Rolapitant

Mechanism of Action

Selective, long-acting neurokinin receptor (NK)-1 antagonist

NK-1 receptors are highly concentrated in the vomiting center of the brain and bind a neurokinin termed substance P; activation of NK-1 receptors by substance P plays a central role in eliciting chemotherapy-induced nausea and vomiting

Blocking the interaction of substance P at the NK-1 receptor, NK-1 receptor antagonists improve the management of nausea and vomiting

Absorption

Peak plasma time: 4 hr; 120 hr (active metabolite)

Peak plasma concentration: 968 ng/mL

Distribution

Protein bound: 99.8%

Vd: 387 L

Metabolism

Metabolized primarily by CYP3A4 to form a major active metabolite, M19 (C4­pyrrolidine-hydroxylated rolapitant)

Elimination

Half-life: 169-183 hr

Excretion: 73% feces; 14.2% urine

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• headache with chest pain and severe dizziness, fainting, fast or pounding heartbeats;
• pain or burning when you urinate;
• low red blood cells (anemia)--pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
• low white blood cell counts--fever, swollen gums, painful mouth sores, pain when swallowing, skin sores, cold or flu symptoms, cough, trouble breathing.

Common side effects may include:

• hiccups;
• mouth sores;
• dizziness;
• indigestion, stomach pain, loss of appetite; or
• low blood cell counts.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

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 rolapitant, it could affect other medicines you are using.

Rolapitant is a prescription medication used with other medications to help prevent nausea and vomiting that happens later with certain chemotherapy. 

It belongs to a group of drugs called antiemetics. These work to block the receptor that plays a big part in nausea and vomiting induced by certain cancer chemotherapies. 

Rolapitant is available in tablet form and is typically taken before you receive your chemotherapy. It can be taken with or without food. 

Common side effects include low white blood cell count, hiccups, decreased appetite and dizziness.

Do not drive or operate heavy machinery until you know how this medication affects you. 

Rolapitant may be found in some form under the following brand names:

• Varubi

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take: 

• thioridazine. Taking rolapitant with thioridazine can cause serious or life-threatening heart rhythm changes.
• pimozide (Orap). Your doctor will have to monitor you for prolongation of your QTc interval if you have to take both medications.
• other medications that use the enzyme CYP2D6 such as dextromethorphan
• BCRP substrates with a narrow therapeutic index such as methotrexate, topotecan, or irinotecan
• P-gp substrates with a narrow therapeutic index such as digoxin

Serious side effects have been reported with rolapitant including the following:

Rolapitant can change the level of some medicines in your blood. Serious or life-threatening reactions, including heart rhythm changes, may occur if rolapitant is used with certain other medicines.

Do not take rolapitant if you are:

• allergic to rolapitant or any of its ingredients
• taking pimozide or thioridazine

Tell your doctor if you are pregnant or plan to become pregnant.

There is no available data on rolapitant use in pregnant women. In animal reproduction studies, there were no teratogenic or embryo-fetal effects observed with rolapitant.

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

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

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

If you take too much rolapitant, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

• Varubi

CrCl 30 to 90 mL/minute: There are 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).

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

After administration of a single oral dose equivalent to 22.5 mg/kg rolapitant free base, the mean milk/plasma radioactivity concentration ratios 1 to 48 hours post-dose in lactating rats were 1.24 to 3.25. Based on average daily consumption of milk (2 mL/day) and the maximum milk radioactivity determined, offspring exposure is expected to be 0.32% of the dose.

Benefit should outweigh risk. Excreted into human milk: Unknown Excreted into animal milk: Yes