Index of drugs

Metastatic breast cancer. The preparation is indicated for the treatment of adult patients with HER2 positive metastatic breast cancer. Monotherapy for the treatment of patients who have received at least two chemotherapy regimens for metastatic disease; previously used chemotherapy regimens must contain at least anthracyclines and taxanes, unless there were contraindications to this type of treatment; in patients with a positive test for the presence of hormone receptors in which hormone therapy has failed, unless there were contraindications to this type of treatment. In combination with Paclitaxel for the treatment of those patients who have not previously received chemotherapy for metastatic disease and for whom an anthracycline is not recommended. In combination with docetaxel for the treatment of those patients who have not yet received chemotherapy for metastatic disease. In combination with an aromatase inhibitor for the treatment of postmenopausal women who have been successfully tested for the presence of hormone receptors in which metastatic tumor disease has not been treated with trastuzumab.Early stage of breast cancer. The preparation is indicated for the treatment of adult patients with HER2-positive breast cancer at an early stage: after surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if used); after chemotherapy adjuvanted with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel; in combination with chemotherapy adjuvanted with docetaxel and carboplatin; in combination with neoadjuvant chemotherapy and then in adjuvant therapy based on trastuzumab in locally advanced (including inflammatory) breast cancer or in the case of tumor> 2 cm in diameter. The preparation should only be used in patients with metastatic or early breast cancer who have been found, by appropriately validated tests, in tumor cells, either HER2 receptor overexpression or HER2 gene amplification.Gastric cancer with metastases. The preparation in combination with capecitabine or 5-fluorouracil and Cisplatin is indicated for the treatment of adult patients with HER2 positive gastric adenocarcinoma or gastro-oesophageal junction, which have not been treated with anticancer therapy due to disseminated disease. The drug should only be used in patients with metastatic gastric cancer who have been found in HER2 overexpression cells, referred to as IHC2 + and confirmed by SISH or FISH results or by the IHC3 + result. In tumor diagnostics, appropriate and validated assessment methods should be used.

1 vial contains 150 mg of trastuzumab (prepared solution contains 21 mg / ml trastuzumab).

An anti-cancer drug. Trastuzumab is a recombinant humanized monoclonal IgG1 antibody that binds selectively to the human type 2 epidermal growth factor receptor (HER2 receptor). Trastuzumab binds with high affinity and specificity to membrane-bound subdomain IV in the HER2 extracellular domain of the receptor. Binding of trastuzumab to the HER2 receptor inhibits ligand-independent signaling by HER2 and prevents proteolytic cleavage of the extracellular domain as a HER2 activation mechanism. As a result, trastuzumab inhibits the proliferation of tumor cells that overexpress the HER2 receptor. In addition, it is a strong mediator of antibody dependent cellular cytotoxicity (ADCC).In vitro ADT stimulated with trastuzumab was shown to be preferentially exerted on tumor cells overexpressing HER2 compared to tumor cells without HER2 overexpression. Due to non-linear elimination, total clearance increases with decreasing concentration. Therefore, a constant value for T can not be predicted_0,5 trastuzumab. The simulation results indicate that at least 95% of patients achieve concentrations below <1 μg / ml in 7 months.

Hypersensitivity to trastuzumab, mouse protein or any of the excipients. Severe dyspnoea at rest due to complications associated with advanced cancer or requiring oxygen therapy.

