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ONTRUZANT is a brand name for Trastuzumab, supplied as a powder for solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Indications have been granted on the basis of similarity between ONTRUZANT and the reference biologic drug HERCEPTIN. Early Breast Cancer (EBC) ONTRUZANT (trastuzumab) is indicated for the treatment of patients with early stage breast cancer with ECOG 0-1 status, whose tumours overexpress HER2, following surgery and…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations There is a risk of medication errors between ONTRUZANT (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 ONTRUZANT (trastuzumab) and not KADCYLA (trastuzumab emtansine).
Ensure that the recommended ONTRUZANT (trastuzumab) dose is administered (see Recommended Dose and Dosage Adjustment section). ONTRUZANT should be prescribed using both the trade name and non-proprietary name. Do not substitute ONTRUZANT 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.
2 Recommended Dose and Dosage Adjustment Health Canada has not authorized an indication for pediatric use (see WARNINGS AND PRECAUTIONS, Special Populations, Pediatrics).
Early Breast Cancer (EBC) 3-Weekly Schedule:
The recommended initial loading dose is 8 mg/kg ONTRUZANT (trastuzumab) administered as a 90-minute infusion. The recommended maintenance dose is 6 mg/kg ONTRUZANT 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 ONTRUZANT is 4 mg/kg followed by 2 mg/kg every week. Ontruzant Page 7 of 128 See Clinical Trials – Reference Biologic Drug section for chemotherapy combination dosing.
Metastatic Breast Cancer (MBC) Weekly schedule:
The recommended initial loading dose is 4 mg/kg ONTRUZANT administered as a 90-minute infusion. The recommended weekly maintenance dose is 2 mg/kg ONTRUZANT and can be administered as a 30-minute infusion if the initial loading dose was well tolerated.
The adverse drug reaction profiles reported in clinical studies that compared ONTRUZANT to the reference biologic drug were comparable. The description of adverse reactions in this section is based on clinical experience with the reference biologic drug.
2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials may be useful for identifying and approximating rates of adverse drug reactions in real-world use. Early Breast Cancer (EBC) HERA (adjuvant sequential: use of trastuzumab following surgery and after chemotherapy) Please see WARNINGS AND PRECAUTIONS: Cardiovascular/Cardiotoxicity/Early Breast Cancer – Table 5, Table 6, Table 7 and Table 8 for a description of the absolute numbers and rates of cardiac endpoints in HERA as well as the median time to return to baseline LVEF/ stabilizations of LVEF in the HERA trial.
The HERA trial is a randomized, open label study in patients with HER2 positive EBC. Table 14 displays adverse events which were reported after 8 years of median follow up in ≥ 1% of patients, by study treatment. 0 Classification Adverse Event Term Observation Only Trastuzumab 1 year N = 1744 N = 1682 No.
(%) No. 0 Classification Adverse Event Term Observation Only Trastuzumab 1 year N = 1744 N = 1682 No. (%) No. 0 Classification Adverse Event Term Observation Only Trastuzumab 1 year N = 1744 N = 1682 No. (%) No. 0 Classification Adverse Event Term Observation Only Trastuzumab 1 year N = 1744 N = 1682 No.
(%) No. (%) Psychiatric Disorders Depression 59 (3) 87 (5) Insomnia 49 (3) 94 (6) Anxiety 32 (2) 56 (3) Sleep Disorder 5 (< 1) 13 (< 1) Renal and Urinary Disorders Dysuria 3 (< 1) 20 (1) Reproductive System and Breast Disorders Breast Pain 26 (1) 36 (2) Vaginal Haemorrhage 20 (1) 23 (1) Vulvovaginal Dryness 16 (< 1) 23 (1) Breast Mass 22 (1) 17 (1) Vaginal Discharge 9 (< 1) 15 (< 1) Endometrial Hyperplasia 13 (< 1) 17 (1) Respiratory, Thoracic and Mediastinal Disorders Cough 61 (3) 116 (7) Dyspnea 46 (3) 81 (5) Oropharnygeal Pain 14 (< 1) 40 (2) Epistaxis 3 (< 1) 29 (2) Dyspnea Exertional 16 (< 1) 32 […]
Please see the Serious Warnings and Precautions Box at the beginning of Part I:
Health Professional Information. General Therapy with ONTRUZANT should only be initiated under supervision of a physician experienced in the treatment of cancer patients. When using in combination with PERJETA (pertuzumab) and docetaxel, consult Product Monographs for PERJETA and docetaxel for further information on these drugs.
