II. Indications

  1. Prevention of Nausea, Vomiting with highly emetogenic Chemotherapy
    1. Typically used in combination with 5-HT3 Antagonists and Dexamethasone 20 mg daily

III. Mechanism

  1. Blocks the neurokinin-1 receptor (a tachykinin)
  2. Cross the blood brain barrier to inhibit CNS substance-P activity
  3. Effects
    1. Antiemetic (synergistic with 5-HT3 Antagonists)
    2. Anxiolysis and Antidepressant properties

IV. Dosing: Aprepitant

  1. Typically administered with 5-HT3 Antagonists and Dexamethasone before Chemotherapy
  2. Oral (Emend) before Chemotherapy
    1. Adult: 125 mg orally 1 hour before Chemotherapy, then 80 mg orally daily in AM on days 2 and 3
    2. 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
  3. Oral (Emend) post-op Vomiting prophylaxis
    1. Adult: 40 mg orally given 3 hours or less prior to Anesthesia
  4. IV before Chemotherapy
    1. Fosaprepitant (Aprepitant prodrug)
      1. Adult: 150 mg infused over 20 to 30 minutes
      2. 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)
    2. Cinvanti
      1. Adult: 130 mg IV over 2 minutes (or infused over 30 min) OR 100 mg IV followed by oral Emend on days 2, 3

V. Dosing: Rolapitant (Varubi)

  1. Typically administered with 5-HT3 Antagonists and Dexamethasone before Chemotherapy
  2. Take 180 mg orally 1 to 2 hours prior to Chemotherapy

VI. Dosing: Netupitant/Palonosetron (Akynzeo)

  1. See Akynzeo
  2. Combined 5HT-3 Antagonist (Palonosetron) with the NK1 Antagonist Netupitant
  3. Contraindicated in severe renal disease (including ESRD) and severe hepatic disease
  4. Oral: Take 1 capsule orally one hour before Chemotherapy
  5. IV: Give one injectable vial diluted in 50 ml over 30 min prior to Chemotherapy

VII. Adverse Effects

VIII. Drug Interactions

X. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. (2003) Med Lett Drugs Ther 45(W1162B): 62-4 [PubMed]

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Related Studies

Ontology: netupitant (C1700730)

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