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Pharmaco-therapeutic group: Hepatitis vaccines. ATC code: J07BC20.
Pharmacology: Pharmacodynamics: Twinrix confers immunity against HAV and HBV infection by inducing specific anti-HAV and anti-HBs antibodies.
Children and adolescents of 1 to 15 years of age: In clinical studies involving subjects aged 1 to 15 years old, seropositivity rates for anti-HAV antibodies were 99.1% one month after the first dose and 100% after the second dose given at month 6 (i.e. month 7). Seropositivity rates for anti-HBs antibodies were 74.2% one month after the first dose and 100% after the second dose given at month 6 (i.e. month 7). The anti-HBs seroprotection rates (titres ≥ 10mlU/ml) at these time points were 37.4% and 98.2% respectively.
In a comparative study conducted in subjects (from 12 years up to and including 15 years of age) vs an alternative schedule of 3 doses with the combined vaccine containing 360 ELISA Units inactivated HA virus and 10 μg HBsAg in a dose volume of 0.5 ml, seroprotection rates for anti-HBs at intermediate time points before the 2nd dose of Twinrix were lower compared to those obtained with the alternative schedule comprising 3 doses, but non-inferiority was shown after completion of the schedule (month 7).
Anti-HAV and anti-HBs antibodies have been shown to persist for at least 10 years following the initiation of a 0, 6 month schedule of Twinrix.
After 10 years, the anti-HAV seropositivity rates and the anti-HBs seroprotection rates in subjects aged 1-11 years at primary vaccination were 100% and 77.3% respectively. After 15 years, the anti-HAV seropositivity rates and the anti-HBs seroptotection rates in subjects aged 12-15 years at primary vaccination, were 100% and 81.1% respectively. A challenge dose of a HBV vaccine was given to a limited number of subjects (n=8) whose anti-HBs antibody concentrations decreased to < 10 mIU/ml and all mounted an anamnestic response.
After 15 years, the immune response for both antigen components was comparable to that seen after a 3-dose regimen of the combined vaccine containing 360 ELISA Units of inactivated hepatitis A virus and 10 μg of recombinant hepatitis B surface antigen in a dose volume of 0.5 ml.
In a clinical study conducted among 12 years up to and including 15 years old subjects who received the second dose of Twinrix at month 12, seropositivity rates for anti-HAV were 99.0% and seropositivity rates for anti-HBs were 99.0% at month 13 with seroprotection rates of 97.0%.
In a 6 year long term follow-up study involving subjects aged 12-15 years at primary vaccination, anti-HAV seropositivity rates were 100% following a 0, 6 month or a 0, 12 month schedule. The anti-HBs seroprotection rates were 84.8% and 92.9%, respectively.
Adults and adolescents of 16 years of age and above: In subjects aged 16 years and above administered a 3-dose schedule of Twinrix, protection against hepatitis A and hepatitis B develops within 2-4 weeks. In the clinical studies, specific humoral antibodies against hepatitis A were observed in approximately 94% of the adults one month after the first dose and in 100% one month after the third dose (i.e. month 7). Specific humoral antibodies against hepatitis B were observed in 70% of the adults after the first dose and approximately 99% after the third dose.
For use in exceptional circumstances in adults, the 0, 7 and 21 day primary schedule plus a fourth dose at month 12 results in 82% and 85% of vaccinees having seroprotective levels of anti-HBV antibodies at 1 and 5 weeks respectively following the third dose. One month after the fourth dose, all vaccinees demonstrated seroprotective levels of antibody. Seropositivity rates for anti-HAV antibodies were 100% and 99.5% at 1 and 5 weeks respectively following the third dose, and reached 100% one month after the fourth dose.
In a clinical study conducted in subjects over 40 years of age, the seropositivity rate for anti-HAV antibodies and seroprotection rate against hepatitis B following Twinrix on a 0, 1, 6 month schedule were compared with the seropositivity and seroprotection rates of monovalent hepatitis A and B vaccines when administered separately.
The seroprotection rates against hepatitis B after the administration of Twinrix were 92% and 57% at 7 and 48 months following the first dose respectively, versus 80% and 40% after the GlaxoSmithKline Biologicals monovalent 20 μg hepatitis B vaccine, and 71% and 27% after another licensed monovalent 10 μg hepatitis B vaccine. In all groups, anti-HBs antibody concentrations decreased as age and body mass index increased; concentrations were also lower in males compared with females.
The seropositivity rates for anti-HAV antibodies after Twinrix were 97% at both 7 and 48 months following the first dose versus 99% and 94% after the GlaxoSmithKline Biologicals monovalent hepatitis A vaccine and 99% and 96% after another licensed monovalent hepatitis A vaccine.
Subjects received an additional dose of Twinrix to assess the immune memory 48 months after the first dose of the primary vaccination course with the same vaccine. One month after this dose, 95% of subjects elicited anti-HBV antibody concentration ≥ 10 mIU/ml and Geometric Mean Concentrations (GMC) increased by 179-fold (GMC of 7233.7 mIU/ml) indicative of an immune memory response.
In two long-term clinical studies conducted in adults, 20 years after the primary vaccination with Twinrix the anti-HAV seropositivity rates were 100% and 96% respectively and the anti-HBs seroprotection rates were 94% and 92%, respectively (n=43).
Pharmacokinetics: Evaluation of pharmacokinetic properties is not required for vaccines.
Toxicology: Preclinical safety data: Preclinical data reveal no special hazards for humans based on general safety studies (see Pregnancy & Lactation).