In order to improve traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file. Early Breast Cancer The safety of the various combination chemotherapy regimens prior to trastuzumab therapy was not separately analyzed in the HERA trial.
The data provided in the Product Monograph reflects the safety and efficacy of trastuzumab for the recommended 1-year treatment duration. Ontruzant Page 13 of 128 Benzyl Alcohol Benzyl alcohol, used as a preservative in BWFI, has been associated with toxicity in neonates and children up to 3 years old.
For patients with a known hypersensitivity to benzyl alcohol (the preservative in BWFI), reconstitute ONTRUZANT with Sterile Water for Injection (SWFI). Use SWFI-reconstituted ONTRUZANT immediately and discard the vial (see DOSAGE AND ADMINISTRATION).
Selection of Patients / Diagnostic Tests Early Breast Cancer (EBC)/Metastatic Breast Cancer (MBC): ONTRUZANT should only be used in patients whose tumours overexpress HER2 as determined by immunohistochemistry. CISH or FISH testing for HER2 status also may be used, provided that the testing is done in experienced laboratories that have validated the test.
To ensure accurate and reproducible results, the protocol described in the package insert of an appropriate diagnostic test needs to be strictly followed. However, based on the current scientific knowledge, no standard test can be recommended at this time.
ONTRUZANT (trastuzumab) is contraindicated in patients with known hypersensitivity to trastuzumab, Chinese Hamster Ovary (CHO) cell proteins, or any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see Dosage Forms, Strengths, Composition and Packaging. When using in combination with PERJETA (pertuzumab) and docetaxel, consult Product Monographs for PERJETA and docetaxel for further information on these drugs.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Trastuzumab in Canada.
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Brand names are compiled from public regulatory records for active-ingredient mapping only. Drugvu is not affiliated with any manufacturer. This is not medical advice.
ONTRUZANT 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 ONTRUZANT administered as a 90-minute infusion. The recommended maintenance dose is 6 mg/kg ONTRUZANT 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 Patients with MBC or MGC should be treated with ONTRUZANT until progression of disease or unmanageable toxicity.
Patients with EBC should be treated for 1 year or until disease recurrence or unacceptable toxicity, whichever occurs first (see WARNINGS AND PRECAUTIONS, Cardiovascular). Extending treatment in EBC beyond one year is not recommended (see Clinical Trials - Reference Biologic Drug, Early Breast Cancer (EBC), HERA).
Dose Reduction If the patient develops an infusion-related reaction (IRR), the infusion rate of ONTRUZANT may be slowed or interrupted. No reductions in the dose of trastuzumab were made during clinical trials. Patients may continue therapy with ONTRUZANT 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 1 depicts the criteria for permanent discontinuation of trastuzumab for cardiac dysfunction in pivotal studies in adjuvant breast cancer.
Table 1 Criteria for Permanent Discontinuation for Cardiac Dysfunction in Pivotal St udies 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 trastuzumab held for 2 consecutive cycles NSABP B-31, NCCTG N9831 and BCIRG- 006 required required if trastuzumab held for 2 consecutive cycles, or for 3 intermittent cycles; investigator may choose to discontinue permanently sooner Ontruzant Page 8 of 128 Dose Holding Monitoring of Cardiac Function (also see WARNINGS AND PRECAUTIONS, Cardiovascular, Cardiotoxicity) Table 2 Recommendations for Continuation or Withdrawal of Trastuzumab 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 Ontruzant Continue Ontruzant Hold Ontruzant and repeat MUGA or ECHO after 4 weeks 1–5 percentage points below LLN Continue Ontruzantb Hold Ontruzant and repeat MUGA or ECHO after 4 weeksb,c Hold Ontruzant and repeat MUGA or ECHO after 4 weeksc,d ≥ 6 percentage points below LLN Continue Ontruzant and repeat MUGA or ECHO after 4 weeksd Hold Ontruzant and repeat MUGA or ECHO after 4 weeksc,d Hold Ontruzant and repeat MUGA or ECHO after 4 weeksc,c a Based on NSABP B-31 trial protocol.
