Rotarix

Rotarix

vaccine, rotavirus

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Live attenuated human rotavirus.
Description
Each 1.5 mL dose contains live attenuated human rotavirus RIX4414 strain (produced on Vero cells) of the GIP [8] type not less than 106.0 CCID50.
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.
Excipients/Inactive Ingredients: Sucrose, Di-sodium Adipate, Dulbecco's Modified Eagle Medium (DMEM), Sterile water.
Action
Pharmacotherapeutic group: Viral vaccines. ATC code: J07BH01.
Pharmacology: Pharmacodynamics:
Protective efficacy of the 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] and G9P[8]. In addition, efficacy against uncommon rotavirus genotypes G8P[4] (severe gastro-enteritis) and G12P[6] (any gastro-enteritis) has been demonstrated. These strains are circulating worlwide.
Clinical studies have been conducted in Europe, Latin America and Africa to evaluate the protective efficacy of Rotarix against any and severe rotavirus gastro-enteritis.
Severity of gastro-enteritis was defined according to two different criteria: the Vesikari 20-point scale, which evaluates the full clinical picture of rotavirus gastro-enteritis 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: 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 4000 subjects. Severity of gastro-enteritis was defined according to the Vesikari 20-point scale which evaluates the full clinical picture of rotavirus gastro-enteritis 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.
After two doses of Rotarix, the protective vaccine efficacy observed during the first and second year of life is presented in Table 1. (See Table 1.)

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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.
Protective efficacy in Latin America: A clinical study performed in Latin America evaluated Rotarix in more than 20,000 subjects. Severity of gastro-enteritis was defined according to WHO criteria. The protective vaccine efficacy against severe rotavirus gastro-enteritis requiring hospitalisation and/or rehydration therapy in a medical facility and the strain specific vaccine efficacy after two doses of Rotarix are presented in Table 2. (See Table 2.)

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A pooled analysis of five efficacy studies*, showed a 71.4% (95% CI:20.1; 91.1) efficacy against severe rotavirus gastro-enteritis (Vesikari score ≥11) caused by rotavirus G2P[4] type during the first year of life.
*In these studies, the doses of Rotarix used ranged from 105.3 to 106.6 CCID50, and the point estimates and confidence intervals were respectively: 100% (95% CI: -1858.0; 100), 100% (95% CI: 21.1; 100), 45.4% (95% CI: -81. 5; 86.6), 74.7% (95% CI :-386.2; 99.6). No point estimate was available for the remaining study.
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 gastro-enteritis 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 gastro-enteritis is presented in Table 3. (See Table 3.)

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Protective Efficacy in Asia: 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). Severity of gastro-enteritis was defined according to the Vesikari 20-point scale. After two doses of Rotarix, the protective vaccine efficacy observed up to 3 years of age is shown at Table 4. (See Table 4.)

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Protective efficacy of the liquid formulation: 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.
Immune response: The immunologic mechanism by which Rotarix protects against rotavirus gastro-enteritis is not completely understood. A relationship between antibody responses to rotavirus vaccination and protection against rotavirus gastro-enteritis has not been established.
The following table shows the percentage of subjects initially seronegative for rotavirus (IgA antibody titres <20 U/ml (by ELISA) ) and with serum anti-rotavirus IgA antibody titers ≥20 U/ml one to two months after the second dose of vaccine or placebo as observed in different studies with Rotarix lyophilised formulation. (See Table 5.)

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In three comparative controlled trials, the immune response elicited by Rotarix liquid formulation was comparable to the one elicited by Rotarix lyophilised formulation.
Data are insufficient to establish the safety and efficacy of Rotarix in premature infants less than 37 weeks gestation. Moreover, it is not known whether premature infants are at higher risk for rotavirus hospitalisation when compared with full-term infants. Until such data become available, physicians should individually weigh the potential benefits and risks of administering Rotarix to a premature infant.
Rotarix does not protect against non-rotaviral gastro-enteritis, or against diarrhoea due to other infectious and non-infectious causes.
Effectiveness: Table 6 shows the results of several matched case-control studies conducted to evaluate the effectiveness of Rotarix against severe rotavirus gastro-enteritis leading to hospitalisation. (See Table 6.)

