rolapitant

Therapeutic Classification: antiemetics

Pharmacologic Classification: neurokinin antagonists

Indications ⬆ ⬇

REMS

To prevent delayed nausea and vomiting associated with initial/repeat courses of emetogenic cancer chemotherapy (in combination with dexamethasone and a 5-HT₃ antagonist).

Action ⬆ ⬇

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

Therapeutic effects:

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/Excretion: Mostly metabolized, primarily by the CYP3A4 isoenzyme; one metabolite, C4–pyrrolidine-hydroxylated rolapitant (M19), has antiemetic activity. Excretion is mainly via hepatic/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 ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	within 30 min	4 hr	unknown

Contraind./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 in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be more sensitive to drug effects.

Adv. Reactions/Side Effects ⬆ ⬇

CV: dizziness

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

GU: ↓fertility (females)

Hemat: anemia, neutropenia

Misc: infusion reactions

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, including irinotecan, methotrexate, rosuvastatin, and topotecan; dose reduction may be necessary.
May ↑ levels and risk of toxicity of P-glycoprotein (P-gp) substrates, including digoxin; avoid concurrent use with P-gp substrates with a narrow therapeutic index.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

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

Availability ⬆ ⬇

Assessment ⬆ ⬇

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

Lab Test Considerations:

May cause ↓ WBC.

Implementation ⬆ ⬇

PO: Administer 2 hr before starting chemotherapy without regard to food. Due to long action, administer no more frequently than once every 14 days. Given with dexamethasone and a 5-HT₃ antagonist.

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).
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. May impair fertility in females; impairment is reversible.

Evaluation/Desired Outcomes ⬆ ⬇

Decreased delayed nausea and vomiting associated with emetogenic chemotherapy.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

69656- Tesaro, Inc.
- 69656-101- Varubi
  - 69656-101-02- 2 TABLET in 1 BLISTER PACK (69656-101-02)

69656- Tesaro, Inc.
- 69656-102- Varubi
  - 69656-102-10- 1 VIAL, SINGLE-DOSE in 1 CARTON (69656-102-10) > 92.5 mL in 1 VIAL, SINGLE-DOSE

70720- TerSera Therapeutics LLC
- 70720-101- Varubi
  - 70720-101-02- 2 TABLET in 1 BLISTER PACK (70720-101-02)

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Pronunciation ⬇

Classifications ⬆ ⬇