Typhoid Vaccine Live Oral (Systemic)


VA CLASSIFICATION
Primary: IM100


Note: This monograph is specific for the typhoid vaccine prepared with the Salmonella typhi Ty21a strain.

Commonly used brand name(s): Vivotif Berna.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Immunizing agent (active)—

Indications

Accepted

Salmonella typhi infection (prophylaxis)—Typhoid vaccine is indicated for immunization of adults and children 6 years of age and older against disease caused by Salmonella typhi {10}.
—Routine typhoid vaccination is no longer recommended in the U.S. {10} {12} However, selective vaccination is indicated for the following groups:    • Travelers to areas that have a recognized risk of exposure to S. typhi {10} {12}. Risk is greatest for travelers to developing countries (especially countries in Latin America, Asia, and Africa) who have prolonged exposure to potentially contaminated food and drink {06} {10} {12}. Such travelers should be cautioned that typhoid vaccine is not a substitute for careful selection of food and drink, since the vaccine is not 100% effective and the protection it offers can be overwhelmed by large inocula of S. typhi {06} {10} {12}.
   • Persons with intimate exposure, such as continued household contact, to a documented typhoid fever carrier {06} {10} {12}.
   • Workers in microbiology laboratories who frequently work with S. typhi {06} {10} {12}.

—An optimal booster dose has not yet been established {10}. However, it is recommended that a booster dose consisting of 4 vaccine capsules taken on alternate days be given every 5 years if there is repeated or continued exposure to typhoid fever {10}.
—Routine vaccination of sewage sanitation workers is warranted only in areas with endemic typhoid fever {06} {12}. There is no evidence that typhoid vaccine is useful in controlling common-source outbreaks {10} {12}. Also, the use of typhoid vaccine is not indicated for persons attending rural summer camps or in areas in which natural disasters, such as floods, have occurred {10} {12}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Typhoid vaccine Ty21a is a live attenuated vaccine for oral administration {10} {12}. The vaccine contains the attenuated strain Salmonella typhi Ty21a {10} {12}. The vaccine strain is grown under controlled conditions in a medium containing dextrose, galactose, a digest of bovine tissues, and an acid digest of casein {10}. The bacteria are collected by centrifugation, mixed with a stabilizer containing lactose and amino acids, and then lyophilized {10}. The lyophilized bacteria mixture is placed in gelatin capsules, which are coated with an organic solution to render them resistant to dissolution by stomach acids {10}.

Mechanism of action/Effect:

The precise mechanism by which typhoid vaccine Ty21a confers protection against typhoid fever is unknown {10} {12}. However, it is known that immunization of adult subjects can elicit a humoral anti–S. typhi lipopolysaccharide (LPS) antibody response {03} {04} {10} {12}.

This vaccine will not afford protection against species of Salmonella , other than Salmonella typhi , or against other bacteria that cause enteric disease {10}.

The ability of S. typhi to cause disease and induce a protective immune response is dependent upon the bacteria possessing a complete LPS {10}. The S. typhi Ty21a vaccine strain, because of a reduction in enzymes essential for LPS biosynthesis, is restricted in its ability to produce complete LPS {03} {04} {10}. However, enough complete LPS is synthesized to induce a protective immune response {03} {10} Despite the low levels of LPS synthesis, the cells lyse before regaining a virulent phenotype. {03} {04} {10}. This occurs because of the intracellular build-up of toxic metabolic intermediates during LPS synthesis {04} {06} {10}.


Protective effect

Vaccine efficacy is approximately 65% and is {16} similar to the efficacy of the heat-phenol-inactivated injectable typhoid vaccine, which is 51 to 77% {03} {05} {06} {07} {12}.


Time to protective effect

Immunization (ingestion of all 4 doses of the vaccine) should be completed at least 1 week prior to potential exposure to S. typhi {10}.


Duration of protective effect

Follow-up studies of vaccine trial subjects showed continued efficacy 5 to 7 years after immunization {06} {10} {12} {16}.

Elimination:
    At the recommended dosage, the S. typhi Ty21a vaccine strain is not excreted in the feces {10} {12}. However, clinical studies in volunteers have shown that overdosing can increase the possibility of shedding the S. typhi Ty21a vaccine strain in the feces {03} {10}.


Precautions to Consider

Carcinogenicity/Mutagenicity

Long-term studies in animals have not been performed to evaluate the carcinogenic or mutagenic potential of this vaccine {10}.

Pregnancy/Reproduction
Fertility—
Studies have not been done in humans or animals {10} {12}.

Pregnancy—
It is recommended that the vaccine be administered during pregnancy only if clearly needed {06} {10}.

Studies have not been done in humans or animals {10} {12}.

FDA Pregnancy Category C {10}.

Breast-feeding

It is not known whether typhoid vaccine is excreted in breast milk {10}. However, problems in humans have not been documented.

