CINVANTI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CINVANTI (CINVANTI).

How it works

Selective serotonin 5-HT3 receptor antagonist; blocks serotonin binding at 5-HT3 receptors in the chemoreceptor trigger zone and gastrointestinal tract, reducing nausea and vomiting.

What the body does with it

Metabolism	Extensively metabolized in the liver via multiple CYP450 enzymes, including CYP2D6, CYP3A4, CYP1A2, and CYP2E1; also metabolized via conjugation and other pathways.
Excretion	Approximately 95% eliminated via hepatic metabolism, with 5% excreted unchanged in urine and feces. Biliary excretion accounts for <2%.
Half-life	Terminal elimination half-life is approximately 40 hours (range 30-50 h) in adults, supporting single-dose prophylactic use.
Protein binding	Approximately 69% bound to plasma proteins, primarily albumin.
Volume of Distribution	Mean Vd is approximately 3.0 L/kg (range 2.4-3.8 L/kg), indicating extensive extravascular distribution.
Bioavailability	Oral capsule: approximately 59% (absolute bioavailability).
Onset of Action	IV: Onset within 30 minutes; oral capsule: Onset within 1-2 hours.
Duration of Action	Duration of antiemetic effect: at least 24 hours post-chemotherapy; sustained up to 48 hours.

Classification & Brands

Dosing & administration

CINVANTI (aprepitant) injectable emulsion: 130 mg intravenously over 30 minutes on Day 1 of chemotherapy, as part of a 3-day regimen with oral aprepitant on Days 2 and 3 (80 mg orally once daily).

Dosage form	EMULSION
Renal impairment	No dosage adjustment is required for patients with renal impairment, including those with end-stage renal disease (ESRD) undergoing hemodialysis. However, data are limited in ESRD.
Liver impairment	For mild-to-moderate hepatic impairment (Child-Pugh class A or B): no dosage adjustment necessary. For severe hepatic impairment (Child-Pugh class C): no clinical studies have been conducted; use with caution.
Pediatric use	CINVANTI is not approved for pediatric use. Safety and efficacy have not been established in patients <18 years of age.
Geriatric use	No specific dosage adjustment is recommended for elderly patients (≥65 years) based on pharmacokinetic data. Clinical studies included a limited number of elderly subjects, but no overall differences in safety or efficacy were observed.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CINVANTI (CINVANTI).

Breastfeeding	It is not known whether aprepitant is excreted in human breast milk. The M/P ratio is unknown. Caution should be exercised when administered to a breastfeeding woman due to potential adverse effects in nursing infants.
Teratogenic Risk	CINVANTI (aprepitant) is classified as FDA Pregnancy Category B. Animal studies have not demonstrated teratogenic effects, but no adequate and well-controlled studies exist in pregnant women. First trimester: Limited data, potential risk unknown; second and third trimesters: No identified fetal risk. However, use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

No FDA boxed warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to palonosetron or any component of the formulation","Concurrent use with apomorphine (increased risk of hypotension and loss of consciousness)"]

Clinical Precautions

Precautions

["Serotonin syndrome: Risk when used with other serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs)","QT interval prolongation: Avoid in patients with congenital long QT syndrome, electrolyte abnormalities, or concurrent use of other QT-prolonging drugs","Hypersensitivity reactions: including anaphylaxis and injection site reactions","Masking of progressive ileus and/or gastric distention after abdominal surgery","Serotonin syndrome risk with concomitant use of serotonergic drugs"]

Clinical Tips & Counseling

Drug interactions

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CINVANTI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CINVANTI (CINVANTI).

How it works

Selective serotonin 5-HT3 receptor antagonist; blocks serotonin binding at 5-HT3 receptors in the chemoreceptor trigger zone and gastrointestinal tract, reducing nausea and vomiting.

What the body does with it

Metabolism	Extensively metabolized in the liver via multiple CYP450 enzymes, including CYP2D6, CYP3A4, CYP1A2, and CYP2E1; also metabolized via conjugation and other pathways.
Excretion	Approximately 95% eliminated via hepatic metabolism, with 5% excreted unchanged in urine and feces. Biliary excretion accounts for <2%.
Half-life	Terminal elimination half-life is approximately 40 hours (range 30-50 h) in adults, supporting single-dose prophylactic use.
Protein binding	Approximately 69% bound to plasma proteins, primarily albumin.
Volume of Distribution	Mean Vd is approximately 3.0 L/kg (range 2.4-3.8 L/kg), indicating extensive extravascular distribution.
Bioavailability	Oral capsule: approximately 59% (absolute bioavailability).
Onset of Action	IV: Onset within 30 minutes; oral capsule: Onset within 1-2 hours.
Duration of Action	Duration of antiemetic effect: at least 24 hours post-chemotherapy; sustained up to 48 hours.

Classification & Brands

Dosing & administration

CINVANTI (aprepitant) injectable emulsion: 130 mg intravenously over 30 minutes on Day 1 of chemotherapy, as part of a 3-day regimen with oral aprepitant on Days 2 and 3 (80 mg orally once daily).

Dosage form	EMULSION
Renal impairment	No dosage adjustment is required for patients with renal impairment, including those with end-stage renal disease (ESRD) undergoing hemodialysis. However, data are limited in ESRD.
Liver impairment	For mild-to-moderate hepatic impairment (Child-Pugh class A or B): no dosage adjustment necessary. For severe hepatic impairment (Child-Pugh class C): no clinical studies have been conducted; use with caution.
Pediatric use	CINVANTI is not approved for pediatric use. Safety and efficacy have not been established in patients <18 years of age.
Geriatric use	No specific dosage adjustment is recommended for elderly patients (≥65 years) based on pharmacokinetic data. Clinical studies included a limited number of elderly subjects, but no overall differences in safety or efficacy were observed.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CINVANTI (CINVANTI).

Breastfeeding	It is not known whether aprepitant is excreted in human breast milk. The M/P ratio is unknown. Caution should be exercised when administered to a breastfeeding woman due to potential adverse effects in nursing infants.
Teratogenic Risk	CINVANTI (aprepitant) is classified as FDA Pregnancy Category B. Animal studies have not demonstrated teratogenic effects, but no adequate and well-controlled studies exist in pregnant women. First trimester: Limited data, potential risk unknown; second and third trimesters: No identified fetal risk. However, use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

No FDA boxed warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to palonosetron or any component of the formulation","Concurrent use with apomorphine (increased risk of hypotension and loss of consciousness)"]