In order to improve the traceability of biological preparations, the trade name of the administered drug should be clearly written (or circled) in the patient's records. In order to ensure satisfactory reliability of results, the HER2 designation must be performed in a specialized laboratory. Currently, no data are available from clinical trials that concern patients undergoing re-treatment after prior adjuvant therapy with the preparation. Patients undergoing treatment with the preparation have an increased risk of heart failure (NYHA class II-IV) or asymptomatic cardiac dysfunction. These disorders have been reported in patients treated with the product as monotherapy, in combination with paclitaxel or docetaxel, especially after anthracycline-containing chemotherapy (doxorubicin or epirubicin). The severity of these disorders was moderate or large and could lead to death of the patient. In addition, caution should be exercised when treating patients with an increased risk of cardiac complications, for example hypertension, documented coronary artery disease, heart failure, LVEF <55%, or in elderly patients. All patients initially qualified for treatment, especially patients previously treated with anthracyclines and cyclophosphamide (AC), should be subjected to initial assessment of cardiac function with physical and physical examination, ECG and / or isotopic heart gating (MUGA) or magnetic resonance. Cardiac evaluation should be performed initially, and then repeated every 3 months during the therapy and every 6 months after the end of treatment for 24 months after the last dose of the preparation. The benefit and risk should be carefully assessed before starting the therapy. Trastuzumab may be circulating up to 7 months after the end of treatment with the preparation. Patients who receive anthracycline after discontinuation of trastuzumab may be at an increased risk of developing cardiac dysfunction. If possible, anthracycline-based therapy should be avoided up to 7 months after the end of trastuzumab treatment. If anthracyclines are administered, the heart should be monitored carefully. An appropriate cardiological assessment should be performed in patients who have doubts after initial assessment of cardiovascular capacity. During the therapy, the heart should be monitored (eg every 12 weeks) in all patients. In patients with asymptomatic cardiac disorders, more frequent monitoring is recommended (eg every 6-8 weeks). If patients develop left ventricular insufficiency without clinical symptoms, discontinuation should be considered if no clinical benefit has been observed so far. The safety of continuation or resumption of therapy with the preparation in patients with impaired cardiac function has not been evaluated in prospective clinical trials. If the LVEF value is reduced from baseline by at least 10 percentage points and is <50%, treatment should be withheld and the LVEF repeated for approximately 3 weeks. If the ejection fraction is not improved or further reduced or symptomatic occurs heart failure, it is strongly recommended to discontinue the preparation unless the benefits to the patient outweigh the risks. All such patients should be consulted by a cardiologist and then followed up. If symptomatic heart failure occurs during treatment with the product, standard pharmacological treatment should be instituted. In the majority of patients with heart failure or asymptomatic cardiac dysfunction during fundamental clinical trials, the disorder resolved with standard heart failure therapy consisting of an ACE inhibitor or an angiotensin receptor blocker and a β-blocker. The majority of patients with cardiac symptoms who benefited from the clinical treatment continued treatment without additional cardiac events. The preparation in combination with anthracyclines should not be used simultaneously in metastatic breast cancer. Patients with metastatic breast cancer who have previously been treated with anthracyclines are also at risk for developing cardiac dysfunction during treatment with the product, but it is less than when the product is administered concomitantly with anthracyclines. In patients with early breast cancer, cardiac assessments performed prior to treatment should be repeated every 3 months.during treatment, and then, every 6 months from the moment of discontinuation of treatment until 24 months after the last dose of the preparation. In patients receiving an anthracycline-containing chemotherapy, follow-up testing is recommended and should be repeated once a year until 5 years after the last dose or longer if a continuous decrease in LVEF is observed. Patients with a history of myocardial infarction, angina requiring medication, past or present heart failure (NYHA class II - IV), LVEF <55%, other cardiomyopathy, cardiac arrhythmias requiring treatment, clinically significant heart valve defect, poorly controlled hypertension ( without cases of pharmacologically well-controlled hypertension) or with haemodynamically significant pericardial effusion were excluded from participation in fundamental clinical trials with the use of adjuvant or neo-adjuvant, non-advanced breast cancer. For this reason, treatment with the preparation is not recommended in these patients. The preparation in combination with anthracyclines should not be used simultaneously in adjuvant treatment. In patients with early breast cancer an increase in the incidence of symptomatic and asymptomatic cardiac events has been observed in the population in which the formulation was administered after anthracycline-containing chemotherapy compared to the population receiving an anthracycline-free schedule composed of docetaxel and carboplatin, and this increase was more pronounced in cases when the preparation was administered simultaneously with taxanes, than when the drug was used sequentially after taxanes. Regardless of the used regimen, the majority of symptomatic cardiac events occurred within the first 18 months. The following risk factors for cardiac complications were determined: older age (> 50 years), small LVEF (<55%) at baseline, before or during treatment with Paclitaxel, reduction LVEF by 10-15 percentage points and the use of antihypertensive drugs today or in the past. In patients undergoing treatment with the preparation, the risk of cardiac disorders after chemotherapy was higher with a higher total dose of anthracycline before the start of therapy and in patients with overweight (BMI> 25 kg / m²). In patients with early breast cancer eligible for neoadjuvant-adjuvant treatment, the preparation should be used simultaneously with anthracyclines only in patients not previously treated with chemotherapy and only with a low dose of anthracyclines (eg maximum cumulative dose: doxorubicin 180 mg / m² or epirubicin 360 mg / m²). If the patients were treated simultaneously with the preparation and a low dose of anthracycline in neoadjuvant therapy, no additional chemotherapy should be used after the surgical treatment. In other clinical situations, the decision about the need for additional chemotherapy depends on the individual factors. The experience with the simultaneous administration of trastuzumab and a low dose of an anthracycline is currently limited to two clinical studies. The preparation was administered simultaneously with neoadjuvant chemotherapy, consisting of 3 or 4 cycles of anthracycline-containing chemotherapy (the cumulative dose of doxorubicin was 180 mg / m²and epirubicin 300 mg / m²). The incidence of symptomatic heart dysfunction was low in the study arms in which the preparation was used (up to 1.7% of patients). Clinical experience in patients over 65 is limited. In case of adverse reactions associated with the infusion, the infusion should be stopped or released and the patient should be observed until all symptoms are resolved. Premedication can be used to reduce the risk of these complications. In the treatment of these symptoms can be used analgesics / antipyretics, such as pethidine or Paracetamol, or antihistamines, such as diphenhydramine. Most of these side effects occur during or within 2.5 hours of the first infusion. In the majority of patients the symptoms subsided and then they received further infusions of the preparation. In the treatment of serious adverse reactions, adjuvant therapy such as oxygen therapy, β -agonist agonists and corticosteroids have been successfully used. In rare cases, the reactions are associated with a sudden clinical course ending in the patient's death. In patients with resting dyspnoea associated with complications of advanced cancer and associated diseases, the risk of complications resulting in death associated with the infusion may be increased (in these patients treatment with the preparation is contraindicated). Initial improvement with subsequent deterioration and delayed reactions with rapid clinical course has also been reported. Complications ending in death occurred in the period from several hours, up to one week following the infusion.Very rarely, the onset of symptoms associated with infusion and respiratory distress occurred in patients more than 6 hours after the start of the infusion. Patients should be warned about the possibility of such a delay and should be instructed to contact their doctor if these symptoms occur. When using the preparation, there is a risk of severe respiratory reactions (sometimes fatal to the patient). Cases of interstitial lung disease have been reported. Risk factors for interstitial lung disease include previous or current ongoing anticancer therapies that are known to be associated with it: the use of taxanes, gemcitabine, vinorelbine and radiotherapy. These adverse events may occur as part of the infusion reactions or as delayed reactions. Caution should be exercised due to the possibility of pneumonia, especially in patients receiving taxanes at the same time. It is not appropriate to use the preparation in children and adolescents.

Do not use during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus. After post-marketing use, there were cases of growth and / or renal dysfunction related to oligohydramnios in some of the pregnant women receiving the drug, some associated with fatal underdevelopment of the fetal lung. Pregnant women should be informed about the possibility of fetal damage. If a pregnant woman is being treated with trastuzumab or if the patient becomes pregnant while receiving the medicine or within 7 months after receiving the last dose, she should be inspected by a multidisciplinary team. Women of childbearing potential should use effective contraception during treatment and for at least 7 months afterwards. It is not known whether trastuzumab is excreted in human milk - you should not breastfeed during treatment with the preparation and for 7 months after the last dose.