Modified to include recommendations for cardiology consultation or treatment of cardiac dysfunction (or both) w hen appropriate, as indicated in the subsequent footnotes. b Consider cardiac assessment and initiation of angiotensin converting-enzyme inhibitor therapy.
c After tw o holds, consider permanent discontinuation of Ontruzant. d Initiate angiotensin converting-enzyme inhibitor therapy and refer to cardiologist. LLN = low er limit of normal; MUGA = multiple-gated acquisition scan; ECHO = echocardiography.
*Source: Mackey JR, Clemons M, Côté MA, et al. Cardiac management […]
There is no standard method of staining and no standard for the type of antibodies used. The grading for overexpression is subjective, and the signal may fade with time on stored slides. The test method for HER2 overexpression used to determine eligibility of patients for inclusion in the MBC clinical trials employed immunohistochemical staining for HER2 of fixed material from tissue biopsy using the murine monoclonal antibodies CB11 and 4D5.
Patients classified as staining 2+ or 3+ were included, while those staining 0 or 1+ were excluded. Greater th an 70% of patients enrolled exhibited 3+ overexpression. The data suggest that beneficial effects were greater among those patients with higher levels of overexpression of HER2.
In the studies, an investigative clinical trial assay was employed which utilized a 0 to 3+ scale. The degree of HER2 overexpression indicated by different test methods may not correlate with that used as the eligibility criterion for inclusion in the clinical trials.
For example, a validated immunohistochemical (IHC) test also utilizes a scale of 0 to 3+. A reading of 3+ with the validated IHC test is likely to correspond to that of a 2+ or 3+ with the investigative clinical tr ial assay. A 2+ reading with the validated IHC test would likely incorporate a significant number of patients who were scored as 1+ by the investigative clinical trial assay.
These patients (1+) would not have met the inclusion criteria. Test methods having increased sensitivity, relative to the investigative clinical trial assay, may alter the benefit-to-risk ratio compared to that seen in the clinical trials.
In deciding which patients should receive ONTRUZANT, the risk of cardiac dysfunction (see WARNINGS and PRECAUTIONS) must be weighed against the potential benefits of treatment, especially for those not in the high range of HER2 overexpression.
For inclusion criteria in terms of HER2 expression in clinical trials in EBC, see Clinical Trials – Reference Biologic Drug section.
Metastatic Gastric Cancer (MGC):
ONTRUZANT should only be administered to patients with MGC whose tumours have HER2 overexpression as determined by validated immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) testing. The testing should be done in experienced laboratories that have validated the test.
Ontruzant Page 14 of 128 Patients are eligible for ONTRUZANT treatment if they demonstrate strong HER2 protein overexpression, defined by a 3+ score by IHC, or a 2+ score by IHC and a positive FISH result.
Cardiovascular Cardiotoxicity:
Administration of ONTRUZANT can result in the development of ventricular dysfunction and congestive heart failure. In the adjuvant treatment setting, the incidence of cardiac dysfunction was higher in patients who received trastuzumab plus chemotherapy versus chemotherapy alone.
In patients with EBC, an increase in the incidence of symptomatic and asymptomatic cardiac events was observed when trastuzumab was administered after anthracycline-containing chemotherapy compared to administration with a non-anthracycline regimen of docetaxel and carboplatin.
The incidence was more marked when trastuzumab was administered concurrently with a taxane than when administered sequentially to a taxane. In the metastatic setting, the incidence and severity of cardiac dysfunction were particularly high in patients who received trastuzumab concurrently with anthracyclines and cyclophosphamide.
The incidence of cardiac adverse events was also higher in patients with previous exposure to anthracyclines based on post-marketing data. 8 days), trastuzumab may persist in the circulation for approximately 24 weeks (range: 22-28 weeks) after stopping treatment with ONTRUZANT.
Since the use of an anthracycline during this period could possibly be associated with an increased risk of cardiac dysfunction, a thorough assessment of the risks versus the potential benefits is […]