Pediatrics

Appropriate studies on the relationship of age to the effects of the vaccine have not been performed in infants and children up to 6 years of age {10}. Safety and efficacy have not been established and use is not recommended {10}.


Geriatrics


Appropriate studies on the relationship of age to the effects of typhoid vaccine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antibacterials, systemic, or{04}{09}{10}{16}
» Antimalarials{16}    (concurrent use of systemic antibacterials {10} {16} or antimalarials {16} with typhoid vaccine may prevent the vaccine bacteria from multiplying sufficiently to induce a protective immune response; antimalarials should be administered 24 hours prior to administration of the typhoid vaccine {16})


» Immunosuppressive agents or{10}{15}{18}
» Radiation therapy{15}{16}{18}    (because normal defense mechanisms are suppressed, concurrent use with live oral typhoid vaccine may potentiate the replication of the vaccine bacteria, may increase the side/adverse effects of the vaccine, and/or may decrease the patient's antibody response to the vaccine {15} {16}. The precaution does not apply to corticosteroids used as replacement therapy, for short-term [less than 2 weeks] systemic therapy, or by other routes of administration that do not cause immunosuppression {15} {16})


Live vaccines, other{15}{16}    (when live virus vaccines are administered on different days within 1 month of each other, the chance exists that the immune response may be impaired; therefore, live virus vaccines not administered on the same day should be given at least 1 month apart; there is no consensus among USP medical experts that the same would apply to live bacterial vaccines {16})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Diarrhea, persistent, or{10}
» Febrile illness, acute, or{06}{10}
» Gastrointestinal illness, acute, or{10}
» Vomiting, persistent{10}    (administration of live oral typhoid vaccine should be postponed or avoided, since acute illnesses may interfere with the replication of typhoid vaccine bacteria and therefore with final immunity {16}; minor illnesses, such as mild upper respiratory infections, do not preclude administration of vaccine {15} {16})


» Immune deficiency conditions, congential or hereditary, or{06}{10}{12}{15}{16}
» Immune deficiency conditions, primary or acquired{06}{10}{12}{15}    (because of reduced or suppressed defense mechanisms, the use of live oral typhoid vaccine may potentiate the replication of the vaccine bacteria, may increase the side/adverse effects of the vaccine, and/or may decrease the patient's antibody response to the vaccine {15} {16} {18})

    (persons infected with human immunodeficiency virus [HIV], whether asymptomatic or symptomatic, should not receive live oral typhoid vaccine {06} {12} {15} {18})


Risk-benefit should be considered when the following medical problems exist
Sensitivity to live oral typhoid vaccine, sucrose, lactose, or beef{06}{10} ; however, a history of a severe reaction to the parenteral typhoid vaccine is not a precaution for receiving the live oral vaccine{06}{16}


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Anaphylactic reaction (difficulty in breathing or swallowing; hives; itching, especially of soles or palms; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; sudden and severe unusual tiredness or weakness)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare {04} {06}
    
Abdominal discomfort or cramps (stomach cramps or pain)
    
{04}{06}{10}{12}diarrhea
    
{06}fever
    
{06}nausea
    
{06}{10}{12}skin rash
    
{04}{06}{10}{12}urticaria (hives)
    
{10}{12}vomiting{06}{10}{12}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Typhoid Vaccine Live Oral (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to oral {16} typhoid vaccine, sucrose, lactose, or beef





Use in children—Safety and efficacy have not been established for infants and children up to 6 years of age; use is not recommended

Other medications, especially antibacterials, antimalarials, immunosuppressive agents, or radiation therapy
Other medical problems, especially persistent diarrhea, acute gastrointestinal illness, persistent vomiting, acute febrile illness, primary or acquired immune deficiency conditions, or congenital or hereditary immune deficiency conditions

Proper use of this medication
» Taking all 4 doses of vaccine exactly as directed for maximal protective immune response

Replacing any broken or cracked capsules

Leaving vaccine at room temperature will cause it to lose its effectiveness

Taking dose approximately 1 hour before a meal; taking with a cold or lukewarm drink (temperature not to exceed body temperature, e.g., 37 °C [98.6 °F])

Swallowing capsule whole and as soon as possible after placing in mouth; not chewing capsule
Missed dose: If remembered on the day it should be taken, taking as directed; however, if not remembered until the next day, taking the missed dose at that time and rescheduling your every-other-day doses from then {16}; it is essential that vaccine be taken exactly as directed to get the most protection against typhoid fever {16}

» Proper storage: Keeping vaccine refrigerated at all times; replacing unused vaccine in the refrigerator between doses

Precautions while using this medication
Checking with physician before receiving:

Any other live vaccine within 1 month of this vaccine {16}


Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction


General Dosing Information
Immunization (ingestion of all 4 doses of the vaccine) should be completed at least 1 week prior to potential exposure to S. typhi {10}.

Since this is an enteric dosage form, the vaccine capsules should be inspected to ensure that the foil seal and capsules are intact {10}; any that are damaged should be replaced.

