Adult Dosing

Nausea and vomiting associated with emetogenic cancer chemotherapy

• Rolapitant is used in combination with a 5-HT3 receptor antagonist and dexamethasone
• Dose adjustment for dexamethasone is not required because it does not interact with rolapitant
• Administer rolapitant before initiation of each cycle, but at minimum 2 week intervals
• Administer without regards to meals

Prevention of nausea and vomiting associated with cisplatin-based highly emetogenic cancer chemotherapy

• Day 1: Varubi 180 mg PO 1-2 hrs prior to chemotherapy plus dexamethasone 20 mg 30 min prior to chemotherapy plus 5HT-3 receptor antagonist as per the manufacturer’s prescribing information
• Days 2, 3, and 4: Varubi none, Dexamethasone 8 mg bid, 5HT-3 receptor antagonist none

Prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy and combinations of anthracycline and cyclophosphamide

• Day 1: Varubi 180 mg PO 1-2 hrs prior to chemotherapy plus dexamethasone 20 mg 30 min prior to chemotherapy plus 5HT-3 receptor antagonist as per the manufacturer’s prescribing information
• Days 2, 3, and 4: Varubi none, Dexamethasone none, 5HT-3 antagonist as per the manufacturer’s prescribing information

Pediatric Dosing

• Safety and efficacy in pediatric patient have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Prevention of delayed nausea and vomiting associated with emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy in adults
• Used in combination with other antiemetic agents

• Hypersensitivity to any of the ingredients of the product
• In patients receiving thioridazine (a CYP2D6 substrate)

• N/A

Renal Dose Adjustment

• Renal impairment: No dose adjustments

Hepatic Dose Adjustment

• Mild hepatic impairment (Child-Pugh Class A): No dose adjustments
• Moderate hepatic impairment (Child-Pugh Class B): No dose adjustments
• Severe hepatic impairment (Child-Pugh Class C): Clinical or pharmacokinetic data are not available. However, avoid use and if the use cannot be avoided, monitor patients for rolapitant-related adverse reactions

• CYP2D6 substrates with narrow therapeutic index (e.g. thioridazine, pimozide): Rolapitant is a moderate CYP2D6 inhibitor. Increased plasma concentration of CYP2D6 may cause potential adverse reactions. Monitor for adverse reactions if concomitant use with CYP2D6 substrate with a narrow therapeutic index cannot be avoided.|Avoid concomitant use of rolapitant with thioridazine because significant increase in plasma concentrations of thioridazine may cause QT prolongation and Torsades de Pointes
• Avoid use of rolapitant with pimozide. Monitor for QT prolongation if concomitant use cannot be avoided.
• Breast-cancer-resistance protein (BCRP) substrates with a narrow therapeutic index (e.g. methotrexate, topotecan, irinotecan): Increased plasma concentrations of BCRP substrates may result in potential adverse reactions
• Use the lowest effective dose of rosuvastatin
• P-glycoprotein (P-gp) substrates with a narrow therapeutic index (e.g. digoxin): Increased plasma concentrations of P-gp substrates may result in potential adverse reactions. Monitor for adverse reactions if concomitant use with P-gp substrate with a narrow therapeutic index cannot be avoided
• Strong CYP3A4 inducers (e.g. rifampin): Avoid use of rolapitant in patients who require prolonged use of strong CYP3A4 inducers because concomitant use can significantly reduce the plasma concentrations of rolapitant thereby reducing the efficacy of the drug

Pregnancy Category:NR (Not rated)

Breastfeeding: Safety Unknown

In patients receiving cisplatin-based highly emetogenic cancer chemotherapy (Cycle 1)

• HEMA: Neutropenia
• GI: Abdominal pain, hiccups

In patients receiving moderately emetogenic cancer chemotherapy and combinations of anthracycline and cyclophosphamide

• HEMA: Neutropenia, Anemia
• GI: Decreased appetite, dyspepsia, stomatitis
• CNS: Dizziness
• GU: Urinary tract infection

• Substance P/neurokinin-1 (NK1) receptor antagonist; NK-1 receptors are concentrated in the vomiting center of the brain which bind substance P (a neurokinin). Activation of NK-1 receptors by substance P evokes chemotherapy-induced nausea and vomiting. NK-1 receptor antagonists (e.g. rolapitant) block the interaction of substance P at the NK-1 receptor and help in management of chemotherapy-induced nausea and vomiting
• Metabolism: Metabolized in liver by CYP3A4 to form an active metabolite M19
• Excretion: Excreted in urine (14.2%) and feces (73%)
• Half-life: 169 to 183 hours (approximately 7 days)

US Trade Name(s)

• Varubi

US Availability

Varubi

• TABS: 90 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Hematology/Oncology

Antiemetics

Neurokinin Antagonist

Gastrointestinal

Antiemetics

Neurokinin Antagonists