Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
In clinical trials ADACEL was given to a total of 4,546 persons, including 298 children (4 to 6 years), 1,313 adolescents (11 to 17 years) and 2,935 adults (18 to 64 years). Most commonly reported reactions following vaccination included local reactions at the injection site (pain, redness and swelling) that occurred in 21% - 78% of the vaccinees, headache and tiredness that occurred in 16% - 44% of vaccinees.
These signs and symptoms usually were mild in intensity and occurred within 48 hours following vaccination. They all resolved without sequelae.

Safety analysis was conducted in 1,042 healthy adolescent males and females aged 10 to 17 years during a clinical trial. They received quadrivalent human papillomavirus types 6/11/16/18 vaccine (Gardasil) concurrently with a dose of ADACEL and a dose of quadrivalent meningococcal conjugate vaccine serogroup A, C, Y and W135. The safety profiles were similar in both concomitant and non concomitant groups. Higher frequencies of swelling at the Gardasil injection site, bruising and pain at ADACEL injection sites were observed in the concomitant administration group. The differences observed between concomitant and non concomitant groups were less than 7% and in a 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)
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 worldwide. 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 trials and worldwide post-marketing experience 
Children           Adolescents             Adults
System Organ Class         Frequency         (4 to 6 Years)     (11 to 17 Years)     (18 to 64 Years) 
Immune system                                 Hypersensitivity (Anaphylactic) reaction (Angioedema, Not known disorders                                                    Oedema, Rash, Hypotension)* Anorexia
Metabolism and
Very common           (decreased nutrition disorders appetite)
Very common                               Headache
Nervous system                                     Paraesthesia*, Hypoaesthesia*, Guillain-Barré disorders                   Not known              Syndrome*, Brachial Neuritis*, Facial Palsy*, Convulsions*, Syncope*, Myelitis*
Cardiac disorders           Not known                              Myocarditis* Diarrhoea,
Very common          Diarrhoea                                Diarrhoea Gastrointestinal                                                      Nausea disorders                                         Nausea,
Common                                  Vomiting         Nausea, Vomiting Vomiting
Skin and subcutaneous        Common                                     Rash system disorders            Not known                           Pruritus*, Urticaria* Generalized aching or          Generalized
Muscular            aching or
Very common weakness,            Muscular
Arthralgia or         weakness
Musculoskeletal and                                               Joint swelling connective tissue                              Generalized disorders                                        aching or
Muscular                               Arthralgia or
Common weakness,                              Joint swelling
Arthralgia or
Joint swelling
Not known                                Myositis*

Children           Adolescents             Adults
System Organ Class            Frequency    (4 to 6 Years)     (11 to 17 Years)     (18 to 64 Years) 
Fatigue/Asthenia, Fatigue/Asthenia,
Fatigue/Asthenia
Malaise, Chills           Malaise
Very common
Injection site pain, Injection site erythema, Injection site
General disorders and                                               swelling administrative site                       Pyrexia, Chills,                            Pyrexia, Chills, conditions                                                     Pyrexia, Axillary Common        Axillary                                     Axillary adenopathy adenopathy                                  adenopathy
Injection site bruising*, Injection site sterile abscess*,
Not known
Injection site nodule*
*         Post-marketing Adverse Events

Description of selected adverse reactions

General Disorders and Administration Site Conditions:
Large injection site reactions (>50 mm), including extensive limb swelling from the injection site beyond one or both joints occur after administration of ADACEL in adolescents and adults. These reactions usually start within 24 - 72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at the injection site and resolve spontaneously within 3 - 5 days.

Paediatric population

The safety profile of ADACEL as presented in Table 1 includes data from a clinical trial in 298 children 4 to 6 years of age who had previously received a total of 4 doses, including primary immunization, with DTaP-IPV combined with Hib, at approximately 2, 4, 6 and 18 months of age. In this clinical study, the most common adverse events reported within 14 days post-vaccination were pain at the injection site (in 39.6 % of subjects) and tiredness (in 31.5% of subjects).

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