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HERZUMA is a brand name for Trastuzumab, supplied as a kit. 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 HERZUMA® and the reference biologic drug HERCEPTIN®. • Early Breast Cancer (EBC) HERZUMA® (trastuzumab) is indicated for the treatment of patients with early stage breast cancer with ECOG 0-1 status, whose tumours overexpress HER2, • following surgery…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations There is a risk of medication errors between HERZUMA® (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 HERZUMA® (trastuzumab) and not KADCYLA® (trastuzumab emtansine).
Ensure that the recommended HERZUMA® (trastuzumab) dose is administered (see Recommended Dose and Dosage Adjustment section). HERZUMA® should be prescribed using both the trade name and non-proprietary name. Do not substitute HERZUMA® for or with KADCYLA® (trastuzumab emtansine).
When using in combination with pertuzumab and docetaxel for treatment of patients with HER- 2-positive metastatic breast cancer, consult Product Monographs for pertuzumab 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 Early Breast Cancer (EBC) 3-Weekly Schedule: The recommended initial loading dose is 8 mg/kg HERZUMA® (trastuzumab) administered as a 90-minute infusion. The recommended maintenance dose is 6 page 7 / 117 mg/kg HERZUMA® 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 HERZUMA® is 4 mg/kg followed by 2 mg/kg every week. See clinical trial – reference biological drug section for chemotherapy combination dosing.
Metastatic Breast Cancer (MBC) Weekly schedule:
The recommended initial loading dose is 4 mg/kg HERZUMA® administered as a 90-minute infusion. The recommended weekly maintenance dose is 2 mg/kg HERZUMA® and can be administered as a 30-minute infusion if the initial loading dose was well tolerated.
HERZUMA® 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 adverse drug reaction profiles reported in clinical studies that compared HERZUMA® 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.
1 Clinical Trial Adverse Drug 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 drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. 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 5~8 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. (%) Blood and Lymphatic System Disorders Anemia 4 (<1) 15 (<1) Cardiac Disorders Cardiac Failure Congestive 19 (1) 93 (6)* Palpitations 20 (1) 73 (4) Tachycardia 5 (<1) 25 (1) Ear and Labyrinth Disorders Vertigo 14 (<1) 33 (2) Tinnitus 6 (<1) 7 (<1) Eye Disorders Conjunctivitis 7 (<1) 21 (1) Vision blurred 6 (<1) 16 (<1) Lacrimation Increased 1 (<1) 12 (<1) Gastrointestinal Disorders Diarrhea 23 (1) 156 (9) Nausea 37 (2) 134 (8) Vomiting 17 (<1) 76 (5) Constipation 27 (2) 55 (3) Abdominal Pain 25 (1) 60 (4) Abdominal Pain Upper 30 (2) 45 (3) Dyspepsia 14 (<1) 42 (2) Stomatitis 1 (<1) 33 (2) Gastritis 17 (<1) 27 (2) Hemorrhoids 8 (<1) 18 (1) Mouth Ulceration 2 (<1) 13 (<1) General Disorders and Administration Site Conditions Fatigue 83 (5) 198 (12) Edema Peripheral 64 (4) 114 (7) Pyrexia 12 (<1) 119 (7) Asthenia 42 (2) 102 (6) Chills 1 (<1) 101 (6) Chest Pain 36 (2) 65 (4) Influenza Like Illness 7 (<1) 51 (3) Pain 24 (1) 23 (1) Spinal Pain 21 (1) 21 (1) Chest Discomfort 6 (<1) 27 (2) Axillary Pain 17 (<1) 18 (1) Edema 10 (<1) 23 (1) Mucosal Inflammation 1 (<1) 18 (1) Malaise 1 (<1) 18 (1) Immune System Disorders Seasonal Allergy 6 (<1) 14 (<1) Infections and Infestations# Nasopharyngitis 65 (4) 192 (11) Influenza 17 (<1) 95 (6) Upper Respiratory Tract Inflection 31 (2) 53 (3) Urinary Tract Infection 19 (1) 54 (3) Rhinitis 11 (<1) 44 (3) Bronchitis 25 (1) 36 (2) Cystitis 15 (<1) 28 (2) page 29 / 117 Adverse Event Term Observation Only trastuzumab 1 year N = 1744 N = 1682 No.
