Enhertu Dosage

​HER2-Low or HER2-Ultralow Unresectable or Metastatic Breast Cancer

​Select patients for treatment of unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer with ENHERTU based on HER2 expression.

HER2-Mutant Unresectable or Metastatic NSCLC

Select patients for the treatment of unresectable or metastatic HER2-mutant NSCLC with ENHERTU based on the presence of activating HER2 (ERBB2) mutations in tumor or plasma specimens. If no mutation is detected in a plasma specimen, test tumor tissue.

HER2-Positive Locally Advanced or Metastatic Gastric Cancer

Select patients with locally advanced or metastatic HER2-positive gastric cancer based on HER2 protein overexpression or HER2 gene amplification (IHC 3+ or IHC 2+/ISH positive). Reassess HER2 status if it is feasible to obtain a new tumor specimen after prior trastuzumab-based therapy and before treatment with ENHERTU.

​HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors

​Select patients for treatment of unresectable or metastatic solid tumors with ENHERTU based on HER2-positive (IHC 3+) specimens. An FDA-approved test for the detection of HER2-positive (IHC 3+) solid tumors for treatment with ENHERTU is not currently available.

Additional Patient Selection Information

Information on FDA-approved tests for the detection of HER2 protein expression, HER2 gene amplification, and activating HER2 mutations is available at: http://www.fda.gov/CompanionDiagnostics.

​Premedication

​ENHERTU is highly emetogenic, which includes delayed nausea and/or vomiting. Administer prophylactic antiemetic medications per local institutional guidelines for prevention of chemotherapy-induced nausea and vomiting.

​Recommended Dosage for HER2-Positive, HER2-Low, or HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant Unresectable or Metastatic NSCLC, and HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors.

The recommended dosage of ENHERTU is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

Recommended Dosage for HER2-Positive Locally Advanced or Metastatic Gastric Cancer

The recommended dosage of ENHERTU is 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

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.

Reconstitution

• 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.
• 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, protect the vial from light. Do not freeze.
• The product does not contain a preservative. Discard unused ENHERTU after 24 hours refrigerated.

Dilution

• ​Withdraw the calculated amount from the vial(s) using a sterile syringe. 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.
• 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.
• Discard any unused portion left in the vials.

​Administration

• ​If not used immediately, store the diluted ENHERTU in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours or at room temperature between 20ºC to 25ºC (68ºF to 77 ºF) for up to 4 hours including preparation and infusion time.
• ​Protect from light. Do not freeze.
• ​The maximum time from reconstitution of the vial through the end of administration should not exceed 24 hours.
• If the prepared infusion solution was stored refrigerated (2ºC to 8ºC [36ºF to 46ºF]), allow the solution to reach room temperature prior to administration. Cover the infusion bag to protect from light.
• Administer ENHERTU as an intravenous infusion only with an infusion set made of polyolefin or polybutadiene.
• Administer ENHERTU with a 0.20 or 0.22 micron in-line polyethersulfone (PES) or polysulfone (PS) filter.
• Do NOT administer as an intravenous push or bolus.
• Cover the infusion bag to protect from light during administration.
• Do not mix ENHERTU with other drugs or administer other drugs through the same intravenous line.
• First infusion: Administer infusion over 90 minutes.
• Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated.