netupitant/palonosetron (oral)

REMS

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).

Contraind./Precautions

⬆ ⬇

Contraindicated in:

Cross-sensitivity may occur with other 5-HT₃ antagonists;
Severe renal impairment;
Severe hepatic 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 in older adults.

Adv. Reactions/Side Effects

⬆ ⬇

Derm: erythema

GI: constipation, dyspepsia

Neuro: fatigue, headache, weakness

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), SEROTONIN SYNDROME

Interactions

⬆ ⬇

Drug-drug:

Netupitant is a moderate inhibitor of CYP3A4 and can ↑ levels of drugs that are CYP3A4 substrates, including alprazolam, cyclophosphamide, dexamethasone, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, midazolam, erythromycin, paclitaxel, triazolam, vinorelbine, vinblastine, and vincristine; avoid concomitant use for one wk; if avoiding use not feasible, ↓ dose of CYP3A4 substrate.
CYP3A4 inducers, including rifampin, may ↓ netupitant levels and effectiveness; avoid concurrent use.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, buspirone, tramadol, amphetamines, and triptans, ↑ risk of serotonin syndrome

Availability

⬆ ⬇

Capsules: netupitant 300 mg/palonosetron 0.5 mg
Solution for injection: fosnetupitant 235 mg/palonosetron 0.25 mg/20 mL

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.

US Brand Names

⬆ ⬇

netupitant/palonosetron (oral): Akynzeo,

fosnetupitant/palonosetron (injection): Akynzeo

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 effects:

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

Classifications

⬆ ⬇

Therapeutic Classification: antiemetics

Pharmacologic Classification: neurokinin antagonists, five ht3 antagonists

Pharmacokinetics

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Netupitant

Absorption: Extent of absorption following oral administration unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: >99.5%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme and to a lesser extent by the CYP2C9 and CYP2D6 isoenzymes to three metabolites that have antiemetic activity; <1% excreted unchanged in urine.

Half-Life: 80 hr.

Fosnetupitant

Absorption: Following IV administration, fosnetupitant is rapidly converted to netupitant, the active component. IV administration results in complete bioavailability.

Distribution: Extensively distributed to tissues.

Protein Binding: 92–95%.

Metabolism/Excretion: Netupitant is primarily metabolized in the liver via the CYP3A4 isoenzyme and to a lesser extent by the CYP2C9 and CYP2D6 isoenzymes to three metabolites that have antiemetic activity; <1% excreted unchanged in urine.

Half-Life: Netupitant: 80 hr.

Palonosetron

Absorption: 97% absorbed following oral administration. IV administration results in complete bioavailability.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: 50% metabolized by the liver (mostly by the CYP2D6 isoenzyme) and to a lesser extent by the CYP3A4 and CYP1A2 isoenzymes; 40% excreted unchanged in urine.

Half-Life: 40 hr.

Time/Action Profile

⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	within 1 hr	5 hr	unknown
IV	rapid	30 min	unknown

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 or if breastfeeding.

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Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆

Indications

Contraind./Precautions

Adv. Reactions/Side Effects

Interactions

Availability

Route/Dosage

US Brand Names

Action

Classifications

Pharmacokinetics

Time/Action Profile

Patient/Family Teaching

Pronunciation