APREPITANT ARX

What it is

Aprepitant is available in 40 mg, 80 mg, 125 mg or 165 mg capsules for oral administration. Aprepitant is a selective high affinity antagonist at human substance-P neurokinin-1 (NK1) receptors. Aprepitant showed at least 3,000-fold selectivity for the NK1 receptor over other enzyme, transporter, ion-channel and receptor sites, including the dopamine and serotonin (5HT3) receptors that are targets for existing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV) therapies.

Approved indications

— 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. — Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy, in combination with other antiemetic agents. — Prevention of postoperative nausea and vomiting.

Dosing overview

For the 1-day regimen, the recommended dose is 165 mg orally 1 hour prior to chemotherapy treatment on Day 1 only. For the 3-day regimen, the recommended dose is 125 mg orally 1 hour prior to chemotherapy treatment on Day 1 and 80 mg orally once daily in the morning on Days 2 and 3. For postoperative nausea and vomiting, the recommended oral dosage is 40 mg within 3 hours prior to induction of anaesthesia.

Key safety warnings

Aprepitant is a dose-dependent inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant orally administered medicinal products that are primarily metabolised through CYP3A4. Moderate inhibition of CYP3A4 by aprepitant (125 mg/80 mg 3-day oral regimen or 165 mg single dose) could result in elevated plasma concentrations of these concomitant medicinal products. Coadministration of aprepitant with warfarin may result in a clinically significant decrease in International Normalised Ratio (INR) of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the 2-week period, particularly at 7 to 10 days, following initiation of treatment with aprepitant. The efficacy of hormonal contraceptives during and for 28 days after administration of aprepitant may be reduced. Alternative or back-up methods of contraception should be used during treatment with aprepitant and for one month following the last dose.

Contraindications

Aprepitant is contraindicated in patients who are hypersensitive to any component of the product. Aprepitant should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride. Dose-dependent inhibition of cytochrome P450 isoenzyme 3A4 (CYP3A4) by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

PBS listing

The 165 mg capsule is listed on the PBS with streamlined restriction, listed at an ex-manufacturer price of A$49.52.

Regulatory history

Aprepitant ARX was first listed on the ARTG on 2019-06-11 across four capsule strengths (40 mg, 80 mg, 125 mg and 165 mg). In November 2014, PBAC recommended aprepitant for an amendment to the PBS listing to allow use for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy in patients who have failed to respond to a 5HT3 antagonist and dexamethasone. PBAC also recommended in November 2014 a change to the PBS listing to allow use in combination with a 5-HT3 antagonist and dexamethasone for the prevention of nausea and vomiting associated with highly or moderately emetogenic cancer chemotherapy.