Consumer medicine information

Rotarix

Rotavirus vaccine, live, oral

BRAND INFORMATION

Brand name

Rotarix Oral Liquid

Active ingredient

Rotavirus vaccine, live, oral

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Rotarix.

What is in this leaflet?

Please read this leaflet carefully before your child receives ROTARIX vaccine.

This leaflet answers some common questions about ROTARIX. It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines and vaccines have risks and benefits. Your doctor has weighed the expected benefits of your child having ROTARIX against the possible risks.

If you have any concerns about your child having this vaccine, ask your doctor or pharmacist.

Keep this leaflet with the vaccine. You may need to read it again.

What is ROTARIX used for?

ROTARIX is a viral vaccine that helps to protect your child against gastro-enteritis (diarrhoea and vomiting) caused by rotavirus infection.

Rotavirus infection is the most common cause of severe diarrhoea in infants and young children. Rotavirus is easily spread by hand-to-mouth contact with stool from an infected person. Most children with rotavirus diarrhoea recover on their own. Some children become very ill with severe vomiting, diarrhoea and life-threatening loss of fluids that requires hospitalisation. Rotavirus infections are responsible for hundreds of thousands of deaths worldwide every year especially in developing countries, where nutrition and health care are not optimal.

When a person is given the vaccine, the immune system (the body’s natural defences) will make antibodies against the most commonly occurring types of rotavirus. These antibodies may help protect against disease caused by these types of rotavirus.

As with all vaccines, ROTARIX may not completely protect all people who are vaccinated against the disease it is intended to prevent. The vaccine will not protect against gastro-enteritis caused by other types of viruses or organisms.

ROTARIX is not addictive.

Before having ROTARIX

ROTARIX should not be given if:

  • your child has previously had an allergic reaction to ROTARIX or any of the ingredients listed toward the end of this leaflet. (See “Ingredients”) Signs of an allergic reaction include itchy skin rash, shortness of breath and swelling of the face or tongue.
  • your child was born with a defect of the gastro-intestinal system.
  • your child has a rare inherited illness which affects their immune system called Severe Combined Immunodeficiency (SCID).
  • your child has a severe infection with a high temperature. It might be necessary to postpone the vaccination until recovery. A minor infection such as a cold should not be a problem, but talk to your doctor first.
  • your child has diarrhoea or is vomiting. It might be necessary to postpone the vaccination until recovery.
  • your child has previously had intussusception (part of the intestine gets blocked or twisted).
  • the expiry date (EXP) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering.

Tell your doctor if:

  • your child is allergic to foods, dyes, preservatives or any other medicines.
    In these cases, your doctor can determine the right time of vaccination for your child.
  • your child is taking any prescription or OTC (over-the-counter) medicines. Some vaccines may be affected by other vaccines or medicines. Your doctor, nurse or pharmacist will be able to tell you what to do if ROTARIX is to be given with another vaccine or medicine.
  • your child has a history of chronic gastrointestinal disease.

How is ROTARIX given?

The doctor or nurse will administer the recommended dose of ROTARIX to your child. THE VACCINE WILL BE GIVEN ORALLY.

How much is given

ROTARIX is given as a 1.5 mL liquid dose.

How it is given

ROTARIX is given into the mouth. Under no circumstance should this vaccine be given by injection.

When will it be given?

Your child will receive two doses of the vaccine. Each dose will be given on a separate occasion with an interval of at least 4 weeks between the two doses. The first dose will be given between 6 and 14 weeks of age and the second dose must be given by 24 weeks of age.

There are no restrictions on your child’s consumption of food or liquids, including breast milk, either before or after vaccination.

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 important that you follow the instructions of your doctor or nurse regarding return visits for the follow-up dose.

IF A DOSE IS MISSED

If you forget to go back to your doctor at the scheduled time, ask your doctor for advice.

After having ROTARIX

Things you must do

After your child has received ROTARIX, contact your doctor/health care professional right away if your child experiences severe stomach pain, persistent vomiting, blood in stools, a swollen belly and/or high fever.

If you are in close contact with a recently vaccinated baby/child, ensure your hands are washed thoroughly:

  • after changing nappies
  • before eating or handling food.

What are the side-effects?

