Authors: Amy Babb, MD, AND Amanpreet Kalsi, MBBS, FRCA - Vanderbilt University Medical Center -
Monroe Carell Jr. Children's Hospital at Vanderbilt
A 16-year-old female with a history of truncus arteriosus presents for RV-PA conduit change via sternotomy and cardiopulmonary bypass. She recently underwent a cardiac catheterization procedure for attempted percutaneous pulmonary valve placement and had severe post operative nausea and vomiting despite ondansetron and dexamethasone. Aprepitant is chosen for PONV prophylaxis after this surgery. What class of medication does aprepitant belong to?
EXPLANATION
Aprepitant is a neurokinin 1 receptor antagonist used to decrease the risk of nausea and vomiting in adults and children with chemotherapy-induced and post-operative nausea and vomiting (PONV). These drugs target receptors in both central and peripheral nervous systems. In the central nervous system, aprepitant crosses the blood brain barrier inihibiting g-protein coupled signals at the NK1 receptor. Inhibition at the NK1 receptors prevents substance P formation at multiple sites in the brain known to induce nausea and vomiting. In addition, NK1 receptors present in the peripheral nervous system and gut are inihibited by aprepitant leading to an overall deceased vomiting signal to the central nervous system.
Aprepitant can be given orally (tab or liquid) or intravenously. Fosaprepitant is a prodrug of aprepitant that is only available as an IV formulation. Dosing in pediatric patients is limited to the available prescribing information for chemotherapy-induced nausea and vomiting, with few studies describing pediatric patients receiving aprepitant for PONV. Consensus guidelines for PONV published in 2020 by Gan et al recommend a dose of aprepitant 40 mg PO given within 3 hours of anesthesia induction for adults and dosing of aprepitant 3 mg/kg up to 125 mg for PONV prophylaxis in children1.
A 2019 study evaluating noncardiac pediatric surgical patients from birth to 17 years demonstrated efficacy and safety for PONV with doses of 10 mg, 40 mg and 125 mg2. In 2023, Belk J, et al. described a single-center experience with preoperative aprepitant administration for pediatric cardiac surgical and catheterization patients with a history of severe PONV. This small subset of patients were older, with a mean age of 16 years, and received either 80 mg PO (if over 50 kg) and 40 mg PO (if less than 50 kg)3.
Described risks of aprepitant include decreased INR in patients taking warfarin as well as reduced efficacy of hormonal contraceptives for up to 28 days after administration4. As a general precaution, aprepitant is a weak inhibitor and inducer of CYP3A44. NK1 receptor antagonists have no effect on the QT interval, providing a potential advantage to its use in pediatric cardiac patients with risk factors for PONV. Multimodal management of PONV after pediatric cardiac surgery is an important aspect to any enhanced recovery protocol and NK1 receptor inhibitors may prove to be a useful addition.
REFERENCES
1. Gan TJ, Belani KG, Bergese S, et al. Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting Anesth Analg. 2020;131(2):411-448. doi:10.1213/ANE.0000000000004833
2. Salman FT, DiCristina C, Chain A, et al. Pharmacokinetics and pharmacodynamics of aprepitant for the prevention of postoperative nausea and vomiting in pediatric subjects. Journal of Pediatric Surgery. 2019; 54(7): 1384-1390. https://doi.org/10.1016/j.jpedsurg.2018.09.006.
3. Belk JW, Twite MD, Klockau KS, Silveira LJ and Clopton RG (2023) Effects of aprepitant on post-operative nausea and vomiting in patients with congenital heart disease undergoing cardiac surgery or catheterization procedures: a retrospective study with subjects as their own historical control. Front. Anesthesiol. 2023; 2:1190383. doi: 10.3389/fanes.2023.1190383
4. Merck & Co. Emend (Aprepitant). US Food and Drug Administration website. Issued July 2009. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021549s012lbl.pdf
