Varubi

Contraindications

Coadministration with thioridazine, a CYP2D6 substrate; significant increase in plasma concentrations of thioridazine may result in QT prolongation and torsades de pointes

Cautions

Coadministration with long-term administration of strong CYP3A4 inducers may significantly decrease rolapitant efficacy

CYP2D6 substrates

• Rolapitant’s inhibitory effect on CYP2D6 lasts at least 7 days and possibly longer after a single dose
• Contraindicated with thioridazine (see Contraindications)
• Avoid use in patients taking pimozide (a CYP2D6 substrate); increased pimozide plasma concentrations may result in QT prolongation
• Monitor for adverse reactions if coadministration with other CYP2D6 substrates with a narrow therapeutic index cannot be avoided

Pregnancy

No available data on use in pregnant women

Animal data

• In animal reproduction studies, no teratogenic or embryo-fetal effects were observed with oral administration 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)

Lactation

Unknown if distributed in human breast milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Keep all appointments with your doctor.

Do not let anyone else take your medication.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Varubi, there are no specific foods that you must exclude from your diet when receiving this medication.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The recommended dose of Varubi is 180 mg 1 to 2 hours prior to the start of chemotherapy.

Take Varubi with dexamethasone and a 5-HT3 receptor antagonist. 

Rolapitant has the following uses:

Rolapitant 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.1

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling.1

Advise patients to tell their healthcare provider when they start or stop taking any concomitant medications. Rolapitant is a moderate CYP2D6 inhibitor and can increase plasma concentrations of CYP2D6 substrates if they are co-administered. The inhibitory effect of rolapitant on CYP2D6 lasts at least 7 days and may last longer than 7 days after a single dose.1

Use Varubi as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Follow how to take this medicine as you have been told by your doctor. Do not use more than you were told to use.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Hiccups.
• Belly pain.
• Not hungry.
• Dizziness.
• Upset stomach.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Effect of Varubi on Other Drugs

Rolapitant is not an inhibitor or inducer of CYP3A4. Therefore, no dosage adjustment for dexamethasone (CYP3A4 substrate) is needed when co-administered with Varubi [see Dosage and Administration (2)].

Rolapitant is a moderate CYP2D6 inhibitor, an inhibitor of Breast-Cancer-Resistance Protein (BCRP) and an inhibitor of P-glycoprotein (P-gp) [see Clinical Pharmacology (12.3)].

CYP2D6 Substrates with a Narrow Therapeutic Index: Increased plasma concentration of CYP2D6 substrates may result in potential adverse reactions. A 3-fold increase in the exposure of dextromethorphan, a CYP2D6 substrate, was observed 7 days after a single dose of Varubi. The duration of CYP2D6 inhibition was not studied beyond 7 days and may last longer [see Clinical Pharmacology (12.3)]. Concomitant use with Thioridazine is contraindicated [see Contraindications (4)]. Avoid use of Varubi with pimozide [see Warnings and Precautions (5.1)]. Monitor for QT prolongation if concomitant use with pimozide cannot be avoided. Monitor for adverse reactions if concomitant use with CYP2D6 substrates with a narrow therapeutic index cannot be avoided.

BCRP Substrates with a Narrow Therapeutic Index (e.g., Methotrexate, topotecan, or irinotecan): Increased plasma concentrations of BCRP substrates may result in potential adverse reactions. Monitor for adverse reactions related to the concomitant drug if use of Varubi cannot be avoided. Use the lowest effective dose of rosuvastatin (see prescribing information for additional information on recommended dosing).

P-gp Substrates with a Narrow Therapeutic Index: Increased plasma concentrations of digoxin, or other P-gp substrates, may result in potential adverse reactions [see Clinical Pharmacology (12.3)]. Monitor for increased digoxin concentrations. Monitor for adverse reactions if concomitant use of Varubi with other P-gp substrates with a narrow therapeutic index cannot be avoided.

Effect of Other Drugs on Varubi

Strong CYP3A4 Inducers (e.g., rifampin): significantly reduced plasma concentrations of rolapitant can decrease the efficacy of Varubi; avoid use of Varubi in patients who require chronic administration of such drugs.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Drug Interactions

Advise patients to tell their healthcare provider when they start or stop taking any concomitant medications. Varubi is a moderate CYP2D6 inhibitor and can increase plasma concentrations of CYP2D6 substrates if they are co-administered. The inhibitory effect of Varubi on CYP2D6 lasts at least 7 days and may last longer than 7 days after a single dose [see Contraindications (4), Warnings and Precautions (5.1), Drug Interactions (7)].

Manufactured for: TESARO, Inc. 1000 Winter St., #3300, Waltham, MA 02451

Varubi (rolapitant) blocks the actions of chemicals in the body that trigger nausea and vomiting.

Varubi is used together with other medicines to prevent nausea and vomiting caused by cancer chemotherapy.

Varubi may also be used for purposes not listed in this medication guide.

You should not use Varubi if you are allergic to rolapitant.

Some medicines can cause unwanted or dangerous effects when used with Varubi. Your doctor may need to change your treatment plan if you use any of the following drugs:

• pimozide (Orap); or

• thioridazine (Mellaril).

To make sure this medicine is safe for you, tell your doctor if you have:

• liver disease.

It is not known whether Varubi will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether rolapitant passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Varubi is not approved for use by anyone younger than 18 years old.

Other drugs may interact with rolapitant, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. For at least 7 days after you take Varubi, it could affect other medicines you are using.

Applies to rolapitant: oral tablet

Along with its needed effects, rolapitant (the active ingredient contained in Varubi) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking rolapitant:

• Black, tarry stools
• chills
• cough
• fever
• lower back or side pain
• painful or difficult urination
• pale skin
• shortness of breath
• sore throat
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

• Bladder pain
• bloody or cloudy urine
• difficult, burning, or painful urination
• frequent urge to urinate
• troubled breathing with exertion

Some side effects of rolapitant may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Decreased appetite
• dizziness

• Acid or sour stomach
• belching
• heartburn
• hiccups
• indigestion
• stomach discomfort, upset, or pain