Please see the Serious Warnings and Precautions Box at the beginning of Part I:
Health Professional Information. General Therapy with HERZUMA® should only be initiated under supervision of a physician experienced in the treatment of cancer patients. page 13 / 117 When using in combination with pertuzumab and docetaxel, consult Product Monographs for pertuzumab 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 (EBC) 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.
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 HERZUMA® with Sterile Water for Injection (SWFI).
Use SWFI-reconstituted HERZUMA® immediately and discard the vial (see DOSAGE AND ADMINISTRATION).
Cardiovascular Cardiotoxicity:
Administration of HERZUMA® 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.
• HERZUMA® (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 pertuzumab and docetaxel, consult Product Monographs for pertuzumab 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.
The recommended initial loading dose is 8 mg/kg HERZUMA® administered as a 90-minute infusion. The recommended maintenance dose is 6 mg/kg HERZUMA® 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 trastuzumab 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 – Reference Biological Drug, Early Breast Cancer (EBC), HERA).
Dose Reduction No reductions in the dose of trastuzumab were made during clinical trials. Patients may continue therapy with HERZUMA® 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 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 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 page 8 / 117 Dose Holding Monitoring of Cardiac Function (also see WARNINGS AND PRECAUTIONS, Cardiovascular, Cardiotoxicity) Table 2 Recommendations for Continuation or Withdrawal of HERZUMA® 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 HERZUMA® Continue HERZUMA® Hold HERZUMA® and repeat MUGA or ECHO after 4 weeks 1–5 percentage points below LLN Continue HERZUMA® b Hold HERZUMA® and repeat MUGA or ECHO after 4 weeks b,c Hold HERZUMA® and repeat MUGA or ECHO after 4 weeks c,d ≥6 percentage points below LLN Continue HERZUMA® and repeat MUGA or ECHO after 4 weeksd Hold HERZUMA® and repeat MUGA or ECHO after 4 weeks c,d Hold HERZUMA® 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 HERZUMA®. 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.
Health Canada has not authorized an indication for pediatric use (see […]
(%) No. (%) Sinusitis 7 (<1) 36 (2) Pharyngitis 12 (<1) 33 (2) Herpes Zoster 14 (<1) 31 (2) Lower Respiratory Tract Infection 14 (<1) 17 (1) Gastroenteritis 10 (<1) 9 (<1) Oral Herpes 5 (<1) 15 (<1) Cellulitis 6 (<1) 14 (<1) Vaginal Infection 10 (<1) 13 (<1) Ear Infection 6 (<1) 9 (<1) Localised Infection - 18 (1) Injury, Poisoning and Procedural Complications Confusion 12 (<1) 13 (<1) Investigations Ejection Fraction Decreased 11 (<1) 64 (4) Weight Increased 23 (1) 42 (2) Weight Decreased 10 (<1) 10 (<1) Metabolism and Nutrition Disorders Decreased Appetite 17 (<1) 25 (1) Hypercholesterolemia 15 (<1) 16 (<1) Musculoskeletal and Connective Tissue Disorders Arthralgia 148 (8) 223 (13) Back Pain 105 (6) 145 (9) Pain in Extremity 73 (4) 94 (6) Musculoskeletal Pain 66 (4) 75 (4) Myalgia 28 (2) 86 (5) Muscle Spasms 13 (<1) 68 (4) Bone Pain 31 (2) 54 (3) Musculoskeletal Chest Pain 37 (2) 43 (3) Osteoporosis 29 (2) 30 (2) Neck Pain 18 (1) 29 (2) Osteoarthritis 18 (1) 28 (2) Osteopenia 12 (<1) 19 (1) Musculoskeletal Stiffness 8 (<1) 14 (<1) Neoplasms Benign, Malignant and Unspecified (Incl Cysts And Polyps) Contralateral Breast Cancer 10 (<1) 23 (1) Uterine Letomyoma 7 (<1) 9 (<1) Nervous System Disorders Headache 73 (4) 199 (12) Dizziness 39 (2) 80 (5) Paraesthesia 21 (1) 42 (2) Hypoaesthesia 15 (<1) 25 (1) Lethargy 8 (<1) 20 (1) Migraine 3 (<1) 15 (<1) Peripheral Sensory Neuropathy 6 (<1) 14 (<1) Pregnancy, Puerperium and Perinatal Conditions Pregnancy 11 (<1) 22 (1) 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) page 30 / 117 Adverse Event Term Observation Only trastuzumab 1 year N = 1744 N = 1682 No.