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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% to 56% in children less than 5 years of age, within 2 to 3 years after vaccine introduction.
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 reduct ion of 59%, 75 % and 81%, respectively. In addition, three impact studies on all cause diarrhoea hospitalisation conducted in Latin America showed a reduction of 29% to 37% two years after vaccine introduction.
§NOTE: Impact studies are meant to establish a temporal relationship but not a casual 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
Rotarix is indicated for the active immunisation of infants from the age of 6 weeks for prevention of gastro-enteritis due to rotavirus infection (see Pharmacology: Pharmacodynamics under Actions, Dosage & Administration, and Precautions).
Dosage/Direction for Use
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.
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.
Method of administration: Rotarix is for oral use only. Administer the entire content (1.5 mL) of the oral applicator ORALLY on the inside of the cheek.
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, breast-feeding does not reduce the protection against rotavirus gastro-enteritis afforded by Rotarix. Therefore, breast-feeding may be continued during the vaccination schedule.
For information on instructions for administration, (see Cautions for Usage).
Overdosage
There is limited information on overdosage.
Contraindications
Rotarix should not be administered to subjects who have on-going diarrhoea or vomiting.
Rotarix should not be administered to subjects with known hypersensitivity after previous administration of Rotarix vaccine or to any component of the vaccine (see Description).
Subjects with history of intussusception.
Subjects with uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for intussusception.
Rotarix should not be administered to subjects with known or suspected immune deficiency diseases and conditions such as combined immunodeficiency, hypogammaglobulinemia, agammaglobulinemia, human immunodeficiency virus (HIV) infection, thymic abnormalities, malignancy, leukemia, lymphoma, or advanced debilitating conditions.
Rotarix should not be administered to subjects who may be immunosuppressed or have an altered or compromised immune status, such as those who are being treated with systemic corticosteroids, alkylating drugs, antimetabolites, radiation, or other immunosuppressive therapies.
Subjects with Severe Combined Immunodeficiency (SCID) disorder (see Adverse Reactions).
Special Precautions
Prior to administration of this vaccine, health care personnel should inform the parent or guardian of the benefits and risks to the vaccinee, and the importance of completing the immunisation series. Parents or guardians should be instructed to report any serious adverse reactions to their health care provider.
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 (>38.5°C). However, the presence of a minor infection, such as cold, should not result in the deferral of vaccination.
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 (see Adverse Reactions).
However, post-marketing safety studies indicate a transient increased incidence of intussusception after vaccination, mostly within 7 days of the first dose and, to a lesser extent, the second 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. 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, such as 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.
Contacts of recent vaccinees should be advised to observe personal hygiene (e.g. wash their hands after changing child's nappies).
Information is not available regarding the administration of Rotarix to individuals who had recently received immune globulin-containing products either orally or parenterally.
Limited data in 140 premature children indicate that Rotarix can be given to premature children, however the level of clinical protection remains unknown.
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 gastro-enteritis due to other pathogens than rotavirus.
ROTARIX TM SHOULD UNDER NO CIRCUM STANCES BE INJECTED.
Effects on Ability to Drive and Use Machines: 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.
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 below is based on data from clinical trials conducted with either the lyophilised or the liquid for mulation 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, 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 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 7. (See Table 7.)

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Parents and caretakers should be advised to contact their doctors urgently if the vaccinated child develops any or all features of intussusception (abdominal bloating or severe colicky pain, bloody or black stools, or persistent vomiting). Doctors should consider this diagnosis in children with these symptoms.
Safety in preterm infants: In a clinical study, 1009 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 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: intussusception (see Precautions), haematochezia, gastroenteritis with vaccine viral shedding in infants with Severe Combined Immunodeficiency (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 gastro-enteritis was shown to be maintained in a clinical trial involving more than 4200 subjects who received Rotarix concomitantly with OPV.
Antibodies to rotavirus may be detected in breast milk. 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.
Caution For Usage
Instructions for Use and Handling: The vaccine is presented as a clear, colourless liquid, free of visible particles, for oral administration.
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.
Instruction for administration of the vaccine: 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.
Incompatibilities: This medicinal product must not be mixed with other medicinal products.
Storage
Store in a refrigerator (2°C-8°C). Do not freeze.
Store in the original package in order to 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 (clear and colourless liquid) 1.5 mL x 1's.
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