Kadcyla · 4.3 Contraindications · 1

HOS-096118 · has-adverse-reaction-information · PDF-Seite 11

Summary of the safety profile The safety of trastuzumab emtansine has been evaluated in 2 611 breast cancer patients in clinical studies. In this patient population:  the most common serious adverse drug reactions (ADRs) (> 0.5% of patients) were haemorrhage, pyrexia, thrombocytopenia, dyspnoea, abdominal pain, musculoskeletal pain, and vomiting.  the most common ADRs (≥ 25%) with trastuzumab emtansine were nausea, fatigue, musculoskeletal pain, haemorrhage, headache, transaminases increased, thrombocytopenia, and peripheral neuropathy. The majority of ADRs reported were of Grade 1 or 2 severity.  the most common National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≥ 3 ADRs (> 2%) were thrombocytopenia, increased transaminases, anaemia, neutropenia, fatigue and hypokalaemia. Tabulated list of adverse reactions The ADRs in 2 611 patients treated with trastuzumab emtansine are presented in Table 3. The ADRs are listed below by MedDRA system organ class (SOC) and categories of frequency. Frequency categories are defined as 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) and not known (cannot be estimated from the available data). Within each frequency grouping and SOC, adverse reactions are presented in order of decreasing seriousness. ADRs were reported using NCI-CTCAE for assessment of toxicity. 11 Table 3 Tabulated list of ADRs in patients treated with trastuzumab emtansine in clinical studies System Organ Class Frequency Adverse reactions Infections and infestations Very common Urinary tract infection Blood and lymphatic system Very common Thrombocytopenia, Anaemia disorders Common Neutropenia, Leukopenia Immune system disorders Common Drug hypersensitivity Metabolism and nutrition Common Hypokalaemia disorders Psychiatric disorders Very common Insomnia Nervous system disorders Very common Neuropathy peripheral, Headache Common Dizz

Auszug; vollständigen Abschnitt im Original lesen.

HOS-096114 · has-contraindication-information · PDF-Seite 7

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-096113 · has-indication-information · PDF-Seite 2

Early Breast Cancer (EBC) Kadcyla, as a single agent, is indicated for the adjuvant treatment of adult patients with HER2-positive early breast cancer who have residual invasive disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted therapy. Metastatic Breast Cancer (MBC) Kadcyla, as a single agent, is indicated for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:  Received prior therapy for locally advanced or metastatic disease, or  Developed disease recurrence during or within six months of completing adjuvant therapy. 2

HOS-096116 · has-interaction-information · PDF-Seite 10

No formal interaction studies have been performed. In vitro metabolism studies in human liver microsomes suggest that DM1, a component of trastuzumab emtansine, is metabolised mainly by CYP3A4 and, to a lesser extent, by CYP3A5. Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity. Consider an alternate medicinal product with no or minimal potential to inhibit CYP3A4. If concomitant use of strong CYP3A4 inhibitors is unavoidable, consider delaying trastuzumab emtansine treatment until the strong CYP3A4 inhibitors have cleared from the circulation (approximately 3 elimination half-lives of the inhibitors) when possible. If a strong CYP3A4 inhibitor is co-administered and trastuzumab emtansine treatment cannot be delayed, patients should be closely monitored for adverse reactions.

HOS-096117 · has-pregnancy-information · PDF-Seite 10

Contraception in males and females Women of childbearing potential should use effective contraception while receiving trastuzumab emtansine and for at least 7 months following the last dose of trastuzumab emtansine. Male patients with female partners of childbearing potential should use effective contraception while receiving trastuzumab emtansine and for at least 4 months following the last dose of trastuzumab emtansine. Pregnancy There are no data from the use of trastuzumab emtansine in pregnant women. Trastuzumab, a component of trastuzumab emtansine, can cause foetal harm or death when administered to a pregnant woman. In the post-marketing setting, cases of oligohydramnios, some associated with fatal pulmonary hypoplasia, have been reported in pregnant women receiving trastuzumab. Animal studies of maytansine, a closely related chemical entity of the same maytansinoid class as DM1, suggest that DM1, the microtubule inhibiting cytotoxic component of trastuzumab emtansine, is expected to be teratogenic and potentially embryotoxic (see section 5.3). Administration of trastuzumab emtansine to pregnant women is not recommended and women should be informed of the possibility of harm to the foetus before they become pregnant. Women who 10 become pregnant must immediately contact their doctor. If a pregnant woman is treated with trastuzumab emtansine, close monitoring by a multidisciplinary team is recommended. Breast-feeding It is not known whether trastuzumab emtansine is excreted in human milk. Since many medicinal products are excreted in human milk and because of the potential for serious adverse reactions in breast-feeding infants, women should discontinue breast-feeding prior to initiating treatment with trastuzumab emtansine. Women may begin breast-feeding 7 months after concluding treatment. Fertility No reproductive and developmental toxicology studies have been conducted with trastuzumab emtansine.

HOS-096115 · has-warning-information · PDF-Seite 7

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. In order to prevent medicinal product errors it is important to check the vial labels to ensure that the medicinal product being prepared and administered is Kadcyla (trastuzumab emtansine) and not another trastuzumab-containing product (e.g. trastuzumab or trastuzumab deruxtecan). Thrombocytopenia Thrombocytopenia, or decreased platelet counts, was commonly reported with trastuzumab emtansine and was the most common adverse reaction leading to treatment discontinuation, dose reduction, and dose interruption (see section 4.8). In clinical studies, the incidence and severity of thrombocytopenia were higher in Asian patients (see section 4.8). It is recommended that platelet counts are monitored prior to each trastuzumab emtansine dose. Patients with thrombocytopenia (≤ 100 000/mm3) and patients on anticoagulant treatment (e.g. warfarin, heparin, low molecular weight heparins) should be monitored closely while on trastuzumab emtansine treatment. Trastuzumab emtansine has not been studied in patients with platelet counts 7 ≤ 100 000/mm3 prior to initiation of treatment. In the event of decreased platelet count to Grade 3 or greater (< 50 000/mm3), do not administer trastuzumab emtansine until platelet counts recover to Grade 1 (≥ 75 000/mm3) (see section 4.2). Haemorrhage Cases of haemorrhagic events, including central nervous system, respiratory and gastrointestinal haemorrhage, have been reported with trastuzumab emtansine treatment. Some of these bleeding events resulted in fatal outcomes. In some of the observed cases the patients had thrombocytopenia, or were also receiving anti-coagulant therapy or antiplatelet therapy; in others there were no known additional risk factors. Use caution with these agents and consider additional monitoring when concomitant use is medically necessary. Hepatotoxicity Hepatotoxicity, predominantly in the form of asymptomatic increases in the concentrations of serum transaminases (Grade 1-4 transaminitis), has been observed during treatment with trastuzumab emtansine in clinical studies (see section 4.8). Transaminase elevations were generally transient with peak elevation at day 8 after administration of therapy and subsequent recovery to Grade 1 or less prior to the next cycle. A cumulative effect

Auszug; vollständigen Abschnitt im Original lesen.