rolapitant

General

Pronunciation:
rol-ap-i-tant


Trade Name(s)

  • Varubi

Ther. Class.
antiemetics

Pharm. Class.
neurokinin antagonists

Indications

To prevent delayed nausea and vomiting associated with initial/repeat courses of emetogenic cancer chemotherapy (to be used with dexamethasone and a 5–HT3  antagonist).

Action

Acts as a selective antagonist at substance P/neurokinin 1 (NK1 ) receptors in the brain.

Therapeutic Effect(s):

  • Decreased nausea and vomiting associated with chemotherapy.
  • Augments the antiemetic effects of dexamethasone and 5-HT3  antagonists.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: 99.8%

Metabolism and Excretion: Mostly metabolized, primarily by CYP3A4; one metabolite, C4–pyrrolidine-hydroxylated rolapitant (M19) has antiemetic activity. Excretion is mainly via hepato/biliary elimination. 14% excreted in urine (8% as metabolites), 73% in feces (38% as unchanged drug).

Half-life:  Rolapitant– 7 days;  M19– 7 days.

TIME/ACTION PROFILE (blood levels)

ROUTEONSETPEAKDURATION
POwithin 30 min4 hrunknown

Contraindication/Precautions

Contraindicated in:

  • Concurrent use of CYP2D6 substrates with a narrow therapeutic index.

Use Cautiously in:

  • Concurrent use of other CYP2D6 substrates;
  • Severe hepatic impairment (avoid if possible; if unavoidable, monitor carefully);
  • OB:  Safety not established;
  • Lactation: Weigh maternal benefits against risks to the infant;
  • Pedi:  Safety and effectiveness not established;
  • Geri:  May be more sensitive to drug effects.

Adverse Reactions/Side Effects

CV: dizziness

GI: abdominal pain, ↓ appetite, dyspepsia, hiccups, stomatitis

GU: ↓ fertility (females)

Hemat: anemia, neutropenia

Misc: infusion reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • ↑ levels and risk of serious cardiac toxicity with  CYP2D6 substrates  with a narrow therapeutic index, including  thioridazine  and  pimozide ; concurrent use contraindicated.
  • May ↑ levels and risk of toxicity of other  CYP2D6 substrates  for an extended period of time (≥28 days).
  • May ↑ levels and risk of toxicity of Breast-Cancer-Resistance Protein (BCRP) substrates, includingirinotecan, methotrexate,  rosuvastatin  and  topotecan ; dose reduction may be necessary.
  • May ↑ levels and risk of toxicity of P-glycoprotein substrates, including digoxin ; avoid concurrent use with P-gp substrates with a narrow therapeutic index.
  • Strong CYP3A4 inducers, including rifampin , ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage

PO  (Adults)  180 mg within 2 hr prior to start of chemotherapy.

Availability

Tablets: 90 mg

Assessment

  • Assess nausea, vomiting, appetite, bowel sounds, and abdominal pain prior to and following administration.

Lab Test Considerations:

May cause ↓ WBC.

Potential Diagnoses

Implementation

  • PO  Administer 2 hr before starting chemotherapy without regard to food. Due to long action, administered no more frequently than once every 14 days. Given with dexamethasone and a 5-HT3  antagonist.
  • Intermittent Infusion:  Administer 2 hr before starting chemotherapy. Solution is translucent white and does not need to be shaken; do not inject solutions that are discolored or contain particulate matter. Insert a vented IV set through septum of vial and use immediately; do not dilute. Infuse through a Y-site of 0.9% NaCl. D5W, D5/LR, or LR.
  • Rate: Infuse over 30 min.

Patient/Family Teaching

  • Instruct patient to take rolapitant as directed. Direct patient to read the  Patient Package Insert  before starting therapy and each time Rx renewed in case of changes.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise patient and family to use general measures to decrease nausea (begin with sips of liquids and small, nongreasy meals; provide oral hygiene; remove noxious stimuli from environment).
  • Advise patient to notify health care professional if pregnancy is planned or suspected, or if breast feeding.

Evaluation/Desired Outcomes

Decreased delayed nausea and vomiting associated with emetogenic chemotherapy.

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