Adverse reactions : תופעות לוואי

6     ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling: 
•    Myelodysplastic Syndrome/Acute Myeloid Leukemia [see Warnings and Precautions (5.1)] •    Myelosuppression [see Warnings and Precautions (5.2)]

6.1       Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
 gBRCAm HER2-negative Locally Advanced or Metastatic Breast Cancer
EMBRACA
The safety of TALZENNA as a single agent was evaluated in gBRCAm patients with HER2-negative locally advanced or metastatic breast cancer who had previously received no more than 3 lines of chemotherapy for the treatment of locally advanced/metastatic disease [see Clinical Studies (14.1)]. EMBRACA was a randomized, open-label, multi-center study in which 412 patients received either TALZENNA 1 mg once daily (N=286) or a chemotherapy agent (capecitabine, eribulin, gemcitabine, or vinorelbine) of the healthcare provider’s choice (N=126) until disease progression or unacceptable toxicity. The median duration of study treatment was 6.1 months in patients who received TALZENNA and 3.9 months in patients who received chemotherapy.

Serious adverse reactions of TALZENNA occurred in 32% of patients. Serious adverse reactions reported in >2% of patients included anemia (6%) and pyrexia (2%). Fatal adverse reactions occurred in 1% of patients, including cerebral hemorrhage, liver disorder, veno-occlusive liver disease, and worsening neurological symptoms (1 patient each).

Permanent discontinuation due to adverse reactions occurred in 5% of TALZENNA patients. Dosing interruptions due to an adverse reaction of any grade occurred in 65% of patients receiving TALZENNA; dose reductions due to any cause occurred in 53% of TALZENNA patients.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased, neutrophils decreased, lymphocytes decreased, platelets decreased, fatigue, glucose increased, aspartate 
aminotransferase increased, alkaline phosphatase increased, alanine aminotransferase increased, calcium decreased, nausea, headache, vomiting, alopecia, diarrhea, and decreased appetite.

Table 5 and Table 6 summarize the most common adverse reactions and laboratory abnormalities, respectively, in patients treated with TALZENNA or chemotherapy in the EMBRACA study.

Table 5.      Adverse Reactionsa (>20%) in Patients Receiving TALZENNA in EMBRACA TALZENNA                          Chemotherapy
N=286 (%)                         N=126 (%)
Adverse Reactions          Grades 1-4     Grade 3          Grade 4     Grades 1-4     Grade 3       Grade 4 General disorders and administration site conditions
Fatigueb                        62            3               0             50            5              0 Gastrointestinal disorders
Nausea                          49           0.3              0             47            2              0 Vomiting                        25            2               0             23            2              0 Diarrhea                        22            1               0             26            6              0 Nervous system disorders
Headache                        33            2               0             22            1              0 Skin and subcutaneous tissue disorders
Alopecia                        25            0               0             28            0              0 Metabolism and nutrition disorders
Decreased appetite              21           0.3              0             22            1              0 Abbreviation: N=number of patients.
a.
Graded according to NCI CTCAE 4.03.
b.
Includes fatigue and asthenia.

Clinically relevant adverse reactions in <20% of patients who received TALZENNA included abdominal pain (19%), dizziness (17%), dysgeusia (10%), dyspepsia (10%), stomatitis (8%), and febrile neutropenia (0.3%).



Table 6. Select Laboratory Abnormalities (≥25%) of Patients in EMBRACA TALZENNA                                  Chemotherapy
Na=286 (%)                                Na=126 (%)
Parameter         Grades 1-4    Grade 3       Grade 4        Grades 1-4   Grade 3                                     Grade 4 Hemoglobin            90           39              0            77            6                                          0 decreased
Neutrophils           68           17              3            70           21                                          17 decreased
Lymphocytes           76           17            0.7            53            8                                          0.8 decreased
Platelets             55           11              4            29            2                                           0 decreased
Glucose               54            2              0            51            2                                           0 b increased
Aspartate             37            2              0            48            3                                           0 aminotransferase
Increased
Alkaline              36            2              0            34            2                                           0 phosphatase increased
Alanine               33            1              0            37            2                                           0 aminotransferase increased
Calcium               28            1              0            16            0                                           0 decreased
Abbreviation: N=number of patients.
a.
This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
b.
This number represents non-fasting glucose.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il