Aprepitant

Aprepitant is an antiemetic chemical compound that belongs to a class of drugs called substance P antagonists. It mediates its effect by blocking the neurokinin 1 receptor.

Aprepitant

Aprepitant; MK-869; Emend; Aprepitantum

Aprecap, Aprelief, Apretero, Apriset, Apristar, Empov, Emvoid

3-{[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholin-4-yl]methyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

• Absorption: Oral (Bioavailability 60-65%)
• Distribution: >95% protein binding
• Metabolism: Metabolized primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19.
• Excretion: Primarily by metabolism. 

It is a P/neurokinin 1 (NK1) receptor antagonist, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy in combination with other antiemetic agents. 

40 mg within 3 hr prior to induction of anaesthesia. Prophylaxis of postoperative nausea and vomiting.

For the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy.

• Hypersensitivity reactions
•  Steven-Johnsons syndrome.
• Headache, nausea, dizziness, vomiting, thirst, hiccups, constipation, dyspepsia, abdominal pain, diarrhoea, fatigue, dehydration, cough, hypertension, hypotension, angioedema, proteinuria, elevated ALT and AST levels, increased BUN.

• Concurrent use with CYP3A4 inducers (e.g. carbamazepine, rifampicin, phenytoin, primidone, and phenobarbital) may lead to reduced efficacy of Aprepitant.
• May increase plasma levels of benzodiazepine (e.g. midazolam, diazepam, alprazolam).
• Concurrent use with CYP3A4 inhibitors (e.g. clarithromycin, diltiazem, troleandomycin, verapamil, ketoconazole, itraconazole, nefazodone, ritonavir, nelfinavir) may lead to increased plasma levels of Aprepitant
• Serum concentrations of colchicine may increase with Aprepitant.
• May increase toxicity of chemotherapy drug metabolised by CYP3A4 e.g. docetaxel, etoposide, ifosfamide, imatinib, paclitaxel, vincristine, vinblastin.
• May result in increased serum levels of astemizole, cisapride, pimozide and terfenadine which can lead to life-threatening torsade de pointes arrhythmias.
• May reduce efficacy of oral contraceptives, use additional methods of contraception during treatment and for at least 1 mth following the last dose of Aprepitant.
• St John's wort may decrease Aprepitant levels.
• Avoid grapefruit juice, may raise serum concentrations of Aprepitant. 

Caution when used during lactation

Store at room temperature 20-25°C

Molecular weight

534.4267

Molecular formula

C23H21F7N4O3

CAS number

170729-80-3

Precautions

• Concurrent use with strong/moderate CYP3A4 inhibitors, inducers or substrates.
• Not recommended in lactation. Pregnancy.
• Moderate to severe hepatic impairment
• Monitor INR closely for patients on warfarin.