Pharmacology · NK1 receptor antagonists
Aprepitant !
An oral NK1 blocker that prevents acute and delayed vomiting from chemotherapy, given with a setron and dexamethasone. It interacts through CYP3A4.
Updated 2026-11-01
Crystal structure of the human NK1 receptor with aprepitant bound deep in the transmembrane pocket where substance P would act.
Mechanism of action
Aprepitant is a selective, high-affinity antagonist of the human NK1 receptor. After cisplatin and other emetogenic drugs, substance P released in the brainstem activates NK1 receptors and sustains vomiting, especially in the days after treatment. Aprepitant crosses the blood–brain barrier, occupies brain NK1 receptors and blocks that signal. It barely binds 5-HT3, dopamine or corticosteroid receptors and enhances the effect of ondansetron and dexamethasone.
- Emetogenic chemotherapy releases substance P in the brainstem
- Substance P activates NK1 receptors and sustains vomiting
- Aprepitant crosses into the brain and occupies NK1 receptors
- Acute and delayed vomiting are prevented, on top of the setron
Pharmacokinetics
- Absorption
- Oral bioavailability about 60–65%; food has no meaningful effect.
- Distribution
- More than 95% bound to plasma proteins; crosses the blood–brain barrier.
- Metabolism
- Extensive in the liver, mainly by CYP3A4 (minor CYP1A2 and CYP2C19). It is a substrate, a moderate inhibitor and an inducer of CYP3A4, and induces CYP2C9.
- Half-life
- About 9–13 hours.
Indications
- Prevention of acute and delayed nausea and vomiting from highly emetogenic chemotherapy (including high-dose cisplatin) and moderately emetogenic chemotherapy, with a 5-HT3 antagonist and dexamethasone.
- Prevention of post-operative nausea and vomiting in adults.
Adverse effects
Common
- Fatigue and weakness
- Diarrhoea and dyspepsia
- Hiccups
- Loss of appetite
Contraindications
- Hypersensitivity to aprepitant or any component
- Use with pimozide (CYP3A4 inhibition raises pimozide levels and can prolong QT)
Key interactions
- Dexamethasone and methylprednisolone
- Higher corticosteroid levels through CYP3A4 inhibition; the corticosteroid dose in the antiemetic regimen is reduced.
- Warfarin
- Clinically significant fall in INR; the INR is checked in the two weeks after the aprepitant course.
- Hormonal contraceptives
- Lower efficacy during treatment and for about a month afterwards; a back-up method is used.
- Strong CYP3A4 inhibitors (ketoconazole, diltiazem) and inducers (rifampicin)
- Inhibitors raise aprepitant levels and adverse effects; inducers lower its levels and efficacy.
- CYP3A4-metabolised chemotherapy and benzodiazepines (midazolam, alprazolam, triazolam)
- Higher levels and more adverse effects of those drugs.
What is monitored
- INR in patients on chronic warfarin after each course
- Signs of hypersensitivity
- Control of nausea and vomiting in the days after chemotherapy (delayed phase)
Administration and safety
- Oral capsules, started before chemotherapy as part of a combined regimen with a setron and dexamethasone
- Not studied for treating vomiting that has already started, and not meant for chronic continuous use
- Check the full medication list for CYP3A4 interactions before each course
Nursing care
- Confirm that the dexamethasone dose was adjusted for the combination
- Ask about warfarin, pimozide and hormonal contraception before the first dose
- Teach women using hormonal contraception to use a back-up method during treatment and for a month after
- Record nausea and vomiting over the following days, not only on the day of chemotherapy
Pregnancy and breastfeeding
Data in pregnant women are not enough to define a risk; animal studies at exposures near human levels showed no developmental harm.
Test yourself
Think of the answer, then tap the question to see it.
Which neurotransmitter does aprepitant block, and at which receptor?
Substance P, at the neurokinin-1 (NK1) receptor in the brainstem.
Which drug is contraindicated with aprepitant, and why?
Pimozide: aprepitant inhibits CYP3A4, pimozide levels rise and QT can prolong dangerously.
Why does aprepitant lower the INR in a patient on warfarin?
It induces CYP2C9, which metabolises S-warfarin, so warfarin is cleared faster.
Related drugs
← Back to the class: NK1 receptor antagonists
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - APREPITANT capsule APREPITANT kit (DailyMed (U.S. National Library of Medicine), 2026); Aprepitant: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 6HLO: Crystal structure of the Neurokinin 1 receptor in complex with the small molecule antagonist Aprepitant (RCSB Protein Data Bank, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.