Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Emulsion, Intravenous:
Varubi: 166.5 mg/92.5 mL (92.5 mL) [contains soybean oil]
Tablet, Oral:
Varubi: 90 mg [contains fd&c blue #2 aluminum lake]
Pharmacology
Mechanism of Action
Rolapitant prevents delayed nausea and vomiting associated with emetogenic chemotherapy by selectively and competitively inhibiting the substance P/neurokinin 1 (NK1) receptor.
Pharmacokinetics/Pharmacodynamics
Distribution
Oral: Vd/F: 387 L (cancer patients); IV: Vd: 392 L (healthy subjects)
Metabolism
Hepatic; primarily by CYP3A4 to form active metabolite M19 (major)
Excretion
Feces (73%); urine (~14%; primarily as metabolites)
Time to Peak
Oral: ~4 hours
Half-Life Elimination
Oral: ~7 days (range: 169 to 183 hours); IV: 7.6 days (range: 138 to 205 hours)
Protein Binding
99.8%
Use: Labeled Indications
Chemotherapy-induced nausea and vomiting (CINV), prevention: Prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to highly emetogenic chemotherapy (in combination with other antiemetic agents).
Contraindications
Hypersensitivity to rolapitant or any component of the formulation (including soybean oil); concurrent use of CYP2D6 substrates with a narrow therapeutic index, such as thioridazine or pimozide
Dosage and Administration
Dosing: Adult
Chemotherapy-induced nausea and vomiting (prevention): Note: Do not administer rolapitant at less than 2-week intervals. No dosage adjustment for concomitant dexamethasone is required.
IV:
Highly emetogenic chemotherapy (cisplatin-based): 166.5 mg administered within 2 hours prior to initiation of chemotherapy on day 1 only (in combination with dexamethasone given on days 1, 2, 3, and 4 and a 5-HT3 receptor antagonist given on day 1).
Moderately emetogenic chemotherapy and anthracycline/cyclophosphamide combinations: 166.5 mg administered within 2 hours prior to initiation of chemotherapy on day 1 only (in combination with dexamethasone given on day 1 and a 5-HT3 receptor antagonist given as appropriate based on the agent selected).
Oral:
Highly emetogenic chemotherapy (cisplatin-based): 180 mg administered within 2 hours prior to initiation of chemotherapy on day 1 only (in combination with dexamethasone given on days 1, 2, 3, and 4 and a 5-HT3 receptor antagonist given on day 1).
Moderately emetogenic chemotherapy and anthracycline/cyclophosphamide combinations: 180 mg administered within 2 hours prior to initiation of chemotherapy on day 1 only (in combination with dexamethasone given on day 1 and a 5-HT3 receptor antagonist given as appropriate based on the agent selected).
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Rolapitant IV is a translucent white homogeneous emulsion; no shaking is required prior to administration. Do not add other medications or diluents directly to the rolapitant vial. Insert a vented IV set through the septum of the vial to puncture stopper, then use immediately.
Administration
Administer within 2 hours prior to initiation of chemotherapy cycle (on day 1 only).
IV: Infuse over 30 minutes. Insert a vented IV set through the septum of the vial to puncture stopper, then use immediately (do not dilute prior to infusion). Do not add other medications directly to the rolapitant vial. Rolapitant IV is a translucent white homogeneous emulsion; no shaking is required prior to administration. Rolapitant is compatible via the Y-site with NS, D5W, D5LR, and LR.
Oral: May be administered without regard to meals.
Storage
Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F)
Drug Interactions
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling recommends avoiding combination if possible. If used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Monitor therapy
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Consider therapy modification
Amphetamines: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines. Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
BCRP/ABCG2 Substrates: Rolapitant may increase the serum concentration of BCRP/ABCG2 Substrates. Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. Monitor therapy
Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose. Monitor therapy
BuPROPion: CYP2B6 Inhibitors (Weak) may increase the serum concentration of BuPROPion. Monitor therapy
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Consider therapy modification
CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. Consider therapy modification
CYP2D6 Substrates (High risk with Inhibitors): CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Tamoxifen. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Rolapitant. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Rolapitant. Management: Avoid rolapitant use in patients requiring chronic administration of strong CYP3A4 inducers. Monitor for reduced rolapitant response and the need for alternative or additional antiemetic therapy even with shorter-term use of such inducers. Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy
Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Monitor therapy
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Consider therapy modification
Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification
Metoprolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol. Monitor therapy
Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide. Monitor therapy
Pimozide: Rolapitant may increase the serum concentration of Pimozide. Avoid combination
Pitolisant: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant. Monitor therapy
Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Sibutramine: CYP2B6 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP2B6 Inhibitors (Weak) may increase the serum concentration of Sibutramine. Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs. Monitor therapy
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Consider therapy modification
Tamsulosin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. Monitor therapy
Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Monitor therapy
Thioridazine: Rolapitant may increase the serum concentration of Thioridazine. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Monitor therapy
Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (if needed) of 50 mg when used with a P-gp inhibitor. Consider therapy modification
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Adverse Reactions
Percentages reported as part of combination regimens.
1% to 10%:
Central nervous system: Dizziness (6%)
Gastrointestinal: Decreased appetite (9%), hiccups (5%), dyspepsia (4%), stomatitis (4%), abdominal pain (3%)
Genitourinary: Urinary tract infection (4%)
Hematologic & oncologic: Neutropenia (7% to 9%), anemia (3%)
Miscellaneous: Infusion-related reactions (3%)
<1%, postmarketing, and/or case reports: Anaphylactic shock (FDA Safety Alert, Jan 16, 2018), anaphylaxis (FDA Safety Alert, Jan 16, 2018)
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions (some requiring hospitalization) have occurred with IV rolapitant; symptoms may include wheezing, difficulty breathing, face or throat swelling, hives, abdominal symptoms (cramping, pain, vomiting), itching, back pain, chest pain, flushing, hypotension, and/or shock. Reactions have occurred during or shortly after infusion, although most reactions occurred within the first few minutes of administration. Monitor patients with known allergies to legumes or other related allergens closely; medications for the treatment of hypersensitivity reactions should be available for immediate use. Do not administer IV rolapitant to patients with a potential hypersensitivity. Stop infusion immediately and permanently discontinue IV rolapitant if anaphylaxis or other serious reactions occur; manage symptoms appropriately.
Disease-related concerns:
- Hepatic impairment: Avoid use in patients with severe hepatic impairment; if use cannot be avoided, monitor for adverse reactions related to rolapitant.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Rolapitant is a moderate inhibitor of CYP2D6; CYP2D6 inhibition may persist for 28 days (or longer). Increased plasma concentrations of certain CYP2D6 substrates may result in serious QT prolongation and torsades de pointes. Concurrent use with thioridazine or pimozide is contraindicated.
Monitoring Parameters
Monitor for signs/symptoms of hypersensitivity during infusion, particularly in patients with known legume or related allergies.
Pregnancy
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience hiccups, lack of appetite, mouth sores, or nausea. Have patient report immediately to prescriber flushing, abdominal cramps, abdominal pain, vomiting, back pain, chest pain, severe dizziness, passing out, signs of infection, signs of a urinary tract infection (blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain, severe loss of strength and energy (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
