CINVANTI—an advanced NK1 RA formulation


Product Active pharmaceutical ingredient Formulation1-4
Oral Emend® (aprepitant)* Aprepitant
  • Oral capsules
Emend® IV
(fosaprepitant) for injection*
Aprepitant
  • IV formulation with PS 80
  • Prodrug of aprepitant
  • A prodrug is an inactive compound that is converted to an active drug as it is metabolized by the body
CINVANTI (aprepitant)
injectable emulsion
Aprepitant
  • IV formulation without PS 80
CINVANTI is the first and only polysorbate 80-free IV NK1 RA approved for acute and delayed CINV prevention1,2,5

The goal of antiemetic therapy is to prevent CINV across both acute and delayed phases6

Neurotransmitter Receptor Graph for Brand
Adapted with permission from S. Karger AG. Martin M. Oncology. 1996;53:26–31. 10.1159/000227637.
5-HT3 and NK1 receptors play important roles in both acute
and delayed phases of CINV8
CINV=chemotherapy-induced nausea and vomiting; NK1 RA=substance P/neurokinin-1 (NK1) receptor antagonist; PS 80=polysorbate 80.
* Emend is a registered trademark of Merck & Co., Inc.

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.

References:
  1. CINVANTI [package insert]. Heron Therapeutics, Inc., San Diego, CA; November 2017.
  2. Emend IV [package insert]. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ; August 2017.
  3. Emend oral [package insert]. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ; December 2015.
  4. Dictionary.com. http://www.dictionary.com/browse/prodrug?s=t. The American Heritage® Stedman’s Medical Dictionary Copyright © 2002, 2001, 1995 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved. Accessed October 25, 2017.
  5. Varubi [package insert]. Tesaro, Inc., Waltham, MA; October 2017.
  6. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Antiemesis V.2.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed October 10, 2017.
  7. Martin M. The severity and pattern of emesis following different cytotoxic agents. Oncology. 1996;53(suppl1):26-31.
  8. Grunberg SM. Chemotherapy-induced nausea and vomiting: prevention, detection, and treatment—how are we doing? J Support Oncol. 2004;2(suppl1):1-12.