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rolapitant (Varubi)

 

Classes: Antiemetic Agents; NK1 Receptor Antagonists

Dosing and uses of Varubi (rolapitant)

 

Adult dosage forms and strengths

tablet

  • 90mg

 

Chemotherapy-Induced Nausea & Vomiting

Indicated in combination with other antiemetic agents (eg, dexamethasone and 5HT-3 antagonist) 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

Highly emetogenic chemotherapy

  • Day 1: Rolapitant 180 mg PO 1-2 hr before chemotherapy PLUS dexamethasone 20 mg PO 30 minutes before chemotherapy PLUS 5HT-3 antagonist according the manufacturer’s prescribing information
  • Days 2-4: Dexamethasone 8 mg PO BID

Moderately emetogenic chemotherapy

  • Day 1: Rolapitant 180 mg PO 1-2 hr before chemotherapy PLUS dexamethasone 20 mg PO 30 minutes before chemotherapy PLUS 5HT-3 antagonist according the manufacturer’s prescribing information
  • Days 2-4: 5HT-3 antagonist according the manufacturer’s prescribing information

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Varubi (rolapitant) adverse (side) effects

1-10%

Note: Adverse effects listed below only slightly exceeded control (ie, dexamethasone and 5HT-3 antagonist) in clinical trials

Decreased appetite (9%)

Neutropenia (7-9%)

Dizziness (6%)

Hiccups (5%)

Dyspnea (4%)

Urinary tract infection (4%)

Stomatitis (4%)

Anemia (3%)

Abdominal pain (3%)

 

Warnings

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

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.

 

Pharmacology of Varubi (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

 

Administration

Instructions

May take with or without food

 

Storage

Store at controlled room temperature (20-25ºC [68-77ºF])

Excursions are permitted between 15-30°C (59-86°F)