Substitution by any other biological medicinal product requires the consent of the prescribing physician.
Dosing Considerations
There is a risk of medication errors between HERCEPTIN (trastuzumab) and KADCYLA (trastuzumab emtansine). In order to prevent medication errors, it is important to check the vial labels to ensure that the drug being prepared and administered is HERCEPTIN (trastuzumab) and not KADCYLA (trastuzumab emtansine). Ensure that the recommended HERCEPTIN (trastuzumab) dose is administered (see Recommended Dose and Dosage Adjustment section). HERCEPTIN should be prescribed using both the trade name and non-proprietary name. Do not substitute HERCEPTIN for or with KADCYLA (trastuzumab emtansine).
When using in combination with PERJETA (pertuzumab) and docetaxel for treatment of patients with HER-2-positive metastatic breast cancer, consult Product Monographs for PERJETA and docetaxel for further information, such as dose adjustment, sequence of administration of each medication and duration of treatment.
Recommended Dose and Dosage Adjustment Early Breast Cancer (EBC)
3-Weekly Schedule: The recommended initial loading dose is 8 mg/kg HERCEPTIN
(trastuzumab) administered as a 90-minute infusion. The recommended maintenance dose is 6 mg/kg HERCEPTIN 3 weeks later and then 6 mg/kg repeated at 3-weekly intervals
administered as infusions over approximately 90 minutes. If the prior dose was well tolerated, the dose can be administered as a 30-minute infusion. Do not administer as an IV push or
bolus (see Preparation for Administration)
Weekly schedule: As a weekly regimen, the recommended initial loading dose of HERCEPTIN
is 4 mg/kg followed by 2 mg/kg every week.
See clinical trial section for chemotherapy combination dosing.
Weekly schedule: The recommended initial loading dose is 4 mg/kg HERCEPTIN administered
as a 90-minute infusion. The recommended weekly maintenance dose is 2 mg/kg HERCEPTIN and can be administered as a 30-minute infusion if the initial loading dose was well tolerated. HERCEPTIN may be administered in an outpatient setting. Do not administer as an IV push or
bolus (see Preparation for Administration). Metastatic Gastric Cancer (MGC)
3-Weekly Schedule: The recommended initial loading dose is 8 mg/kg HERCEPTIN
administered as a 90-minute infusion. The recommended maintenance dose is 6 mg/kg HERCEPTIN 3 weeks later and then 6 mg/kg repeated at 3-weekly intervals administered as infusions over approximately 90 minutes. If the prior dose was well tolerated, the dose can be administered as a 30-minute infusion. Do not administer as an IV push or bolus (see Preparation for Administration)
Duration of Treatment
In clinical studies, patients with MBC or MGC were treated with HERCEPTIN until progression of disease. Patients with EBC should be treated for 1 year or until disease recurrence or
unacceptable cardiac toxicity, whichever occurs first (see WARNINGS AND PRECAUTIONS, Cardiovascular). Extending treatment in EBC beyond one year is not recommended (see Clinical Trials, Early Breast Cancer (EBC), HERA).
Dose Reduction
No reductions in the dose of HERCEPTIN were made during clinical trials. Patients may continue therapy with HERCEPTIN during periods of reversible, chemotherapy-induced myelosuppression, but they should be monitored carefully for complications of neutropenia during this time. The specific instructions to reduce or hold the dose of chemotherapy should be followed.
Table 22 depicts the criteria for permanent discontinuation of HERCEPTIN for cardiac dysfunction in pivotal studies in adjuvant breast cancer.
