Varubi (Rolapitant) is a long-acting, highly selective, and potent Neurokinin-1 receptor antagonist. It has been approved for the prevention of delayed chemotherapy-induced nausea and vomiting in adults.
Varubi (Rolapitant) Uses:
-
For the Prevention of chemotherapy-induced nausea and vomiting (CINV):
- Prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy, including, but not limited to highly emetogenic chemotherapy (in combination with other antiemetic agents).
Varubi (Rolapitant) Dose in Adults
Varubi (Rolapitant) Dose in the prevention of Chemotherapy-induced nausea and vomiting:
Note:
- rolapitant should not be administered at less than 2-week intervals.
- No dosage adjustment for concomitant dexamethasone is required.
Intravenous Varubi injection:
-
Highly emetogenic chemotherapy (cisplatin-based):
- 5 mg administered within 2 hours before initiation of chemotherapy on day 1 only (in combination with dexamethasone given on days 1, 2, 3, and 4 and a 5-HT receptor antagonist given on day 1).
-
Moderately emetogenic chemotherapy and anthracycline/ cyclophosphamide combinations:
- 5 mg administered within 2 hours before initiation of chemotherapy on day 1 only
- (in combination with dexamethasone administered on day 1 and a 5-HT receptor antagonist given as appropriate based on the agent selected).
Oral Varubi tablets:
-
Highly emetogenic chemotherapy (cisplatin-based):
- 180 mg administered within 2 hours before initiation of chemotherapy on day 1 only
- (in combination with dexamethasone given on days 1, 2, 3, and 4 and a 5-HT receptor antagonist given on day 1).
-
Moderately emetogenic chemotherapy and anthracycline/ cyclophosphamide combinations:
- 180 mg administered within 2 hours before initiation of chemotherapy on day 1 only
- (in combination with dexamethasone given on day 1 and a 5-HT receptor antagonist given as appropriate based on the agent selected).
Varubi (Rolapitant) Dose in Childrens
It has not been studied in Children.
Pregnancy Risk Category: Not assigned
- Adverse events were reported in some animal reproduction studies.
Rolapitant use during breastfeeding:
- No data is available if rolapitant is present in breast milk.
- According to the manufacturer, the decision to breastfeed during therapy should take into consideration the risk of exposure to the infant and the benefits of treatment to the mother.
Varubi Dose in Kidney Disease:
- CrCl 30 to 90 mL/minute:
- no dosage adjustments provided in the manufacturer's labeling;
- however, based on pharmacokinetics, dosage adjustment is not likely necessary.
- CrCl <30 ml/minute and end-stage renal disease (ESRD):
- There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Varubi Dose in Liver disease:
- Child-Pugh classes A and B:
- No dosage adjustment is necessary.
- Child-Pugh class C:
- Avoid use if possible (has not been studied);
- if use cannot be avoided, monitor closely for adverse reactions related to rolapitant.
Side Effects of Varubi (Rolapitant):
-
Central Nervous System:
- Dizziness
-
Gastrointestinal:
- Decreased Appetite
- Hiccups
- Dyspepsia
- Stomatitis
- Abdominal Pain
-
Genitourinary:
- Urinary Tract Infection
-
Hematologic & Oncologic:
- Neutropenia
- Anemia
-
Miscellaneous:
- Infusion-related Reactions
Contraindications to Rolapitant Include:
- Allergy to any component of the formulation, including soybean oil (rolapitant)
- concurrent use of CYP2D6 substrates with a narrow therapeutic index, such as thioridazine or pimozide
Warnings and precautions
-
Hypersensitivity
- Anaphylaxis, anaphylactic stress, and other severe hypersensitivity reactions have been reported with IV rolapitant.
- Wheezing, difficulty breathing and facial swelling are all possible symptoms.
- Although reactions have been reported during and shortly after infusions, most reactions occur within the first few minutes.
- Patients with allergies to legumes and other allergens should be closely monitored. In an emergency, medications for hypersensitivity reactions should always be on hand.
- Patients with possible hypersensitivity should not be given IV rolapitant.
- If you experience anaphylaxis, stop infusion immediately and discontinue IV rolapitant permanently.
- Anaphylaxis, anaphylactic stress, and other severe hypersensitivity reactions have been reported with IV rolapitant.
-
Hepatic impairment
- Patients with severe hepatic impairment should not use this product.
- If you cannot avoid it, be aware of any adverse reactions to the rolapitant.
Rolapitant: Drug Interaction
|
Ajmaline |
CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. |
|
Amphetamines |
CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines. |
|
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. |
|
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. |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
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. |
|
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. |
|
BuPROPion |
CYP2B6 Inhibitors (Weak) may increase the serum concentration of BuPROPion. |
|
Celiprolol |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. |
|
CloZAPine |
CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. |
|
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. |
|
CYP2D6 Substrates (High risk with Inhibitors) |
CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Tamoxifen. |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of Rolapitant. |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Everolimus |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. |
|
Fesoterodine |
CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. |
|
Indoramin |
CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Larotrectinib |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. |
|
Metoprolol |
CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol. |
|
Naldemedine |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. |
|
Naloxegol |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. |
|
Nebivolol |
CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. |
|
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. |
|
Pitolisant |
CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant. |
|
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. |
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Prucalopride |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. |
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Ranolazine |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. |
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RifAXIMin |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
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. |
|
Silodosin |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Talazoparib |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs. |
|
Talazoparib |
BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. |
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Tamsulosin |
CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin. |
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Tegaserod |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
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. |
|
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. Iif used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. |
|
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. |
|
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. |
|
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. |
|
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. |
|
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. |
|
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. |
|
Dabigatran Etexilate |
P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. |
|
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). |
|
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. |
|
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. |
|
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. |
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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. |
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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. |
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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. |
|
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. |
|
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. |
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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. |
|
St John's Wort |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
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. |
|
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. |
|
PAZOPanib |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. |
|
PAZOPanib |
BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. |
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Pimozide |
Rolapitant may increase the serum concentration of Pimozide. |
|
Thioridazine |
Rolapitant may increase the serum concentration of Thioridazine. |
|
Topotecan |
BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. |
|
Topotecan |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. |
|
VinCRIStine (Liposomal) |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). |
Monitoring parameters:
Monitor for signs/symptoms of hypersensitivity during infusion, particularly in patients with known legume or related allergies.
How to administer Rolapitant (Varubi)?
- Do not administer chemotherapy within two hours of the start of day 1.
- IV:
- For 30 minutes, infuse.
- To puncture the stopper, insert a vented IV through the septum of your vial.
- Do not add any other medication directly to the rolapitant vial.
- Rolapitant IV, a transparent white homogeneous oil emulsion is available.
- No shaking is necessary before administration.
- Rolapitant can be accessed via the Y site with D5W and D5LR.
- Oral: Can be given without regard for meals.
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Mechanism of action of Rolapitant (Varubi):
- Rolapitant acts by inhibiting selectively and competitively the substance P/neurokinin (NK) receptor.
Protein binding99.8% of the population is protein-bound
Metabolism: It is metabolized primarily by the liver enzymes CYP3A4 in order to form active metabolite (major).
Half-life eliminationAfter oral administration, it takes approximately 7 days (range 169 to 183 hours), and 7.6 days after intravenous administration (range 138 to 220 hours).
Time to get therepeak serum concentrationAfter oral administration, it takes approximately 4 hours
Excretion:
- Feces (73%);
- urine (~14%; primarily as metabolites)
International Brands of Rolapitant:
- Varubi
- Varuby
Rolapitant Brands Names in Pakistan:
No Brands Available in Pakistan.
