netupitant/palonosetron (oral)

General

netupitant/palonosetron (oral)

Pronunciation:
ne-too-pi-tant/pa-lone-o-se-tron


Trade Name(s)

  • Akynzeo

fosnetupitant/palonosetron (injection)

Pronunciation:
fos-ne-too-pi-tant/pa-lone-o-se-tron

Trade Name(s)

  • Akynzeo

Ther. Class.
antiemetics

Pharm. Class.
neurokinin antagonists
five ht3 antagonists

Indications

  • PO Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to highly emetogenic chemotherapy (in combination with dexamethasone).
  • IV Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (in combination with dexamethasone).

Action

  • Netupitant– Acts as a selective antagonist at substance P/neurokinin 1 (NK1) receptors in the CNS; prevents nausea and vomiting in the acute and delayed phases after chemotherapy.
  • Palonosetron– Blocks the effects of serotonin at receptor sites (selective antagonist) located in vagal nerve terminals and in the chemoreceptor trigger zones in the CNS; prevents nausea and vomiting in the acute phase.

Therapeutic Effect(s):

Decreased incidence and severity of nausea and vomiting following emetogenic chemotherapy.

Pharmacokinetics

Absorption: Netupitant– Extent of absorption following oral administration unknown;  Fosnetupitant– Following IV administration, fosnetupitant is rapidly converted to netupitant, the active component. IV administration results in complete bioavailability;  Palonosetron– 97% absorbed following oral administration.

Distribution: Netupitant, fosnetupitant, and palonosetron– Extensively distributed to tissues.

Protein Binding: Netupitant– >99.5%;  Fosnetupitant– 92–95%.

Metabolism and Excretion: Netupitant– Primarily metabolized in the liver (mostly by CYP3A4, and to a lesser extent by CYP2C9 and CYP2D6) to three metabolites that have anti-emetic activity; <1% excreted unchanged in urine;  Palonosetron– 50% metabolized (mostly by CYP2D6, and to a lesser extent by CYP3A4 and CYP1A2); 40% excreted unchanged in urine.

Half-life: Netupitant– 80 hr;  Palonosetron– 40 hr.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
POwithin 1 hr5 hrunknown
IVrapid30 minunknown

Contraindication/Precautions

Contraindicated in:

  • Cross-sensitivity may occur with other 5–HT3  antagonists;
  • Severe hepatic or renal impairment.

Use Cautiously in:

  • OB:  Safety not established in pregnancy;
  • Lactation: Safety not established in breastfeeding;
  • Pedi:  Safety and effectiveness not established in children
  • Geri:  Consider age-related ↓ in renal, hepatic and cardiac function, concurrent disease states and drug therapies.

Adverse Reactions/Side Effects

Derm: erythema

GI: constipation, dyspepsia

Neuro: fatigue, headache, weakness

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), SEROTONIN SYNDROME

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

Interactions

Drug-Drug

Route/Dosage

Netupitant/Palonosetron

PO (Adults): Highly emetogenic chemotherapy (included cisplatin-based)– One capsule (netupitant 300 mg/palonosetron 0.5 mg) 1 hr before chemotherapy on Day 1.  Anthracycline and cyclophosphamide–based chemotherapy and other chemotherapy not considered highly emetogenic– One capsule (netupitant 300 mg/palonosetron 0.5 mg) 1 hr before chemotherapy on Day 1.

Fosnetupitant/Palonosetron

IV (Adults): Highly emetogenic chemotherapy (included cisplatin-based)– Fosnetupitant 235 mg/palonosetron 0.25 mg administered 30 min before chemotherapy on Day 1.

Availability

Capsules: netupitant 300 mg/palonosetron 0.5 mg

Lyophilized powder for injection: netupitant 235 mg/palonosetron 0.25 mg/vial

Solution for injection: netupitant 235 mg/palonosetron 0.25 mg/20 mL

Assessment

  • Assess patient for nausea, vomiting, abdominal distention, and bowel sounds prior to and following administration.
  • Assess for serotonin syndrome (mental changes [agitation, hallucinations, delirium, coma], autonomic instability [tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia], neuromuscular aberrations [tremor, rigidity, myoclonus, hyperreflexia, incoordination], seizure, and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).

Lab Test Considerations:

May cause transient ↑ in serum bilirubin, AST, and ALT levels.

Implementation

  • For highly emetogenic chemotherapy,  administer with dexamethasone PO 12 mg 30 min prior to chemotherapy on day 1 and 8 mg PO on days 2 and 4.  For chemotherapy not considered highly emetogenic,  administer dexamethasone 30 min prior to chemotherapy on Day 1 (day 2 and 4 not needed).
  • PO Administer netupitant/palonosetron 1 hr prior to start of chemotherapy without regard to food.

IV Administration

  • Intermittent Infusion:   Reconstitution: Reconstitute with 20 mL D5W or 0.9% NaCl into vial along vial wall to prevent foaming; swirl gently to mix. Prepare an infusion vial or bag filled with 30 mL D5W or NaCl. Withdraw entire volume of reconstituted solution and transfer it into infusion vial or bag containing 30 mL of D5W or 0.9% NaCl for a total volume of 50 mL. Gently invert bag until complete dissolution. Solution is clear; do not administer solutions that are cloudy, discolored or contain particulate matter. Total time from reconstitution to the start of infusion should not exceed 24 hrs. Store reconstituted solution and final diluted solution at room temperature. Dexamethasone can be given concomitantly or added to solution.
  • Rate: Infuse over 30 min starting 30 min before chemotherapy. Flush line with 0.9% NaCl at end of infusion.
  • Y-Site Compatibility:
    • dexamethasone
  • Y-Site Incompatibility:
    • solutions containing calcium
    • solutions containing magnesium
    • lactated Ringer's solution
    • MORE...
      • Hartmann's solution

Patient/Family Teaching

  • Instruct patient to take netupitant/palonosetron as directed. Advise patient to read  Patient Information  prior to starting therapy and with each Rx refill in case of changes.
  • Advise patient to notify health care professional promptly if signs and symptoms of anaphylaxis (shortness of breath, rash, hives, swelling of mouth, throat, and lips) or serotonin syndrome occur.
  • 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.
  • Rep:  May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy.

Evaluation/Desired Outcomes

Decrease in frequency and severity of nausea and vomiting.

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