Table 22
Criteria for Permanent Discontinuation for Cardiac Dysfunction in Pivotal Studies in Adjuvant Breast Cancer
STUDY If Symptomatic CHF If Held for Asymptomatic LVEF Decrease (per algorithm used in each study protocol)
HERA required required if HERCEPTIN held for 2 consecutive cycles
NSABP B-31, NCCTG N9831 and BCIRG-006
required required if HERCEPTIN held for 2 consecutive cycles, or
for 3 intermittent cycles; investigator may choose to discontinue permanently sooner
Dose Holding
Cardiovascular, Cardiotoxicity)
Table 23
Recommendations for Continuation or Withdrawal of HERCEPTIN Therapy in Asymptomatic Patients Based on Serial Measurements of Left Ventricular Ejection
Fraction (LVEF)a
(Adapted from the Canadian Consensus Guidelines*)
Relationship of LVEF to LLN
Asymptomatic decrease in LVEF from baseline
≤ 10 percentage points 10–15 percentage points ≥ 15 percentage points
Within radiology facility’s
normal limits Continue HERCEPTIN Continue HERCEPTIN
Hold HERCEPTIN and repeat MUGA or ECHO after 4 weeks
1–5 percentage points
below LLN Continue HERCEPTIN
b
Hold HERCEPTIN and repeat MUGA or ECHO after 4 weeks b,c
Hold HERCEPTIN and repeat MUGA or ECHO after 4 weeks c,d
≥6 percentage points below LLN
Continue HERCEPTIN and repeat MUGA or
ECHO after 4 weeksd
Hold HERCEPTIN and repeat MUGA or ECHO after 4 weeks c,d
Hold HERCEPTIN and repeat MUGA or ECHO after 4 weeks c,c
a Based on NSABP B-31 trial protocol. Modified to include recommendations for cardiology consultation or
treatment of cardiac dysfunction (or both) when appropriate, as indicated in the subsequent footnotes.
b Consider cardiac assessment and initiation of angiotensin converting-enzyme inhibitor therapy.
c After two holds, consider permanent discontinuation of HERCEPTIN.
d Initiate angiotensin converting-enzyme inhibitor therapy and refer to cardiologist. LLN = lower limit of normal;
MUGA = multiple-gated acquisition scan; ECHO = echocardiography.
*Source: Mackey JR, Clemons M, Côté MA, et al. Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab Working Group. Curr Oncol. 2008 Jan;15(1):24-35.
For the frequency of cardiac monitoring see WARNINGS AND PRECAUTIONS, Cardiovascular, Cardiotoxicity.
Missed Dose
Weekly schedule: If the patient has missed a dose of HERCEPTIN by one week or less, then the
usual maintenance dose (2 mg/kg) should be given as soon as possible (do not wait until the next planned cycle). Subsequent maintenance HERCEPTIN doses of 2 mg/kg should be administered 7 days later according to the weekly schedule.
If the patient has missed a dose of HERCEPTIN by more than one week, a re-loading dose of HERCEPTIN should be administered (4 mg/kg over approximately 90 minutes) as soon as possible. Subsequent maintenance HERCEPTIN doses of 2 mg/kg should be administered 7 days later according to the weekly schedule.
3-Weekly Schedule: If the patient has missed a dose of HERCEPTIN by one week or less, then
the usual maintenance dose (6 mg/kg) should be administered as soon as possible (do not wait until the next planned cycle). Subsequent maintenance HERCEPTIN doses of 6 mg/kg should be administered 21 days later according to the 3-weekly schedule.
If the patient has missed a dose of HERCEPTIN by more than one week, a re-loading dose of HERCEPTIN should be administered (8 mg/kg over approximately 90 minutes) as soon as possible. Subsequent maintenance HERCEPTIN doses of 6 mg/kg should be administered 21 days later according to the 3-weekly schedule.
Preparation for Administration
Use appropriate aseptic technique. Each vial of HERCEPTIN should be reconstituted with 20 mL of BWFI, containing 1.1% benzyl alcohol, as supplied, to yield a multi-dose solution containing 21 mg/mL trastuzumab. Immediately upon reconstitution with BWFI, the vial of HERCEPTIN must be labelled in the area marked “Do not use after:” with the future date that is 28 days from the date of reconstitution.