Very common: infection, nasopharynx, neutropenic fever, anemia, neutropenia, leukopenia, thrombocytopenia, weight loss, anorexia, insomnia, tremors, dizziness, headache, paresthesia, taste disturbances, conjunctivitis, increased tearing, low blood pressure, increased pressure, irregular heartbeat, palpitation, flutter, decreased ejection fraction (in combination therapy after anthracyclines in combination with taxanes), hot flushes, wheezing, shortness of breath, cough, nosebleed, watery runny nose, diarrhea, vomiting, nausea, swelling lips, abdominal pain, indigestion, constipation, stomatitis, erythema, rash, facial swelling, nails diseases, palm-solitary erythrodysaesthesia, joint pain, muscle tension, myalgia, weakness, chest pain, chills, fatigue, flu-like symptoms , infusion-related reactions, pain, fever, thirst sieve, mucositis, peripheral edema. Common: pneumonia, neutropenic sepsis, cystitis, shingles, influenza, sinusitis, skin infections, rhinitis, upper respiratory tract infections, urinary tract infections, rose, cellulitis, pharyngitis, hypersensitivity, anxiety, depression, thinking disorders, peripheral neuropathy, increased tension, excessive drowsiness, ataxia, dry eye syndrome, congestive heart failure, supraventricular tachyarrhythmia, cardiomyopathy, hypotension, vasodilation, asthma, lung disorders, pleural effusion, pancreatitis, haemorrhoids, dry mucous membrane of the cavity oral, liver cell damage, hepatitis, liver tenderness, acne, dry skin, ecchymosis, hyperhidrosis, maculopapular rash, pruritus, nail fragility, arthritis, back pain, bone pain, muscle cramps, neck pain, pain limbs, kidney disorders, mastitis / inflammation nipple, malaise, edema, bruises, dermatitis. Uncommon: sepsis, deafness, pericardial effusion, urticaria. Rare: paresis, pneumonia, jaundice. Not known: malignancy, progression of cancer, hypoproteromiaemia, thrombocytopenia, anaphylactic reaction, anaphylactic shock, hyperkalemia, cerebral edema, congestive disc, retinal hemorrhage, cardiac shock, pericarditis, bradycardia, presence of gallop rhythm, pulmonary fibrosis, dysfunction respiratory insufficiency, pulmonary infiltrates, acute pulmonary edema,acute respiratory syndrome, bronchoconstriction, hypoxia, decreased oxygen saturation, laryngeal edema, normal breathing only in upright position, pulmonary edema, interstitial lung disease, hepatic failure, angioneurotic edema, membranous glomerulonephritis, glomerulonephropathy, renal failure, oligohydramnios, renal hypoplasia , pulmonary hypoplasia. Patients undergoing therapy with trastuzumab experienced symptoms of cardiac dysfunction, such as dyspnoea (also in a supine position), worsening of cough, pulmonary edema, presence of the third heart tone or reduction of the LVEF value. In clinical trials with adjuvant therapy with trastuzumab given in combination with chemotherapy, the incidence of grade 3/4 heart failure (particularly symptomatic congestive heart failure) was similar in patients who received chemotherapy alone (ie did not receive trastuzumab) and in patients who received trastuzumab sequentially after chemotherapy with a taxane. This frequency was highest in patients who received trastuzumab simultaneously with a taxane. Data on the concurrent use of trastuzumab and low-dose anthracycline in neoadjuvant treatment are limited. In fundamental clinical trials in which trastuzumab was used as a palliative treatment, the incidence of cardiac dysfunction was 9-12%, in combination with paclitaxel versus 1-4% in patients treated with paclitaxel as monotherapy. In contrast, in patients with whom trastuzumab was used as monotherapy, the incidence of cardiac disorders was 6-9%. Cardiac dysfunction was most commonly found in patients receiving both trastuzumab and chemotherapy with anthracycline and cyclophosphamide (27%), which was significantly higher compared with the incidence of this complication in patients treated with anthracycline and cyclophosphamide chemotherapy alone (7-10%). . In a study in which cardiac function was monitored prospectively, symptomatic heart failure occurred in 2.2% of patients treated with trastuzumab and docetaxel, while in patients with docetaxel as monotherapy, no complications were observed. In the majority of patients (79%) participating in palliative care trials in whom cardiac abnormalities occurred, an improvement in health was observed after using standard pharmacological treatment. It is estimated that approximately 40% of patients who have been treated with trastuzumab have experienced some form of an infusion-related reaction. Most infusion-related reactions are mild to moderate in intensity and usually occur at the beginning of therapy, e.g. during the 1st, 2nd and 3rd infusions, reducing the incidence of subsequent infusions. The following reactions were observed: chills, fever, shortness of breath, hypotension, wheezing, bronchospasm, tachycardia, decreased blood saturation, respiratory failure, rash, nausea, vomiting and headache. Severe anaphylactic reactions requiring immediate additional intervention may usually occur during the 1st or 2nd infusion and may be associated with the patient's death. In isolated cases, anaphylactoid reactions have occurred. The risk of neutropenia may be slightly increased when administering trastuzumab with docetaxel in patients after treatment with anthracyclines. There have been serious adverse reactions from the respiratory system that may be associated with patient death (including lung infiltration, acute respiratory distress syndrome, pneumonia, pleural effusion, respiratory distress, acute pulmonary edema and respiratory failure).