Check with your doctor as soon as possible if you think your child is experiencing any side effects or allergic reactions due to having ROTARIX, even if the problem is not listed below.

Like other medicines, ROTARIX can cause some side-effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

Side effects that occurred during clinical trial use of ROTARIX include:

The most commonly reported side-effects are:

  • loss of appetite, irritability, fever, fatigue, diarrhoea, vomiting, regurgitation of food, flatulence, abdominal pain (see also below for signs of very rare side effects of intussusception), crying, disturbed sleep, sleepiness and constipation.

Rarely reported side-effects are:

  • chest infection, hoarseness, runny nose, dermatitis, rash and muscle cramp.

Side effects that occurred during routine use of ROTARIX include:

Rare (these may occur with up to 1 in 1,000 doses of the vaccine)

  • blood in stools
  • children with a rare inherited illness called Severe Combined Immunodeficiency (SCID) may have an inflamed stomach or gut (gastroenteritis) and pass the vaccine virus in their stools. The signs of gastroenteritis may include feeling sick, being sick, stomach cramps or diarrhoea.

Very rare (these may occur with up to 1 in 10,000 doses of the vaccine):

  • intussusception (part of the intestine gets blocked or twisted). The signs may include severe stomach pain, persistent vomiting, blood in stools, a swollen belly and/or high fever. Contact a doctor/health care professional right away if your child experiences one of these symptoms.

Tell your doctor immediately if you notice any of the following:

  • Wheezing, swelling of the lips/mouth, difficulty in breathing, hayfever, lumpy rash (hives) or fainting. These could be symptoms of an allergic reaction.

This is not a complete list of all possible side-effects. Others may occur in some people and there may be some side-effects not yet known.

Tell your doctor or pharmacist if you notice any side effects from your child’s vaccine which are not mentioned here.

Do not be alarmed by this list of possible side-effects. Your child may not experience any of them.

How do I store ROTARIX?

ROTARIX is usually stored at the doctor’s clinic or surgery, or at the pharmacy. But if you need to store ROTARIX always:

  • Keep ROTARIX in the refrigerator stored between +2 C and +8 C. Do not freeze. Do not store it in the bathroom, or leave it in the car. Avoid exposing the vaccine to sunlight. HEAT CAN DESTROY THE VACCINE.
  • Keep the vaccine out of the reach of children.
  • Keep ROTARIX in the original pack until it is time for it to be given.

Ask your pharmacist what to do with any left over ROTARIX that has expired or has not been used.

Product Description

What ROTARIX looks like

ROTARIX is presented as a suspension for oral administration.

ROTARIX is supplied as a clear, colourless liquid, free of visible particles, presented in a single dose squeezable tube (fitted with a membrane and a cap), or as 5 single dose tubes (connected by a bar – pack size of 50 tubes) or a single dose oral applicator (syringe type applicator with a plunger stopper).

Ingredients

The active ingredient of ROTARIX is live attenuated human rotavirus RIX4414 strain.

ROTARIX also contains sucrose, di-sodium adipate, Dulbecco’s Modified Eagle Medium (DMEM), and sterile water.

The manufacture of this product includes exposure to bovine derived materials. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.

Supplier

Your ROTARIX is supplied by:

GlaxoSmithKline Australia Pty Ltd
Level 4, 436 Johnston Street
Abbotsford, Victoria, 3067
Australia.

Distributed in New Zealand by:

GlaxoSmithKline NZ Ltd
Private Bag 106600
Downtown Auckland
Ph: (09) 367 2900
Fax: (09) 367 2910

Where to go for further information

Pharmaceutical companies are not in a position to give people an individual diagnosis or medical advice. Your doctor or pharmacist is the best person to give you advice on the treatment of your condition.

This leaflet was prepared on 13 February 2020.

The information provided applies only to: ROTARIX.

Trade marks are owned by or licensed to the GSK group of companies.

ROTARIX: AUST R 146776, 326141 and 320221

© 2019 GSK group of companies or its licensor.

Version 10.0

Published by MIMS April 2020

BRAND INFORMATION

Brand name

Rotarix Oral Liquid

Active ingredient

Rotavirus vaccine, live, oral

Schedule

S4

 

1 Name of Medicine

Human Rotavirus (live attenuated oral vaccine).

