Herceptin S.C

/ Roche

HER2 testing is mandatory prior to initiation of therapy. Treatment should only be initiated by a physician experienced in the administration of cytotoxic chemotherapy, and should be administered by a healthcare professional only. It is important to check the product labels to ensure that the correct formulation (intravenous or subcutaneous fixed dose) is being administered to the patient, as prescribed. This subcutaneous formulation is not intended for intravenous administration and should be administered via a subcutaneous injection only. In order to prevent medication errors it is important to check the vial labels to ensure that the drug being prepared and administered is Herceptin (trastuzumab) and not Kadcyla (trastuzumab emtansine).
Posology: The recommended dose for Trastuzumab subcutaneous formulation is 600 mg irrespective of the patient’s body weight. No loading dose is required. This dose should be administered subcutaneously over 2-5 minutes every three weeks. In the pivotal trial (BO22227) Trastuzumab subcutaneous formulation was administered in the neoadjuvant/adjuvant setting in patients with early breast cancer. The preoperative chemotherapy regimen consisted of docetaxel (75 mg/m²) followed by FEC (5FU, epirubicin and cyclophosphamide) at a standard dose. For chemotherapy combination  dosing. See prescribing information for full details.
Duration of treatment: Patients with MBC 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 the drug 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 for paclitaxel, docetaxel or aromatase inhibitor for information on dose reduction or delays. If left ventricular ejection fraction (LVEF) percentage drops ≥ 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 has declined further, or if symptomatic congestive heart failure (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.
Missed doses: If the patient misses a dose of subcutaneous formulation, it is recommended to administer the next 600 mg dose (i.e. the missed dose) as soon as possible. The interval between consecutive subcutaneous formulation administrations should not be less than three weeks.
Special populations: Dedicated pharmacokinetic studies in older people and those with renal or hepatic impairment have not been carried out. In a population pharmacokinetic analysis, age and renal impairment were not shown to affect trastuzumab disposition.
Paediatric population: There is no relevant use of Trastuzumab in the paediatric population.
Method of administration: The 600 mg dose should be administered as a subcutaneous injection only over 2-5 minutes every three weeks. The injection site should be alternated between the left and right thigh. New injections should be given at least 2.5 cm from the old site and never into areas where the skin is red, bruised, tender, or hard. During the treatment course with Trastuzumab subcutaneous formulation other medicinal products for subcutaneous administration should preferably be injected at different sites. Patients should be observed for six hours after the first injection and for two hours after subsequent injections for signs or symptoms of administration-related reactions.
see prescribing information for full details.

Breast cancer: Metastatic breast cancer: Treatment of Adult Patients with HER2 Positive Metastatic Breast Cancer (MBC): As Monotherapy for the treatment of those patients who have received at least two chemotherapy regimens for their metastatic disease. Prior chemotherapy must have included at least an anthracycline and a taxane unless patients are unsuitable for these treatments. Hormone receptor positive patients must also have failed hormonal therapy, unless patients are unsuitable for these treatments. In combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease and for whom an anthracycline is not suitable. In combination with docetaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease. In combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormonereceptor positive MBC, not previously treated.
Early breast cancer: Treatment of adult patients with HER2 positive early breast cancer (EBC). Following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable). Following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel. In combination with adjuvant  chemotherapy consisting of docetaxel and carboplatin. In combination with neoadjuvant chemotherapy followed by adjuvant Trastuzumab therapy, for locally advanced (including inflammatory) disease or tumours > 2 cm in diameter. Trastuzumab should only be used in patients with metastatic or early breast cancer whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay.

Hypersensitivity to trastuzumab, murine proteins, hyaluronidase or to any of the other. Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.

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. 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 exposure, should undergo baseline cardiac assessment including history and physical examination and electrocardiogram (ECG), echocardiogram, and/or multigated acquisition (MUGA) scan or magnetic resonance imaging.
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 the adjuvant treatment setting. In patients with EBC an increase in the incidence of symptomatic and asymptomatic cardiac events was observed when Trastuzumab (intravenous formulation) was administered after anthracycline-containing chemotherapy compared to administration with a non-anthracycline regimen of docetaxel and carboplatin and was more marked when Trastuzumab (intravenous formulation) 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., with 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.
Administration-related reactions: Administration-related reactions (ARRs) are known to occur with Trastuzumab subcutaneous formulation. Premedication may be used to reduce risk of occurrence of ARRs. Pulmonary events: Caution is recommended with Trastuzumab subcutaneous formulation as severe pulmonary events have been reported with the use of the intravenous formulation in the post-marketing setting. These events have occasionally been fatal and may occur as part of an infusion-related reaction or with delayed onset.
See prescribing information for full details.

Nasopharyngitis, Neutropenic sepsis, Cystitis, Herpes zoster, Influenza, Sinusitis Skin infection, Rhinitis, Upper respiratory tract infection, Urinary tract infection Erysipelas, Cellulitis, Pharyngitis, Febrile neutropenia, Anaemia, Neutropenia, White blood cell count decreased/leucopenia.
See prescribing information for full details.

No formal drug interaction studies have been performed. Clinically significant interactions between this drug and the concomitant medicinal products used in clinical trials have not been observed.
See prescribing information for full details.

Pregnancy: Women of childbearing potential should be advised to use effective contraception during treatment with Trastuzumab and for 7 months after treatment has concluded.
Lactation: 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.
See prescribing information for full details.

Single doses of up to 960 mg of Trastuzumab subcutaneous formulation have been administered with no reported untoward effects.

Storage: Once transferred from the vial to the syringe the medicinal product is physically and chemically stable for 48 hours at 2°C – 8°C and subsequently 6 hours at ambient temperature (max. 30°C) in diffused daylight, and that for one single period of storage. As this formulation does not contain any antimicrobial-preservative, from a microbiological point of view, the medicine should be used immediately.
Compatibility: Subcutaneous formulation is a ready to use solution which should not be mixed or diluted with other products.