APREPITANT ARX

What it is

APREPITANT LUPIN is available as capsules containing 40 mg, 80 mg, 125 mg or 165 mg of aprepitant. 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 and postoperative nausea and vomiting 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 one-day oral regimen, the recommended dose of APREPITANT LUPIN is 165 mg orally one hour prior to chemotherapy treatment on Day 1 only. For the three-day oral regimen, the recommended dose of APREPITANT LUPIN is 125 mg orally one hour prior to chemotherapy treatment on Day 1 and 80 mg orally once daily in the morning on Days 2 and 3. For prevention of postoperative nausea and vomiting, the recommended oral dosage of APREPITANT LUPIN is 40 mg within three 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 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 of prothrombin time. In patients on chronic warfarin therapy, the INR should be closely monitored in the two-week period, particularly at seven to ten days, following initiation of the three-day regimen of APREPITANT LUPIN or administration of a single 165 mg dose or a single 40 mg dose. The efficacy of hormonal contraceptives during and for 28 days after administration of APREPITANT LUPIN may be reduced. Alternative or back-up methods of contraception should be used during treatment with APREPITANT LUPIN and for one month following the last dose.

Contraindications

APREPITANT LUPIN is contraindicated in patients who are hypersensitive to any component of the product. APREPITANT LUPIN should not be used concurrently with pimozide, terfenadine, astemizole, or cisapride, as dose-dependent inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions.

PBS listing

APREPITANT LUPIN is listed on the PBS under Section 100 (Efficient Funding of Chemotherapy-Related Benefits) and General Schedule with Authority Required (Streamlined) restriction. The listing covers chemotherapy-induced nausea and vomiting associated with carboplatin and oxaliplatin regimens from the first chemotherapy cycle, and nausea and vomiting in the same indications as the branded comparator.

Regulatory history

APREPITANT LUPIN aprepitant 40 mg, 80 mg, 125 mg and 165 mg capsules were first listed on the ARTG on 3 July 2019. In March 2016, the PBAC recommended listing aprepitant as an Authority Required (Streamlined) benefit on the General Schedule and under the Section 100 program for use with carboplatin and oxaliplatin regimens from the first chemotherapy cycle. In July 2019, the PBAC recommended a new Section 100 and General Schedule Authority Required (Streamlined) listing for nausea and vomiting.