If the patient has a known hypersensitivity to benzyl alcohol, HERCEPTIN must be reconstituted with Sterile Water for Injection (see WARNINGS AND PRECAUTIONS). HERCEPTIN which
has been reconstituted with SWFI must be used immediately and any unused portion discarded. Use of other reconstitution diluents should be avoided.
HERCEPTIN should be carefully handled during reconstitution. Causing excessive foaming during reconstitution or shaking the reconstituted HERCEPTIN may result in problems with the amount of HERCEPTIN that can be withdrawn from the vial.
Reconstitution:
1. Using a sterile syringe, slowly inject 20 mL of Bacteriostatic Water for Injection in the vial containing the lyophilized HERCEPTIN directing the stream into the lyophilized cake.
2. Swirl vial gently to aid reconstitution. Do not shake.
Slight foaming of the product upon reconstitution is not unusual. Allow the vial to stand
undisturbed for approximately 5 minutes. The reconstituted HERCEPTIN results in a colorless to pale yellow transparent solution and should be essentially free of visible particles.
Determine the volume in mL of HERCEPTIN solution needed:
Weekly Schedule: based on a loading dose of 4 mg trastuzumab/kg body weight or a
maintenance dose of 2 mg trastuzumab/kg body weight.
Volume (mL) = [Body Weight (kg) x Dose (4 mg/kg for loading OR 2 mg/kg for
maintenance)]
21 mg/mL (concentration of reconstituted solution)
subsequent 3 weekly dose of 6 mg trastuzumab/kg body weight:
Volume (mL) = [Body Weight (kg) x Dose (8 mg/kg for loading OR 6 mg/kg for
maintenance)]
21 mg/mL (concentration of reconstituted solution)
Withdraw the appropriate volume of solution calculated from the vial and add it to an infusion bag containing 250 mL of 0.9% sodium chloride, USP. Dextrose (5%) solution should not be
used since it causes aggregation of the protein. To mix the solution and avoid foaming, invert the bag gently. The reconstituted preparation results in a colourless to pale yellow transparent solution. Parenteral drug products should be inspected visually for particulates and
discolouration prior to administration. No incompatibilities between HERCEPTIN and polyvinylchloride,polyethylene or polypropylene bags have been observed.
Administration
Weekly Schedule: Treatment may be administered in an outpatient setting by administration of a
4 mg/kg loading dose of HERCEPTIN by intravenous (IV) infusion over 90 minutes. Do not
administer as an IV push or bolus. Patients should be observed for fever and chills or other
infusion associated symptoms. Serious adverse reactions to infusions of HERCEPTIN including dyspnea, hypotension, hypertension, wheezing, bronchospasm, tachycardia, reduced oxygen saturation and respiratory distress have been reported infrequently (also see ADVERSE
REACTIONS). Interruption of the infusion may help control such symptoms. The infusion may be resumed when symptoms abate.
If prior infusion was well tolerated, subsequent weekly doses of 2 mg/kg HERCEPTIN may be administered over 30 minutes (see Recommended Dose and Dosage Adjustment). Patients should still be observed for fever and chills or other infusion-associated symptoms (see ADVERSE REACTIONS).
3-Weekly Schedule: Treatment may be administered in an outpatient setting by administration
of a 8 mg/kg loading dose of HERCEPTIN by intravenous (IV) infusion over 90 minutes. Do not
administer as an IV push or bolus. Patients should be observed for fever and chills or other
infusion associated symptoms (see ADVERSE REACTIONS). Interruption of the infusion may help control such symptoms. The infusion may be resumed when symptoms abate.
If prior infusion was well tolerated, subsequent 3-weekly doses of 6 mg/kg HERCEPTIN may be administered over 30 minutes (see Recommended Dose and Dosage Adjustment). Patients should still be observed for fever and chills or other infusion-associated symptoms (see ADVERSE REACTIONS).
HERCEPTIN should not be mixed or diluted with other drugs. Infusions of HERCEPTIN should not be administered or mixed with dextrose solutions.