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  • OGIVRI 420 mg
    / Dexcel


    Active Ingredient
    Trastuzumab 420 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    420 mg of lyophilised powder & 20 ml of BWFI).: 1+1

    full basket chart

    Dosage

    Metastatic breast cancer
    Weekly schedule:
    The recommended initial loading dose of trastuzumab is 4 mg/kg body weight. The recommended weekly maintenance dose of trastuzumab is 2 mg/kg body weight, beginning one week after the loading dose.
    Administration in combination with paclitaxel or docetaxel:
    In the pivotal trials (H0648g, M77001), paclitaxel or docetaxel was administered the day following the first dose of trastuzumab (for dose, see the prescribing information of paclitaxel or docetaxel) and immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.
    Administration in combination with an aromatase inhibitor:
    In the pivotal trial (BO16216) trastuzumab and anastrozole were administered from day 1. There were no restrictions on the relative timing of trastuzumab and anastrozole at administration (for dose, of anastrozole or other aromatase inhibitors- Please refer to the license holder for further details.).
    Early breast cancerThree-weekly and weekly schedule:
    As a three-weekly regimen the recommended initial loading dose of trastuzumab is 8 mg/kg body weight. The recommended maintenance dose of trastuzumab 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.
    Breast cancer and gastric cancer
    Duration of treatment:
    Patients with MBC or MGC should be treated with trastuzumab until progression of disease. Patients with EBC should be treated with trastuzumab for 1 year or until disease recurrence, whichever occurs first, extending treatment in EBC beyond one year is not recommended.
    Dose reduction:
    No reductions in the dose of trastuzumab were made during clinical trials. Patients may continue therapy during periods of reversible, chemotherapy-induced myelosuppression but they should be monitored carefully for complications of neutropenia during this time. Refer to the prescribing information of paclitaxel, docetaxel or aromatase inhibitor for information on dose reduction or delays.
    Paedatric Patients
    There is no relevant use of trastuzumab in the paediatric population.


    Indications

    Metastatic Breast Cancer (MBC)
    Indicated for the treatment of patients with metastatic breast cancer who have tumors that overexpress HER2;

    As a single agent, for the treatment of those patients who have received one or more chemotherapy regimens for their metastatic disease

    1. In combination with Paclitaxel or Docetaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease.
    2. 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.

    Ogivri 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)
    Trastuzumab 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.
    Trastuzumab 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.


    Contra-Indications

    Hypersensitivity to the active substance, murine proteins, or to any of the excipients.
    Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.


