APONVIE: A New Frontier for Postoperative Nausea and Vomiting?

Postoperative nausea and vomiting (PONV) can be a challenging problem for patients undergoing plastic surgery. To address this issue, Heron Therapeutics has developed APONVIE, the first and only intravenous formulation of aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist. In a recent interview with Plastic Surgery Practice, Heron CEO Craig Collard and Randy Robbins, MD, a board-certified anesthesiologist, discussed the benefits of APONVIE for PONV prevention and its potential impact on plastic surgery procedures. 

PSP: In a nutshell, what is APONVIE?

Craig Collard: APONVIE is the first and only intravenous (IV) formulation of aprepitant, which is a substance P/neurokinin-1 (NK₁) receptor antagonist. APONVIE is approved for use in adults for the prevention of postoperative nausea and vomiting, or PONV. APONVIE’s IV formulation ensures rapid, consistent exposure in patients undergoing surgery and overcomes the need to take the oral formulation up to 3 hours before anesthesia, providing a better experience for patients. 

APONVIE is a ready-to-use 32 mg single dose vial for direct administration as a 30 second IV injection, prior to the induction of anesthesia. It is the only IV NK₁ receptor antagonist approved for PONV. What’s more, APONVIE was approved by the FDA in September 2022 and became commercially available in March 2023.

Randy Robbins, MD: APONVIE is a drug I’ve been waiting to be available for several years.  The oral formulation has proven to be a great treatment option for those patients with moderate to high risk factors for PONV. Oral delivery leaves a lot to be desired from an anesthesia standpoint. As anesthesiologists, we often don’t see our patients until the day of surgery and typically moments before going to the OR. Not having an IV option for aprepitant has been frustrating. Historically, I have utilized a multi-modal approach including ondansetron, dexamethasone, scopolamine, and other drugs but still saw patients with significant breakthrough PONV. With APONVIE, we have an option that provides 97% receptor occupancy within 5 minutes.

I’ve given this drug to multiple patients since the U.S. launch, and most of them were high-risk candidates who experienced PONV with previous surgeries. Up to this point, we haven’t had one patient with emesis in the PACU, Phase 2, or after discharge home during the first 48 hours.

PSP: What sets APONVIE apart from other therapeutics available for PONV?  How is APONVIE administered?

Robbins: APONVIE’s administration differentiates it from other treatments. APONVIE is delivered via a 30-second IV push, and the convenience of the IV formulation allows the drug to enter directly into systemic circulation without the delay associated with absorption processes. 

Anesthesiologists now have an IV formulation of the drug that has proven to be a superior standalone option for PONV prevention. We’re not a discipline that utilizes a lot of oral medication, and it’s difficult to organize patients through risk stratification and preoperative interviews so we can provide a prescription for them to take several hours before their surgery. It’s difficult to find retail pharmacies that stock the drug—and getting patients to understand the importance of timing of administration is a challenge. APONVIE has answered those challenges and allows us to provide injectable medicines as a solution.  

PSP: Why is APONVIE a good fit for plastic surgery procedures? 

Collard: It’s estimated that the overall incidence of PONV in plastic surgery is about 35%. Plastic surgery patients’ satisfaction is based on overall experience as much as the final result, and the prevention of PONV can positively influence patients’ experience, leading to greater satisfaction and improved outcomes.

Robbins: Plastic surgery patients are a subset population of patients and often have some of the highest demands and expectations. Patient satisfaction is extremely important for surgeon marketing and referrals. Prevention of potential complications from postoperative emesis is exceedingly important. As anesthesiologists, we should be attacking every receptor we can to help prevent PONV in this population subset and APONVIE should be the cornerstone of therapy for any patient at moderate to high risk. 

PSP: In the context of the plastic surgery space, what type of procedures would APONVIE be beneficial for?

Robbins: There are several procedures where retching and vomiting are extremely concerning—specifically, abdominoplasty, rhinoplasty, facelifts, and even simple procedures like breast augmentation. The potential for incision dehiscence or hematoma development under the flaps is a big concern for both patients and providers.