6.7 Physicochemical Properties

Not relevant to vaccines.

2 Qualitative and Quantitative Composition

Rotarix is a liquid suspension of the live attenuated RIX4414 strain of human rotavirus of the G1P(8) type for use in the prevention of rotavirus gastroenteritis. The virus strain derived from the 89-12 strain is obtained by propagation on a well characterised Vero cell line.
Each 1.5 mL dose of the vaccine contains not less than 106.0 CCID50 (cell culture infectious dose 50%) of the RIX 4414 strain of human rotavirus.
The manufacture of this product includes exposure to bovine derived materials at the very early steps of the production process. No bovine materials are used in routine production. No evidence exists that any case of vCJD (considered to be the human form of bovine spongiform encephalopathy) has resulted from the administration of any vaccine product.
Porcine Circovirus type 1 (PCV-1) material has been detected in Rotarix vaccine. PCV-1 is not known to cause disease in animals and is not known to infect or cause disease in humans. There is no evidence that the presence of PCV-1 poses a safety risk.
The vaccine also contains sucrose. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Rotarix is presented as a clear, colourless liquid, free of visible particles, for oral administration only.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Rotavirus is likely to affect all children up to the age of five years of age. The peak incidence of rotavirus gastroenteritis is between 6-24 months of age. Dehydration from rotavirus gastroenteritis can lead to hospitalisation, which is most common in children under 2 years of age.

Mechanism of action.

The immunologic mechanism by which Rotarix protects against rotavirus gastroenteritis is not entirely understood. A relationship between antibody responses to rotavirus vaccination and protection against rotavirus gastroenteritis has not been established. Rotarix, which is derived from the most common human rotavirus type G1P(8), has been demonstrated to induce protective immunity against both the G1P(8) type and also against other non-G1 prevalent strains (see Section 5.1 Pharmacodynamic Properties, Clinical trials).

Clinical trials.

Protective efficacy of the Rotarix lyophilised formulation.

In clinical trials, efficacy was demonstrated against gastro-enteritis due to rotavirus of the most common genotypes G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8] and against uncommon rotavirus genotypes G8P[4] (severe gastro-enteritis) and G12P[6] (any gastro-enteritis). All of these strains are circulating worldwide.
Clinical studies have been conducted in Europe, Latin America, Africa and Asia to evaluate the protective efficacy of Rotarix against any and severe rotavirus gastroenteritis in countries with different levels of burden of disease.
Severity of gastroenteritis was defined according to two different criteria:
the Vesikari 20 point scale, which evaluates the full clinical picture of rotavirus gastroenteritis by taking into account the severity and duration of diarrhoea and vomiting, the severity of fever and dehydration as well as the need for treatment; or
the clinical case definition based on World Health Organization (WHO) criteria for determination of degree of dehydration (A: no dehydration, B: some dehydration, C: severe dehydration).
In the Rotarix clinical studies, severe gastroenteritis is being defined as a gastroenteritis episode requiring hospitalisation and/or rehydration therapy (equivalent to the World Health Organization plan B or C) in a medical facility with a score of 11 or greater on the Vesikari scale.
Protective efficacy has been shown to be higher against severe rotavirus gastroenteritis than rotavirus gastroenteritis of any severity.

Protective efficacy in Europe.

A clinical study performed in Europe evaluated Rotarix given according to different European schedules (2, 3 months; 2, 4 months; 3, 4 months; 3, 5 months) in 3,994 subjects (2,646 subjects receiving Rotarix and 1,348 subjects receiving placebo). The first dose was given between 6 and 14 weeks of age and the second dose was administered 4 to 8 weeks later.
After two doses of Rotarix, the protective vaccine efficacy observed during the first and second year of life and the two years combined is presented in Table 3.
The type specific vaccine efficacy is presented in Table 4.
When the severity of rotavirus gastroenteritis was scored using the 20 point Vesikari scale, vaccine efficacy during the first year of life progressively increased with increasing disease severity, reaching 100% (95% CI: 84.7; 100) for Vesikari scores ≥ 17.

Between dose efficacy.

