Varubi

VARUBI- rolapitant hydrochloride tablet
TerSera Therapeutics LLC

1 INDICATIONS AND USAGE

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.

2 DOSAGE AND ADMINISTRATION

The recommended dosage of VARUBI in adults in combination with a 5-HT3 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-HT3 receptor antagonist See the prescribing information for the co-administered 5-HT3 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-HT3 receptor antagonist See the prescribing information for the co-administered 5-HT3 receptor antagonist for appropriate dosing information. See the prescribing information for the co-administered 5-HT3 receptor antagonist for appropriate dosing information.

3 DOSAGE FORMS AND STRENGTHS

Tablets: 90 mg rolapitant; film-coated, blue capsule shaped, debossed with T0101 on one side and 100 on the other side.

4 CONTRAINDICATIONS

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)].

VARUBI is contraindicated in pediatric patients less than 2 years of age because of irreversible impairment of sexual development and fertility observed in juvenile rats at clinically relevant dosages [see Use in Specific Populations (8.4)].

5 WARNINGS AND PRECAUTIONS

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)].

Before starting treatment with VARUBI, consider whether patients require treatment with thioridazine or pimozide. If patients require these drugs, use an alternative antiemetic to VARUBI or an alternative to thioridazine or pimozide that is not metabolized by CYP2D6.

Other Drugs

VARUBI can also increase plasma concentrations of other CYP2D6 substrates for at least 28 days following administration of VARUBI and may result in adverse reactions.

Before starting treatment with VARUBI, consult the prescribing information for CYP2D6 substrates to obtain additional information about interactions with CYP2D6 inhibitors.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

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-HT3 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.

In Cycle 1 adverse reactions were reported in approximately 7% of patients treated with VARUBI compared with approximately 6% of patients treated with control therapy. The most common adverse reactions reported with an incidence of ≥3% and greater than control are listed in Table 2 and Table 3.

Table 2: Most Common Adverse Reactions in Patients Receiving Cisplatin-Based Highly Emetogenic Chemotherapy (Cycle 1)*

* all reactions occurring at ≥3% in the VARUBI group and for which the rate for VARUBI exceeds the rate for control

VARUBI Regimen (VARUBI, Dexamethasone, and5-HT 3 Receptor Antagonist) N = 624 Control (Placebo, Dexamethasone, and5-HT 3 Receptor Antagonist) N = 627
Neutropenia 9% 8%
Hiccups 5% 4%
Abdominal Pain 3% 2%
Table 3: Most Common Adverse Reactions in Patients Receiving Moderately Emetogenic Chemotherapy and Combinations of Anthracycline and Cyclophosphamide (Cycle 1)*

*all reactions occurring at ≥3% in the VARUBI group and for which the rate for VARUBI exceeds the rate for control.

VARUBI Regimen (VARUBI, Dexamethasone, and5-HT 3 Receptor Antagonist) N = 670 Control (Placebo, Dexamethasone, and5-HT 3 Receptor Antagonist) N = 674
Decreased appetite 9% 7%
Neutropenia 7% 6%
Dizziness 6% 4%
Dyspepsia 4% 2%
Urinary tract infection 4% 3%
Stomatitis 4% 2%
Anemia 3% 2%

Adverse reactions in the multiple-cycle extensions of highly and moderately emetogenic chemotherapy studies for up to 6 cycles of chemotherapy were generally similar to that observed in Cycle 1.

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