Dosage, Administration, and Preparation

ENHERTU is given as an intravenous (IV) infusion once every 3 weeks3

Patient selection considerations for locally advanced or metastatic
gastric cancer3

  • Select patients based on HER2 protein overexpression or HER2 gene amplification
  • Reassess HER2 status if it is feasible to obtain a new tumor specimen after prior trastuzumab-based therapy and before treatment with ENHERTU

Information on FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification in gastric cancer is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended weight-based dosage and schedule3

  • ENHERTU is always given as a monotherapy
Recommended weight-based ENHERTU dosage schedule Recommended weight-based ENHERTU dosage schedule

ENHERTU advanced gastric cancer dosage (6.4 mg/kg) differs from that of other approved indication(s).

Until disease progression or unacceptable toxicity1

  • Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine
  • Slow or interrupt the infusion rate if the patient develops infusion-related symptoms
  • Permanently discontinue ENHERTU in case of severe infusion reactions
  • Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of ENHERTU per dose modifications provided in the tables below
  • Do not re-escalate the ENHERTU dose after a dose reduction is made
  • If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3-week interval between doses. Administer the infusion at the dose and rate the patient tolerated in the most recent infusion
Dose reduction schedule
Advanced gastric cancer
starting dose 6.4 mg/kg
First dose reduction 5.4 mg/kg
Second dose reduction 4.4 mg/kg
Requirement for further dose reduction Discontinue treatment
Adverse Reaction Severity Treatment Modification
Interstitial Lung Disease (ILD/Pneumonitis) Asymptomatic ILD/pneumonitis (Grade 1)
  • Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected
  • Interrupt ENHERTU until resolved to Grade 0, then:
    • If resolved in 28 days or less from date of onset, maintain dose
    • If resolved in greater than 28 days from date of onset, reduce dose one level (see table above)
Symptomatic ILD/pneumonitis (Grade 2 or greater)
  • Permanently discontinue ENHERTU
  • Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected
Neutropenia Grade 3 (less than 1.0 to 0.5 x 109/L)
  • Interrupt ENHERTU until resolved to Grade 2 or less,
    then maintain dose
Grade 4 (less than 0.5 x 109/L)
  • Interrupt ENHERTU until resolved to Grade 2 or less
  • Reduce dose by one level (see table above)
Febrile Neutropenia Absolute neutrophil count of less than
1.0 x 109/L and temperature greater than 38.3°C or a sustained temperature of 38°C or greater for more than one hour
  • Interrupt ENHERTU until resolved
  • Reduce dose by one level (see the table above)
Thrombocytopenia Grade 3 (platelets less than 50 to 25 x 109/L)
  • Interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose
Grade 4 (platelets less than 25 x 109/L)
  • Interrupt ENHERTU until resolved to Grade 1 or less
  • Reduce dose by one level (see table above)
Left Ventricular Dysfunction LVEF greater than 45% and absolute decrease from baseline is 10% to 20%
  • Continue treatment with ENHERTU
LVEF 40% to 45% And absolute decrease from baseline is less than 10%
  • Continue treatment with ENHERTU
  • Repeat LVEF assessment within 3 weeks

And absolute decrease from baseline is 10% to 20%

  • Interrupt ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU
  • If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose
LVEF less than 40% or absolute decrease from baseline is greater than 20%
  • Interrupt ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • If LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed, permanently discontinue ENHERTU
Symptomatic congestive heart failure (CHF)
  • Permanently discontinue ENHERTU
Adverse
Reaction
Severity Treatment Modification
Interstitial Lung Disease
(ILD/Pneumonitis)
Asymptomatic
ILD/
pneumonitis
(Grade 1)
  • Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected
  • Interrupt ENHERTU until resolved to Grade 0, then:
    • If resolved in 28 days or less from date of onset, maintain dose
    • If resolved in greater than 28 days from date of onset, reduce dose one level (see table above)
Symptomatic
ILD/
pneumonitis
(Grade 2
or greater)
  • Permanently discontinue ENHERTU
  • Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected
Neutropenia Grade 3
(less than 1.0
to 0.5 x 109/L)
  • Interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose
Grade 4
(less than
0.5 x 109/L)
  • Interrupt ENHERTU until resolved to Grade 2 or less
  • Reduce dose by one level (see table above)
Febrile Neutropenia Absolute neutrophil count of less than

