Aprepitant

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]

↑ ^1.0 ^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
↑ Aapro, M. S.; Walko, C. M. (2010). "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.

Top contributors: Cornel Chiu, Olivia Sutton and Chris Rishel

[:0-1] 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). "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.

[1]

[2]