4.1. Therapeutic indications

Rotarix is indicated for the active immunisation of infants aged 6 to 24 weeks for prevention of gastro-enteritis due to rotavirus infection (see sections 4.2, 4.4 and 5.1).

The use of Rotarix should be based on official recommendations.

4.2. Posology and method of administration

Posology

The vaccination course consists of two doses. The first dose may be administered from the age of 6 weeks. There should be an interval of at least 4 weeks between doses. The vaccination course should preferably be given before 16 weeks of age, but must be completed by the age of 24 weeks.

Rotarix may be given with the same posology to preterm infants born after at least 27 weeks of gestational age (see sections 4.8 and 5.1).

In clinical trials, spitting or regurgitation of the vaccine has rarely been observed and, under such circumstances, a replacement dose was not given. However, in the unlikely event that an infant spits out or regurgitates most of the vaccine dose, a single replacement dose may be given at the same vaccination visit.

It is recommended that infants who receive a first dose of Rotarix complete the 2-dose regimen with Rotarix. There are no data on safety, immunogenicity or efficacy when Rotarix is administered for the first dose and another rotavirus vaccine is administered for the second dose or vice versa.

Paediatric population

Rotarix should not be used in children over 24 weeks of age.

Method of administration

Rotarix is for oral use only.

Rotarix should under no circumstances be injected.

For instructions for administration, see section 6.6.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Hypersensitivity after previous administration of rotavirus vaccines.

History of intussusception.

Subjects with uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusception.

Subjects with Severe Combined Immunodeficiency (SCID) disorder (see section 4.8).

Administration of Rotarix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection is not a contra-indication for immunisation.

The administration of Rotarix should be postponed in subjects suffering from diarrhoea or vomiting.

4.4. Special warnings and precautions for use

It is good clinical practice that vaccination should be preceded by a review of the medical history especially with regard to the contraindications and by a clinical examination.

Appropriate medical treatment should always be readily available in case of an anaphylactic event following the administration of the vaccine (see section 4.8).

There are no data on the safety and efficacy of Rotarix in infants with gastrointestinal illnesses or growth retardation. Administration of Rotarix may be considered with caution in such infants when, in the opinion of the physician, withholding the vaccine entails a greater risk.

As a precaution, healthcare professionals should follow-up on any symptoms indicative of intussusception (severe abdominal pain, persistent vomiting, bloody stools, abdominal bloating and/or high fever) since data from observational safety studies indicate an increased risk of intussusception, mostly within 7 days after rotavirus vaccination (see section 4.8). Parents/guardians should be advised to promptly report such symptoms to their healthcare provider.

For subjects with a predisposition for intussusception, see section 4.3.

Asymptomatic and mildly symptomatic HIV infections are not expected to affect the safety or efficacy of Rotarix. A clinical study in a limited number of asymptomatic or mildly symptomatic HIV positive infants showed no apparent safety problems (see section 4.8).

Administration of Rotarix to infants who have known or suspected immunodeficiency, including in utero exposure to an immunosuppressive treatment, should be based on careful consideration of potential benefits and risks.

Excretion of the vaccine virus in the stools is known to occur after vaccination with peak excretion around the 7th day. Viral antigen particles detected by ELISA were found in 50% of stools after the first dose of Rotarix lyophilised formulation and 4% of stools after the second dose. When these stools were tested for the presence of live vaccine strain, only 17% were positive. In two comparative controlled trials, vaccine shedding after vaccination with Rotarix liquid formulation was comparable to that observed after vaccination with Rotarix lyophilised formulation.

Cases of transmission of this excreted vaccine virus to seronegative contacts of vaccinees have been observed without causing any clinical symptom.

Rotarix should be administered with caution to individuals with immunodeficient close contacts, such as individuals with malignancies, or who are otherwise immunocompromised or individuals receiving immunosuppressive therapy.

Contacts of recent vaccinees should observe personal hygiene (e.g. wash their hands after changing child's nappies).

The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered when administering the primary immunisation series to very premature infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity.

As the benefit of the vaccination is high in this group of infants, vaccination should not be withheld or delayed.

A protective immune response may not be elicited in all vaccinees (see section 5.1).

The extent of protection that Rotarix might provide against other rotavirus strains that have not been circulating in clinical trials is currently unknown. Clinical studies from which efficacy data were derived were conducted in Europe, Central and South America, Africa and Asia (see section 5.1).

Rotarix does not protect against gastro-enteritis due to other pathogens than rotavirus.

No data are available on the use of Rotarix for post-exposure prophylaxis.

Rotarix should under no circumstances be injected.

Excipients

This vaccine contains sucrose and glucose as excipients. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this vaccine.

This vaccine contains 0.15 microgram phenylalanine in each dose. Phenylalanine may be harmful for patients with phenylketonuria (PKU).

This vaccine contains 32 mg sodium in each dose.

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

4.5. Interaction with other medicinal products and other forms of interaction

Rotarix can be given concomitantly with any of the following monovalent or combination vaccines [including hexavalent vaccines (DTPa-HBV-IPV/Hib)]: diphtheria-tetanus-whole cell pertussis vaccine (DTPw), diphtheria-tetanus-acellular pertussis vaccine (DTPa), Haemophilus influenzae type b vaccine (Hib), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), pneumococcal conjugate vaccine and meningococcal serogroup C conjugate vaccine. Clinical studies demonstrated that the immune responses and the safety profiles of the administered vaccines were unaffected.

Concomitant administration of Rotarix and oral polio vaccine (OPV) does not affect the immune response to the polio antigens. Although concomitant administration of OPV may slightly reduce the immune response to rotavirus vaccine, clinical protection against severe rotavirus gastro-enteritis was shown to be maintained in a clinical trial involving more than 4 200 subjects who received Rotarix concomitantly with OPV.

There are no restrictions on the infant's consumption of food or liquid, either before or after vaccination.

4.6. Fertility, pregnancy and lactation

Rotarix is not intended for use in adults. There are no data on the use of Rotarix during pregnancy and lactation.

Based on evidence generated in clinical trials, breast-feeding does not reduce the protection against rotavirus gastro-enteritis afforded by Rotarix. Therefore, breast-feeding may be continued during the vaccination schedule.

4.7. Effects on ability to drive and use machines

Not relevant.

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

Common

Uncommon

Rare

Very rare

(≥ 1/10)

(≥ 1/100 to < 1/10)

(≥ 1/1 000 to < 1/100)

(≥ 1/10 000 to < 1/1 000)

(< 1/10 000)

System Organ Class

Frequency

Adverse reactions

Immune system disorders

Not known*

Anaphylactic reaction

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 disorders

Uncommon

Dermatitis

Very rare

Urticaria

General disorders and administration site conditions

Common

Irritability

Respiratory, thoracic and mediastinal disorders

Not known*

Apnoea in very premature 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.

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Some cases of overdose have been reported. In general, the adverse event profile reported in these cases was similar to that observed after administration of the recommended dose of Rotarix.