Rolapitant

Rolapitant is a selective and competitive antagonist of human substance P/NK1 receptors. Rolapitant does not have significant affinity for the NK2 or NK3 receptors or for a battery of other receptors, transporters, enzymes and ion channels.

• VARUBI ® is indicated in combination with other antiemetic agents 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. VARUBI is a substance P/neurokinin 1 (NK1) receptor antagonist indicated in combination with other antiemetic agents 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.ICD-10: R11.2

• VARUBI is contraindicated in patients taking CYP2D6 substrates with a narrow therapeutic index, such as thioridazine and pimozide. VARUBI can significantly increase the plasma concentrations of thioridazine and pimozide, which may result in QT prolongation and Torsades de Pointes [see Warnings and Precautions (5.1) ] .contraindicated

The recommended dosage of VARUBI in adults in combination with a 5-HT 3 receptor antagonist and dexamethasone for the prevention of nausea and vomiting with emetogenic cancer chemotherapy is shown in Table 1 . There is no drug interaction between rolapitant and dexamethasone, so no dosage adjustment for dexamethasone is required. Administer a dexamethasone dose of 20 mg on Day 1 [see Clinical Pharmacology (12.3) ] . Administer VARUBI prior to the initiation of each chemotherapy cycle, but at no less than 2 week intervals. Administer VARUBI without regards to meals. Table 1: Recommended Dosing Regimen of VARUBI Day 1 Day 2 Day 3 Day 4 Prevention of Nausea and Vomiting Associated with Cisplatin-Based Highly Emetogenic Cancer Chemotherapy VARUBI 180 mg as a single dose orally within 2 hours prior to initiation of chemotherapy None Dexamethasone 20 mg; 30 min prior to initiation of chemotherapy 8 mg twice daily 8 mg twice daily 8 mg twice daily 5-HT 3 receptor antagonist See the prescribing information for the co-administered 5-HT 3 receptor antagonist for appropriate dosing information. None Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Cancer Chemotherapy and Combinations of Anthracycline and Cyclophosphamide VARUBI 180 mg as a single dose orally within 2 hours prior to initiation of chemotherapy None Dexamethasone 20 mg; 30 min prior to initiation of chemotherapy None 5-HT 3 receptor antagonist See the prescribing information for the co-administered 5-HT 3 receptor antagonist for appropriate dosing information.

CYP2D6 Substrates : Rolapitant is a moderate inhibitor of CYP2D6 and significantly increases the plasma concentrations of CYP2D6 substrates for at least 28 days following single dose administration of VARUBI. Before starting VARUBI, consider if patients require: thioridazine or pimozide; if so, use an alternative antiemetic to VARUBI or an alternative to thioridazine or pimozide that is not metabolized by CYP2D6. other CYP2D6 substrates; if so, consult the prescribing information for the CYP2D6 substrate for additional information about interactions with CYP2D6 inhibitors. ( 4 , 5.1 , 7 ) 5.1 Interaction with CYP2D6 Substrates Rolapitant is a moderate inhibitor of CYP2D6. Exposure to dextromethorphan, a CYP2D6 substrate, following a single dose of rolapitant increased about 3-fold on Days 8 and Day 22. The inhibition of CYP2D6 persisted on Day 28 with a 2.3-fold increase in dextromethorphan (CYP2D6 substrate) concentrations, the last time point measured. The inhibitory effect of rolapitant on CYP2D6 is expected to persist beyond 28 days for an unknown duration following administration of VARUBI [see Drug Interactions (7) , Clinical Pharmacology (12.3) ] . Narrow Therapeutic Index Drugs (Thioridazine and Pimozide) VARUBI is contraindicated in patients taking CYP2D6 substrates with a narrow therapeutic index such as thioridazine and pimozide. Increased plasma concentrations of thioridazine and pimozide are associated with serious and/or life-threatening events of QT prolongation and Torsades de Pointes [see Contraindications (4) ] .

The following adverse reactions are discussed in greater detail in other sections of the labeling: Interaction with CYP2D6 Substrates [see Contraindications (4) , Warnings and Precautions (5.1) ] Most common adverse reactions (≥3%) are: Cisplatin Based Highly Emetogenic Chemotherapy: neutropenia, hiccups and abdominal pain. ( 6.1 ) Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide: decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infection, stomatitis and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact TerSera Therapeutics at 1-844-334-4035 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In 4 controlled clinical trials in patients receiving emetogenic cancer chemotherapy, VARUBI was given in combination with a 5-HT 3 receptor antagonist and dexamethasone. On Day 1 of Cycle 1 of chemotherapy, 1567 patients were treated with VARUBI and 1198 of these patients continued into the optional multiple cycle extension for up to 6 cycles of chemotherapy. The median number of cycles administered 180 mg of VARUBI was four. VARUBI 180 mg was administered to 1294 patients.

8.1 Pregnancy Risk Summary The limited data with VARUBI use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies, there were no adverse developmental effects observed with oral administration of rolapitant in rats and rabbits during the period of organogenesis at doses up to 1.2 times and 2.9-times, respectively, the maximum recommended human dose (MRHD) (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data The potential embryo-fetal toxicity of rolapitant was assessed in pregnant rats administered oral doses up to 22.5 mg/kg per day throughout the period of organogenesis. Rats administered doses of 13.5 or 22.5 mg/kg per day rolapitant exhibited evidence of maternal toxicity including decreased body weight gain and/or body weight loss and a concomitant decrease in food consumption during the first week of dosing.

