TYPHIM VI Solution for injection Ref.[11099] Active ingredients: Typhoid purified polysaccharide antigen

Allergic reactions have been reported rarely in the post-marketing experience (see ADVERSE REACTIONS section).

The safety and immunogenicity of Typhim Vi vaccine in children under two years of age has not been established. As with other polysaccharide vaccines, the antibody response may be inadequate. The decision whether to vaccinate children under 2 years of age depends upon the risk incurred by the child on the basis of the epidemiological context.

Typhim Vi vaccine provides protection against the risk of infection related to Salmonella typhi, but gives no protection against Salmonella paratyphi A or B, non-S typhi species of Salmonella enterica serovar Typhi, or other bacteria that cause enteric disease.

If the vaccine is used in persons deficient in producing antibodies, whether due to genetic defect, immunodeficiency disease, or immunosuppressive therapy, the expected immune response may not be obtained. This includes patients with asymptomatic or symptomatic HIV-infection, severe combined immunodeficiency, hypogammaglobulinemia, or agammaglobulinemia; altered immune states due to diseases such as leukemia, lymphoma, or generalized malignancy; or an immune system compromised by treatment with corticosteroids, alkylating drugs, antimetabolites or radiation. (16)

As with any vaccine, vaccination with Typhim Vi vaccine may not protect 100% of individuals.

Adverse event information is derived from clinical trials and worldwide post-marketing experience.

Data From Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates.

Safety of Typhim Vi vaccine, the US licensed liquid formulation, has been assessed in clinical trials in more than 4,000 subjects both in countries of high and low endemicity. In addition, the safety of the lyophilized formulation has been assessed in more than 6,000 individuals. The adverse reactions were predominately minor and transient local reactions. Local reactions such as injection site pain, erythema, and induration almost always resolved within 48 hours of vaccination. Elevated oral temperature, above 38°C (100.4°F), was observed in approximately 1% of vaccinees in all studies. No serious or life-threatening systemic events were reported in these clinical trials. (10) (11)

Adverse reactions from two trials evaluating Typhim Vi vaccine lots in the US (18- to 40-year-old adults) are summarized in Table 3. No severe or unusual side effects were observed. Most subjects reported pain and/or tenderness (pain upon direct pressure). Local adverse experiences were generally limited to the first 48 hours. (10) (11)

Table 3 (10) (11). PERCENTAGE OF 18- TO 40-YEAR-OLD US ADULTS PRESENTING WITH LOCAL OR SYSTEMIC REACTIONS WITHIN 48 HOURS AFTER THE FIRST IMMUNIZATION WITH TYPHIM Vi VACCINE:

No studies were conducted in US children. Adverse reactions from a trial in Indonesia in children one to twelve years of age are summarized in Table 4. (10) (11) No severe or unusual side effects were observed.

Table 4 (10) (11). PERCENTAGE OF INDONESIAN CHILDREN ONE TO TWELVE YEARS OF AGE PRESENTING WITH LOCAL OR SYSTEMIC REACTIONS WITHIN 48 HOURS AFTER THE FIRST IMMUNIZATION WITH TYPHIM Vi VACCINE:

^* Subjective feeling of fever.

In the US Reimmunization Study, subjects who had received Typhim Vi vaccine 27 or 34 months earlier, and subjects who had never previously received a typhoid vaccination, were randomized to placebo or Typhim Vi vaccine, in a double-blind study. Safety data from the US Reimmunization Study are presented in Table 5. (10) (11) (13) In this study 5/30 (17%) primary immunization subjects and 10/45 (22%) reimmunization subjects had a local reaction. No severe or unusual side effects were observed. Most subjects reported pain and/or tenderness (pain upon direct pressure). Local adverse experiences were generally limited to the first 48 hours. (10) (11) (13)

Table 5 (10) (11) (13): US REIMMUNIZATION STUDY, SUBJECTS PRESENTING WITH LOCAL AND SYSTEMIC REACTIONS WITHIN 48 HOURS AFTER IMMUNIZATION WITH TYPHIM Vi VACCINE

^* At 27 or 34 months following a previous dose given in different studies.

Solicited Injection Site and Systemic Reactions When Given With Menactra Vaccine

The majority (70%-77%) of solicited injection site reactions at the Typhim Vi and at the Menactra injection sites were reported as Grade 1 and resolved within 3 days post-vaccination. The most common systemic reactions were headache (41% when Menactra and Typhim Vi were given concomitantly; 42% when Typhim Vi was given with Placebo, and 33% when Menactra vaccine was given alone one month after Typhim Vi vaccination) and fatigue (38% when Menactra vaccine and Typhim Vi were given concomitantly; 35% when Typhim Vi was given with Placebo, and 27% when Menactra vaccine was given alone one month after Typhim Vi vaccination). Fever ≥40.0°C and seizures were not reported.

