CINVANTI—demonstrated fewer adverse events within 30 minutes of infusion vs fosaprepitant in healthy subjects1


Two bioequivalence studies were conducted for CINVANTI and fosaprepitant in healthy subjects who were not being treated with chemotherapy. This allowed for an assessment of the adverse events likely caused by each NK1 RA without interference of the chemotherapy.*1

Treatment Related Adverse Events Information
* In 2 pivotal, open-label, randomized, crossover bioequivalence studies, subjects received 130 mg of CINVANTI and 150 mg of fosaprepitant (corresponding to CINVANTI 130 mg) for injection. Infusion time was 30 minutes for CINVANTI and either 20 or 30 minutes for fosaprepitant for injection. Systemic exposure was equivalent for CINVANTI and fosaprepitant.1

Fewer infusion site reactions and systemic adverse events vs fosaprepitant1

Adverse events in ≥2% of subjects within 30 minutes of infusion
Adverse Events CINVANTI 130 mg (n=196) Fosaprepitant 150 mg (n=200)
Infusion site pain 0% 7.0%
Dyspnea 0.5% 3.0%
Nausea 0.5% 2.0%
In 2 pivotal, open-label, randomized, crossover bioequivalence studies, subjects received 130 mg of CINVANTI and 150 mg of fosaprepitant for injection. Infusion time was 30 minutes for CINVANTI and either 20 or 30 minutes for fosaprepitant for injection. Systemic exposure was equivalent for CINVANTI and fosaprepitant.1
Dyspnea led to study discontinuation in 2 subjects in the fosaprepitant arm and 1 subject in the CINVANTI arm.1

Indication

CINVANTI is a substance P/neurokinin-1 (NK1) receptor antagonist, indicated in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin and nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC).

Limitations of Use: CINVANTI has not been studied for treatment of established nausea and vomiting.

Important Safety Information

Contraindications

CINVANTI is contraindicated in patients with hypersensitivity to any of the components of CINVANTI.

Concurrent use of pimozide with CINVANTI is contraindicated.

Warnings and Precautions

Clinically Significant CYP3A4 Drug Interactions

Aprepitant is a substrate, weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4.

  • Use with other drugs that are CYP3A4 substrates may result in increased plasma concentration of the concomitant drug.
    • Use of pimozide with CINVANTI is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide.
  • Use of CINVANTI with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to CINVANTI.
  • Use of CINVANTI with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of aprepitant.

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported with fosaprepitant, a prodrug of aprepitant, and with oral aprepitant. Symptoms including flushing, erythema, dyspnea, hypotension and syncope have been reported. If symptoms occur, discontinue CINVANTI. Do not reinstate if symptoms occur with first time use.

Decrease in INR with Concomitant Warfarin

Co-administration of CINVANTI with warfarin, a CYP2C9 substrate, may result in a clinically significant decrease in the International Normalized Ratio (INR) of prothrombin time. Monitor the INR in patients on chronic warfarin therapy in the 2-week period, particularly at 7 to 10 days, following initiation of CINVANTI with each chemotherapy cycle.

Risk of Reduced Efficacy of Hormonal Contraceptives

The efficacy of hormonal contraceptives may be reduced during administration of and for 28 days following the last dose of CINVANTI. Advise patients to use effective alternative or back-up methods of non-hormonal contraception during treatment with CINVANTI and for 1 month following administration of CINVANTI or oral aprepitant, whichever is administered last.

Use in Specific Populations

Avoid use of CINVANTI in pregnant women as alcohol is an inactive ingredient for CINVANTI. There is no safe level of alcohol exposure in pregnancy.

Adverse Reactions

The most common adverse reactions with the 3-day oral aprepitant regimen in conjunction with MEC (≥1% and greater than standard therapy) were fatigue and eructation.

The most common adverse reactions with the single-dose intravenous fosaprepitant regimen in conjunction with HEC were generally similar to that seen in prior HEC studies with oral aprepitant. In addition, infusion site reactions (3%) occurred.

The most common adverse reactions with single-dose CINVANTI (≥2%) were headache and fatigue.

For more information about CINVANTI, please see full Prescribing Information.

Reference:
  1. Data on file [Clinical Summary] Heron Therapeutics, Inc., San Diego, CA.