GlaxoSmithKline UK

section 6.1.

Section 4.2 - Subjects who remain at risk of typhoid fever should be revaccinated using a single dose of Vi polysaccharide vaccine every 3 years

(see section 5.1). Hepatyrix may be used to revaccinate against typhoid fever in subjects that also need to have a dose of hepatitis A vaccine.

Section 4.8 - Clinical trials
In controlled clinical studies, the most commonly reported reactions after administration of Hepatyrix were those at the site of injection. All local and general symptoms resolved without any sequelae.
Frequencies are reported as:
Very common: ( 1/10)
Common: (=1/100 to <1/10)
Uncommon: (=1/1,000 to <1/100)
Rare: (=1/10,000 to <1/1,000)
Very rare: (<1/10,000)
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness
Nervous system disorders:
Common: headache
Gastrointestinal disorders:
Common: nausea
Skin and subcutaneous tissue disorders:
Very common: erythema
Common: itching
General disorders and administration site conditions:
Very common: pain
Common: fever, general aches, malaise, swelling
Post-marketing surveillance
The following undesirable events have been reported in temporal association with Hepatyrix vaccination:
Immune system disorders:
Very rare: allergic reactions, including anaphylaxis and anaphylactoid reactions
Nervous system disorders:
Very rare: syncope
Skin and subcutaneous tissue disorders:
Very rare: skin rashes
Experience with the GlaxoSmithKline monovalent hepatitis A vaccine:
Clinical trials:
The following undesirable effects have been reported during clinical trials conducted with the GlaxoSmithKline monovalent hepatitis A vaccine:
Metabolism and nutrition disorders:
Common: loss of appetite
Gastrointestinal disorders:
Common: vomiting
Post-marketing surveillance:
During post-marketing surveillance, the following undesirable effects have been reported with the
GlaxoSmithKline monovalent hepatitis A vaccine:
Nervous system disorders:
Very rare: neurological manifestations including transverse myelitis, Guillain-Barre syndrome and neuralgic amyotrophy, convulsions
Musculoskeletal and connective tissue disorders:
Very rare: arthralgia, myalgia

Section 5.1 - Pharmacotherapeutic group: Bacterial and viral vaccines combined, ATC code J07CA10

Hepatyrix confers immunity against typhoid fever and HAV infection by inducing specific anti-Vi and anti-HAV antibodies.
In clinical studies involving 462 subjects of 15-50 years of age, seropositivity rates for anti-HAV and anti-Vi antibodies were 89.8% and 97.5% respectively two weeks after primary immunisation. At month 1, seropositivity rates for anti-HAV and anti-Vi antibodies were 99.0% and 95.7% respectively.

In a clinical study where a group of 99 subjects received a booster dose of hepatitis A vaccine 12 months following the initial dose of Hepatyrix, all subjects were seropositive for anti-HAV antibodies one month later (i.e. at month 13).
When Hepatyrix was given 12 months following primary vaccination with the hepatitis A vaccine in a cohort of 97 subjects, the seropositivity rates for anti-Vi and anti-HAV antibodies were 88.2% and 100% respectively one month later (i.e. at month 13).

In two long-term clinical studies (TypHA-002 and TypHA-009), the persistence of anti-Vi and anti-HAV antibodies has been evaluated up to 36 months after vaccination with Hepatyrix and a booster dose of Havrix 1440 (GlaxoSmithKline Biologicals monovalent inactivated hepatitis A vaccine) administered six months later. In one of these two studies TypHA-009) the seropositivity rates obtained with Hepatyrix were compared to those obtained with co-administration of Typherix (GlaxoSmithKline Biologicals monovalent purified Vi polysaccharide vaccine) and Havrix 1440, followed by a booster dose of Havrix 1440 administered six months later.
The anti-Vi seropositivity rates observed in these two studies are presented below: