II. Indications
- Prevention of Nausea, Vomiting with highly emetogenic Chemotherapy
- Typically used in combination with 5-HT3 Antagonists and Dexamethasone 20 mg daily
III. Mechanism
- Blocks the neurokinin-1 receptor (a tachykinin)
- Cross the blood brain barrier to inhibit CNS substance-P activity
- Effects
- Antiemetic (synergistic with 5-HT3 Antagonists)
- Anxiolysis and Antidepressant properties
IV. Dosing: Aprepitant
- Typically administered with 5-HT3 Antagonists and Dexamethasone before Chemotherapy
- Oral (Emend) before Chemotherapy
- Adult: 125 mg orally 1 hour before Chemotherapy, then 80 mg orally daily in AM on days 2 and 3
- Child (age >6 months): 3 mg/kg (up to 125 mg), then 2 mg/kg (up to 80 mg) orally daily in AM on days 2 and 3
- Oral (Emend) post-op Vomiting prophylaxis
- Adult: 40 mg orally given 3 hours or less prior to Anesthesia
- IV before Chemotherapy
- Fosaprepitant (Aprepitant prodrug)
- Adult: 150 mg infused over 20 to 30 minutes
- Child: 3 mg/kg (up to 125 mg) IV over 20 to 30 minutes, followed by oral Emend on days 2, 3 (see dose above)
- Cinvanti
- Adult: 130 mg IV over 2 minutes (or infused over 30 min) OR 100 mg IV followed by oral Emend on days 2, 3
- Fosaprepitant (Aprepitant prodrug)
V. Dosing: Rolapitant (Varubi)
- Typically administered with 5-HT3 Antagonists and Dexamethasone before Chemotherapy
- Take 180 mg orally 1 to 2 hours prior to Chemotherapy
VI. Dosing: Netupitant/Palonosetron (Akynzeo)
- See Akynzeo
- Combined 5HT-3 Antagonist (Palonosetron) with the NK1 Antagonist Netupitant
- Contraindicated in severe renal disease (including ESRD) and severe hepatic disease
- Oral: Take 1 capsule orally one hour before Chemotherapy
- IV: Give one injectable vial diluted in 50 ml over 30 min prior to Chemotherapy
VIII. Drug Interactions
- See Aprepitant (Emend, Fosaprepitant, Cinvanti)
- See Rolapitant (Varubi)
IX. Resources
- NK1 Receptor Antagonist (Wikipedia)
- Antiemetic Neurokinin-1 Receptor Blockers (Stat Pearls)
- Aprepitant - Emend (DailyMed)
- Aprepitant - Cinvanti (DailyMed)
- Rolapitant (DailyMed)
X. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- (2003) Med Lett Drugs Ther 45(W1162B): 62-4 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
Definition (NCI) | A selective neurokinin 1 (NK1) receptor antagonist with potential antiemetic activity. Netupitant competitively binds to and blocks the activity of the human substance P/NK1 receptors in the central nervous system (CNS), thereby inhibiting NK1-receptor binding of the endogenous tachykinin neuropeptide substance P (SP), which may result in the prevention of chemotherapy-induced nausea and vomiting (CINV). SP is found in neurons of vagal afferent fibers innervating the brain-stem nucleus tractus solitarii and the area postrema, which contains the chemoreceptor trigger zone (CTZ), and may be elevated in response to chemotherapy. The NK-receptor is a G-protein receptor coupled to the inositol phosphate signal-transduction pathway and is found in both the nucleus tractus solitarii and the area postrema. |
Concepts | Organic Chemical (T109) |
MSH | C508854 |
English | Netupitant, 2-[3,5-bis(Trifluoromethyl)phenyl]-N,2-dimethyl-N-[4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]propanamide, netupitant, NETUPITANT |
Ontology: Neurokinin-1 Receptor Antagonists (C3543440)
Definition (MSH) | Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS. |
Concepts | Molecular Function (T044) |
MSH | D064729 |
English | Blockers, Neuroleukin-1 Receptor, Neuroleukin 1 Receptor Blockers, Neurokinin 1 Receptor Antagonists, Receptor Antagonists, Neurokinin-1, Neuroleukin-1 Receptor Blockers, Antagonists, Neurokinin-1 Receptor, Tachykinin Receptor 1 Antagonists, Blockers, Neurokinin-1 Receptor, Receptor Blockers, Neurokinin-1, Receptor Blockers, Neuroleukin-1, Neurokinin-1 Receptor Blockers, Substance P Receptor Blockers, Tachykinin Receptor 1 Blockers, Neurokinin 1 Receptor Blockers, Substance P Receptor Antagonists, Neurokinin-1 Receptor Antagonists |
Czech | antagonisté neurokininových receptorů typu 1, antagonisté NK1-receptorů, receptory substance P - blokátory, antagonisté receptorů substance P |
French | Bloqueurs du récepteur de la neurokinine-1, Antagonistes du récepteur de la substance P, Bloqueurs du récepteur de la substance P, Antagonistes du récepteur de la neurokinine-1, Bloqueurs du récepteur-1 de tachykinine, Antagonistes du récepteur-1 de tachykinine |
German | Tachykinin-Rezeptor-1-Antagonisten, Substanz P-Rezeptor-Antagonisten, NK-1-Rezeptor-Antagonisten, Tachykinin-Rezeptor-1-Blocker, Neuroleukin-1-Rezeptor-Blocker, Neurokinin-1-Rezeptor-Antagonisten, Neurokinin-1-Rezeptor-Blocker, Substanz P-Rezeptor-Blocker |
Italian | Antagonisti del recettore della neurochinina 1 |
Russian | НЕЙРОКИНИНА-1 РЕЦЕПТОРОВ АНТАГОНИСТЫ, ВЕЩЕСТВА P РЕЦЕПТОРОВ АНТАГОНИСТЫ, РЕЦЕПТОРОВ НЕЙРОКИНИНА-1 БЛОКАТОРЫ, ТАХИКИНИНА РЕЦЕПТОРА 1 БЛОКАТОРЫ, NEIROKININA-1 RETSEPTOROV ANTAGONISTY, TAKHIKININA RETSEPTORA 1 BLOKATORY, VESHCHESTVA P RETSEPTOROV ANTAGONISTY, RETSEPTOROV NEIROKININA-1 BLOKATORY |