Salmonella typhi (Ty 2 strain) polysaccharides.
One dose of 0.5 ml of vaccine contains: Purified Vi capsular polysaccharides of Salmonella typhi (Ty2 strain) 25 micrograms.
Typhim Vi may contain traces of formaldehyde or casein, which are used during the manufacturing process (see Contraindications).
Excipients/Inactive Ingredients: Phenol and a buffer solution containing sodium chloride, disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate and water for injections.
Pharmacotherapeutic group: bacterial vaccines. ATC code: J07AP03.
Pharmacology: Pharmacodynamics: Vaccine prepared from purified Vi capsular polysaccharides of Salmonella typhi. Immunity appears about 1 to 3 weeks after the injection. Protection lasts around 3 years.
A double-blind, randomized, controlled efficacy clinical study was conducted in a highly endemic area in Nepal, in children and adults from 5 to 44 years. A total of 3,457 subjects received TYPHIM Vi. Compared with the control group (23 valence-pneumococcal polysaccharide vaccine), vaccine efficacy conferred by a single dose of vaccine TYPHIM Vi was 74% (CI 95%: 49; 87) against blood culture-confirmed cases of typhoid fever throughout the 20 months of active surveillance.
Seroconversion rate (defined as 4-fold rise of anti-Vi antibody levels) was collected in 19 clinical trials. These trials were conducted in endemic and non-endemic areas in adults and children from 2 years of age representing a total of 2,137 evaluable subjects. In the adult population, the seroconversion rate ranged from 62.5% to 100% four weeks after a single injection, with similar magnitude of anti-Vi immune response in non-endemic areas compared to endemic areas.
Anti-Vi antibody persistence depends on endemicity, with a trend for better persistence in endemic areas (documented up to 10 years in 83 children at levels equal or above 1 μg/mL considered as a serological indicator of protection against typhoid fever). In non-endemic areas, anti-Vi antibodies persist for 2 to 3 years with rates above 1 μg/mL around 41% after two years and 35.6% after 3 years of vaccination with TYPHIM Vi. Revaccination should be carried out with a maximum interval of 3 years if the subject is still exposed to the risk.
Paediatric population: In a double-blind, randomized, controlled efficacy clinical study conducted in a highly endemic area in South Africa, a total of 5,692 subjects from 5 to 15 years of age received TYPHIM Vi. Compared with the control group (meningococcal polysaccharide vaccine of groups A and C), vaccine efficacy conferred by a single dose of vaccine TYPHIM Vi was 55% (CI 95%: 30; 71) against blood culture-confirmed cases of typhoid fever during a 3-year follow-up.
Immunogenicity was assessed in both endemic and non-endemic areas in paediatric population aged from 2 to 17 years. In 9 clinical studies including 733 evaluable children, four weeks after a single injection of TYPHIM Vi, the seroconversion rate ranged from 67% to 100%, with a magnitude of anti-Vi immune response similar to that documented in adult.
Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Non-clinical data revealed no special hazard for humans based on conventional studies of acute toxicity, repeat dose toxicity, local safety and hypersensitivity.
Prevention of typhoid fever in adults and in children over 2 years of age, and especially: travelers to endemic areas, migrants, health care professionals and military personnel.
Posology: Restricted To Adults and Children Over 2 Years of Age.
A single injection of 0.5 ml. If exposure to risk continues, revaccination will be performed every 3 years.
Paediatric population: The vaccination schedule is the same for children and adults.
Method of administration: Intramuscular or subcutaneous route.
Hypersensitivity to the active substance, to any of the excipients listed in Description to formaldehyde or to casein (which may be present as traces in each dose, owing to its use during the manufacturing process).
Vaccination should be postponed in case of acute febrile disease.
Do not inject by the intravascular route.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection, especially in adolescents. This may be accompanied by several neurological signs such as transient sight disorders, paraesthesia and tonic-clonic limb movements during the recovery phase. It is important that procedures be in place to avoid any injury from faints.
This vaccine protects against the risks of infection by Salmonella typhi but not against Salmonella paratyphi A or B or non-typhoidal salmonella.
