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 drug cannot be directly compared to rates in the clinical trials of another drug 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 drug 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), 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

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 DATA FROM WORLDWIDE POST-MARKETING EXPERIENCE

The following adverse events have been reported during post-approval use of Typhim Vi vaccine. These events have been very rarely reported, however, because they were reported voluntarily from a population of uncertain size, it is not always possible to reliably calculate their frequencies or to establish a causal relationship to Typhim Vi vaccine exposure.

Data are organized by MedDRA system organ class and within system organ class, by order of descreasing frequency.

- Gastro intestinal disorders

Nausea, vomiting, diarrhea.

- General disorders and administration site condition

Local Reactions: injection site pain, injection site inflammation, injection site induration, injection site erythema, and lymphadenopathy. Fever, asthenia, malaise, flu-like episode, abdominal pain.

-Immune system disorders

Allergic-type reactions such as pruritus, rash, urticaria, difficulty breathing, hypotension. Serum sickness.

- Musculoskeletal and connective tissue disorders

Myalgia, arthralgia, cervical pain.

- Nervous system disorders

Headache, loss of consciousness, tremor.

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.

There are no known interactions of Typhim Vi vaccine with drugs or foods.

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, yellow fever and meningococcus). (See ADVERSE REACTIONS section.)

As with other intramuscular injections, Typhim Vi vaccine should be given with caution to individuals on anticoagulant therapy.

REFERENCES

10. Unpublished data available from Sanofi Pasteur Inc., compiled 1991

11. Unpublished data available from Sanofi Pasteur SA

12. Klugman KP, et al. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. The Lancet, 1165-1169, 1987

13. Keitel WA, et al. Clinical and serological responses following primary and booster immunization with Salmonella typhi Vi capsular polysaccharide vaccines. Vaccines 12: 195-199, 1994

17. CDC. Vaccine Adverse Event Reporting System - United

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