PSP: PONV can lead to poor patient outcomes and decreased patient satisfaction. Why is managing PONV important in aesthetic procedures? 

Collard: Nausea and vomiting after surgery are significant challenges facing patients undergoing these procedures. PONV is a major cause of patient dissatisfaction and can result in costly complications after surgery. There is an estimated incidence of 30% in the general surgical population and up to 80% in high-risk patients, presenting a significant need for effective treatment options. PONV may result in increased hospital stays, increased healthcare costs, and prolonged recovery time. With APONVIE providing relief for at least 48 hours, patients are discharged sooner and have a better experience postoperatively.

PSP: What factors are assessed when determining if a patient would benefit from APONVIE?

Robbins:  The biggest thing I consider when assessing a patient for PONV prophylaxis is previous experience with anesthesia. If a patient states that they always vomit after surgery, the other risk factors are irrelevant to me. Those patients should be treated with multimodal therapy and, in my opinion, that should include APONVIE. If a patient hasn’t been exposed to anesthesia before and has three or more risk factors, I treat them as moderate to high-risk individuals. A history of motion sickness puts them in the higher risk category at baseline also.   

While APONVIE is approved for all patients undergoing surgery, patients at moderate-to-high risk for PONV will derive the greatest benefit. Approximately 36 million patients a year fall into the group. Patients at moderate-to-high risk of PONV include females, non-smokers, those with a history of PONV or motion sickness, and patients who are treated with opioids previously. And patients undergoing surgical procedures who are at risk for PONV should consult their doctor to see if APONVIE would be an effective solution. 

PSP: Let’s delve into patient safety now. What’s the efficacy, duration, and safety of APONVIE?

Collard: Two studies comparing oral aprepitant with IV ondansetron for the prevention of PONV in patients during the 48 hours following open abdominal surgery demonstrated that aprepitant was more effective than ondansetron in preventing vomiting. Treatment with aprepitant resulted in approximately 50% fewer patients vomiting in the first 24 and 48 hours compared to ondansetron. Additionally, in a Phase 1 clinical trial, APONVIE 32 mg as a 30-second IV push was demonstrated to be bioequivalent to oral aprepitant 40 mg.

PSP: If any, what are the potential side effects and/or contraindications? Should any patient population avoid APONVIE?

Collard: APONVIE is contraindicated in patients with a history of hypersensitivity and in patients taking pimozide due to possible life-threatening reactions. (See Full Prescribing Information here.) The most common adverse reactions for APONVIE are constipation, fatigue, and headache, and those for oral aprepitant are constipation and hypotension. Also, pregnant women should avoid use as alcohol is an active ingredient in APONVIE.

PSP: What should plastic surgeons know about incorporating APONVIE?

Robbins: The plastic surgery patient population is concerned about their entire experience. Surgeons should be aware of the role PONV plays in patient dissatisfaction. With the release of APONVIE, we now have a drug that can address a top concern about anesthesia. I highly recommend surgeons and anesthesiologists pursue appropriate utilization of this new drug formulation as I have seen great success in my patients.  

PSP: Does Heron Therapeutics offer any other solutions that are applicable to the postoperative experience for the plastic surgery space? 

Collard: We have submitted a second supplemental New Drug Application (sNDA) for our postoperative pain management drug, ZYNRELEF, proposing to expand the indication to other soft tissue and orthopedic procedures. This potential expanded indication includes breast reconstruction, augmentation, abdominoplasty, and other plastic surgery procedures. Plastic surgery is a space we are looking to establish ourselves in and look forward to delivering additional treatments for plastic surgery patients.

PSP: What’s next for the company? 

Collard: We’re looking to utilize the 2020 consensus guidelines to change the practice and grow the market by addressing PONV. We have submitted an sNDA for ZYNRELEF proposing to expand the indication to other soft-tissue and orthopedic procedures. Our goal is to provide surgeons with practical solutions to effectively manage postoperative nausea and vomiting through APONVIE and reduce postoperative pain and eliminate the need for opioids by using ZYNRELEF. More information is available here.