(%) No. (%) 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 (2) Rhinorrhoea 5 (<1) 27 (2) Nasal Dryness 1 (<1) 25 (1) Asthma 7 (<1) 9 (<1) Skin and Subcutaneous Tissue Disorders Rash 25 (1) 98 (6) Onychoclasis 2 (<1) 53 (3) Nail Disorder 2 (<1) 52 (3) Pruritus 14 (<1) 58 (3) Dry Skin 4 (<1) 22 (1) Erythema 8 (<1) 39 (2) Alopecia 6 (<1) 18 (1) Scar Pain 18 (1) 21 (1) Eczema 9 (<1) 19 (1) Hyperhidrosis 10 (<1) 17 (1) Urticaria 4 (<1) 13 (<1) Acne 3 (<1) 17 (1) Vascular Disorders Hot Flush 129 (7) 163 (10) Hypertension 61 (3) 104 (6) Lymphoedema 69 (4) 80 (5) Flushing 10 (<1) 14 (<1) Hypotension 4 (<1) 14 (<1) Multiple occurrences of the same adverse even in one individual counted only once.
* 69 out of the total 93 Cardiac Failure Congestive events reported in the 1-year trastuzumab arm occurred within 365 […]
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-market data. 8 days), trastuzumab may persist in the circulation for approximately 24 weeks (range: 22-28 weeks) after stopping treatment with HERZUMA®.
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 recommended in addition to careful cardiac monitoring.
If possible, physicians should avoid anthracycline based therapy while trastuzumab persists in the circulation. Patients who receive HERZUMA® either as a component of adjuvant treatment or as a treatment for metastatic HER2 positive breast cancer may experience signs and symptoms of cardiac dysfunction such as dyspnea, increased cough, paroxysmal nocturnal dyspnea, peripheral edema, S3 gallop, or reduced ejection fraction.
Cardiac dysfunction associated with therapy with HERZUMA® may be severe and has been associated with disabling cardiac failure, death, and mural thrombosis leading to stroke. Left ventricular function should be evaluated in all patients prior to and during treatment with HERZUMA®.
If LVEF drops 10 ejection points from baseline and/or to below 50%, HERZUMA® page 14 / 117 should be withheld and a repeat LVEF assessment performed within approximately 3 weeks. If LVEF has not improved, or declined further, discontinuation of HERZUMA® should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks.
The scientific basis of cardiac dysfunction has been incompletely investigated in pre-clinical studies. Extreme caution should be exercised in treating patients with pre-existing cardiac dysfunction, and in EBC, in those patients with an LVEF of 55% or less.
Candidates for treatment with HERZUMA® as part of adjuvant treatment for operable breast cancer or for MBC, especially those with prior anthracycline and cyclophosphamide (AC) exposure, should undergo thorough baseline cardiac assessment including history and physical exam, electrocardiogram (ECG) and either 2D echocardiogram or multiple gated acquisition (MUGA) scan.
A careful risk-benefit assessment should be made before deciding to treat with HERZUMA®. Cardiac assessments, as performed at baseline, should be repeated every 3 months during treatment and every 6 months following discontinuation of treatment until 24 months from the last administration of HERZUMA®.
In patients with EBC who receive anthracycline containing chemotherapy further monitoring is recommended, and should occur yearly up to 5 years from the last administration of HERZUMA®, or longer if a continued decrease of LVEF is observed.
Monitoring may help to identify patients who develop cardiac dysfunction. g. every 6-8 weeks). If patients have a continued decrease in left ventricular function, but remain asymptomatic, the physician should consider discontinuing therapy unless the benefits for the individual patient are deemed to outweigh the risks.
If symptomatic cardiac failure develops during therapy with HERZUMA®, it should be treated with the standard medications for this purpose. Discontinuation of HERZUMA® should be strongly considered in patients who develop clinically significant congestive heart failure.
In the MBC clinical trials, approximately two-thirds of patients with cardiac dysfunction were treated for cardiac symptoms, most patients responded to appropriate medical therapy […]