Metabolism

Absorption Following a single oral dose administration of 180 mg VARUBI under fasting conditions to healthy subjects, rolapitant was measurable in plasma within 30 minutes and the peak plasma concentration (C max ) for rolapitant which was reached in about 4 hours and mean C max was 968 ng/mL (%CV:28%). Following multiple oral doses of 9 to 45 mg once daily of rolapitant (5% to 25% of the recommended dose) for 10 days, accumulation of rolapitant (ratio of AUC 0-24hr ) ranged from 5.0 to 5.3 fold.

There are no data on overdose with VARUBI. There is no antidote for VARUBI overdose. Discontinue VARUBI in the event of overdose, and institute general supportive measures and close observation.

• Sep 1, 2015NDANDA206500Tersera

1. 1Death14327%
2. 2Nausea7915%
3. 3Fatigue519.5%
4. 4Infusion Related Reaction407.4%
5. 5Dyspnoea346.3%
6. 6Decreased Appetite336.1%
7. 7Flushing326.0%
8. 8Diarrhoea305.6%
9. 9Thrombocytopenia295.4%
10. 10Dehydration224.1%
11. 11Vomiting224.1%
12. 12Chest Discomfort213.9%
13. 13Anaemia203.7%
14. 14Back Pain193.5%
15. 15Weight Decreased173.2%

The 10 most recently updated of 13 ClinicalTrials.gov registrations naming Rolapitant as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Cohort Study on the Prevention of Nausea and Vomiting Induced by Concurrent Chemoradiotherapy for Lung Cancer Using Rolapitant and Palonosetron
  Not yet recruiting · Interventional · 238 enrolled · Henan Cancer Hospital
  NCT07442890updated 2026-03-02
• Rolapitant as an Antiemetic in Malignant Glioma Patients Receiving Radiotherapy and Temozolomide
  Completed · Phase 2 · Interventional · 48 enrolled · Duke University
  NCT02991456updated 2023-07-11
• Rolapitant Hydrochloride in Preventing Nausea/Vomiting in Patients With Sarcoma Receiving Chemotherapy
  Terminated · Phase 2 · Interventional · 37 enrolled · M.D. Anderson Cancer Center
  NCT02732015updated 2021-08-09
• Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy
  Withdrawn · Phase 2 · Interventional · 0 enrolled · Costantine Albany
  NCT03960151updated 2019-05-22
• Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy
  Completed · Phase 3 · Interventional · 532 enrolled · Tesaro, Inc.
  NCT01499849updated 2016-05-19
• Ph 3 Safety/Efficacy Study of Rolapitant for Prevention of CINV in Subjects Receiving Moderately Emetogenic Chemotherapy
  Completed · Phase 3 · Interventional · 1,369 enrolled · Tesaro, Inc.
  NCT01500226updated 2016-03-02
• Ph3 Safety/Efficacy Study of Rolapitant for the Prevention of CINV in Subjects Receiving Highly Emetogenic Chemotherapy
  Completed · Phase 3 · Interventional · 555 enrolled · Tesaro, Inc.
  NCT01500213updated 2016-03-02
• An Open-Label, Randomized, Pivotal, Bioequivalence Study of Oral and Intravenous Rolapitant
  Completed · Phase 1 · Interventional · 138 enrolled · Tesaro, Inc.
  NCT02285647updated 2015-08-25
• An Open Label, Single Dose, Three Part Study to Assess the Effects of Rolapitant (2 mg/mL IV Solution) on the Pharmacokinetics of Digoxin; Sulfasalazine; and the Cooperstown Cocktail (Midazolam, Omeprazole, Warfarin, Caffeine, and Dextromethorphan in Healthy Subjects
  Completed · Phase 1 · Interventional · 102 enrolled · Tesaro, Inc.
  NCT02434861updated 2015-08-25
• A Phase 1, 2-Part, Single Ascending Dose Assessment of the Safety, Tolerability, and Pharmacokinetics of Rolapitant Intravenous in Healthy Volunteers
  Completed · Phase 1 · Interventional · 100 enrolled · Tesaro, Inc.
  NCT02382666updated 2015-08-25

Frequently asked questions

How does Rolapitant work?

Rolapitant is a selective and competitive antagonist of human substance P/NK1 receptors. Rolapitant does not have significant affinity for the NK2 or NK3 receptors or for a battery of other receptors, transporters, enzymes and ion channels.

What is Rolapitant used for?

According to FDA labeling, Rolapitant carries indications including: VARUBI ® is indicated in combination with other antiemetic agents 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. VARUBI is a substance P/neurokinin 1 (NK1) receptor antagonist indicated in combination with other antiemetic agents 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Rolapitant?

Rolapitant is classified as Other antiemetics, Substance P/Neurokinin-1 Receptor Antagonist, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 2D6 Inhibitors, Neurokinin 1 Antagonists, P-Glycoprotein Inhibitors, Decreased Brain Stem Substance P Activity, Decreased Kinin Activity, Emesis Suppression.

What are the brand names for Rolapitant?

Rolapitant is marketed under brand names including Varubi.

What are the contraindications for Rolapitant?

Rolapitant labeling lists contraindications including: VARUBI is contraindicated in patients taking CYP2D6 substrates with a narrow therapeutic index, such as thioridazine and pimozide. VARUBI can significantly increase the plasma concentrations of thioridazine and pimozide, which may result in QT prolongation and Torsades de Pointes [see Warnings and Precautions (5.1) ] .. Always consult the full prescribing information and a clinician.