A febrile, A typical, A noxia and now A ponvie (Aprepitant)
Myron Yaster MD and Lynne G. Maxwell MD
I received a blast email from Anesthesiology News last week, in which they reported that the US FDA approved APONVIE (Heron Therapeutics) for the prevention of postoperative nausea and vomiting (PONV). Aponvie is an IV formulation of aprepitant, a neurokinin-1 receptor antagonist, that has been used in its oral formulation for almost a decade for cancer and postoperative nausea and vomiting. But what really struck me and the reason it went to the top of my PAAD review list was its name A PONV ie. Without PONV….What a surprise, really what a shock…a drug name that actually says what the drug actually does. For many years, the FDA vetoed drug names that suggested the drug’s effect (hence the IV acetaminophen is Ofirmev, a name/word only useful in Scrabble). Hopefully this is the beginning of a new wave of FDA drug naming. Myron Yaster MD
Original articles
Thomas Wiesmann, Peter Kranke, Leopold Eberhart. Postoperative nausea and vomiting - a narrative review of pathophysiology, pharmacotherapy and clinical management strategies. Expert Opin Pharmacother. 2015 May;16(7):1069-77. PMID: 25866213
Jin Z, Daksla N, Gan TJ. Neurokinin-1 Antagonists for Postoperative Nausea and Vomiting. Drugs. 2021 Jul;81(10):1171-1179. PMID: 34106456
Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, Watcha M, Chung F, Angus S, Apfel CC, Bergese SD, Candiotti KA, Chan MT, Davis PJ, Hooper VD, Lagoo-Deenadayalan S, Myles P, Nezat G, Philip BK, Tramèr MR; Society for Ambulatory Anesthesia. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg. 2014 Jan;118(1):85-113 PMID: 24356162
Several kinds of antiemetics including serotonin 5-HT3 receptor antagonists, dopamine receptor antagonists, histamine H2 receptor antagonists, anticholinergic agents, and corticosteroids have been used in the prevention and treatment of PONV.[1-3] These drugs mainly act by interfering with neurotransmitter receptor signaling in the central nervous system and gastrointestinal tract except corticosteroids. Neurokinin-1 receptor (NK-1R) is widely expressed in human gastrointestinal vagal afferents and brain areas that are involved in the vomiting reflex such as the nucleus of solitary tract (NST) (also known as nucleus tractus solitarius). Substance P, the natural ligand of NK-1R, was found to be able to trigger NK-1R signaling, thereby causing nausea and vomiting.[4] Suppression of neuronal signaling in the NST, the central regulator of visceral function, is thought to be responsible for the antiemetic effect of NK-!R antagonists. NK-1R antagonists such as aprepitant have shown good antiemetic efficacy for PONV and chemotherapy-induced nausea and vomiting (CINV).[5]
Aponvie is administered by a 30-second IV push, recommended to be administered prior to induction of anesthesia, achieves drug levels associated with 97% receptor occupancy within 5 minutes of administration, and provides vomiting prevention for 48-72 hours. It is effective alone and can be combined with dexamethasone. It is the first and only IV NK-1 receptor antagonist approved for PONV by the US FDA. Although administration prior to anesthesia induction is recommended in adults, timing of administration, efficacy, and safety have not been evaluated in children. Even after calling the company, we couldn’t find any information on pediatric dosing or ongoing or potential clinical trials. Hopefully as we get more information on this drug and pediatric indications we will pass it on to you.
References
1. Gan, T.J., et al., Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg, 2014. 118(1): p. 85-113.
2. Watcha, M.F. and P.F. White, Postoperative nausea and vomiting. Its etiology, treatment, and prevention [see comments]. Anesthesiology, 1992. 77(1): p. 162-184.
3. Wiesmann, T., P. Kranke, and L. Eberhart, Postoperative nausea and vomiting - a narrative review of pathophysiology, pharmacotherapy and clinical management strategies. Expert Opin Pharmacother, 2015. 16(7): p. 1069-77.
4. Muñoz, M. and R. Coveñas, Involvement of substance P and the NK-1 receptor in human pathology. Amino Acids, 2014. 46(7): p. 1727-50.
5. dos Santos, L.V., et al., Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review. J Natl Cancer Inst, 2012. 104(17): p. 1280-92.