Varubi (rolapitant HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Rolapitant hydrochloride, a highly selective and competitive antagonist at substance P/neurokinin-1 (NK1) receptors, is an antiemetic.
Rolapitant is a selective and competitive antagonist of human substance P/neurokinin-1 (NK1) receptors. Rolapitant does not have substantial affinity for the NK2 or NK3 receptors or for a battery of other receptors, transporters, enzymes, and ion channels. Rolapitant crosses the blood-brain barrier and occupies NK1 receptors in the brain.
The drug demonstrates a dose-dependent increase in mean NK1 receptor occupancy in the dose range of 4.5-180 mg. At a rolapitant dose of 180 mg, the mean NK1 receptor occupancy was 73% in the striatum at 120 hours after the dose was administered to healthy individuals. However, the relationship between NK1 receptor occupancy and clinical efficacy of rolapitant is yet to be determined.
Rolapitant has a high bioavailability (greater than 90%) and is highly bound to plasma proteins (99.8%). Peak plasma concentrations are attained in approximately 4 hours following administration of a single oral dose of 180 mg under fasting conditions in healthy individuals. Accumulation of rolapitant is approximately 5-fold following multiple oral doses of 9-45 mg once daily.
Systemic exposure of rolapitant increases in a dose-proportional manner over the dose range of 4.5 to 180 mg. Following single oral doses of rolapitant, the mean terminal half-life ranges from 169 to 183 hours (approximately 7 days) and is independent of dose. Rolapitant is metabolized principally by cytochrome P-450 (CYP) 3A4 to a major active metabolite (M19).
Formation of M19 is relatively slow resulting in a delayed median time to peak plasma concentration of 120 hours (range: 24-168 hours); mean half-life of M19 is 158 hours. Exposure ratio of M19 to rolapitant is approximately 50% in plasma. Following administration of a single oral 180-mg radiolabeled dose of rolapitant, 14.2% (range 9-20%) and 73% (range 52-89%) of the dose is recovered in the urine and feces, respectively, over 6 weeks.
In pooled samples collected over 2 weeks, 8.3% of the dose is recovered in the urine principally as metabolites, and 37.8% of the dose is recovered in the feces principally as unchanged drug. Unchanged rolapitant or M19 was not found in the pooled urine sample. Age, sex, and race have no substantial effect on the pharmacokinetics of rolapitant.
USES: Rolapitant is used with other medications to help prevent delayed nausea and vomiting caused by cancer drug treatment (chemotherapy). It works by blocking one of the body's natural substances (substance P/neurokinin 1) that causes vomiting. This drug is not recommended for use in children younger than 2 years due to risk of serious side effects.
Generic name: rolapitant HCl
Pronunciation: (roe-LA-pi-tant)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Varubi
Indications
The following indications are listed for Varubi:
- Prevention Of Cancer Chemotherapy-Induced Nausea And Vomiting
Also known as: Cancer Chemotherapy-Induced N & V Prophylaxis.
Dosing
Rolapitant is administered orally on day 1 as part of a 4-day regimen that includes a 5-HT3 receptor antagonist and dexamethasone.
Rolapitant is commercially available as the hydrochloride salt; dosage is expressed in terms of rolapitant.
Rolapitant is administered prior to initiation of each chemotherapy cycle, but at intervals of no less than 2 weeks. Rolapitant should be administered within 2 hours prior to initiation of chemotherapy.
Rolapitant is administered orally without regard to meals.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Rolapitant is metabolized by cytochrome P-450 (CYP) 3A4 isoenzyme. The drug does not inhibit or induce CYP3A4 when given as a single oral dose. Rolapitant is a moderate inhibitor of CYP2D6, an inhibitor of P-glycoprotein (P-gp), and an inhibitor of breast cancer resistance protein (BCRP).
In vitro studies suggest that rolapitant is not an inhibitor of CYP1A2 or CYP2E1. Rolapitant inhibits CYP2A6; however, clinically meaningful interaction via inhibition of CYP2A6 is unlikely.
Oral rolapitant is unlikely to inhibit organic anion transporting polypeptides (OATP) 1B1 and 1B3, organic anion transporters (OAT1 and OAT3), organic cation transporter (OCT) 2, and multidrug and toxin extrusion proteins (MATE1 and MATE2K).
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Concurrent therapy with CYP2D6 substrates with a narrow therapeutic index such as pimozide or thioridazine.
*Pediatric patients <2 years of age.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Cisplatin-based highly emetogenic chemotherapy: Adverse effects reported in >=3% of patients include neutropenia, hiccups, and abdominal pain.
Moderately emetogenic chemotherapy and combinations of anthracycline and cyclophosphamide: Adverse effects reported in >=3% of patients include decreased appetite, neutropenia, dizziness, dyspepsia, urinary tract infection, stomatitis, and anemia.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of rolapitant have not been established in pediatric patients. Rolapitant is contraindicated in pediatric patients <2 years of age.
Administration of rolapitant to juvenile rats at the human age equivalent of birth to 2 years resulted in abnormal ovarian and uterine development, early sexual development in female rats, delayed sexual development in male rats, and impaired fertility.
Data are insufficient to inform a drug-associated risk of adverse developmental outcomes when rolapitant is used in pregnant women. Animal reproduction studies revealed no teratogenic or embryofetal effects when the drug was administered to pregnant rats and rabbits during the period of organogenesis; however, maternal toxicity, including reduced body weight gain and/or body weight loss and a concomitant reduction in food consumption during the first week of dosing in rats, was observed.
It is not known whether rolapitant is distributed in human milk or whether the drug has any effects on the breastfed infant or on milk production. Rolapitant was found to distribute into the milk of lactating rats.
Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for rolapitant and any potential adverse effects on the breastfed infant from the drug or underlying maternal condition or the use of concomitant chemotherapy.
The manufacturer makes no special dosage recommendations at this time.
Of the 1294 patients who received rolapitant in clinical studies, 25% were >=65 years of age, and 5% were >=75 years of age. No overall differences in safety and efficacy were observed between geriatric patients and younger adults. However, the possibility of greater sensitivity of some older patients cannot be ruled out.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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