Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1.    Pharmacodynamic properties
Pharmacotherapeutic group: Rabies vaccines, ATC code: J07BG01.
Mechanism of action
Protection after vaccination is ensured by the induction of rabies neutralising antibodies.
Clinical studies have been conducted to assess the immunogenicity of the vaccine as pre- and post-exposure prophylaxis. A rabies neutralising antibody level of ≥ 0.5 IU/mL is considered to be protective by the WHO.
Pre-exposure prophylaxis
In clinical trials assessing a 3-dose vaccination schedule (D0, D7, and D28 (or D21)) in adults and children, an adequate immune response was obtained in all subjects with serum neutralising antibody titres ≥ 0.5 IU/mL on D14 after the end of primary vaccination.
A ten-year follow-up in 49 patients who had received a 3-dose regimen (D0, D7 and D28) followed by a booster dose at one year, demonstrated persistence of the immune response with neutralising antibody titres being maintained for up to 10 years in 96.9% of the vaccinated subjects.
The one-week IM pre-exposure regimen (0.5 mL dose on D0 and 0.5 mL dose on D7) was assessed in a study (VAJ00001) in 75 subjects (including 35 children aged 2 to 17 years).
On D21, 98.6% of the vaccinated subjects had achieved serum antibody levels ≥ 0.5 IU/mL.
One year later, following simulated post-exposure prophylaxis (PEP) with two 0.5 mL doses 3 days apart (on D0 and D3) via IM injection, a rapid and robust anamnestic response was demonstrated in all subjects from D7 (7 days after the 1st PPE dose).
During 5 additional studies conducted with VERORAB in a total of 392 subjects assessing the standard three-dose regimen (on D0, D7, and D21 or D28) by IM injection, all the subjects achieved serum antibody levels ≥ 0.5 IU/mL. after two doses (on D0 and D7), just before the third dose on D21 or D28.
Post-exposure prophylaxis
In clinical trials assessing the 5-dose intramuscular Essen regimen (D0, D3, D7, D14 and D28) and the 4-dose intramuscular Zagreb regimen (2 doses on D0 then one dose on D7 and one dose on D21) in children and adults, vaccination with VERORAB resulted in neutralising antibody titres (≥0.5 IU/mL) in almost all the vaccinated subjects on D14 and in all the subjects on D28.
The administration of human rabies immunoglobulin (HRIG) or equine rabies immunoglobulin (ERIG) at the same time as the rabies vaccine may cause a slight decrease in the mean neutralising antibody titre because of immune interference.
The efficacy of Verorab was assessed in 44 adult subjects bitten by rabid animals in a phase 4 clinical trial. Subjects received the vaccine according to the 5-dose Essen regimen (D0, D3, D7, D14 and D28 by IM injection) and immunoglobulins, if applicable. All the subjects were alive 3 years after the post-exposure prophylaxis.
Paediatric population
There is no clinically significant difference in the immunogenicity of the vaccine in the paediatric population compared to adults.

Pharmacokinetic Properties

5.2.    Pharmacokinetic properties
No pharmacokinetic studies have been performed.