Although Rotarix is a 2 dose vaccine, efficacy has been observed as from the first dose. In Europe, vaccine efficacy against rotavirus gastroenteritis of any severity from dose 1 up to dose 2 was 89.8% (95% CI: 8.9; 99.8).

Protective efficacy in Latin America.

A clinical study performed in Latin America evaluated Rotarix in more than 20,000 subjects. The first dose was given between 6 and 12 weeks of age and the second dose was administered 4 to 8 weeks later. After two doses of Rotarix, the protective vaccine efficacy against severe rotavirus gastroenteritis requiring hospitalisation and/or rehydration therapy in a medical facility was 84.7% (95% CI: 71.7; 92.4). Protective efficacy of Rotarix was maintained during the second year of life with a vaccine efficacy against severe rotavirus gastroenteritis of 79.0% (95% CI: 66.4; 87.4).

Protective efficacy in Africa.

A clinical study performed in Africa in more than 4,900 subjects evaluated Rotarix given at approximately 10 and 14 weeks of age (2 doses) or 6, 10 and 14 weeks of age (3 doses). The vaccine efficacy against severe rotavirus gastroenteritis (scored using the 20 point Vesikari scale) during the first year of life was 61.2% (95% CI: 44.0; 73.2). The study was not powered to evaluate a difference in vaccine efficacy between the 2 and 3 dose regimens.
The protective vaccine efficacy observed against any and severe rotavirus gastroenteritis is presented in Table 5.

Sustained efficacy up to 3 years of age in Asia.

A clinical study conducted in Asia (Hong Kong, Singapore and Taiwan) in more than 10,000 subjects evaluated Rotarix given according to different schedules (2, 4 months of age; 3, 4 months of age).
After two doses of Rotarix, the protective vaccine efficacy observed up to 3 years of age is presented in Table 6.
Rotarix does not protect against nonrotaviral gastroenteritis or against diarrhoea due to other infectious and noninfectious causes.

Effectiveness.

In observational studies, vaccine effectiveness was demonstrated against severe gastro-enteritis leading to hospitalisation due to rotavirus of common genotypes G1P[8], G2P[4], G3P[8] and G9P[8] as well as the less common rotavirus genotype G9P[4] and G9P[6]. All of these strains are circulating worldwide.
Table 7 shows the results of several matched case control studies conducted to evaluate the effectiveness of Rotarix against severe rotavirus gastroenteritis leading to hospitalisation.

Impact on hospitalisation#.

In a retrospective database study in Belgium conducted in children 5 years of age and younger, the direct and indirect impact of Rotarix vaccination on rotavirus related hospitalisation ranged from 64% (95% CI: 49; 76) to 80% (95% CI: 77; 83) two years after vaccine introduction. Similar studies in Brazil, Australia and El Salvador showed a reduction of 45 to 88%. In addition, two impact studies on all cause diarrhoea hospitalisation conducted in Latin America showed a reduction of 38 to 40% four years after vaccine introduction.

Impact on mortality#.

Impact studies with Rotarix conducted in Panama, Brazil and Mexico showed a decrease in all cause diarrhoea mortality ranging from 22% to 56% in children less than 5 years of age, within 2 to 3 years after vaccine introduction.

# Note.

Impact studies are meant to establish a temporal relationship but not a causal relationship between the disease and vaccination.

Immune response in preterm infants.

In a clinical study conducted in preterm infants (N = 1,009; with gestational age of 27 to 36 weeks) 670 subjects received the lyophilised formulation and the immunogenicity of Rotarix was assessed in a subset of 147. Rotarix was immunogenic; 85.7% of subjects achieved serum anti-rotavirus IgA antibody titres ≥ 20 U/mL (by ELISA) one month after the second dose of vaccine.

Immunogenicity of the Rotarix liquid formulation.

The immune response observed after 2 doses of Rotarix liquid formulation was comparable to the immune response observed after 2 doses of Rotarix lyophilised formulation in terms of antirotavirus IgA antibody seroconversions and geometric mean concentrations.

5.2 Pharmacokinetic Properties

Not relevant to vaccines.

5.3 Preclinical Safety Data

Genotoxicity.

Rotarix has not been evaluated for genotoxicity.

Carcinogenicity.

