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 conducted with either the lyophilised or the liquid formulation of Rotarix.
In a total of four clinical trials, approximately 3,800 doses of Rotarix liquid formulation were administered to approximately 1,900 infants. Those trials have shown that the safety profile of the liquid formulation is comparable to the lyophilised formulation.

In a total of twenty-three clinical trials, approximately 106,000 doses of Rotarix (lyophilised or liquid formulation) were administered to approximately 51,000 infants.

In three placebo-controlled clinical trials (Finland, India and Bangladesh), in which Rotarix was administered alone (administration of routine paediatric vaccines was staggered), the incidence and severity of the solicited events (collected 8 days post-vaccination), diarrhoea, vomiting, loss of appetite, fever, irritability and cough/runny nose were not significantly different in the group receiving Rotarix when compared to the group receiving placebo. No increase in the incidence or severity of these events was seen with the second dose.

In a pooled analysis from seventeen placebo-controlled clinical trials (Europe, North America, Latin America, Asia, Africa) including trials in which Rotarix was co-administered with routine paediatric vaccines (see section 4.5), the following adverse reactions (collected 31 days post-vaccination) were considered as possibly related to vaccination.

Tabulated list of adverse reactions
Adverse reactions reported are listed according to the following frequency: 
Frequencies are reported as:
Very common (1/10)
Common (1/100to <1/10)
Uncommon (1/1,000to <1/100)
Rare (1/10,000to <1/1,000)
Very rare (<1/10,000)

System Organ Class                 Frequency                      Adverse reactions 
Gastrointestinal disorders         Common                         Diarrhoea Uncommon                       Abdominal pain, flatulence
Very rare                      Intussusception (see section
4.4)
Not known*                    Haematochezia
Not known*                     Gastroenteritis with vaccine viral shedding in infants with
Severe Combined
Immunodeficiency (SCID) disorder
Skin and subcutaneous tissue       Uncommon                       Dermatitis disorders
General disorders and              Common                         Irritability administration site conditions
Respiratory, thoracic and          Not known*                     Apnoea in very premature mediastinal disorders                                             infants (≤ 28 weeks of gestation) (see section 4.4)
* Because these events were reported spontaneously, it is not possible to reliably estimate their frequency.


Description of selected adverse reactions
Intussusception

Data from observational safety studies performed in several countries indicate that rotavirus vaccines carry an increased risk of intussusception, mostly within 7 days of vaccination. Up to 6 additional cases per 100,000 infants have been observed in these countries against a background incidence of 25 to 101 per 100,000 infants (less than one year of age) per year, respectively.
There is limited evidence of a smaller increased risk following the second dose.
It remains unclear whether rotavirus vaccines affect the overall incidence of intussusception based on longer periods of follow-up (see section 4.4).

Other special populations

Safety in preterm infants
In a clinical study, 670 pre-term infants from 27 to 36 weeks of gestational age were administered Rotarix lyophilised formulation and 339 received placebo. The first dose was administered from 6 weeks after birth. Serious adverse events were observed in 5.1% of recipients of Rotarix as compared with 6.8% of placebo recipients. Similar rates of other adverse events were observed in Rotarix and placebo recipients. No cases of intussusception were reported.

Safety in infants with human immunodeficiency (HIV) infection

In a clinical study, 100 infants with HIV infection were administered Rotarix lyophilised formulation or placebo. The safety profile was similar between Rotarix and placebo recipients.

Post-marketing surveillance data

Gastrointestinal disorders:
Intussusception (including death), recurrent intussusception (including death) 
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
(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic @moh.gov.il).
Additionally, you should also report to GSK Israel (il.safety@gsk.com).