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{{Infobox drug reference
{{Infobox drug reference
| trade_names = Emend
| trade_names = Emend
| drug_class = Anti-emetic
| drug_class = Antiemetic
| drug_class_color =  
| drug_class_color =  
| uses = Postoperative Nausea and Vomiting
| uses = Postoperative Nausea and Vomiting
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125 mg PO followed by 2 days of 80 mg PO for CINV
125 mg PO followed by 2 days of 80 mg PO for CINV
| dosage_calculation = aprepitant
| dosage_calculation = aprepitant
| mechanism = Neurokinin 1 receptor antagonist
| mechanism = Neurokinin-1 receptor antagonist
| adverse_effects = Anaphylaxis
| adverse_effects = Decreased efficacy of hormonal contraceptives
CYP interactions
| metabolism = CYP3A4 oxidation
| metabolism = CYP3A4 oxidation
| protein_binding = 95%
| protein_binding = 95%
}}
}}


Aprepitant is a neurokinin 1 (NK1) antagonist that is used in combination with standard anti-emetic regimen to prevent acute and delayed chemotherapy induced nausea and vomiting as well as prevention of post-operative nausea and vomiting.  
'''Aprepitant''' is a neurokinin-1 (NK1) antagonist that is used in combination with standard antiemetic regimen to prevent postoperative nausea and vomiting, as well as prevention of acute and delayed chemotherapy-induced nausea and vomiting.  


== Uses<!-- Describe uses of the drug. If appropriate, add subsections for each indication. --> ==
== Uses<!-- Describe uses of the drug. If appropriate, add subsections for each indication. --> ==


* Supplement standard anti-emetic regimen in chemotherapy induced nausea and vomiting  
* Prevention of postoperative nausea and vomiting
* Supplement standard anti-emetic regimen in post operative nausea and vomiting  
*Prevention of chemotherapy-induced nausea and vomiting


== Contraindications<!-- List contraindications and precautions for use of the drug. --> ==
== Contraindications<!-- List contraindications and precautions for use of the drug. --> ==
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=== Precautions<!-- List precautions for use of the drug. If none, this section may be removed. --> ===
=== Precautions<!-- List precautions for use of the drug. If none, this section may be removed. --> ===


* Coadministration with warfarin may result in a clinically significant decrease in International Normalized Ratio (INR)<ref name=":0">{{Citation|last=Zabirowicz|first=Eric S.|title=Pharmacology of Postoperative Nausea and Vomiting|date=2019|url=http://dx.doi.org/10.1016/b978-0-323-48110-6.00034-x|work=Pharmacology and Physiology for Anesthesia|pages=671–692|publisher=Elsevier|access-date=2023-01-05|last2=Gan|first2=Tong J.}}</ref>
* Decreases the efficacy of hormonal contraceptives for up to 28 days<ref name=":0">{{Citation|last=Zabirowicz|first=Eric S.|title=Pharmacology of Postoperative Nausea and Vomiting|date=2019|url=http://dx.doi.org/10.1016/b978-0-323-48110-6.00034-x|work=Pharmacology and Physiology for Anesthesia|pages=671–692|publisher=Elsevier|access-date=2023-01-05|last2=Gan|first2=Tong J.}}</ref>
* Decreases the efficacy of hormonal contraceptives<ref name=":0" />
*Inhibits CYP3A4 and induces CYP2C9<ref>{{Cite journal|last=Aapro|first=M. S.|last2=Walko|first2=C. M.|date=2010-12|title=Aprepitant: drug-drug interactions in perspective|url=https://pubmed.ncbi.nlm.nih.gov/20488873/|journal=Annals of Oncology: Official Journal of the European Society for Medical Oncology|volume=21|issue=12|pages=2316–2323|doi=10.1093/annonc/mdq149|issn=1569-8041|pmid=20488873}}</ref>
* Avoid IV aprepitant in pregnant patients as it contains alcohol<ref name=":0" />
**Some other drugs may need close monitoring and/or dose adjustment postoperatively (e.g. warfarin)
* Some formulations of IV aprepitant may contain alcohol which should be avoided in pregnant patients<ref name=":0" />
**IV fosaprepitant is not prepared with alcohol


== Pharmacology ==
== Pharmacology ==
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==== Mechanism of action<!-- Describe the mechanism of action for the primary uses of the drug. --> ====
==== Mechanism of action<!-- Describe the mechanism of action for the primary uses of the drug. --> ====
Antagonism of neurokinin-1 (NK1) receptors centrally (requires > 95% blockade to have maximum efficacy) and peripherally (located in the gut). NK1 receptor antagonists exert their main anti-emetic action by depressing the neural activity of the nucleus tracts solitaires lying ventrally to the to the area postrema<ref name=":0" />. Peripherally, the blockade of receptors in the gut may decrease the intensity of the emetic afferent signal to the central emetic structures.  
Antagonism of neurokinin-1 (NK1) receptors centrally (requires > 95% blockade to have maximum efficacy) and peripherally (located in the gut). NK1 receptor antagonists exert their main antiemetic action by depressing the neural activity of the nucleus tracts solitaires lying ventrally to the to the area postrema<ref name=":0" />. Peripherally, the blockade of receptors in the gut may decrease the intensity of the emetic afferent signal to the central emetic structures.  


