Adverse reactions : תופעות לוואי

7 ADVERSE REACTIONS
The following clinically important adverse reactions, that can become serious are described elsewhere in the labeling:
Hypertension [see Warnings and Precautions (7.1)]
Hepatotoxicity [see Warnings and Precautions (7.2)]
Diarrhea [see Warnings and Precautions (7.3)]
Neutropenia [see Warnings and Precautions (7.4)]

7.1 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.
TAVALISSE was studied in two randomized, double-blind, placebo-controlled trials that were identical in design. The data described below reflect exposure to TAVALISSE in 102 patients with chronic ITP who had received one or more prior ITP treatment(s). Groups were stratified with respect to splenectomy and severity of thrombocytopenia. Patients randomized to the TAVALISSE arm received 100 mg orally twice daily. Based upon platelet count and tolerability, if a patient's platelet count did not increase to at least 50 × 109/L, the TAVALISSE dose could be increased to 150 mg twice daily after one month. In the placebo controlled studies, the median duration of TAVALISSE exposure in these studies was 86 days (range 8 to 183) [see Clinical Studies (14) for additional details for patients on TAVALISSE].
In the ITP double-blind studies, serious adverse drug reactions were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which each occurred in 1% of patients receiving TAVALISSE. In addition, severe adverse reactions observed in patients receiving TAVALISSE included dyspnea and hypertension (both 2%); and neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope and hypoxia (all 1%) [see Warnings and Precautions (7.1)]. Table 3 presents the common adverse reactions from these studies.

Table 3: Incidence of Common (≥ 5%) Adverse Reactions from Double-Blind Clinical Studies (FIT 1 and FIT 2)
TAVALISSE                                       Placebo
(N=102)                                      (N=48)
Mild    Moderate Severe        TOTAL         Mild    Moderate Severe         TOTAL Adverse Reaction         %         %          %           %            %        %          %            % Diarrhea*                 21       10         1           31           13        2         0            15 Hypertension†             17        9         2           28           10        0         2            13 Nausea                    16        3         0           19            8        0         0             8 Dizziness                  8        2         1           11            6        2         0             8 ALT increased              5        6         0           11            0        0         0             0 AST increased              5        4         0            9            0        0         0             0 Respiratory
7         4            0         11         6            0          0            6 infection‡
Rash§                   8         1            0         9          2            0          0            2 Abdominal pain¶         5         1            0         6          2            0          0            2 Fatigue                 4         2            0         6          0            2          0            2 Chest pain              2         3            1         6          2            0          0            2 Neutropenia   #         3         2            1         6          0            0          0            0 ALT = Alanine aminotransferase
AST = Aspartate aminotransferase
Note: Common adverse reactions defined as all adverse reactions occurring at a rate of ≥ 5% of patients in the TAVALISSE group and greater than placebo rate.
* Includes diarrhea and frequent bowel movement.
† Includes hypertension, blood pressure (BP) increased, BP diastolic abnormal, and BP diastolic increased.
‡ Includes upper respiratory tract infection, respiratory tract infection, lower respiratory tract infection, and viral upper respiratory tract infection.
§ Includes rash, rash erythematous and rash macular.
¶ Includes abdominal pain, and abdominal pain upper.
# Includes neutropenia and neutrophil count decreased.


Table 4: Elevations in Hepatic Transaminases During Placebo-
Controlled Clinical Studies
Number of Patients (%)
Maximum Level
Enzyme                                        TAVALISSE          Placebo of Elevation
(N=102)          (N=48)
Alanine             >3 and ≤5 × ULN                     3 (3)              0 aminotransferase >5 and ≤10 × ULN                       5 (5)              0 (ALT) and/or
Aspartate aminotransferase ≥10 × ULN                       1 (1)                 0 (AST)
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