1.0 x 109/L

and temperature greater than 38.3°C or a sustained temperature of 38°C or greater for more than one hour
  • Interrupt ENHERTU until resolved
  • Reduce dose by one level (see the table above)
Thrombocytopenia Grade 3 (platelets less than

50 to 25 x 109/L)

  • Interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose
Grade 4
(platelets less than
25 x 109/L)
  • Interrupt ENHERTU until resolved to Grade 1 or less
  • Reduce dose by one level (see table above)
Left Ventricular Dysfunction LVEF greater than 45% and absolute decrease from baseline is 10% to 20%
  • Continue treatment with ENHERTU
LVEF 40% to 45% And absolute decrease from baseline is less than 10%
  • Continue treatment with ENHERTU
  • Repeat LVEF assessment within 3 weeks
And absolute decrease from baseline is 10% to 20%
  • Interrupt ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU
  • If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose
LVEF less than 40% or absolute decrease from baseline is greater than 20%
  • Interrupt ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • If LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed, permanently discontinue ENHERTU
Symptomatic congestive heart failure (CHF)
  • Permanently discontinue ENHERTU

Toxicity grades are in accordance with National Cancer Institute – Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v.4.03).

LVEF, left ventricular ejection fraction.

ENHERTU preparation for administration3

ENHERTU (fam-trastuzumab deruxtecan-nxki) 100 mg vial

In order to prevent medication errors, check the vial labels to ensure that the drug being prepared and administered is ENHERTU and not trastuzumab or ado-trastuzumab emtansine.3

Reconstitute and further dilute ENHERTU prior to intravenous infusion. Use appropriate aseptic technique.3

ENHERTU is a cytotoxic drug. Follow applicable special handling and
disposal procedures.7

ENHERTU (fam-trastuzumab deruxtecan-nxki) 100 mg vial
  • Reconstitute immediately before dilution
  • More than one vial may be needed for a full dose. Calculate the dose (mg), the total volume of reconstituted ENHERTU solution required, and the number of vial(s) of ENHERTU needed
  • Reconstitute each 100 mg vial by using a sterile syringe to slowly inject 5 mL of Sterile Water for Injection, USP into each vial to obtain a final concentration of 20 mg/mL
  • Swirl the vial gently until completely dissolved. Do not shake
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless to light yellow. Do not use if visible particles are observed or if the solution is cloudy or discolored
  • If not used immediately, store the reconstituted ENHERTU vials in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours from the time of reconstitution, protected from light. Do not freeze
  • The product does not contain a preservative. Discard unused ENHERTU after 24 hours refrigerated
  • Dilute the calculated volume of reconstituted ENHERTU in an intravenous infusion bag containing
    100 mL of 5% Dextrose Injection, USP. Do not use Sodium Chloride Injection, USP. ENHERTU is compatible with an infusion bag made of polyvinylchloride or polyolefin (copolymer of ethylene and polypropylene)
  • Gently invert the infusion bag to thoroughly mix the solution. Do not shake
  • Cover the infusion bag to protect from light
  • If not used immediately, store at room temperature for up to 4 hours including preparation and infusion, or in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours, protected from light. Do not freeze
  • Discard any unused portion left in the vial
  • If the prepared infusion solution was stored refrigerated (2ºC to 8ºC [36ºF to 46ºF]), allow the solution to equilibrate to room temperature prior to administration
  • Administer ENHERTU as an intravenous infusion only with an infusion set made of polyolefin or polybutadiene and a 0.20 or 0.22 micron in-line polyethersulfone (PES) or polysulfone (PS) filter. Do not administer as an intravenous push or bolus
  • Do not mix ENHERTU with other drugs or administer other drugs through the same intravenous line

Please click here for full Prescribing Information, including Boxed WARNINGS, and click here for Medication Guide.

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