Aprepitant (4 brand names, 4 dosage forms, 2 routes)
Available dosage forms: EMULSION, CAPSULE, INJECTION, EMULSION, FOR SUSPENSION.
Routes of administration: INTRAVENOUS, ORAL.
Brand Names
- APONVIE
- APREPITANT
- CINVANTI
- EMEND
Contraindications
Aprepitant is contraindicated in patients: • who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions have been reported [see Adverse Reactions (6.2)] . • taking pimozide. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of this drug which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Warnings and Precautions (5.1)].
Mechanism of Action
Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupies brain NK1 receptors. Animal and human studies show that aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both the acute and delayed phases of cisplatin-induced emesis.
Overdosage
No specific information is available on the treatment of overdosage. Drowsiness and headache were reported in one patient who ingested 1,440 mg of aprepitant (approximately 11 times the maximum recommended single dose). In the event of overdose, aprepitant should be discontinued and general supportive treatment and monitoring should be provided. Because of the antiemetic activity of aprepitant, drug-induced emesis may not be effective in cases of aprepitant overdosage. Aprepitant is not removed by hemodialysis.