Before starting treatment with the preparation, HER2 receptors are mandatory. Treatment with the product should only be initiated by a physician experienced in the use of cytotoxic chemotherapy and should only be administered by medical personnel. The labels should be checked before administration to ensure that the correct form of the preparation is used (intravenous or subcutaneous in a constant dose) as prescribed. The intravenous form of the preparation is not intended for subcutaneous administration and should be administered as an intravenous infusion only. In order to prevent medical mistakes, it is important to check the labels on the vials to ensure that the drug being prepared and administered is trastuzumab and not Kadcyla (trastuzumab emt.Metastatic breast cancer. Three-week schedule: recommended initial loading dose is 8 mg / kg body weight, recommended maintenance dose repeated in 3 weeks. intervals is 6 mg / kg, starting 3 weeks after the loading dose.Weekly scheduleThe recommended initial loading dose is 4 mg / kg, the recommended weekly maintenance dose is 2 mg / kg, starting one week after the loading dose.Use in combination with paclitaxel or docetaxel: in fundamental studies, paclitaxel or docetaxel was administered the day after the first dose of trastuzumab and immediately after subsequent doses of trastuzumab, if the previously administered dose of trastuzumab was well tolerated.Use in combination with an aromatase inhibitor: in the basic study, trastuzumab and anastrozole were administered from the first day; there were no restrictions on the timing of administration of trastuzumab and anastrozole.Period of treatment: patients with metastatic breast cancer should be treated for disease progression.Early stage of breast cancer. Three-week schedule: recommended initial loading dose is 8 mg / kg body weight, recommended maintenance dose repeated in 3 weeks. intervals is 6 mg / kg, starting 3 weeks after the loading dose. Weekly schedule: the initial loading dose is 4 mg / kg, followed by 2 mg / kg weekly, in combination with paclitaxel after chemotherapy with doxorubicin and cyclophosphamide.Period of treatment: pPatients with early breast cancer should be treated with trastuzumab for one year or until disease relapse, whichever occurs first. Therapy is not recommended for more than a year.Gastric cancer with metastases. Three-week schedule: recommended initial loading dose is 8 mg / kg body weight, recommended maintenance dose repeated in 3 weeks. intervals is 6 mg / kg, starting 3 weeks after the loading dose.Period of treatment:Patients with metastatic gastric cancer should be treated with trastuzumab until the disease progresses.Dose reduction. In clinical trials, the dose was not reduced. Patients could continue treatment with reversible chemotherapy-induced myelosuppression, but they should be carefully monitored for complications of neutropenia at this time. For information on dose reduction or delayed administration of paclitaxel, docetaxel or an aromatase inhibitor, see the corresponding SmPC. If the left ventricular ejection fraction (LVEF) decreases from baseline by at least 10 percentage points and below 50%, treatment should be withheld and the LVEF measurement repeated within approximately 3 weeks. If the LVEF value does not improve or becomes more If you continue to reduce or develop symptomatic congestive heart failure, it is strongly recommended to discontinue use unless the benefits to the patient outweigh the risks. All such patients should be consulted by a cardiologist and then followed up.Doses missed. If you miss a week or less, give the usual maintenance dose as soon as possible (weekly schedule: 2 mg / kg, three-week schedule: 6 mg / kg). Do not wait for the Next scheduled cycle. Subsequent maintenance doses should be given after 7 or 21 days, respectively, according to a weekly or three-week administration schedule. If the dose is missed by more than a week, the loading dose should be re-used for approximately 90 minutes. (weekly schedule: 4 mg / kg, three-week schedule: 8 mg / kg). The next maintenance doses should be given 7 days or 21 days, respectively, according to a weekly or three-week administration schedule.Special groups of patients. It has not been established that age or renal failure affect the distribution of trastuzumab. It is not appropriate to use the preparation in children and adolescents.Method of administration. The loading dose should be given as a 90-minute intravenous infusion. Do not administer as an injection or bolus. The intravenous infusion should be carried out by qualified personnel prepared for the treatment of anaphylaxis and having access to a life-saving kit. Patients should be observed for at least 6 hrs from the start of the first infusion and for 2 hours after the beginning of subsequent infusions for symptoms such as fever, chills or other symptoms associated with an intravenous infusion. Stopping or slowing the infusion may help control these symptoms. The infusion may be resumed after reducing the severity of symptoms. If the initial loading dose was well tolerated, subsequent doses may be given in a 30-minute infusion.