Ontruzant

1). 4), and should be administered by a healthcare professional only. Ontruzant intravenous formulation is not intended for subcutaneous administration and should be administered via an intravenous infusion only. g. trastuzumab emtansine or trastuzumab deruxtecan).

4 Posology Metastatic breast 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.

Weekly schedule The recommended initial loading dose of Ontruzant is 4 mg/kg body weight. The recommended weekly maintenance dose of Ontruzant 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 Summary of Product Characteristics (SmPC) for 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, see the SmPC for anastrozole or other aromatase inhibitors).

Early breast cancer Three-weekly and weekly schedule As a three-weekly regimen the recommended initial loading dose of Ontruzant is 8 mg/kg body weight. The recommended maintenance dose of Ontruzant 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. 1 for chemotherapy combination dosing. 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 Ontruzant until progression of disease.

Summary of the safety profile Amongst the most serious and/or common adverse reactions reported in Ontruzant usage to date are cardiac dysfunction, infusion-related reactions, haematotoxicity (in particular neutropenia), infections and pulmonary adverse reactions.

Tabulated list of adverse reactions In this section, the following categories of frequency have been used: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Presented in Table 1 are adverse reactions that have been reported in association with the use of intravenous trastuzumab alone or in combination with chemotherapy in pivotal clinical trials and in the post-marketing setting.

All the terms included are based on the highest percentage seen in pivotal clinical trials. In addition, terms reported in the post marketing setting are included in Table 1. Table 1 Undesirable effects reported with intravenous trastuzumab monotherapy or in combination with chemotherapy in pivotal clinical trials (N=8386) and in post-marketing System organ class Adverse reaction Frequency Infections and infestations Infection Very common Nasopharyngitis Very common Neutropenic sepsis Common Cystitis Common Influenza Common Sinusitis Common Skin infection Common Rhinitis Common Upper respiratory tract infection Common Urinary tract infection Common Pharyngitis Common Neoplasms benign, malignant and unspecified (incl.

Cysts and polyps) Malignant neoplasm progression Not known Neoplasm progression Not known Blood and lymphatic system disorders Febrile neutropenia Very common Anaemia Very common Neutropenia Very common White blood cell count decreased/leukopenia Very common Thrombocytopenia Very common Hypoprothrombinaemia Not known Immune thrombocytopenia Not known Immune system disorders Hypersensitivity Common +Anaphylactic reaction Rare +Anaphylactic shock Rare Metabolism and nutrition disorders Weight decreased/Weight loss Very common Anorexia Very common Tumour lysis syndrome Not known Hyperkalaemia Not known Psychiatric disorders Insomnia Very common 12 System organ class Adverse reaction Frequency Anxiety Common Depression Common Nervous system disorders 1Tremor Very common Dizziness Very common Headache Very common Paraesthesia Very common Dysgeusia Very common Peripheral neuropathy Common Hypertonia Common Somnolence Common Eye disorders Conjunctivitis Very common Lacrimation increased Very common Dry eye Common Papilloedema Not known Retinal haemorrhage Not known Ear and labyrinth disorders Deafness Uncommon Cardiac disorders 1Blood pressure decreased Very common 1Blood pressure increased Very common 1Heart beat irregular Very common 1Cardiac flutter Very common Ejection fraction decreased* Very common +Cardiac failure (congestive) Common +1Supraventricular tachyarrhythmia Common Cardiomyopathy Common 1Palpitation Common Pericardial effusion Uncommon Cardiogenic shock Not known Gallop rhythm present Not known Vascular disorders Hot flush Very common +1Hypotension Common Vasodilatation Common Respiratory, thoracic and mediastinal disorders +Dyspnoea Very common Cough Very common Epistaxis Very common Rhinorrhoea Very common +Pneumonia Common Asthma Common Lung disorder Common +Pleural effusion Common +1Wheezing Uncommon Pneumonitis Uncommon +Pulmonary fibrosis Not known +Respiratory distress Not known +Respiratory failure Not known +Lung infiltration Not known +Acute pulmonary oedema Not known +Acute respiratory distress syndrome Not known +Bronchospasm Not known +Hypoxia Not known +Oxygen saturation decreased Not known Laryngeal oedema Not known Orthopnoea Not known Pulmonary oedema Not known Interstitial lung disease Not known 13 System organ class Adverse reaction Frequency Gastrointestinal disorders Diarrhoea Very common Vomiting Very common Nausea Very common 1Lip swelling Very common Abdominal pain Very common Dyspepsia Very common Constipation Very common Stomatitis Very common Haemorrhoids Common Dry mouth Common Hepatobiliary disorders Hepatocellular injury Common Hepatitis Common Liver tenderness Common Jaundice Rare Skin and subcutaneous tissue disorders Erythema Very common Rash Very common 1Swelling face Very common Alopecia Very common Nail disorder Very common Palmar-plantar erythrodysaesthesia syndrome Very common Acne Common Dry skin Common Ecchymosis Common Hyperhydrosis Common Maculopapular rash Common Pruritus Common Onychoclasis Common Dermatitis Common Urticaria Uncommon Angioedema Not known Musculoskeletal and connective tissue disorders Arthralgia Very common 1Muscle tightness Very common Myalgia Very common Arthritis Common Back pain Common Bone pain Common Muscle spasms Common Neck Pain Common Pain in extremity Common Renal and urinary disorders Renal disorder Common Glomerulonephritis membranous Not known Glomerulonephropathy Not known Renal failure Not known Pregnancy, puerperium and perinatal conditions Oligohydramnios Not known Renal hypoplasia Not known Pulmonary hypoplasia Not known Reproductive system and breast disorders Breast inflammation/mastitis Common General disorders and administration site conditions Asthenia Very common Chest pain Very common Chills Very common Fatigue Very common Influenza-like symptoms Very common 14 System organ class Adverse reaction Frequency Infusion related reaction Very common Pain Very common Pyrexia Very common Mucosal inflammation Very common Peripheral oedema Very common Malaise Common Oedema Common Injury, poisoning and procedural complications Contusion Common + Denotes adverse reactions that have been reported in association with a fatal outcome.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 1). 6 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.

8). 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. 2). 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. g. every 12 weeks).

1 • Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.