Rotarix has not been evaluated for carcinogenicity or mutagenicity.

4 Clinical Particulars

4.1 Therapeutic Indications

Rotarix is indicated for the prevention of rotavirus gastroenteritis. (See Section 5.1 Pharmacodynamic Properties, Clinical trials).

4.3 Contraindications

Rotarix should not be administered to subjects with known hypersensitivity to any components of the vaccine (see Section 6.1 List of Excipients), or to subjects having shown signs of hypersensitivity after previous administration of rotavirus vaccines.
Rotarix should not be administered to subjects with any history of chronic gastrointestinal disease including any uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract.
Subjects with history of intussusception.
Subjects with severe combined immunodeficiency (SCID) disorder (see Section 4.8 Adverse Effects (Undesirable Effects)).
As with other vaccines, administration of Rotarix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection, such as a cold, is not a contraindication for immunisation.

4.4 Special Warnings and Precautions for Use

Rotarix should under no circumstances be injected.
It is good clinical practice that vaccination should be preceded by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination.
The administration of Rotarix should be postponed in subjects suffering from diarrhoea or vomiting.
Administration of Rotarix may be considered with caution in infants with gastrointestinal illnesses, when, in the opinion of the physician, the risk of rotavirus infection by withholding the vaccine entails a greater risk to the infant. No safety or efficacy data are available for the administration of Rotarix to infants with gastrointestinal illnesses.
Administration of Rotarix in immunosuppressed infants, including infants on immunosuppressive therapy, should be based on careful consideration of potential benefits and risks.
The risk of intussusception has been evaluated in a large safety trial (including 63,225 infants) conducted in Latin America and Finland. No increased risk of intussusception was observed in this clinical trial following administration of Rotarix when compared with placebo (see Section 4.8 Adverse Effects (Undesirable Effects)).
Data from postmarketing studies indicate an increased incidence of intussusception shortly after the administration of the first dose and second dose of Rotarix (see Section 4.8 Adverse Effects (Undesirable Effects)). Whether vaccination with Rotarix affects the overall risk of intussusception has not been established. The overall incidence of intussusception remains rare.
Therefore, healthcare professionals should follow up on any symptoms suggestive of intussusception after rotavirus vaccine administration. These symptoms can include severe abdominal pain or distress, persistent vomiting, bloody stools, palpable abdominal mass, abdominal bloating and/or high fever.
Parents/ guardians should be advised to seek medical advice promptly where these signs/ symptoms are evident.
Rotarix should not be administered in subjects with a predisposition for intussusception (see Section 4.3 Contraindications).
Excretion of the vaccine virus in the stools occurs after vaccination and lasts for 10 days on average with peak excretion around the 7th day. Viral antigen particles detected by ELISA were found in 50% of stools after the first dose and 4% of stools after the second dose. When these stools were tested for the presence of live vaccine strain, 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.
In clinical trials, cases of transmission of excreted vaccine virus to seronegative contacts of vaccinees have been observed without causing any clinical symptoms.
There is a potential risk for transmission to nonvaccinated contacts. Therefore Rotarix should be administered with caution to infants with close contacts who are immunodeficient, such as household members with malignancies or who are otherwise immunocompromised or receiving immunosuppressive therapy. Contacts of recent vaccinees should be advised to observe personal hygiene (e.g. washing their hands when changing children's nappies).
As with any vaccine, a protective immune response may not be elicited in all vaccinees (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
The extent of protection that Rotarix might provide against rotavirus strains that have not been circulating in clinical trials is currently unknown (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
Rotarix does not protect against gastroenteritis due to pathogens other than rotavirus.

Use in the elderly.

Rotarix is not intended for use in the elderly. Thus human data on use in the elderly are not available.

Paediatric use.

Rotarix is intended for use in infants in the first six months of life. Rotarix should not be administered to children older than 24 weeks of age as safety has not been demonstrated, particularly in relation to risk of intussusception.

Effects on laboratory tests.

