Rotarix

Rotarix

vaccine, rotavirus

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Rotavirus vaccine.
Description
Each dose (1.5 mL) of oral suspension contains live attenuated human rotavirus RIX4414 strain not less than 106 CCID50. It also contains the following excipients: Sucrose, disodium adipate, Dulbecco's modified eagle medium (DMEM) and sterile water.
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.
Action
Pharmacotherapeutic Group: Viral vaccines. ATC Code: JO7BH01.
Pharmacology: Pharmacodynamics: Protective Efficacy: The protective efficacy of Rotarix lyophilised formulation against any and severe rotavirus gastroenteritis was evaluated in Europe, Latin America, Africa and Asia.
Severity of gastroenteritis was defined according to 2 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
Protective Efficacy in Europe and Latin America: After 2 doses of Rotarix, the protective vaccine efficacy observed in the studies conducted in Europe and Latin America during the 1st and 2nd year of life combined is presented in Tables 1 and 2. (See Tables 1 and 2.)

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The vaccine efficacy against severe rotavirus gastroenteritis was 38.6% (95% CI: <0; 84.2) for G2P[4] strain. The number of cases, on which the estimates of efficacy against G2P[4] were based, were very small.
A pooled analysis of 4 efficacy studies showed a 71.4% (95% CI: 20.1;91.1) efficacy against severe gastroenteritis (Vesikari score ≥11) caused by rotavirus G2P[4] strain.
Since 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, the levels of vaccine efficacy observed with the lyophilised formulation can be extrapolated to the liquid formulation.
Protective Efficacy in Africa: A clinical study performed in Africa in >4900 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 during the 1st year of life was 61.2% (95% CI:44;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 3.

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Sustained Efficacy up to 3 Years of Age in Asia: A clinical study conducted in Asia (Hong Kong, Singapore and Taiwan) in >10,000 subjects evaluated Rotarix given according to different schedules (2, 4 months of age; 3, 4 months of age).
After 2 doses of Rotarix, the protective vaccine efficacy observed up to 3 years of age is presented in Table 4.

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Immune Response: In different clinical studies conducted in Europe, Latin America and Asia, 1957 infants received Rotarix lyophilised formulation and 1006 infants received a placebo according to different vaccination schedules. The percentage of subjects initially seronegative for rotavirus [IgA antibody titres <20 U/mL (by ELISA)] with serum anti-rotavirus IgA antibody titers ≥20 U/mL 1 or 2 months after the 2nd dose of vaccine or placebo ranges from 77.9-100% and from 0-17.1%, respectively.
In 3 comparative trials, the immune response elicited by Rotarix liquid formulation was comparable to the one elicited by Rotarix lyophilised formulation.
In a clinical study conducted in Africa, the immune response was evaluated in 332 infants who received Rotarix (N=221) or placebo (N=111) according to a 10 and 14 weeks schedule (2 doses) or 6, 10 and 14 weeks schedule (3 doses). The percentage of subjects initially seronegative for rotavirus (IgA antibody titres <20 U/mL (by ELISA)) with serum antirotavirus IgA antibody titers ≥20 U/mL 1 month after the last dose of vaccine or placebo was 58.4% (pooled regimens) and 22.5%, respectively.
Immune Response in Pre-Term Infants:
In a clinical study conducted in pre-term infants with the lyophilised formulation, Rotarix was immunogenic; 85.7% of subjects achieved serum anti-rotavirus IgA antibody titers ≥20 units/mL (by ELISA) 1 month after the 2nd dose of vaccine.
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.
Vaccine Shedding: 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 1st dose and 4% of stools after the 2nd dose. When these stools were tested for the presence of live vaccine strain, 17% were positive.
In 2 comparative controlled trials, vaccine shedding after vaccination with Rotarix liquid formulation was comparable to that observed after vaccination with Rotarix lyophilised formulation.
Effectiveness: Table 5 shows the results of several matched case-control studies conducted to evaluate the effectiveness of Rotarix against severe rotavirus gastroenteritis leading to hospitalization.