==== Adverse effects<!-- Describe any potential adverse effects of the drug. --> ====
==== Adverse effects<!-- Describe any potential adverse effects of the drug. --> ====
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* Metabolized by CYP3A4 via oxidation w minor contribution by CYP1A2 and CYP2C19 <ref name=":0" />
* Metabolized by CYP3A4 via oxidation w minor contribution by CYP1A2 and CYP2C19 <ref name=":0" />
* Terminal half-life is 9 to 13 hours<ref name=":0" />
* Terminal half-life is 9 to 13 hours<ref name=":0" />
* Inducer of CYP3A4 and CYP2C9
* Inhibits CYP3A4 and induces CYP2C9


== Chemistry and formulation<!-- Describe the chemistry and formulation of the drug. --> ==
== Chemistry and formulation<!-- Describe the chemistry and formulation of the drug. --> ==

Revision as of 13:13, 8 January 2023

Aprepitant
Trade names

Emend

Clinical data
Drug class

Antiemetic

Uses

Postoperative Nausea and Vomiting

Contraindications

Known hypersensitivity

Routes of administration

PO or IV

Dosage

40 mg PO for PONV 125 mg PO followed by 2 days of 80 mg PO for CINV

Dosage
Pharmacodynamics
Mechanism of action

Neurokinin-1 receptor antagonist

Adverse effects

Decreased efficacy of hormonal contraceptives CYP interactions

Pharmacokinetics
Metabolism

CYP3A4 oxidation

Protein binding

95%

Physical and chemical data
Article quality
Editor rating
Comprehensive
User likes
0

Aprepitant is a neurokinin-1 (NK1) antagonist that is used in combination with standard antiemetic regimen to prevent postoperative nausea and vomiting, as well as prevention of acute and delayed chemotherapy-induced nausea and vomiting.

Uses

  • Prevention of postoperative nausea and vomiting
  • Prevention of chemotherapy-induced nausea and vomiting

Contraindications

Absolute contraindications

  • Known hypersensitivity

Precautions

  • Decreases the efficacy of hormonal contraceptives for up to 28 days[1]
  • Inhibits CYP3A4 and induces CYP2C9[2]
    • Some other drugs may need close monitoring and/or dose adjustment postoperatively (e.g. warfarin)
  • Some formulations of IV aprepitant may contain alcohol which should be avoided in pregnant patients[1]
    • IV fosaprepitant is not prepared with alcohol

Pharmacology

Pharmacodynamics

Mechanism of action

Antagonism of neurokinin-1 (NK1) receptors centrally (requires > 95% blockade to have maximum efficacy) and peripherally (located in the gut). NK1 receptor antagonists exert their main antiemetic action by depressing the neural activity of the nucleus tracts solitaires lying ventrally to the to the area postrema[1]. Peripherally, the blockade of receptors in the gut may decrease the intensity of the emetic afferent signal to the central emetic structures.

Adverse effects

  • Anaphylactic reaction
  • Angioedema
  • Urticaria
  • Toxic epidermal necrolysis
  • Acne vulgaris
  • Photosensitivity
  • Oily skin
  • Skin lesion
  • Headache
  • Dizziness
  • Fatigue

Pharmacokinetics

  • 95% is bound to plasma proteins
  • Crosses the blood brain barrier[1]
  • Metabolized by CYP3A4 via oxidation w minor contribution by CYP1A2 and CYP2C19 [1]
  • Terminal half-life is 9 to 13 hours[1]
  • Inhibits CYP3A4 and induces CYP2C9

Chemistry and formulation

Aprepitant is administered orally and intravenously. Fosaprepitant, a prodrug of aprepitant, is administered intravenously.

History

References

Zabirowicz, Eric S.; Gan, Tong J. (2019), "Pharmacology of Postoperative Nausea and Vomiting", Pharmacology and Physiology for Anesthesia, Elsevier, pp. 671–692, retrieved 2023-01-05[1]

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Zabirowicz, Eric S.; Gan, Tong J. (2019), "Pharmacology of Postoperative Nausea and Vomiting", Pharmacology and Physiology for Anesthesia, Elsevier, pp. 671–692, retrieved 2023-01-05
  2. ↑ Aapro, M. S.; Walko, C. M. (2010-12). "Aprepitant: drug-drug interactions in perspective". Annals of Oncology: Official Journal of the European Society for Medical Oncology. 21 (12): 2316–2323. doi:10.1093/annonc/mdq149. ISSN 1569-8041. PMID 20488873. Check date values in: |date= (help)

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