Chemotherapy-induced nausea and vomiting

Netupitant is a selective substance P/neurokinin (NK1) receptor antagonist, which augments the antiemetic activity of 5-HT3 receptor antagonists and corticosteroids to inhibit acute and delayed chemotherapy-induced emesis.

"Netupitant:
Absorption: Within 15 minutes to 3 hours
Distribution: Vd: 1,982 ± 46 L
Protein binding: >99.5% for netupitant; >97% for major metabolites
Metabolism: Extensively hepatic via CYP3A4 (major), CYP2C9 (minor) and CYP2D6 (minor); forms active metabolites M1, M2, and M3
Half-life elimination: 80 ± 29 hours
Time to peak: ~4 to 5 hours
Excretion: Feces (~71%); urine (~4%)

Palonosetron:
Absorption: Well absorbed
Distribution: Vd: 663 ± 24 L
Bioavailability: Oral: ~97%
Protein binding: ~62%
Metabolism: ~50% metabolized to relatively inactive metabolites (N-oxide-palonosetron and 6-S-hydroxy-palonosetron); CYP2D6, 3A4, and 1A2 contribute to metabolism
Half-life elimination: 50 ± 16 hours
Time to peak: ~5 hours
Excretion: Feces (5% to 8%); urine (85% to 93%; 40% as unchanged drug)"

There are no contraindications listed in the manufacturer's US labeling.

Adverse events were observed in some animal reproduction studies using the components of this combination product. Information related to the use of netupitant and palonosetron during pregnancy is limited.

"It is not known if netupitant or palonosetron are present in breast milk.
According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, the benefits of treatment to the mother, as well as the underlying maternal condition."

">10%: Genitourinary: Urinary tract infection (9%; females: 18%; males: 4%)1% to 10%:Endocrine & metabolic: Dyslipidemia (4%), increased thirst (2%)Gastrointestinal: Nausea (2%)Genitourinary: Increased urine output (3%)Hematologic & oncologic: Increased hematocrit (3% to 4%)Infection: Genitourinary fungal infection (2% to 6%)Frequency not defined: Endocrine & metabolic: Increased LDL cholesterol/>10%:Gastrointestinal: Diarrhea (IR tablet: 12% to 53%; ER tablet: 10% to 17%), nausea and vomiting (IR tablet: 26%; ER tablet: 7%), flatulence (4% to 12%)Infection: Infection (21%)1% to 10%:Cardiovascular: Chest discomfort, flushing, palpitationsCentral nervous system: Headache (5% to 6%), chills, dizziness, taste disorderDermatologic: Diaphoresis, nail disease, skin rashEndocrine & metabolic: Decreased vitamin B12 serum concentrate (7%), hypoglycemiaGastrointestinal: Nausea (7% to 9%), dyspepsia (?7%), abdominal distress (6%), abdominal pain (3% to 4%)"

"Highly emetogenic chemotherapy (including cisplatin-based):
Oral: One capsule 1 hour before chemotherapy on day 1 (Gralla 2014; Hesketh 2017; Roila 2016).
Note: Antiemetic regimen also includes dexamethasone 12 mg orally 30 minutes before chemotherapy on day 1 and 8 mg orally once daily on days 2 to 4.

Anthracycline and cyclophosphamide-based chemotherapy and chemotherapy not considered highly emetogenic:
Oral: One capsule 1 hour before chemotherapy on day 1 (Gralla 2014; Hesketh 2017; Roila 2016).
Note: Antiemetic regimen also includes dexamethasone 12 mg orally 30 minutes before chemotherapy on day 1 (only).
"

"CrCl 30 to 60 mL/minute: No dosage adjustment is necessary.
CrCl <30 mL/minute: Avoid use.
ESRD: Avoid use (has not been studied).
"

"Mild or moderate impairment (Child-Pugh classes A and B): No dosage adjustment is necessary.
Severe impairment (Child-Pugh class C): Avoid use.
"