Data From Worldwide Post-marketing Experience

In addition to reports in clinical trials, worldwide voluntary adverse events reports received since market introduction of Typhim Vi vaccine are listed below. This list includes serious events and/or events which were included based on severity, frequency of reporting or a plausible causal connection to Typhim Vi vaccine. Because these events were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to vaccination.

Gastrointestinal disorders: Nausea, vomiting, diarrhea, abdominal pain

General disorders and administration site condition: Injection site pain, inflammation, induration, and erythema; lymphadenopathy, fever, asthenia, malaise, flu-like episode

Immune system disorders: Anaphylaxis, allergic-type reactions such as pruritus, rash, urticaria, angioedema, difficulty breathing, hypotension; serum sickness

Musculoskeletal and connective tissue disorders: Myalgia, arthralgia, cervical pain

Nervous system disorders: Syncope with and without convulsions, headache, loss of consciousness, tremor

Respiratory system disorders: Asthma

Additional Adverse Events

Post-marketing reports of glomerulonephritis, neutropenia, bilateral retinitis, and polyarthritis have been reported in patients who had also received other vaccines; however, a causal relationship has not been established.

Reporting of Adverse Events

Reporting by parents and patients of all adverse events occurring after vaccine administration should be encouraged. Adverse events following immunization with vaccine should be reported by the health-care provider to the US Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS). Reporting forms and information about reporting requirements or completion of the form can be obtained from VAERS through a toll-free number 1-800-822-7967 or visit the VAERS website at http//www.vaers.org. (17)

Health-care providers also should report these events to the Pharmocovigilance Department, Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370, or call 1-800-822-2463.

Care is to be taken by the health-care provider for the safe and effective use of Typhim Vi vaccine.

Epinephrine injection (1:1000) must be immediately available following immunization should an anaphylactic or other allergic reaction occur due to any component of the vaccine.

Prior to an injection of any vaccine, all known precautions should be taken to prevent adverse reactions. This includes a review of the patient’s history with respect to possible hypersensitivity to the vaccine or similar vaccines.

Acute infection or febrile illness may be reason for delaying use of Typhim Vi vaccine except when, in the opinion of the physician, withholding the vaccine entails a greater risk.

Syncope (fainting) has been reported following vaccination with Typhim Vi. Procedures should be in place to prevent falling injury and manage syncopal reactions.

Safety and immunogenicity data from controlled trials are not available for Typhim Vi vaccine following previous immunization with whole-cell typhoid or live, oral typhoid vaccine (see ADVERSE REACTIONS section).

Information for Vaccine Recipients or Parents / Guardians

Before administration, healthcare providers should inform patients, parents or guardians of the benefits and risks of immunization with Typhim Vi vaccine.

Prior to administration of Typhim Vi vaccine, healthcare providers should ask patients, parents and guardians about the recent health status of the patient to be immunized.

Typhim Vi vaccine is indicated in persons traveling to endemic or epidemic areas. Current CDC advisories should be consulted with regard to specific locales.

Travelers should take all necessary precautions to avoid contact with or ingestion of contaminated food and water.

One dose of vaccine should be given at least 2 weeks prior to expected exposure.

Reimmunization consisting of a single-dose for US travelers every two years under conditions of repeated or continued exposure to the S typhi organism is recommended at this time. (14)

As part of the child’s or adult’s immunization record, the date, lot number, and manufacturer of the vaccine administered should be recorded. (17)

Concomitant Vaccine Administration

Typhim Vi was concomitantly administered with Menactra vaccine in individuals 18 through 55 years of age (see CLINICAL PHARMACOLOGY and ADVERSE REACTIONS).

No studies have been conducted in the US to evaluate interactions or immunological interference between the concurrent use of Typhim Vi vaccine and drugs (including antibiotics and antimalarial drugs), immune globulins or other vaccines (including common travelers vaccines such as tetanus, poliomyelitis, hepatitis A, and yellow fever).

Typhim Vi vaccine must not be mixed with any vaccine in the same syringe. Separate injection sites should be used in case of concomitant administration.

Animal reproduction studies have not been conducted with Typhim Vi vaccine. It is not known whether Typhim Vi vaccine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Typhim Vi vaccine should be given to a pregnant woman only if clearly needed. (14)

When possible, delaying vaccination until the second or third trimester to minimize the possibility of teratogenicity is a reasonable precaution. (18)

It is not known whether Typhim Vi vaccine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Typhim Vi vaccine is administered to a nursing woman.

There is no data on the use of this product in nursing mothers.

Safety and effectiveness of Typhim Vi vaccine have been established in children 2 years of age and older. (10) (11) (See DOSAGE AND ADMINISTRATION section.)

For children below the age of 2 years, safety and effectiveness have not been established.