The immunogenicity of TYPHIM Vi may be reduced by immunosuppressive treatment or immunodeficiency. It is then recommended to wait until the end of the treatment or disease before vaccinating. Nevertheless, vaccination of subjects with chronic immunodeficiency such as HIV infection is recommended even if the immune response may be limited.
Injection must be performed via the subcutaneous route in subjects with thrombocytopenia or bleeding disorders.
As with all injectable vaccines, appropriate medical treatment and supervision must always be readily available, in the event of a rare anaphylactic reaction following administration of the vaccine.
Effects on ability to drive and use machines: The effects on the ability to drive and use machines have not been studied.
Use in Children: This vaccine is not indicated in children under 2 years of age because of the risk of insufficient antibody response.
Pregnancy: No reliable animal teratogenic data are available.
Currently, no sufficiently relevant clinical data are available to assess a potential teratogenic or foetotoxic risk of this vaccine when administered during pregnancy.
Because of the seriousness of the disease, and in case of high risk of exposure to typhoid fever, pregnancy is not a reason not to administer the vaccine.
Lactation: It is not known whether this vaccine is excreted in human milk. Caution must be exercised when Typhim Vi is administered to a nursing mother.
Summary of the safety profile:
More than 15,000 subjects received TYPHIM Vi (either in a single injection or as a second injection) in clinical studies.
The most common adverse reaction, in all age groups, was injection site pain. In adults from 18 years of age, myalgia and fatigue were the most frequently reported systemic reactions. In children and adolescents (from 2 to 17 years of age), myalgia and cephalalgia were the most frequently reported systemic reactions.
Most adverse reactions occurred within three days of vaccination. Most reactions resolved spontaneously within 1 to 3 days after onset.
Tabulated list of adverse reactions:
The adverse reactions listed as follows come from clinical studies (pooled analysis) and worldwide post-marketing experience. The pooled analysis was performed on 6 recent studies sharing the same safety standard integrating data from 1532 subject (97 children and adolescents from 2 to 17 years of age and 1435 adults).
In each System Organ Class, the adverse events are ranked under headings of frequency, the most common reactions coming first, using the following convention: Very common (≥1/10); Common (≥ 1/100 to <1/10); Uncommon (≥ 1/1000 to <1/100); Rare (≥ 1/10 000 to <1/1000); Very rare (<1/10 000) including isolated cases. Not known: cannot be estimated from available data.
The table as follows summarises the frequencies of adverse reactions recorded after any dose of TYPHIM Vi in children and adolescents from 2 to 17 years of age. (See table.)
Click on icon to see table/diagram/image
The most frequently reported adverse reactions in children and adolescents (from 2 to 17 years of age) were injection site reactions: pain (52.6%), swelling/oedema/induration (16.5%) and erythema (14.4%).
In adults from 18 years of age, the most frequently reported adverse reactions were injection site pain (75.6%), myalgia (47.1%) and fatigue/asthenia (25.0%).
Reporting of suspected adverse reactions:
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
This vaccine can be administered with hepatitis A and yellow fever vaccines during the same vaccination session, using separate injection sites.
Data concerning use with other vaccines (diphtheria, tetanus, poliomyelitis, rabies, meningitis A+C and hepatitis B) are limited. However, no interaction is anticipated when vaccines are given at separate sites using separate syringes.
Instructions for use, handling and disposal: The vaccine should be kept at room temperature for a few minutes before use.
For syringes without attached needles, the separate needle must be fitted firmly to the syringe, rotating it by a one quarter turn.
Any unused product or waste material should be disposed of in accordance with local requirements.
The vaccine must not be used if the doctor or nurse notices foreign particles in the syringe.
Incompatibilities: In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.
Store in a refrigerator (2°C - 8°C).
Do not freeze.
Shelf life: 3 years.
J07AP03 - typhoid, purified polysaccharide antigen ; Belongs to the class of typhoid bacterial vaccines.
Pre-filled syringe vaccine inj (single dose) 0.025 mg/0.5 mL (clear, colourless solution) x 1's. Vial vaccine (inj) (multiple-dose) 10 mL x 20 doses x 10's.