Rotarix has not been evaluated for effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Coadministration studies have demonstrated that Rotarix can be given concomitantly with any of the following administered either as monovalent or as combination vaccines: diphtheria tetanus acellular pertussis vaccine (DTPa), Haemophilus influenzae type b vaccine (Hib), inactivated polio vaccine (IPV), hepatitis B vaccine (HBV), hexavalent vaccines DTPa-HBV-IPV/Hib, pneumococcal conjugate vaccine and meningococcal serogroup C conjugate vaccine. The studies demonstrated that the immune responses and the safety profiles of the administered vaccines were unaffected.
Clinical studies, involving more than 2,000 subjects, were performed where Rotarix and oral polio vaccine (OPV) were administered two weeks apart. The immune response to Rotarix and OPV was unaffected. In three immunogenicity studies, involving approximately 1,200 subjects, Rotarix was concomitantly administered with OPV. The immune response to OPV, as well as the response to Rotarix after the second dose, were unaffected. Rotarix can be concomitantly administered with OPV if this is in accordance with local recommendations. In the absence of local recommendations, an interval of two weeks between the administration of OPV and Rotarix should be respected.
Although antibodies to rotavirus may be detected in breast milk, the available data show no reduction in efficacy when Rotarix is administered to breastfed infants.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Rotarix has not been evaluated for its potential to impair fertility.
(Category B2)
Rotarix is not intended for use in adolescents or adults. Thus human data on use during pregnancy are not available and animal reproduction studies have not been performed.
Rotarix is not intended for use in adolescents or adults. Thus human data on use during lactation are not available.
Based on evidence generated in clinical trials, breastfeeding does not reduce the protection against rotavirus gastroenteritis afforded by Rotarix. Therefore, breastfeeding may be continued during the vaccination schedule.

4.8 Adverse Effects (Undesirable Effects)

Clinical trial experience.

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 1,930 infants. These trials have shown that the safety and reactogenicity profile of the liquid formulation is comparable to the lyophilised formulation.
A total of twenty-three clinical trials involved the administration of more than 106,000 doses of Rotarix to approximately 51,000 infants. Twenty of 23 are placebo controlled clinical studies. Serious adverse events (SAEs) were collected for all 20 placebo controlled studies, and solicited and unsolicited adverse events were collected in 17 of 20 placebo controlled studies. In these 17 placebo controlled trials Rotarix was administered either alone or concurrently with routine paediatric vaccines.
Rotarix is generally well tolerated.

Solicited adverse events.

In the 17 placebo controlled clinical trials, the solicited events collected within 8 days of vaccination were diarrhoea, vomiting, loss of appetite, fever, irritability and cough/ runny nose. Irrespective of whether Rotarix was administered with or without other paediatric vaccines no significant difference in frequency and severity of these solicited adverse events was observed between the group receiving Rotarix and the group receiving placebo. No increase in the incidence or severity of these events was seen with the second dose.

Unsolicited adverse events.

In the 17 placebo controlled clinical trials the unsolicited adverse reaction profile observed in the subjects receiving Rotarix was comparable to the subjects receiving the same paediatric vaccines and placebo (total number of subjects in Rotarix group = 10,212 in 17 studies; placebo group = 3,840). Nevertheless, the following vaccine related unsolicited adverse event incidences were observed within 31 days following vaccination with Rotarix: irritability, flatulence, abdominal pain, dermatitis.

Serious adverse events.

In 20 placebo controlled clinical trials, the frequencies and severity of the serious adverse events within 31 days postvaccination with Rotarix were compared between Rotarix and placebo recipients. Following serious adverse events were observed in Rotarix group compared to placebo group regardless of causality (Table 1).
The risk of intussusception has been evaluated in a large safety trial conducted in Latin America and Finland where 63,225 subjects were enrolled. This trial gave evidence of no increased risk of intussusception in the Rotarix group when compared with the placebo group as shown in Table 2.
In a clinical study performed in Africa (see Section 5.1 Pharmacodynamic Properties, Clinical trials), the safety profile was similar in all three groups. There was no statistical difference between groups for the percentage of subjects with serious adverse events and adverse events/ serious adverse events leading to dropout. There were a total of 126 fatal events (83 subjects (2.5%) in the HRV pooled group and 43 subjects (2.6%) in the placebo group), which was in line with the mortality rate existing in the same geographical region.
In a clinical study performed in Asia (see Section 5.1 Pharmacodynamic Properties, Clinical trials) where more than 10,000 subjects were enrolled, there were no definite intussusception cases diagnosed within 31 days (day 0 to day 30) after any Rotarix or placebo dose.
The incidence of definite intussusception was 5.6 cases per 10,000 in Rotarix vaccinated children compared to 3.7 cases per 10,000 in placebo group at 9-10 months of follow-up and 14.9 cases per 10,000 in Rotarix vaccinated children compared to 7.5 cases per 10,000 in placebo group at 21-22 months of follow-up.

