Rolapitant

VARUBI

What it isNK1 receptor antagonist; delayed chemotherapy-induced nausea.

Why this oneA very long half-life covers the whole delayed phase from a single dose.

What limits itIt inhibits CYP2D6 for weeks after one dose, which is easily forgotten. Neutropenia; the IV form was withdrawn for anaphylaxis.

FDA-approved for

FDA dosing	Population	Start	Target	Max
Prevention of delayed nausea/vomiting with emetogenic chemotherapy (with a 5-HT3 antagonist and dexamethasone)	Adults	180 mg single dose	180 mg single dose	180 mg per chemotherapy cycle

Renal Undefined

Hepatic No adjustment for mild-moderate (Child-Pugh A/B); avoid in severe (Child-Pugh C)

Do not administer at intervals shorter than 2 weeks

180 mg as a single oral dose within 2 hours before initiation of chemotherapy on Day 1
Give in combination with dexamethasone and a 5-HT3 receptor antagonist
Administer no more frequently than every 2 weeks
Take without regard to meals

Concomitant CYP2D6 substrates with a narrow therapeutic index (thioridazine, pimozide) - risk of QT prolongation and Torsades de Pointes
Pediatric patients less than 2 years of age (irreversible impairment of sexual development and fertility in juvenile rats)

Moderate CYP2D6 inhibition persists at least 28 days after a single dose - affects thioridazine, pimozide, and other CYP2D6 substrates

Pregnancy Insufficient human data; no adverse developmental effects in animals near human exposures.

Lactation No human data; present in rat milk.

NO BOXED WARNINGS

Principal riskIt inhibits CYP2D6 for weeks after a single dose

Cost, est. cash$300–$2,500/month

Generic entry2032 est.

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability1 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk1 / 4

Legacy pregnancy categoryUnknown / historical label unavailable

Defining liabilitySedation, QT prolongation, extrapyramidal symptoms or anticholinergic toxicity vary by receptor target.

CYP2D6 inhibitor (moderate)