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Impact on Mortality§: Impact studies with Rotarix conducted in Panama, Brazil and Mexico showed a decrease in all cause diarrhoea mortality ranging from 22-56% in children <5 years, within 2-3 years after vaccine introduction.
Impact on Hospitalization§: In a retrospective database study in Belgium conducted in children <5 years, the direct and indirect impact of Rotarix vaccination on rotavirus-related hospitalization ranged from 64% (95% CI:49;76) to 80% (95% CI:77;83) 2 years after vaccine introduction. Similar studies in Brazil, Australia and El Salvador showed a reduction of 59%, 75% and 81%, respectively. In addition, 3 impact studies on all cause diarrhoea hospitalization conducted in Latin America showed a reduction of 29-37% 2 years after vaccine introduction.
§NOTE: Impact studies are meant to establish a temporal relationship but not a causal relationship between the disease and vaccination.
Pharmacokinetics: Evaluation of pharmacokinetic properties is not required for vaccines.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies of repeated-dose toxicity.
Indications/Uses
Prevention of gastroenteritis caused by Rotavirus (see Pharmacology: Pharmacodynamics under Actions and Precautions).
Dosage/Direction for Use
The vaccination course consists of 2 doses. The 1st 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 be completed by 24 weeks of age.
Rotarix may be given to pre-term infants with the same dosage (see Pharmacology: Pharmacodynamics under Actions and Adverse Reactions).
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 1st 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.
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.
Overdosage
Insufficient data are available.
Contraindications
Known hypersensitivity after previous administration of Rotarix vaccine or to any components of the vaccine (see Description).
Subjects with history of intussusception.
Subjects with uncorrected congenital malformations (eg, Meckel's diverticulum) of the gastrointestinal tract that would predispose to intussusception.
Subjects with severe combined immunodeficiency (SCID) disorder (see Adverse Reactions).
Special Precautions
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.
As with other vaccines, administration of Rotarix should be postponed in subjects suffering from acute severe febrile illness. However, the presence of a minor infection eg, cold, should not result in the deferral of vaccination.
The administration of Rotarix should be postponed in subjects suffering from diarrhoea or vomiting.
There are no data on the safety and efficacy of Rotarix in infants with gastrointestinal illnesses. 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.
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.
However, post-marketing safety studies indicate a transient increased incidence of intussusception after vaccination, mostly within 7 days of the 1st dose and, to a lesser extent, the 2nd dose. The overall incidence of intussusception remains rare. Whether Rotarix affects the overall risk of intussusception has not been established.
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). Parents/guardians should be advised to promptly report such symptoms.
For subjects with a predisposition for intussusception, see Contraindications.
Administration of Rotarix in immunosuppressed infants including infants on immunosuppressive therapy, should be based on careful consideration of potential benefits and risks (see Pharmacology: Pharmacodynamics under Actions).
Excretion of the vaccine virus in the stools is known to occur after vaccination and lasts for 10 days on average with peak excretion around the 7th day (see Pharmacology: Pharmacodynamics under Actions). In clinical trials, cases of transmission of excreted vaccine virus to seronegative contacts of vaccinees have been observed without causing any clinical symptoms. Rotarix should be administered with caution to individuals with immunodeficient close contacts eg, individuals with malignancies or who are otherwise immunocompromised or receiving immunosuppressive therapy. Contacts of recent vaccinees should be advised to observe careful hygiene (including washing their hands) when changing children's nappies.
As with any vaccine, a protective immune response may not be elicited in all vaccinees (see Pharmacology: Pharmacodynamics under Actions).
The extent of protection that Rotarix might provide against rotavirus strains that have not been circulating in clinical trials is currently unknown (see Pharmacology: Pharmacodynamics under Actions).
Rotarix does not protect against gastroenteritis due to other pathogens than rotavirus.
Rotarix should under no circumstances be injected.
Effects on the Ability to Drive or Operate Machinery: Rotarix is not intended for use in adults.
Use in Pregnancy & Lactation: Rotarix is not intended for use in adults. Thus, human data on use during pregnancy or lactation are not available and animal reproduction studies have not been performed.
Use In Pregnancy & Lactation
Rotarix is not intended for use in adults. Thus, human data on use during pregnancy or lactation are not available and animal reproduction studies have not been performed.
Adverse Reactions
Clinical Trial Data: The following convention has been used for the classification of frequency: Very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1000 and <1/100); rare (≥1/10,000 and <1/1000); very rare (<1/10,000).
The safety profile presented as follows is based on data from clinical trials conducted with either the lyophilised or the liquid formulation of Rotarix.
In a total of 4 clinical trials, approximately 3800 doses of Rotarix liquid formulation were administered to approximately 1900 infants. Those trials have shown that the safety profile of the liquid formulation is comparable to the lyophilised formulation.
In a total of 23 clinical trials, approximately 106,000 doses of Rotarix (lyophilised or liquid formulation) were administered to approximately 51,000 infants.
In 3 placebo-controlled clinical trials 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 2nd dose.
In a pooled analysis from 17 placebo-controlled clinical trials including trials in which Rotarix was co-administered with routine paediatric vaccines (see Interactions), the following adverse reactions (collected 31 days post-vaccination) were considered as possibly related to vaccination.
Gastrointestinal Disorders: Common: Diarrhoea. Uncommon: Flatulence, abdominal pain.
Skin and Subcutaneous Tissue Disorders: Uncommon: Dermatitis.
General Disorders and Administration Site Conditions: Common: Irritability.
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 6. (See Table 6.)

