Rolapitant

Indications

Rolapitant is used for: Chemotherapy-Induced Nausea & Vomiting,

Adult Dose

Chemotherapy-Induced Nausea & Vomiting Indicated in combination with other antiemetic agents (eg, dexamethasone and 5HT-3 antagonist) in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy Highly emetogenic chemotherapy Includes cisplatin-based highly emetogenic cancer chemotherapy Day 1 Rolapitant 180 mg PO OR 166.5 mg IV over 30 minutes 2 hr before chemotherapy PLUS Dexamethasone 20 mg PO 30 minutes before chemotherapy PLUS 5HT-3 antagonist according the manufacturer’s prescribing information Days 2-4 Dexamethasone 8 mg PO BID Moderately emetogenic chemotherapy Includes anthracycline and cyclophosphamide combinations Day 1 Rolapitant 180 mg PO OR 166.5 mg IV over 30 minutes 2 hr before chemotherapy PLUS Dexamethasone 20 mg PO 30 minutes before chemotherapy PLUS 5HT-3 antagonist according the manufacturer’s prescribing information Hepatic impairment Mild-to-moderate (Child Pugh A to B): No dosage adjustment necessary Severe (Child Pugh C): Avoid use; if use cannot be avoided, monitor for drug-related adverse reactions

Child Dose

Renal Dose

Administration

Oral Administration May take with or without food IV Preparation Rolapitant injectable emulsion is supplied as a single-dose vial The emulsion is homogeneous (no shaking required) and appears translucent white Visually inspect vials for particulate matter and discoloration prior to administration; discard if present; do not use if contamination is suspected Administer dose by inserting a vented IV set through the septum of the vial Once the stopper is punctured, use immediately Do not dilute rolapitant injectable emulsion IV Administration Infuse 92.5 mL from vial over 30 minutes Administer rolapitant prior to the initiation of each chemotherapy cycle, but at no less than 2 week intervals

Contra Indications

Coadministration with CYP2D6 substrates with a narrow therapeutic index (eg, thioridazine and pimozide) Hypersensitivity to any component of the product (including soybean oil)

Precautions

Anaphylaxis and other serious hypersensitivity reactions Anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions, some requiring hospitalization have been reported Reactions have occurred during or soon after the rolapitant infusion; most have occurred within the first few minutes of administration Lactation Unknown if distributed in human breast milk and no data on effects on breastfed infant or on milk production Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition

Pregnancy-Lactation

Pregnancy Limited data in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcome Animal data In animal reproduction studies, no teratogenic or embryo-fetal effects were observed with oral administration in rats and rabbits during the period of organogenesis at doses up to 1.3 times and 2.9 times, respectively, the maximum recommended human dose (MRHD) Lactation Unknown if distributed in human breast milk and no data on effects on breastfed infant or on milk production Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition

Interactions

Avoid the use of rolapitant in patients who require chronic administration of strong CYP3A4 inducers Monitor INR and prothrombin time and adjust warfarin dose, to maintain INR target range, when used concomitantly with rolapitant BCRP substrates with a narrow therapeutic index Oral rolapitant is an inhibitor of breast cancer resistance protein (BCRP); increased plasma concentrations of BCRP substrates (eg, methotrexate, topotecan, or irinotecan) may result in potential adverse reactions Monitor for adverse reactions related to the concomitant drug if use of rolapitant tablets cannot be avoided Use lowest effective dose of rosuvastatin

Adverse Effects

Side effects of Rolapitant : 1-10% IV Infusion-related reactions (2.6%) Tablets HEC Neutropenia (9%) Hiccups (5%) Abdominal pain (3%) MEC Decreased appetite (9%) Neutropenia (7%) Dizziness (6%) Dyspepsia (4%) Urinary tract infection (4%) Stomatitis (4%) Anemia (3%)

Mechanism of Action

Selective, long-acting neurokinin receptor (NK)-1 antagonist NK-1 receptors are highly concentrated in the vomiting center of the brain and bind a neurokinin termed substance P; activation of NK-1 receptors by substance P plays a central role in eliciting chemotherapy-induced nausea and vomiting Blocking the interaction of substance P at the NK-1 receptor, NK-1 receptor antagonists improve the management of nausea and vomiting