Adverse reactions : תופעות לוואי

7            ADVERSE REACTIONS
The most common adverse reactions (>5%) observed in adult subjects were injection site pain, headache, muscle pain, joint pain, dizziness, and fatigue.
The most common adverse reactions (>5%) observed in pediatric patients were injection site pain, headache, pyrexia, pain in extremity, bruising, fatigue, and vomiting.

7.1          Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates of adverse reactions in clinical trials of another drug and may not reflect the rates observed in clinical practice.

KamRAB was evaluated in three single-center, controlled clinical trials in adults. Subjects in these clinical studies of KamRAB were healthy adults, primarily white, and ranged in age from 18 to 72 years. A total of 160 adult subjects were treated in these three studies, including 91 subjects who received single intramuscular doses of KamRAB (20 IU/kg) with or without rabies vaccine.
Table 1 summarizes adverse reactions occurring in >3% of adult subjects in the clinical trials of KamRAB. (Table 1).
Table 1:          Adverse Reactions Occurring in >3% of Subjects in All Combined Studies in Adults
All KamRAB (N=91)                    All Comparator        Saline
HRIG (N=84)     Placebo+Vaccine
(N=8)
Injection site pain              30 (33%)                         26 (31%)          2 (25%) Headache                         14 (15%)                         11 (13%)          3 (38%) Muscle pain                       8 (9%)                           6 (7%)           0 (0%) Joint Pain                        5 (6%)                           0 (0%)           1 (13%) Dizziness                         5 (6%)                           3 (4%)           0 (0%) Fatigue                           5 (6%)                           2 (2%)           0 (0%) Abdominal pain                    4 (4%)                           1 (1%)           0 (0%) Blood in urine                    4 (4%)                           2 (2%)           0 (0%) (Hematuria)
Nausea                            4 (4%)                           3 (4%)           0 (0%) Feeling faint                     4 (4%)                           1 (1%)           0 (0%) Data are presented as number of subjects (% of subjects).

Less frequent adverse reactions (≤3%) in adult subjects were diarrhea, vomiting, decreased appetite, musculoskeletal stiffness, malaise, weakness (asthenia), fainting (syncope), itching (pruritus), tingling sensation (paresthesia), rash, sunburn and elevation in liver function.
KamRAB was also evaluated in a two-center, open-label clinical trial in 30 pediatric patients exposed or possibly exposed to rabies virus. They ranged in age from 0.5 to 14.9 years. Study treatment included a single dose of KamRAB (20 IU/kg) and active rabies vaccine on Days 0, 3, 7 and 14 administered as per ACIP recommendations for rabies post-exposure prophylaxis.
Twelve pediatric patients (40%) experienced adverse reactions within 14 days of receipt of KamRAB and first dose of rabies vaccine. There were no serious adverse reactions. Table 2 summarizes the adverse reactions that occurred in >5% of patients in the pediatric clinical trial within 14 days of receipt of KamRAB and the first dose of the rabies vaccine.


Table 2:           Adverse Reactions Occurring in >5% of Pediatric Patients within 14 Days of Post-exposure Prophylaxis with KamRAB and Active Rabies Vaccine
KamRAB+ Rabies Vaccine
N = 30
Injection site pain                                                   8 (27%) Headache                                                              4 (13%) Fever (Pyrexia)                                                       4 (13%) Pain in extremity                                                     3 (10%) Bruising (hematoma)                                                    2 (7%) Fatigue                                                                2 (7%) Vomiting                                                               2 (7%) Data are presented as number of patients (% of patients).
Less common adverse reactions (≤5%) in pediatric patients were injection site redness (erythema), injection site swelling (edema), muscle pain, oral pain, and wound complication.
Insomnia was reported as a less common adverse reaction (<5%) in pediatric patients occurring after 14 days of administration.


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
Additionally, you should also report to Kamada Ltd to email address: pharmacovigilance@kamada.com