Industry shortages of IV fluid and bags prompted a study of CINVANTI 2-minute IV Push

IV fluid and bag shortages have a widespread and lasting impact

  • Any temporary loss of manufacturing output may result in major shortages of IV fluids and IV bags1
  • From 2007 to 2017 there were 5 saline shortages in the United States, 2 of which remain unresolved as of 20192,3

Heron responded to shortages by completing Study 108 within 20 days to evaluate CINVANTI 2-minute IV Push4

  • Study 108 included a single-center, randomized, open-label, crossover evaluation of 50 healthy subjects to assess the pharmacokinetics, tolerability, and safety of CINVANTI administered by 2-minute IV Push vs 30-minute infusion
108 Study Description for CINVANTI
* Confinement lasted from the morning of Day -1 through the end of period 2, for a total of approximately 12 days (through the pharmacokinetics collection at 72 hours after dose 2).4
In November 2017, the American Society of Health System Pharmacists issued guidance recommending switching from infusion to IV Push (injection of 5 minutes or less) whenever possible4


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


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 during or soon after administration of CINVANTI have occurred. Symptoms including dyspnea, eye swelling, flushing, pruritus, and wheezing have been reported. If hypersensitivity reactions occur, discontinue CINVANTI. Do not reinstate CINVANTI in patients who experience these symptoms with previous 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. The safety profile of CINVANTI in healthy subjects who received a single 2-minute injection was similar to that seen with a 30-minute infusion.

Report side effects to the FDA at 1-800-FDA-1088 or Report side effects to Heron at 1-844-437-6611.

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

  1. 2018 Public-Private Analytic Exchange Program (AEP). Threats to pharmaceutical supply chains. Accessed January 28, 2019.
  2. Mazer-Amirshahi M, Fox ER. Saline shortages—many causes, no simple solution. N Engl J Med. 2018;378(16):1472-1474.
  3. American Society of Health-System Pharmacists. Drug shortages list. Accessed February 14, 2019.
  4. Ottoboni T, Lauw M, Keller MR, et al. HTX-019 via 2-min injection or 30-min infusion in healthy subjects. Future Oncol. 2019;15(8):865-874.