The U.S. Food and Drug Administration has approved Cinvanti (aprepitant) injectable emulsion, for intravenous infusion. Cinvanti is a substance P/neurokinin-1 (NK1) receptor antagonist, indicated in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin and nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).
Cinvanti is the first and only polysorbate 80-free, intravenous formulation of an NK1 receptor antagonist indicated for the prevention of acute and delayed CINV. Cinvanti is the first intravenous formulation to directly deliver aprepitant, the active ingredient in Emend® capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 receptor antagonist to significantly reduce CINV in both the acute phase (0 – 24 hours after chemotherapy) and the delayed phase (24 – 120 hours after chemotherapy).
Cinvanti does not contain polysorbate 80 or any other synthetic surfactant. Pharmaceutical formulations containing polysorbate 80 have been linked to hypersensitivity reactions, including anaphylaxis and irritation of blood vessels resulting in infusion-site pain. Cinvanti was approved based on data demonstrating the bioequivalence of Cinvanti to Emend IV® (fosaprepitant), supporting its efficacy for the prevention of acute and delayed CINV following HEC and MEC.
Results from 2 pivotal randomized, cross-over bioequivalence studies of Cinvanti and Emend IV showed subjects receiving Cinvanti reported fewer adverse events than those receiving Emend IV, including substantially fewer infusion-site reactions.
Cinvanti is contraindicated in patients with hypersensitivity to any of the components of Cinvanti. Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported with fosaprepitant, a prodrug of aprepitant, and with oral aprepitant. Symptoms including flushing, erythema, dyspnea, hypotension and syncope have been reported. If symptoms occur, discontinue Cinvanti. Do not reinstate if symptoms occur with first-time use. Use of pimozide with Cinvanti is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide.
Use of Cinvanti may result in clinically significant CYP3A4 Drug Interactions. Aprepitant is a substrate, weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Use with other drugs that are CYP3A4 substrates may result in increased plasma concentration of the concomitant drug. Use of Cinvanti with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to Cinvanti.
Avoid use of Cinvanti in pregnant women as alcohol is an inactive ingredient for Cinvanti. There is no safe level of alcohol exposure in pregnancy. No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score greater than 9). Additional monitoring for adverse reactions in these patients may be warranted when Cinvanti is administered.
In general, use caution when dosing elderly patients as they have a greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy. The most common adverse reactions with the 3-day oral aprepitant regimen in conjunction with MEC were fatigue and eructation. The most common adverse reactions with the single-dose intravenous fosaprepitant regimen in conjunction with HEC were generally similar to that seen in prior HEC studies with oral aprepitant. The most common adverse reactions with a single-dose of Cinvanti were headache and fatigue.
While chemotherapy is one of the most effective and commonly used therapies to help patients fight cancer, it is accompanied by debilitating side effects, including varying degrees of nausea and vomiting, often attributed as a leading cause of premature discontinuation of cancer treatment. The goal of antiemetic therapy is to prevent CINV in both the acute phase (0 – 24 hours after chemotherapy) and delayed phase (24 – 120 hours after chemotherapy). The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) have categorized chemotherapy regimens based on the degree to which they cause nausea and vomiting: low emetogenic chemotherapy (LEC); moderately emetogenic chemotherapy (MEC); and highly emetogenic chemotherapy (HEC).