Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of the safety profile

In clinical trials ADACEL POLIO was given to a total of 1,384 persons including 390 children 3 through 6 years of age and 994 adolescent and adults. Most commonly reported reactions following vaccination included local reactions at the injection site (pain, redness and swelling). These signs and symptoms usually were mild in intensity and occurred within 48 hours following vaccination (Adverse Events have been observed within 24 hours and 7 days following vaccination in children 3 through 6 years). They all resolved without sequelae.
There was a trend for higher rates of local and systemic reactions in adolescents than in adults. In both age groups, injection site pain was the most common adverse reaction.
Late-onset local adverse reactions (i.e. a local adverse reaction which had an onset or increase in severity 3 to 14 days post-immunization), such as injection site pain, erythema and swelling occurred in less than 1.2%. Most of the reported adverse reactions occurred within 24 hours after the vaccination.
In a clinical trial of 843 healthy adolescent males and females 11-17 years of age, administration of the first dose of Gardasil concomitantly with ADACEL POLIO showed that there was more injection-site swelling and headache reported following concomitant administration. The differences observed were < 10% and in the majority of subjects, the adverse events were reported as mild to moderate in intensity.

Tabulated list of adverse reactions
Adverse reactions are ranked under headings of frequency using the following convention:

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), including individual cases Not known                        cannot be estimated from the available data 
Table 1 presents adverse reactions observed in clinical trials and also includes additional adverse events which have been spontaneously reported during the post- marketing use of ADACEL POLIO worldwide. Adverse events in children were collected from clinical trials conducted in 3 to 5 years of age and 5 to 6 years of age.
The highest frequency from either study is presented. Because post-marketing adverse events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Therefore, the frequency category “Not known” is assigned to these adverse events.

Table 1: Adverse events from clinical trials and worldwide post marketing experience
Adolescents and
System Organ Class Frequency          Children 3 through 6 years
Adults

Blood and lymphatic    Not known
Lymphadenopathy* system disorders
Immune system          Not known    Anaphylactic reactions, such as urticaria, face oedema and disorders                                                    dyspnea* Nervous system         Very
Headache disorders              common
Common                     Headache
Not known    Convulsions, Vasovagal Syncope, Guillain Barré syndrome, Facial Palsy, Myelitis, Brachial Neuritis, Transient paresthesia/hypoesthesia of vaccinated limb, Dizziness*
Gastrointestinal       Very
Diarrhoea                             Nausea disorders              common
Common                  Vomiting, Nausea                   Diarrhoea, Vomiting Not known                             Abdominal pain
Skin and            Common subcutaneous system                                  Rash disorders
Musculoskeletal and    Very                                                     Arthralgia/joint swelling, connective tissue      common                                                           Myalgia disorders              Common             Arthralgia/joint swelling
Not known                        Pain in vaccinated limb*
General disorders and Very               Fatigue/Asthenia, Fever†               Fatigue/Asthenia, Chills administration site   common           Injection site pain, Injection site swelling, Injection site conditions                                                      erythema Common        Irritability, Injection site dermatitis,            Fever† Injection site bruising, Injection site pruritus
Not known      Malaise§, Pallor*, Extensive limb swelling‡, Injection site induration*
* Post marketing adverse events
† Fever was measured as temperature ≥37.5°C in Children groups and measured as temperature ≥38°C in Adolescents and Adults group
‡ See section c)
§ was observed at a frequency of very common in adolescents and adults, in studies with ADACEL (Tdap component of ADACEL-POLIO; containing the same amounts of diphtheria, tetanus and pertussis antigens)

Description of selected adverse reactions
Extensive limb swelling which may extend from the injection site beyond one or both joints and is frequently associated with erythema, and sometimes with blisters has been reported following administration of ADACEL-POLIO. The majority of these reactions appeared within 48 hours of vaccination and spontaneously resolved over an average of 4 days without sequelae.
The risk appears to be dependent on the number of prior doses of d/DTaP vaccine, with a greater risk following the 4th and 5th doses.

Paediatric population
The safety profile of ADACEL-POLIO in 390 children 3 to 6 years of age as presented in Table 1 is derived from two clinical studies:
- In a clinical study, 240 children were primed at 3, 5 and 12 months of age with a DTaP vaccine with no additional dose in the second year of life. These children received ADACEL-POLIO at 5 to 6 years of age.
- One hundred and fifty children primed at 2, 3, and 4 months of age with a DTwP vaccine (with no additional dose in the second year of life) received ADACEL-POLIO at 3 to 5 years of age.
In both studies the rates of most systemic adverse events within 7 to 10 days following vaccination were less than 10%. Only fever (≥37.5°C) and fatigue were reported in more than 10 % of subjects 3 to 6 years of age. In addition, irritability was reported in more than 10% of subjects 3 to 5 years of age. (See Table 1).
Transient severe swelling of the injected upper arm was reported in <1% of children aged 5 to 6 years.

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 (www.health.gov.il) according to the National Regulation by using an online form https://sideeffects.health.gov.il