CINVANTI—2-minute IV Push as safe as 30-minute IV infusion1


CINVANTI 2-minute IV Push demonstrated safety and tolerability comparable to 30-minute IV infusion in healthy subjects1,2

Incidence of any treatment-emergent adverse events within 30 minutes of administration1,2
IV Push Treatment Related Adverse Events Info for CINVANTI

Treatment Related Adverse Events Information

  • In studies 104/106, 15.0% of subjects who received EMEND IV experienced adverse events within 30 minutes of administration vs 2.6% of subjects who received CINVANTI IV infusion2
  • In Study 108, incidence of TEAEs within the first 30 minutes with CINVANTI IV Push was comparable to CINVANTI IV infusion1

Safety of CINVANTI 2-minute IV Push supported by a crossover study in patients with cancer3

  • A single-center prospective study at the University of Alabama at Birmingham was conducted to assess the safety of CINVANTI 2-minute IV Push compared to the 30-minute IV infusion in patients with cancer3
  • This 1:1 randomized, crossover study of 135 patients with cancer evaluated adverse events for 30 minutes from the start of CINVANTI administration, as part of a 3-drug regimen for preventing HEC and MEC, prior to receiving chemotherapy3
  • No TEAEs were related to CINVANTI treatment (within 0-30 and 30-60 minutes of antiemetic regimen administration)3
CINVANTI 2-minute IV Push administration was well tolerated in studies of healthy subjects and patients with cancer1,3
TEAE=treatment-emergent adverse event.

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 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 www.fda.gov/medwatch. Report side effects to Heron at 1-844-437-6611.

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

References:
  1. 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.
  2. Ottoboni T, Lauw M, Keller MR, et al. Safety of HTX-019 (intravenous aprepitant) and fosaprepitant in healthy subjects. Future Oncol. 2018;14(27):2849-2859.
  3. Navari RM, Mosier MC. Crossover safety study of aprepitant: 2-minute injection vs 30-minute infusion in cancer patients receiving emetogenic chemotherapy. OncoTargets and Therapy. 2019 [in press].