| a. Summary of the safety profile In clinical trials REPEVAX was given to a total of 1,384 children, 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. 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 REPEVAX 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.b. 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 REPEVAX 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| System Organ Class | Frequency | Children 3 to 6 years (390 Persons)* | Adolescents and Adults (994 Persons)
| | Blood and Lymphatic System Disorders | Not known
| Lymphadenopathy† | | Immune System Disorders | Not known
| Anaphylactic reactions, such as urticaria, face oedema and dyspnea† | | Nervous System Disorders | Very common
| | Headache
| | Common
| Headache
| | | Not known
| Convulsions, Vasovagal Syncope, Guillain Barré syndrome, Facial Palsy, Myelitis, Brachial Neuritis, Transient paresthesia/hypoesthesia of vaccinated limb, Dizziness† | | Gastrointestinal Disorders | Very common
| | Nausea
| | Common
| Diarrhoea, Vomiting,
Nausea
| Diarrhoea, Vomiting
| | Skin and Subcutaneous System Disorders | Common
| Rash
| | | Musculoskeletal and Connective Tissue Disorders | Very common
| | Arthralgia/joint swelling, Myalgia
| | Common
| Arthralgia/joint swelling
| | | Not known
| Pain in vaccinated limb† | | General Disorders and Administration Site Conditions | Very common
| Fatigue/Asthenia,
Fever‡, Irritability | Fatigue/Asthenia, Chills | | Common
| | Fever‡ | | Not known
| Malaise, Pallor † | | Injection site reactions | Very common
| Pain, Swelling,
Erythema
| | Common
| Dermatitis, Bruising
Pruritus
| | | Not known
| Extensive limb swelling §, Injection site induration † |
| *
| AEs observed within 24 h and 7 days following vaccination
| | † | 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)
|
c. 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 REPEVAX. 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.d. Paediatric population The safety profile of REPEVAX 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 REPEVAX 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 REPEVAX 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 Table1).Transient severe swelling of the injected upper arm was reported in <1% of children aged 5 to 6 years.
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