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Safety in Pre-Term Infants: In a clinical study, 1009 pre-term infants were administered Rotarix lyophilised formulation or placebo (198 were 27-30 weeks gestational age and 801 were 31-36 weeks gestational age). The 1st dose was administered from 6 weeks after birth. Serious adverse events were observed in 5.1% of recipients of Rotarix as compared to 6.8% of placebo recipients. Similar rates of other adverse events were observed in Rotarix and placebo recipients. No cases of intussusception were reported.
Post-Marketing Data: Gastrointestinal Disorders: Rare: Intussusceptions (see Precautions), haematochezia, gastroenteritis with vaccine viral shedding in infants with SCID disorder.
Drug Interactions
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 to 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 gastroenteritis was shown to be maintained.
Incompatibilities: Rotarix must not be mixed with other medicinal products.
Caution For Usage
Instructions for Use and Handling: Rotarix is presented as a clear, colourless liquid, free of visible particles, for oral administration.
Rotarix is ready to use (no reconstitution or dilution is required).
Rotarix is to be administered orally without mixing with any other vaccines or solutions.
Rotarix 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 Rotarix in Squeezable Tube: Getting the Tube Ready: Removing the cap: Hold the tube vertically until ready to give the vaccine, the liquid can spill out if it is tilted to one side. Pull off the cap.
Clearing liquid from the top of the tube: Flick the top of the tube to clear any liquid.
Positioning the cap to open the tube: There is a small hole on the top of the cap in the centre. Turn the cap upside down. Put the small hole over the tip seal of the tube.
Opening the tube: Holding the tube still, twist the cap clockwise. Keep the cap vertical, the tip seal should stay attached to the inside of the cap. Do not snap the cap sideways, the tip seal may fall into the tube.
Checking the Tube has Opened Correctly: Check that the tip seal has been fully detached: There should be a hole at the top of the tube. The tip seal should now be inside the cap.
If the tip seal has not been fully detached: Try to open the tube again. Follow the instructions over "Positioning the cap to open the tube" and "Opening the tube". If the tip seal will not detach, do not give the vaccine.
If the tip seal has fallen into the tube or cannot be seen anywhere: Do not give the vaccine.
Giving the Vaccine: Seat the child leaning slightly backwards. Squeeze the liquid into the child’s mouth, towards the inside of their cheek. May need to squeeze the tube a few times to get all of the liquid out, it is okay for a drop to remain in the tip of the tube.
Instructions for Administration of Rotarix in Oral Applicator: Remove the protective tip cap from the oral applicator. Rotarix is for oral administration only. The child should be seated in a reclining position. Administer orally (ie, into the child's mouth towards the inner cheek) the entire content of the oral applicator. Do not inject.
Storage
Store in a refrigerator (2-8°C). Do not freeze. Protect from light.
ATC Classification
J07BH01 - rota virus, live attenuated ; Belongs to the class of rota virus diarrhea viral vaccines.
Presentation/Packing
Vaccine (oral susp) 1.5 mL (clear, colourless liqd) x 1's (oral applicator).
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