Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The safety profile presented below is based on data from clinical trials in which more than 6,700 doses of Priorix Tetra were administered subcutaneously to more than 4,000 children from 9 to 27 months of age. Events were recorded for up to 42 days after vaccination.

The most common adverse reactions following Priorix Tetra administration were pain and redness at the injection site as well as fever 38°C (rectal) or 37.5°C (axillary/oral).

Tabulated list of adverse reactions

Adverse reactions reported are listed according to the following frequency: 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)

Clinical trial data
System Organ Class                            Frequency              Adverse reactions Infections and infestations                   Uncommon               upper respiratory tract infection Rare                   otitis media
Blood and lymphatic system disorders          Uncommon               lymphadenopathy Metabolism and nutrition disorders            Uncommon               anorexia Psychiatric disorders                         Common                 irritability Uncommon               crying, nervousness, insomnia
Nervous system disorders                      Rare                   febrile convulsions* Respiratory, thoracic and mediastinal         Uncommon               rhinitis disorders                                     Rare                   cough, bronchitis Gastrointestinal disorders                    Uncommon               parotid gland enlargement, diarrhoea, vomiting
Skin and subcutaneous tissue disorders        Common                 rash General disorders and administration          Very common            pain and redness at the injection site conditions                                                      site, fever (rectal 38°C - 39.5°C; axillary/oral: 37.5°C -
39°C)**
Common                 swelling at the injection site, fever
(rectal >39.5°C; axillary/oral
>39°C)**
Uncommon               lethargy, malaise, fatigue

* The risk of febrile convulsions following the first dose vaccination of children aged 9 to 30 months with Priorix Tetra compared with MMR or simultaneous, but separate MMR and varicella vaccination was assessed in a retrospective database analysis.
The study included 82,656 children immunized with MMRV, 149,259 with MMR and 39,203 with separate MMR and varicella vaccines.
Depending on the case definition used to identify febrile convulsions in the main risk period 5 to 12 days following the first dose, incidences of febrile convulsions were 2.18 (95% CI: 1.38; 3.45) or 6.19 (95% CI: 4.71; 8.13) per 10,000 subjects for the MMRV group and 0.49 (95% CI: 0.19; 1.25) or 2.55 (95% CI: 1.67; 3.89) per 10,000 subjects for the matched control cohorts.
These data suggest one additional case of febrile convulsion per 5,882 or 2,747 subjects vaccinated with Priorix Tetra compared to matched control cohorts who received MMR or simultaneous, but separate MMR and varicella vaccination (attributable risk of 1.70 (95% CI:-1.86; 3.46) and 3.64 (95% CI: -6.11; 8.30) per 10,000 subjects, respectively) – see section 5.1.

**Following the administration of the first dose of the combined measles-mumps-rubella-varicella vaccine, higher incidences of fever (approximately 1.5 fold) were observed when compared to the concomitant administration of measles-mumps-rubella and varicella vaccines at separate injection sites.



No clinical studies with Priorix-Tetra (MMRV) have been conducted in subjects > 6 years of age. The safety profile of Priorix-Tetra in subjects > 6 years of age is extrapolated from the available data with GlaxoSmithKline’s MMR vaccine (Priorix) and monovalent Oka varicella vaccine (Varilrix). The spectrum of adverse reactions such as fever, rash, injection site pain, injection site swelling and injection site redness in subjects > 6 years of age who received Priorix or Varilrix was comparable to that observed in children < 6 years of age who received Priorix-Tetra. In these clinical studies evidence has been obtained to conclude that the second dose of the MMR vaccine is better tolerated in terms of fever than the first dose, whereas reactogenicity of the varicella vaccine tends to remain similar irrespective of the dose applied. Injection site swelling is “commonly” reported in children who received Priorix-Tetra, while it is “very commonly” reported in Varilrix studies in adolescents and adults.


Post-marketing surveillance data
The following additional adverse reactions have been identified in rare occasions during post-marketing surveillance. Because they are reported voluntarily from a population of unknown size, a true estimate of frequency cannot be provided.

System Organ Class                           Adverse reactions
Infections and infestations                  meningitis, herpes zoster*, measles-like syndrome, mumps-like syndrome (including orchitis,
epididymitis and parotitis)
Blood and lymphatic system disorders         thrombocytopenia, thrombocytopenic purpura Immune system disorders                      allergic reactions (including anaphylactic and anaphylactoid reactions)
Nervous system disorders                     encephalitis, cerebellitis, cerebrovascular accident, Guillain Barré syndrome, transverse myelitis,
peripheral neuritis, cerebellitis like symptoms
(including transient gait disturbance and transient ataxia)
Vascular disorders                           vasculitis
Skin and subcutaneous tissue disorders       erythema multiforme, varicella-like rash Musculoskeletal and connective tissue        arthralgia, arthritis disorders
* This adverse drug reaction reported after vaccination is also a consequence of wild-type varicella infection. There is no indication of an increased risk of herpes zoster occurrence following vaccination compared with wild-type disease.

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 GSK Israel (il.safety@gsk.com)