Safety in preterm infants.

In a clinical study, 1,009 preterm infants were administered Rotarix lyophilised formulation or placebo (198 were 27-30 weeks gestational age and 801 were 31-36 weeks gestational age). 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 solicited and unsolicited symptoms 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 data.

The following adverse events have been reported since market introduction of Rotarix. Because these 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 vaccination with Rotarix.

Gastrointestinal disorders.

Rare: haematochezia; gastroenteritis with vaccine viral shedding in infants with severe combined immunodeficiency (SCID) disorder.
Very rare: intussusception (see Section 4.4 Special Warnings and Precautions for Use).
A large postmarketing epidemiological safety study in Mexico, representing approximately 1,000,000 vaccinated infants evaluated cases of intussusception in the 31 day period after Rotarix vaccination. Data indicated a small increased incidence of intussusception in the 31 day period (relative incidence 1.751, 95% CI 1.237; 2.477, p = 0.001) and this occurred primarily within the 7 days following the first dose. These observations were not seen following administration of the second dose.
A self controlled case series analysis was undertaken in infants immunised between July 2007 and June 2010 in Australia to evaluate cases of intussusception in the 21 day period following any vaccination with rotavirus vaccines. Results from this study indicate an increased relative risk of intussusception of 6.76 (95% CI 2.40-19.01, p < 0.001) and 3.45 (95% CI 1.33-8.94, p = 0.01) within 1-7 days and 8-21 days, respectively, following the first dose of Rotarix. There was also some evidence of an elevated relative risk of intussusception of 2.84 (95% CI 1.10-7.34, p = 0.03) 1-7 days following receipt of the second dose of Rotarix.
Whether Rotarix affects the overall risk of intussusception has not been established.

Blood and lymphatic disorders.

Idiopathic thrombocytopenic purpura.

Vascular disorders.

Kawasaki disease.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

The vaccination course consists of two doses. The first dose should be given between 6 and 14 weeks of age. The interval between the two doses should not be less than 4 weeks. The vaccine course should be completed by the age of 24 weeks as safety has not been assessed in older children.
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 strongly recommended that infants who receive a first dose of Rotarix complete the 2-dose regimen with Rotarix.

Administration.

Rotarix is for oral use only.
Rotarix should under no circumstances be injected.
There are no restrictions on the infant's consumption of food or liquid, including breast milk, either before or after vaccination.

Instructions for use and handling.

The vaccine is presented as a clear, colourless liquid, free of visible particles, for oral administration only. The vaccine is ready to use (no reconstitution or dilution is required).
The vaccine is to be administered orally without mixing with any other vaccines or solutions.
The vaccine should be inspected visually for any foreign particulate matter and/or abnormal physical appearance. In the event of either being observed, discard the vaccine.
Any unused vaccine or waste material should be disposed of in accordance with local requirements.

Instructions for administration of the vaccine in oral applicator (syringe type applicator with a plunger stopper).

1. Remove the protective tip cap from the oral applicator.
2. This vaccine is for oral administration only. The child should be seated in a reclining position. Administer orally (i.e. into the child's mouth towards the inner cheek) the entire content of the oral applicator.
3. Do not inject.
See manufacturer's insert for diagrams.
Discard the empty oral applicator and tip cap according to local regulations.

Instructions for administration of the vaccine in tube.

See manufacturer's insert for diagrams. (Presentation not currently marketed.)
Please read the instructions for use all the way through before starting to give the vaccine.

A. What you need to do before giving Rotarix.

Check the expiry date.
Check the tube has not been damaged nor is already open.
Check the liquid is clear and colourless, without any particles in it.
If you notice anything abnormal, do not use the vaccine.
This vaccine is given orally - straight from the tube.
It is ready to use - you do not need to mix it with anything.

