chemotherapy-induced nausea and vomiting falls into two major categories-the acute phase, which occurs within 24 hours after administration of chemotherapy; and the delayed phase, which typically starts at least 24 hours after administration. Up to about 25% of patients who have received prior chemotherapy can also experience anticipatory chemotherapy-induced nausea and vomiting, a result of classic conditioning from a prior nausea or vomiting experience that typically occurs within 12 hours prior to administration of chemotherapy.

Chemotherapy-induced nausea and vomiting is a major issue for many patients receiving chemotherapy to treat their cancer. According to some studies, about 40% of patients receiving a new chemotherapy regimen develop acute nausea and vomiting, and as many as 60% of patients experience delayed symptoms.