Adverse reactions : תופעות לוואי

6   ADVERSE REACTIONS
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.
The safety of LIVTENCITY was evaluated in one Phase 3 multicenter, randomized, open-label, active-control trial in which 352 adult transplant recipients were randomized, and treated with LIVTENCITY (N=234) or Investigator-Assigned Treatment (IAT) consisting of monotherapy or dual therapy with ganciclovir, valganciclovir, foscarnet, or cidofovir as dosed by the investigator (N=116) for up to 8-weeks following a diagnosis of CMV infection/disease refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, foscarnet or cidofovir. The mean treatment durations (SD) for LIVTENCITY and IAT were 48.6 (± 13.82) and 31.2 (± 16.91) days, respectively. The most common adverse events occurring in more than 10% of subjects receiving LIVTENCITY are outlined in Table 2.
Table 2: Adverse Events (All Grades) Reported in >10% of Subjects in the LIVTENCITY Group in Trial 303
LIVTENCITY                                    IATa
ADVERSE EVENT                                   N=234                                      N=116 (%)                                        (%)
Taste disturbanceb                                         46                                        4 Nausea                                                     21                                       22 Diarrhea                                                   19                                       21 Vomiting                                                   14                                       16 Fatigue                                                    12                                        9 a
IAT (Investigator-Assigned Treatment) included monotherapy or dual therapy with ganciclovir, valganciclovir, foscarnet, or cidofovir as dosed by the investigator.
b taste disturbance includes the following reported preferred terms: ageusia, dysgeusia, hypogeusia and taste disorder.


Similar proportions of subjects experienced serious adverse events (38% in the LIVTENCITY group and 37% in the IAT group). The most common serious adverse event in both treatment groups occurred in the Infections and Infestations System Organ Class (SOC) (23% in the LIVTENCITY group and 15% in the IAT group) with CMV infection and disease being the most common in both groups.
A higher proportion of subjects in the IAT group discontinued study medication due to an adverse event compared to the LIVTENCITY group (32% in the IAT group vs 13% in the LIVTENCITY group). The most commonly reported causes that led to study drug discontinuation were neutropenia (9%) and acute kidney injury (5%) in the IAT group and dysgeusia, diarrhea, nausea, and recurrence of underlying disease (each reported at 1%) in the LIVTENCITY group.
Taste disturbance occurred in 46% of subjects treated with LIVTENCITY. These events rarely led to discontinuation of LIVTENCITY (1%) and, for 37% of the subjects, these events resolved while on therapy (median duration 43 days; range 7 to 59 days). For the subjects with ongoing taste disturbance after drug discontinuation, resolution occurred in 89%. In subjects with resolution of symptoms after drug discontinuation, the median duration of symptoms off treatment was 6 days (range 2 to 85 days).
Laboratory Abnormalities
Selected laboratory abnormalities reported in subjects with refractory (with or without genotypic resistance) CMV infections in Trial 303 are presented in Table 3.
Table 3: Selected Laboratory Abnormalities Reported in Trial 303
LIVTENCITY                                IAT
Laboratory Parameter                        N=234                                 N=116 n (%)                                 n (%)
Neutrophils (cells/µL)
<500                                              4 (2)                                4 (3) ≥500 to <750                                      7 (3)                                7 (6) ≥750 to <1,000                                   10 (4)                                6 (5) Hemoglobin (g/dL)
<6.5                                              3 (1)                               1 (1) ≥6.5 to <8.0                                     34 (15)                             23 (20) ≥8.0 to <9.5                                     76 (32)                             33 (28) Platelets (cells/µL)
<25,000                                          11 (5)                               6 (5) ≥25,000 to <50,000                              27 (12)                              10 (9) ≥50,000 to <100,000                             41 (18)                             20 (17) Creatinine (mg/dL)
>2.5                                              16 (7)                             12 (10) >1.5 to ≤2.5                                     78 (33)                             29 (25) 

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