VARUBI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VARUBI (VARUBI).
Selective neurokinin-1 (NK1) receptor antagonist; inhibits substance P binding, reducing chemotherapy-induced nausea and vomiting.
| Metabolism | Primarily metabolized by CYP3A4; minor involvement of CYP2C8 and CYP2D6. Active metabolite (hydroxyrolapitant) formed via CYP3A4. |
| Excretion | Primarily hepatic metabolism via CYP3A4, with minimal renal excretion (approximately 15% as unchanged drug and metabolites in urine). Approximately 70% of the dose is eliminated in feces, primarily as metabolites. Biliary excretion of parent drug and metabolites contributes to fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 40 hours (range 30-50 hours). This long half-life supports a single-dose regimen for prevention of delayed chemotherapy-induced nausea and vomiting. |
| Protein binding | Approximately 96% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution at steady state is 70 L (approximately 1.0 L/kg for a 70 kg adult), indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral bioavailability is approximately 59% due to first-pass metabolism. Absolute bioavailability not established for IV formulation (100% systemic availability with IV administration). |
| Onset of Action | Oral administration: onset of antiemetic effect occurs within 1-2 hours; IV administration: onset within 30 minutes, reaching peak effect by 2 hours. |
| Duration of Action | Clinical efficacy lasts up to 5 days following a single dose, covering both acute and delayed phases of chemotherapy-induced nausea and vomiting. The long half-life ensures sustained NK1 receptor antagonism. |
180 mg orally once daily, taken on days 1, 2, and 3 of the chemotherapy cycle; administer 1 hour before chemotherapy on day 1.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Limited data for severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | For Child-Pugh A or B: no adjustment. For Child-Pugh C: not recommended (no data). |
| Pediatric use | Safety and efficacy not established; no approved pediatric dosing. |
| Geriatric use | No specific dose adjustment recommended; but monitor for increased adverse effects due to age-related renal/hepatic decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VARUBI (VARUBI).
| Breastfeeding | It is not known whether rolapitant is excreted in human milk. In lactating rats, rolapitant and its metabolites were detected in milk. Because many drugs are excreted in human milk, caution should be exercised when VARUBI is administered to a nursing woman. The milk-to-plasma (M/P) ratio for rolapitant in humans is unknown. |
| Teratogenic Risk | Rolapitant (VARUBI) is classified as Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of harm to the fetus was observed at exposures up to 10 times the human exposure at the recommended dose. However, because animal studies are not always predictive of human response, VARUBI should be used during pregnancy only if clearly needed. Specific fetal risks by trimester have not been established. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to rolapitant or any component of the formulation.","Concomitant use with strong CYP3A4 inducers (e.g., rifampin)."]
| Precautions | ["Risk of reduced efficacy with strong CYP3A4 inducers (e.g., rifampin).","Potential for increased adverse effects with strong CYP3A4 inhibitors (e.g., ketoconazole).","Hypersensitivity reactions including anaphylaxis reported.","Not recommended for prevention of nausea and vomiting due to highly emetogenic chemotherapy (HEC) as sole agent."] |
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| Fetal Monitoring | No specific maternal or fetal monitoring is routinely required with VARUBI use. Standard prenatal care and monitoring are recommended. If used in pregnancy, clinicians should monitor for adverse effects common to the drug (e.g., headache, fatigue, dyspepsia) and assess maternal and fetal well-being as per routine obstetrical practice. |
| Fertility Effects | There are no data on the effect of rolapitant on human fertility. In animal studies, no adverse effects on fertility were observed in male or female rats at exposures up to 10 times the human exposure at the recommended dose. Based on animal data, rolapitant is not expected to impair fertility in humans at clinically relevant doses. |