    Special Precautions

    Traceability
    In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded.
    HER2 testing must be performed in a specialised laboratory which can ensure adequate validation of the testing procedures.
    Currently no data from clinical trials are available on re-treatment of patients with previous exposure to trastuzumab in the adjuvant setting.
    Cardiac dysfunction
    General considerations
    Patients treated with trastuzumab are at increased risk for developing CHF (New York Heart Association [NYHA] Class II-IV) 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. Monitoring may help to identify patients who develop cardiac dysfunction. 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 trastuzumab. A careful risk-benefit assessment should be made before deciding to treat with trastuzumab.
    Trastuzumab may persist in the circulation for up to 7 months after stopping the 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. If anthracyclines are used, the patient’s cardiac function should be monitored carefully.
    Formal cardiological assessment should be considered in patients in whom there are cardiovascular concerns following baseline screening. In all patients cardiac function should be monitored during treatment (e.g. every 12 weeks). Monitoring may help to identify patients who develop cardiac dysfunction. Patients who develop asymptomatic cardiac dysfunction may benefit from more frequent monitoring (e.g. every 6-8 weeks). If patients have a continued decrease in left ventricular function, but remain asymptomatic, the physician should consider discontinuing therapy if no clinical benefit of trastuzumab therapy has been seen.
    The safety of continuation or resumption of trastuzumab in patients who experience cardiac dysfunction has not been prospectively studied. If LVEF percentage drops ≥10 points from baseline AND to below 50%, treatment should be suspended and a repeat LVEF assessment performed within approximately 3 weeks. If LVEF has not improved, or declined further, or symptomatic CHF has developed, discontinuation of trastuzumab should be strongly considered, unless the benefits for the individual patient are deemed to outweigh the risks. All such patients should be referred for assessment by a cardiologist and followed up.
    If symptomatic cardiac failure develops during trastuzumab therapy, it should be treated with standard medicinal products for CHF.
    Most patients who developed CHF or asymptomatic cardiac dysfunction in pivotal trials improved with standard CHF treatment consisting of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and a beta-blocker. The majority of patients with cardiac symptoms and evidence of a clinical benefit of trastuzumab treatment continued on therapy without additional clinical cardiac events.
    Metastatic breast cancer
    Trastuzumab and anthracyclines should not be given concurrently in combination in the MBC setting.
    Patients with MBC who have previously received anthracyclines are also at risk of cardiac dysfunction with trastuzumab treatment, although the risk is lower than with concurrent use of trastuzumab and anthracyclines.
    Early breast cancer
    For patients with EBC, 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 trastuzumab. In patients who receive anthracycline-containing chemotherapy further monitoring is recommended, and should occur yearly up to 5 years from the last administration of trastuzumab, or longer if a continuous decrease of LVEF is observed.
    Patients with history of myocardial infarction (MI), angina pectoris requiring medical treatment, history of or existing CHF (NYHA Class II –IV), LVEF of < 55%, other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant cardiac valvular disease, poorly controlled hypertension (hypertension controlled by standard medical treatment eligible), and hemodynamic effective pericardial effusion were excluded from adjuvant and neoadjuvant EBC pivotal trials with trastuzumab and therefore treatment cannot be recommended in such patients.
    Adjuvant treatment
    Trastuzumab and anthracyclines should not be given concurrently in combination in the adjuvant treatment setting.
    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 and was more marked when trastuzumab was administered concurrently with taxanes than when administered sequentially to taxanes. Regardless of the regimen used, most symptomatic cardiac events occurred within the first 18 months.
    Neoadjuvant-adjuvant treatment
    In patients with EBC eligible for neoadjuvant-adjuvant treatment, trastuzumab should be used concurrently with anthracyclines only in chemotherapy-naive patients and only with low-dose anthracycline regimens i.e. maximum cumulative doses: of doxorubicin 180 mg/m2 or epirubicin 360 mg/m2.
    If patients have been treated concurrently with a full course of low-dose anthracyclines and trastuzumab in the neoadjuvant setting, no additional cytotoxic chemotherapy should be given after surgery. In other situations, the decision on the need for additional cytotoxic chemotherapy is determined based on individual factors.
    Experience of concurrent administration of trastuzumab with low dose anthracycline regimens is currently limited to the trial MO16432.
    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. These symptoms can be treated with an analgesic/antipyretic such as meperidine or paracetamol, or an antihistamine such as diphenhydramine. The majority of patients experienced resolution of symptoms and subsequently received further infusions of trastuzumab.
    Serious reactions have been treated successfully with supportive therapy such as oxygen, beta- agonists, and corticosteroids. In rare cases, these reactions are associated with a clinical course culminating in a fatal outcome.
    Pulmonary events
    Severe pulmonary events have been reported with the use of trastuzumab in the post-marketing setting. 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. Caution should be exercised for pneumonitis, especially in patients being treated concomitantly with taxanes.
    Sorbitol content
    This drug contains 322.6 mg sorbitol in each vial.
    Patients with hereditary fructose intolerance (HFI) must not be given this medicine unless strictly necessary.
    A detailed history with regards to HFI symptoms has to be taken
    of each patient prior to being given this medicinal product.
    Please refer to the license holder for further details.


    Side Effects

    Asthenia, Chest pain, Chills, Fatigue, Influenza-like symptoms, Infusion related reaction, Pain , Pyrexia, Mucosal inflammation, Arthralgia , Muscle tightness , Myalgia , Erythema , Rash , Swelling face , Alopecia , Nail disorder , Diarrhoea , Vomiting , Nausea , Lip swelling, Abdominal pain, Dyspepsia, Constipation, Wheezing, Cough, Dyspnoea, Epistaxis, Rhinorrhoea, Hot flush, Blood pressure decreased, Blood pressure increased, Heart beat irregular, Palpitation, Cardiac flutter, Ejection fraction decreased, Conjunctivitis, Lacrimation increased, Tremor, Dizziness, Headache, Febrile neutropenia, Anaemia, Neutropenia, White blood cell count decreased/leukopenia, Infection.


    Drug interactions

    No formal drug interaction studies have been performed. Clinically significant interactions between trastuzumab and the concomitant medicinal products used in clinical trials have not been observed.


    Pregnancy and Lactation

    Women of childbearing potential should be advised to use effective contraception during treatment with trastuzumab and for 7 months after treatment has concluded.

     Trastuzumab should be avoided during pregnancy unless the potential benefit for the mother outweighs the potential risk to the foetus.

    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. Please refer to the license holder for further details.

    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.


    Overdose

    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. Please refer to the license holder for further details.


    Manufacturer
    Biocon Biologics India Limited, India
    Licence holder
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