Pharmacotherapeutic group: Hepatitis vaccines. ATC code: J07BC20.
Pharmacology: Pharmacodynamics: Twinrix Adult confers immunity against HAV and HBV infection by inducing specific anti-HAV and anti-HBs antibodies.
Protection against hepatitis A and hepatitis B develops within 2-4 weeks. In the clinical studies for Twinrix Adult, 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 Adult 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 Adult 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 Adult 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 Adult 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, 15 years after the primary vaccination with Twinrix Adult the anti-HAV seropositivity rates were 100% in both studies and the anti-HBs seroprotection rates were 89.3% and 92.9%, respectively (n=56). The kinetics of decline of anti-HAV and anti-HBs antibodies were shown to be similar to those of the monovalent vaccines.
Toxicology: Pre-clinical Safety Data: Pre-clinical data reveal no special hazard for humans based on general safety studies (see Use in Pregnancy & Lactation).