Rotarix

Rotarix Mechanism of Action

vaccine, rotavirus

Manufacturer:

GlaxoSmithKline

Distributor:

Zuellig Pharma
Full Prescribing Info
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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Click on icon to see table/diagram/image

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.
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