Herzuma

/ Padagis Israel Agencies Ltd

Metastatic breast cancer
Weekly schedule: The recommended initial loading dose is 4 mg/kg body weight. The recommended weekly maintenance dose is 2 mg/kg body weight, beginning one week after the loading dose.
Early breast cancer
Three-weekly and weekly schedule:As a three-weekly regimen the recommended initial loading dose is 8 mg/kg body weight. The recommended maintenance dose at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose. As a weekly regimen (initial loading dose of 4 mg/kg followed by 2 mg/kg every week) concomitantly with paclitaxel following chemotherapy with doxorubicin and cyclophosphamide.
Metastatic gastric cancer
Three-weekly schedule:The recommended initial loading dose is 8 mg/kg body weight. The recommended maintenance dose at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose.
See prescribing information for full details

indicated for the treatment of patients with metastatic breast cancer who have tumours that overexpress HER2;
1. As a single agent, for the treatment of those patients who have received one or more chemotherapy regimens for their metastatic disease.
2. In combination with Paclitaxel or Docetaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease.
3. In combination with an aromatase inhibitor for the treatment of postmenopausal patient with hormone-receptor positive metastatic breast cancer.
Early Breast Cancer (EBC);
indicated to treat patients with HER2 positive early breast cancer following surgery and chemotherapy (neoadjuvant or adjuvant) either alone or in combination with chemotherapy excluding anthracyclines. This drug should only be used in patients whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay.
HER2 Metastatic Gastric Cancer (mGC);
This drug in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of patients with HER2 positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease.
This drug should only be used in patients with metastatic gastric cancer whose tumours have HER2 overexpression as defined by IHC2+ and a confirmatory FISH+ result, or IHC 3+, as determined by an accurate and validated assay

* Hypersensitivity to trastuzumab, murine proteins, or to any of the excipients.
* Severe dyspnea at rest

Cardiac dysfunction
Patients treated with trastuzumab are at increased risk for developing CHF or asymptomatic cardiac dysfunction. These events have been observed in patients receiving trastuzumab therapy alone or in combination with paclitaxel or docetaxel, particularly following anthracycline (doxorubicin or epirubicin) containing chemotherapy. These may be moderate to severe and have been associated with death. In addition, caution should be exercised in treating patients with increased cardiac risk, e.g. hypertension, documented coronary artery disease, CHF, LVEF of <55%, older age. All candidates for treatment with trastuzumab, but especially those with prior anthracycline and cyclophosphamide (AC) exposure, should undergo baseline cardiac assessment including history and physical examination, electrocardiogram (ECG), echocardiogram, and/or multigated acquisition (MUGA) scan or magnetic resonance imaging. 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 this medical product. 7 months after stopping the use of trastuzumab, it may still persist in the circulation. Treatment based on population pharmacokinetic analysis of all available data. Patients who receive anthracyclines after stopping trastuzumab may possibly be at increased risk of cardiac dysfunction. If possible, physicians should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab.
Infusion-related reactions (IRRs) and hypersensitivity
Serious IRRs to trastuzumab infusion including dyspnoea, hypotension, wheezing, hypertension, bronchospasm, supraventricular tachyarrhythmia, reduced oxygen saturation, anaphylaxis, respiratory distress, urticaria and angioedema have been reported. Pre-medication may be used to reduce risk of occurrence of these events. The majority of these events occur during or within 2.5 hours of the start of the first infusion. Should an infusion reaction occur the infusion should be discontinued or the rate of infusion slowed and the patient should be monitored until resolution of all observed symptoms.
Pulmonary events
These events have occasionally been fatal. In addition, cases of interstitial lung disease including lung infiltrates, acute respiratory distress syndrome, pneumonia, pneumonitis, pleural effusion, respiratory distress, acute pulmonary oedema and respiratory insufficiency have been reported. Risk factors associated with interstitial lung disease include prior or concomitant therapy with other anti-neoplastic therapies known to be associated with it such as taxanes, gemcitabine, vinorelbine and radiation therapy. These events may occur as part of an infusion-related reaction or with a delayed onset. Patients experiencing dyspnoea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of pulmonary events. Therefore, these patients should not be treated with trastuzumab.
See prescribing information for full details.

Very common: Infection, Nasopharyngitis, Febrile neutropenia, Anaemia, Neutropenia, White blood cell count decreased/leukopenia, Thrombocytopenia, Weight decreased/Weight loss, Anorexia, Insomnia, Tremor, Dizziness, Headache, Paraesthesia, Dysgeusia, Conjunctivitis, Lacrimation increased, Blood pressure decreased, Blood pressure increased, Heart beat irregular, Cardiac flutter, Ejection fraction decreased, Hot flush, Dyspnoea, Cough, Epistaxis, Rhinorrhoea, Diarrhoea, Vomiting, Nausea, Lip swelling, Abdominal pain, Dyspepsia, Constipation, Stomatitis, Erythema, Rash, Swelling face, Alopecia, Nail disorder, Palmar-plantar erythrodysaesthesia syndrome, Arthralgia, Muscle tightness, Myalgia, Asthenia, Chest pain, Chills, Fatigue, Influenza-like symptoms, Infusion related reaction, Pain, Pyrexia, Mucosal inflammation, Peripheral oedema.
Common: Neutropenic sepsis, Cystitis, Influenza, Sinusitis, Skin infection, Rhinitis, Upper respiratory tract infection, Urinary tract infection, Pharyngitis, Hypersensitivity, Anxiety, Depression, Peripheral neuropathy, Hypertonia, Somnolence, Dry eye, Cardiac failure (congestive), Supraventricular tachyarrhythmia, Cardiomyopathy, Palpitation, Hypotension, Vasodilatation, Pneumonia, Asthma, Lung disorder, Pleural effusion, Haemorrhoids, Dry mouth, Hepatocellular injury, Hepatitis, Liver tenderness, Acne, Dry skin, Ecchymosis, Hyperhydrosis, Maculopapular rash, Pruritus, Onychoclasis, Dermatitis, Arthritis, Back pain, Bone pain, Muscle spasms, Neck Pain, Pain in extremity, renal disorder, Breast inflammation/mastitis, Malaise, Oedema, Contusion
See prescribing information for full details.

No formal drug interaction studies have been performed. Clinically significant interactions between trasuzumab and the concomitant medicinal products used in clinical trials have not been observed.
Effect of trastuzumab on the pharmacokinetics of other antineoplastic agents
Capecitabine showed higher concentrations and a longer half-life when combined with trastuzumab.
See prescribing information for full details.

Women of childbearing potential
Women of childbearing potential should be advised to use effective contraception during treatment with trastuzumab and for 7 months after treatment has concluded
Pregnancy: In the post-marketing setting, cases of foetal renal growth and/or function impairment in association with oligohydramnios, some associated with fatal pulmonary hypoplasia of the foetus, have been reported in pregnant women receiving trastuzumab. Women who become pregnant should be advised of the possibility of harm to the foetus. If a pregnant woman is treated with trastuzumab, or if a patient becomes pregnant while receiving trastuzumab or within 7 months following the last dose of trastuzumab, close monitoring by a multidisciplinary team is desirable.
Lactation: It is not known whether trastuzumab is secreted in human milk. As human IgG1 is secreted into human milk, and the potential for harm to the infant is unknown, women should not breast-feed during trastuzumab therapy and for 7 months after the last dose.

There is no experience with overdose in human clinical trials. Single doses of trastuzumab alone greater than 10 mg/kg have not been administered in the clinical trials; a maintenance dose of 10 mg/kg q3w following a loading dose of 8 mg/kg has been studied in a clinical trial with metastatic gastric cancer patients. Doses up to this level were well tolerated.

Trastuzumab has a minor influence on the ability to drive or use machines.
Dizziness and somnolence may occur during treatment with trastuzumab. Patients experiencing infusion-related symptoms should be advised not to drive and use machines until symptoms abate.