B. Get the tube ready.

1. Pull off the cap.

Keep the cap - you need this to pierce the membrane.
Hold the tube upright.

2. Repeatedly flick the top of the tube until it is clear of any liquid.

Clear any liquid from the thinnest section of the tube by flicking just below the membrane.

3. Position the cap to open the tube.

Keep the tube held upright.
Hold the side of tube.
There is a small spike inside the top of the cap - in the centre.
Turn the cap upside down (180°).

4. To open the tube.

You do not need to twist. Press the cap down to pierce the membrane.
Then lift off the cap.

C. Check the tube has opened correctly.

1. Check the membrane has been pierced.

There should be a hole at the top of the tube.

2. What to do if the membrane has not been pierced.

If the membrane has not been pierced return to section B and repeat steps 2, 3 and 4.

D. Give the vaccine.

Once the tube is open check the liquid is clear, without any particles in it.
If you notice anything abnormal, do not use the vaccine.
Give the vaccine straight away.

1. Position the child to give the vaccine.

Seat the child leaning slightly backwards.

2. Administer the vaccine.

Squeeze the liquid gently into the side of the child's mouth - towards the inside of their cheek.
You may need to squeeze the tube a few times to get all of the vaccine out - it is okay if a drop remains in the tip of the tube.

Instructions for administration of the vaccine presented as 5 single dose tubes connected by a bar.

Please read the instructions for use all the way through before starting to give the vaccine.
This vaccine is given orally straight from an individual tube.
One oral tube delivers one dose of vaccine.
This vaccine is ready to use - do not mix it with anything else.

A. What you need to do before giving Rotarix.

1. Check the expiry date on the connecting bar.


2. Check the liquid in the oral tubes is clear, colourless and free from any particles.

Do not use any of the oral tubes on the connecting bar if you notice anything unusual.

3. Check that each individual oral tube is not damaged and is still sealed.

Do not use the affected oral tube if you notice anything unusual.

B. Get the oral tube ready.

1. To separate one oral tube from the others starting at one end.

a) Hold the tab of one of the end oral tubes to separate it from the others.
b) With your other hand, hold the tab of the oral tube next to it.
c) Pull the tab and tear it away from the oral tube next to it.

2. To open the separated oral tube.

d) Keep the separated oral tube held upright.
e) Hold the tab of the separated oral tube in one hand and the connecting bar in the other hand. Do not hold the body of the oral tube, you may squeeze out some of the vaccine.
f) Twist the separated oral tube.
g) Pull it from the connecting bar.

C. Give the vaccine orally immediately after opening.

1. To position the child to receive the vaccine.

Seat the child leaning slightly backwards.

2. To administer the vaccine orally.

Squeeze the liquid gently into the side of the child's mouth, towards the inside of their cheek.
You may need to squeeze the oral tube a few times to get all of the vaccine out - it is okay if a drop stays in the oral tube.

D. Store remaining doses in the fridge immediately.

Unused oral tubes that are still attached to the connecting bar must be put back in the fridge immediately after an oral tube has been used. This is so that the unused oral tubes can be used for the next vaccination.
Discard the used oral tubes in approved biological waste containers according to local regulations.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Rotarix also contains sucrose, di-sodium adipate, Dulbecco's Modified Eagle Medium and sterile water.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine. See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2°C to 8°C. (Refrigerate. Do not freeze.) Store in the original package, in order to protect from light.

6.5 Nature and Contents of Container

1.5 mL of oral suspension in an oral applicator (Type I, Ph. Eur.) with a plunger stopper (butyl rubber). Pack sizes of 1, 5, 10, 25, 50 or 100.
1.5 mL of oral suspension in a squeezable tube Low Density Polyethylene (LDPE) fitted with a membrane and a cap (polypropylene). Pack sizes of 1 or 10.
1.5 mL of oral suspension in a squeezable tube (LDPE) presented in a multi monodose (5 single dose) squeezable tube presentation with a connecting bar. Pack size of 50 tubes.
Not all pack sizes and container types may be distributed in Australia.

6.6 Special Precautions for Disposal

Discard the empty tube and cap according to local regulations.

Summary Table of Changes