Dosing, preparation, and storage for CINVANTI1-5


Get the recommended dosing, preparation, and storage instructions for CINVANTI injectable emulsion as a HEC (130 mg) single day dose or MEC (100 mg) 3-day dosing regimen.


Dosing and administration

  • CINVANTI is polysorbate-80 free
  • Use CINVANTI prior to MEC or HEC in combination with other antiemetics to prevent nausea and vomiting
  • Infuse CINVANTI over 30 minutes prior to chemotherapy
  • Dosing is based on chemotherapy emetogenicity
130 mg: CINVANTI Single-Dose Regimen*
For Patients Receiving HEC
AGENT DAY 1 DAY 2 DAY 3 DAY 4
CINVANTI 130 mg None None None
Oral Dexamethasone 12 mg QD 8 mg QD 8 mg BID 8 mg BID
5-HT3 Antagonist See selected
5-HT3 antagonist PI
None None None

100 mg: CINVANTI 3-Day Dose Regimen
For Patients Receiving MEC
AGENT DAY 1 DAY 2 DAY 3
CINVANTI 100 mg None None
Oral Aprepitant None 80 mg QD 80 mg QD
Oral Dexamethasone§ 12 mg QD None None
5-HT3 Antagonist See selected
5-HT3 antagonist PI
None None
* CINVANTI HEC dosing can refer to the Emend IV study that established efficacy of the single Day 1 IV dose because the 3-year data exclusivity on these data have expired.
Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4. Also administer dexamethasone in the evenings on days 3 and 4. A 50% dosage reduction of dexamethasone on Days 1 and 2 is recommended to account for a drug interaction with aprepitant.
The approved dosing regimen for CINVANTI is 100 mg on Day 1 followed by oral aprepitant on Days 2 and 3. This is due to the 3-year data exclusivity of a study conducted by Merck in 2016 that established the efficacy of the Day 1 IV dose in MEC, which does not expire until 2019. A CINVANTI label update is planned for the MEC dosing regimen to the Day 1 IV in 2019.
§ Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with aprepitant.

Dose preparation

  • Use aseptic methods for bag preparation, withdrawal, and transfer of CINVANTI to infusion bag
  • Diluent: Choose either 0.9% Sodium Chloride Injection, USP or 5% Dextrose for injection, USP
  • Use only non-DEHP tubing and non-PVC infusion bags
  • Emulsion formulation requires no reconstitution
100 mg for MEC Dosing 130 mg for HEC Dosing
INITIATE
  • Fill infusion bag with 100 mL of diluent
  • Withdraw 14 mL from the vial
  • Transfer into the infusion bag
TOTAL VOLUME: 114 mL
  • Fill infusion bag with 130 mL of diluent
  • Withdraw 18 mL from the vial
  • Transfer into the infusion bag
TOTAL VOLUME: 148 mL
INVERT Gently invert the bag 4 to 5 times. Avoid shaking.
INSPECT Before administration, inspect the bag and discard it if particulate and/or discoloration are observed.

Caution: Do not mix CINVANTI with solutions for which physical and chemical compatibility have not been established. CINVANTI injectable emulsion is incompatible with any solutions containing divalent cations (e.g. Ca2+, Mg2+), including Lactated Ringer’s Solution and Hartmann’s Solution.

Product storage

  • Each single-dose glass vial contains 130 mg aprepitant/18 mL
  • Must be refrigerated, stored at 2°C-8°C (36°F-46°F)
  • Can remain at room temperature for up to 60 days
  • Do not freeze

 

  • Stable at ambient room temperature for 6 hours in 0.9% Sodium Chloride Injection, USP or 12 hours in 5% Dextrose for Injection, USP

MEC=moderately emetogenic chemotherapy; HEC=highly emetogenic chemotherapy; PI=prescribing information; DEHP=Di(2-ethylhexyl) phthalate; PVC=polyvinyl chloride.

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 IV [package insert]. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ; August 2014.
  4. Emend IV [package insert]. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ; January 2008.
  5. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Fosaprepitant exclusivity in MEC. 2016:1-2.