APEMEZE 125 mg

Indications

• Prevention of chemotherapy-induced nausea and vomiting
• Prevention of postoperative nausea and vomiting

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing information.

Adults: The usual adult dose for the prevention of chemotherapy-induced nausea and vomiting is 125 mg orally on the first day, followed by 80 mg once daily on days 2 and 3.

Mechanism of action

Aprepitant works by selectively antagonizing the neurokinin-1 receptor, which is involved in the emetic response mediated by substance P, thereby reducing the incidence of nausea and vomiting.

Pharmacodynamics

By blocking the neurokinin-1 receptor, aprepitant prevents the action of substance P, a neuropeptide that is released during the emetic reflex, leading to a decrease in the perception of nausea and vomiting.

Pharmacokinetics

Aprepitant is well absorbed after oral administration, with peak plasma concentrations occurring within 4 hours. It has a high protein binding rate and is metabolized primarily by CYP3A4, with its elimination half-life ranging from 9 to 13 hours.

Contra-indications

• gastro-intestinal obstruction
• gastro-intestinal perforation
• gastro-intestinal haemorrhage
• phaeochromocytoma

Adverse effects

• anxiety
• dizziness
• dyspnoea
• oedema
• skin reactions
• visual impairment

Interactions

• mitotane - severe (decreases exposure)
• corticosteroids - moderate (increases exposure)
• dexamethasone - moderate (increases exposure)
• antiarrhythmics - unknown (increases exposure)
• dronedarone - unknown (increases exposure)
• antifungals, azoles - unknown (increases exposure)
• isavuconazole - unknown (increases exposure)
• cobicistat - unknown (increases exposure)
• coumarins - unknown (decreases anticoagulant effect)
• idelalisib - unknown (increases exposure)

Precautions

• asthma
• atopic allergy

Pregnancy

Not known to be harmful.

Breast-feeding

Small amount present in milk; avoid.

Storage

Store in a cool, dry place away from light.

Formulations

• Metoclopramide hydrochloride 5 mg per 1 ml solution for injection
• Metoclopramide hydrochloride 10 mg/2 ml solution for injection ampoules
• Metoclopramide hydrochloride 1 mg per 1 ml oral solution
• Metoclopramide hydrochloride 10 mg tablets

Mechanism of action

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 ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis.

Pharmacodynamics

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