Drug information of rolapitant

rolapitant

Drug group:

Rolapitant is used together with other medicines to prevent nausea and vomiting caused by cancer chemotherapy.

Mechanism of effect

Rolapitant is an orally active, highly selective Neurokinin-1 Receptor (NK1R) antagonist. NK1 receptors are located primarily in the gut and central nervous system and are activated by Substance P following chemotherapy administration. By binding to the NK1 receptor, rolapitant prevents binding of its ligand Substance P, which is released in the gut following chemotherapy administration.

Pharmacokinetics

Absorption:
    Following administration of rolapitant, plasma concentrations reached peak levels in about 4 hours.
Volume of distribution:
   460 L
Protein binding:
    Rolapitant is 99.8% bound to human plasma protein.
Metabolism:
    Rolapitant is metabolized primarily by Cytochrome P450 enzyme 3A4 (CYP3A4) to its major active and circulating metabolite M19 (C4-pyrrolidine-hydroxylated rolapitant).
 
Route of elimination:
    Rolapitant was found to be 14.2% renally excreted and 73% fecally excreted. Of the fecally excreted compounds
Half-life:
    Mean terminal half life ranged from 169 to 183 hours (~7 days).

Dosage

Highly emetogenic chemotherapy
  • Includes cisplatin-based highly emetogenic cancer chemotherapy
  • Day 1
    • Rolapitant 180 mg PO 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
  • Includes anthracycline and cyclophosphamide combinations
  • Day 1
    • Rolapitant 180 mg PO 2 hr before chemotherapy PLUS
    • Dexamethasone 20 mg PO 30 minutes before chemotherapy PLUS
    • 5HT-3 antagonist according the manufacturer’s prescribing information

Alerts

Coadministration with CYP2D6 substrates with a narrow therapeutic index (eg, thioridazine and pimozide)
Hypersensitivity to any component of the product
<2 years of age

Pregnancy level

Limited data in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcome

Breast feeding warning

Unknown if distributed in human breast milk and no data on effects on breastfed infant or on milk production
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 underlying maternal condition

Related drugs

Aprepitant , fosaprepitant , Netupitant


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