VIVOTIF Typhoid vaccine capsule Ref.[10259] Active ingredients: Typhoid, live attenuated

Vivotif (Typhoid Vaccine Live Oral Ty21a) is not to be taken during an acute gastrointestinal illness. The vaccine should not be administered to individuals receiving sulfonamides and antibiotics since these agents may be active against the vaccine strain and prevent a sufficient degree of multiplication to occur in order to induce a protective immune response. Postpone taking the vaccine if persistent diarrhea or vomiting is occurring. Unless a complete immunization schedule is followed, an optimum immune response may not be achieved. Not all recipients of Vivotif will be fully protected against typhoid fever. Vaccinated individuals should continue to take personal precautions against exposure to typhoid organisms, i.e. travelers should take all necessary precautions to avoid contact or ingestion of potentially contaminated food or water.

Drug Interactions

Several anti-malaria drugs, such as mefloquine, chloroquine and proguanil (not approved for use in US) possess anti-bacterial activity which may interfere with the immunogenicity of Vivotif (17,18). To determine the effect of these anti-malaria drugs on the humoral IgG or IgA anti-S. typhi immune response, healthy adult subjects were given mefloquine (250 mg at weekly intervals; N=30) chloroquine (500 mg at weekly intervals; N=30) or proguanil (200 mg daily; N=30) together with the S. typhi Ty21a vaccine strain (19). Concomitant treatment with mefloquine or chloroquine did not result in a significant reduction in the serum anti-S. typhi immune response compared to subjects receiving vaccine strain only (N=45). The simultaneous administration of proguanil did effect a significant decrease in the immune response rate. These findings indicate that mefloquine and chloroquine can be administered together with Vivotif. Proguanil should be administered only if 10 days or more have elapsed since the final dose of Vivotif was ingested. The concomitant administration of oral polio vaccine or yellow fever vaccine does not suppress the immune response elicited by the Ty21a vaccine strain (19). There are no data regarding simultaneous administration of other parenteral vaccines or immunoglobulins with Vivotif.

More than 1.4 million doses of Ty21a have been administered in controlled clinical trials and more than 150 million doses of Vivotif (Typhoid Vaccine Live Oral Ty21a) have been marketed world-wide. Active surveillance for adverse reactions of enteric-coated capsules was performed in a pilot study (21) and in a subgroup of a large field trial (14) involving a total of 483 individuals receiving 3 vaccine doses. The overall symptom rates from both studies when vaccinated with capsules were combined and shown to be: abdominal pain (6.4%), nausea (5.8%), headache (4.8%), fever (3.3%), diarrhea (2.9%), vomiting (1.5%) and skin rash (1.0%). Only the incidence of nausea occurred at a statistically higher frequency in the vaccinated group as compared to the placebo group (14). Administration of vaccine doses more than 5-fold higher than the currently recommended dose caused only mild reactions in an open study involving 155 healthy adult males (16).

Post-marketing surveillance has revealed that adverse reactions are infrequent and mild (17). Adverse reactions reported to the manufacturer during 1991–1995, during which time over 60 million doses (capsules) were administered, included: diarrhea (N=45), abdominal pain (N=42), nausea (N=35), fever (N=34), headache (N=26), skin rash (N=26), vomiting (N=18), or urticaria in the trunk and/or extremities (N=13). One isolated, non-fatal anaphylactic shock considered to be an allergic reaction to the vaccine was reported.

To report SUSPECTED ADVERSE REACTIONS, contact PaxVax, Inc. at 1-800-533-5899 http://www.paxvax.com; or contact the Vaccine Adverse Event Reporting System (VAERS) at 1-800- 822-7967 or http://www.fda.gov/vaers

The health care provider should take all necessary precautions to ensure the safe and effective use of the vaccine. Patients should be questioned about previous reactions to this or similar products. The previous immunization history of the patient and current antibiotic usage should be obtained by the health care provider.

It is essential that all 4 doses of vaccine be taken at the prescribed alternate day interval to obtain a maximal protective immune response. Vaccine potency is dependent upon storage under refrigeration [between 2°C and 8°C (35.6°F – 46.4°F)]. The vaccine should be stored under refrigeration at all times. It is essential to replace unused vaccine in the refrigerator between doses. The vaccine capsule should be swallowed approximately 1 hour before a meal with a cold or luke-warm [temperature not to exceed body temperature, e.g., 37°C (98.6°F)] drink. Care should be taken not to chew the vaccine capsule. The vaccine capsule should be swallowed as soon after placing in the mouth as possible.

Not all recipients of Vivotif (Typhoid Vaccine Live Oral Ty21a) will be fully protected against typhoid fever. Travelers should take all necessary precautions to avoid contact or ingestion of potentially contaminated food or water. Several anti-malaria drugs, such as mefloquine, chloroquine and proguanil (not approved for use in US) possess antibacterial activity which may interfere with the immunogenicity of Vivotif. Clinical results (see Warnings – Drug Interactions) indicate that mefloquine and chloroquine can be administered together with Vivotif. Proguanil should be administered only if 10 days or more have elapsed since the final dose of Vivotif was ingested. Any serious adverse reactions related to the administration of the vaccine should be reported to your health care provider. You may also report an adverse reaction directly to the Vaccine Adverse Event Reporting System (1–800–822–7967) (20). Your health care provider should inform you of the benefits and risks of the vaccine, the importance of taking all 4 capsules in the correct schedule, and the importance of proper storage temperature of the capsules.

Category C

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

There is no data to warrant the use of this product in nursing mothers. It is not known if Vivotif is excreted in human milk.

The safety and efficacy of Vivotif has not been established in children under 6 years of age. This product is not indicated for use in children under 6 years of age.