Neurokinin-1 Receptor Antagonist

Aka: Neurokinin-1 Receptor Antagonist, NK1 Receptor Antagonist, Aprepitant, Emend, Cinvanti, Fosaprepitant, Rolapitant, Varubi, Netupitant, Akynzeo

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

VII. Pharmacokinetics: Aprepitant

  1. Terminal Half-Life: 9 to 13 hours after oral dose
  2. Absorption is not affected by food
  3. Hepatic Metabolism by CYP3A4, CYP1A2, CYP2C19
  4. Excretion in urine and stool

VIII. Adverse Effects

  1. Asthenia or Fatigue
  2. Hiccups

IX. Safety

  1. Aprepitant Pregnancy Category B
  2. Unknown safety in Lactation

X. Drug Interactions: Aprepitant (Emend, Fosaprepitant, Cinvanti)

  1. May affect drugs metabolized by CYP3A4
  2. CYP2C9 Inducer
  3. Pimozide
    1. Avoid with NK1 Receptor Antagonist
  4. Oral Contraceptives (OCP)
    1. Aprepitant may reduce OCP efficacy (use second form of Contraception)
  5. Warfarin
    1. Aprepitant may affect INR

XI. Drug Interactions: Rolapitant (Varubi)

  1. May effect drugs metabolized by CYP2D6
  2. Thioridazine
    1. Avoid with NK1 Receptor Antagonist
  3. Strong CYP3A4 Inducers (e.g. Rifampin)
    1. May decrease Rolapitant effectiveness

XII. Resources

  1. NK1 Receptor Antagonist (Wikipedia)
    1. https://en.wikipedia.org/wiki/NK1_receptor_antagonist
  2. Antiemetic Neurokinin-1 Receptor Blockers (Stat Pearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK470394
  3. Aprepitant - Emend (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f58b8944-93ee-4be1-a238-cc0061ddd93a
  4. Aprepitant - Cinvanti (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c218d3a-a508-4abc-9ed8-a6e8e191d1b4
  5. Rolapitant (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a52896cd-4a98-49b8-82db-bf1985a64d97

XIII. References

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

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Related Studies

Cost: Medications

aprepitant (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
APREPITANT 40 MG CAPSULE Generic $52.79 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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