A closer look at the heritage of aprepitant


Aprepitant has provided trusted efficacy for the prevention of acute and delayed CINV for nearly 15 years1

Key facts about aprepitant1-3:
  • Aprepitant is the only single-agent NK1 RA approved for CINV prevention in both acute and delayed phases
  • Aprepitant is the only single-agent NK1 RA that can be administered to patients receiving chemotherapy regardless of cycle length
  • No other NK1 RA has been proven more effective than aprepitant

FDA Approval Chart
~1.4 Million Administrations Per Year†14
~90% of which is fosaprepitant
* NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Antiemesis. Category 1: based on high-level evidence and uniform National Comprehensive Cancer Network® (NCCN®) consensus.
Both oral aprepitant and fosaprepitant combined.
Any Phase III/IV trials with aprepitant or fosaprepitant in either the active or control group.

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. Emend oral [package insert]. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ; December 2015.
  2. Varubi [package insert]. Tesaro, Inc., Waltham, MA; October 2017.
  3. 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.
  4. Referenced with permission from the 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. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  5. U.S. National Library of Medicine. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/home. Accessed October 10, 2017.
  6. Herrstedt J, Muss HB, Warr DG, et al. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy. Cancer. 2005;104(7):1548-1555.
  7. Nishimura J, Satoh T, Fukanaga M, et al. Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): A multicentre, randomised, controlled phase 3 trial. Eur J Cancer. 2015;51(10):1274-1282.
  8. Stiff PJ, Fox-Geiman MP, Kiley K, et al. Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biol Blood Marrow Transplant. 2013;19(1):49-55.
  9. Ruhlmann DH, Christensen TB, Dohn LH, et al. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol. 2016;17(4):509-518.
  10. Kim HJ, Shin SW, Song EK, et al. Ramosetron versus ondansetron in combination with aprepitant and dexamethasone for the prevention of highly emetogenic chemotherapy-induced nausea and vomiting: a multicenter, randomized phase III trial, KCSG PC10-21. Oncologist. 2015;20(12):1440-1447.
  11. Schmitt T, Goldschmidt H, Neben K, et al. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial. J Clin Oncol. 2014;32(30):3413-3420.
  12. Schmoll HJ, Aapro MS, Poli-Bigelli S, et al. Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol. 2006;17(6):1000-1016.
  13. Warr DG, Hesketh PJ, Gralla RJ, et al. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol. 2005;20(23):2822-2830.
  14. Data on file [Statistical market data]. Heron Therapeutics, Inc., San Diego, CA.