Aprepitant

Aprepitant

Trade names	Emend
Clinical data
Drug class	Anti-emetic
Uses	Postoperative Nausea and Vomiting
Contraindications	Known hypersensitivity
Routes of administration	PO or IV
Dosage
Pharmacodynamics
Mechanism of action	Substance P/Neurokinin 1 receptor antagonist
Adverse effects	Anaphylaxis
Pharmacokinetics
Metabolism	CYP3A4 oxidation
Protein binding	95%
Physical and chemical data
Article quality
Editor rating	Comprehensive
User likes	0

Aprepitant is a selective substance P neurokinin 1 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.

Uses

• Supplement standard anti-emetic regimen in chemotherapy induced nausea and vomiting
• Supplement standard anti-emetic regimen in post operative nausea and vomiting

Contraindications

Absolute contraindications

• Known hypersensitivity

Precautions

• Coadministration with warfarin may result in a clinically significant decrease in International Normalized Ratio (INR)
• Decreases the efficacy of hormonal contraceptives
• Avoid IV aprepitant in pregnant patients as it contains alcohol

Pharmacology

Pharmacodynamics

Mechanism of action

Antagonism of substance P/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. 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
• Metabolized by CYP3A4 via oxidation w minor contribution by CYP1A2 and CYP2C19
• Terminal half-life is 9 to 13 hours
• Inducer of CYP3A4 and CYP2C9

Chemistry and formulation

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