Each enteric-coated capsule should be swallowed with a cold or lukewarm drink (temperature not to exceed 37 °C [98.6 °F], i.e., body temperature), approximately 1 hour before a meal on alternate days (days 1, 3, 5, and 7) for a total of 4 doses {10} {12}.

The vaccine capsule should not be chewed and should be swallowed as soon as possible after it is placed in the mouth {10}.

A complete immunization schedule is the ingestion of 4 vaccine capsules, as directed {10} {16}. Unless this schedule is followed, an optimal immune response may not be achieved {10}.

Even if the complete immunization schedule is followed, not all recipients of the vaccine will be fully protected against typhoid fever {10}. Travelers should take all necessary precautions to avoid contact with, or ingestion of, potentially contaminated food or water {10}.

The optimal booster schedule for the live oral typhoid vaccine has not been determined {10} {12}. However, efficacy has been shown to persist for 5 to 7 years after administration of a complete primary immunization {06} {10} {12}. Therefore, it is recommended that a booster dose of 4 vaccine capsules taken on alternate days be given every 5 years if repeated or continued exposure to S. typhi occurs {06} {10}.

There is no experience with the use of the live oral typhoid vaccine as a booster in persons previously immunized with parenteral typhoid vaccine {06} {10} {12}. However, if repeated or continued exposure to S. typhi occurs, booster doses of the parenteral vaccine are recommended every 3 years to maintain immunity after vaccination with parenteral typhoid vaccine {06} {12}. Even if more than 3 years have elapsed since the prior parenteral vaccination, a single booster dose of the parenteral vaccine is sufficient {06} {12}. Therefore, it appears that using the primary series of 4 doses of live oral typhoid vaccine as a booster for persons previously vaccinated with the parenteral vaccine is a reasonable alternative to administration of a parenteral booster {06} {12}.

For treatment of adverse effects


Recommended treatment consists of the following:
For adults

   • If anaphylaxis occurs, 0.2 to 0.5 mg of epinephrine (base) may be administered intramuscularly or subcutaneously, the dose being repeated every 10 to 15 minutes as needed {01}. The dosage may be increased up to a maximum of 1 mg per dose, if necessary {01}.
   • If anaphylactic shock occurs:    —0.5 mg of epinephrine (base) may be administered initially intramuscularly or subcutaneously, the dose being repeated every 5 minutes if necessary {01}. If there is an inadequate response to the intramuscular or subcutaneous dose, 0.025 to 0.05 mg of epinephrine (base) may be administered intravenously every 5 to 15 minutes as needed {01}.
   —Alternatively, 0.1 to 0.25 mg of epinephrine (base) may be administered slowly by intravenous injection {01}. The dose may be repeated every 5 to 15 minutes as needed or followed by an intravenous infusion at an initial rate of 0.001 mg per minute, the rate being increased to 0.004 mg per minute if necessary {01}.

For children

   • If anaphylaxis occurs, 0.01 mg of epinephrine (base) per kg of body weight or 0.3 mg of epinephrine (base) per square meter of body surface, up to a maximum of 0.5 mg per dose, may be administered subcutaneously, the dose being repeated every 15 minutes for 2 doses, then administered every 4 hours as needed {01}.
   • If anaphylactic shock occurs, 0.01 mg of epinephrine (base) per kg of body weight, up to a maximum of 0.3 mg, may be administered intramuscularly or subcutaneously, the dose being repeated every 5 minutes if necessary {01}. If there is an inadequate response to the intramuscular or subcutaneous dosage, 0.01 mg of epinephrine (base) per kg of body weight may be administered intravenously every 5 to 15 minutes as needed {01}.



Oral Dosage Forms

TYPHOID VACCINE LIVE ORAL{16} ENTERIC-COATED CAPSULES

Usual adult and adolescent dose
Oral, 1 capsule every other day for a total of four doses {10} {12}.

Usual pediatric dose
Infants and children up to 6 years of age—Safety and efficacy have not been established; use is not recommended {10} {12}.

Children 6 years of age and older—See Usual adult and adolescent dose {10} {12}.

Strength(s) usually available
U.S.—


2 to 6 × 10 9 colony-forming units of viable S. typhi Ty21a, per capsule (Rx) [Vivotif Berna (non-viable S. typhi Ty21a 5 to 50 x 10 9 bacterial cells, sucrose 26 to 130 mg, lactose 100 to 180 mg, per capsule)]{10}

Canada—


2 to 6 × 10 9 colony-forming units of viable S. typhi Ty21a, per capsule (Rx) [Vivotif Berna (non-viable S. typhi Ty21a 5 to 50 x 10 9 bacterial cells, sucrose 26 to 130 mg, lactose 100 to 180 mg, per capsule)]{17}

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F) {10}.

Stability:
Typhoid vaccine is not stable when exposed to ambient temperatures. The vaccine should therefore be shipped and stored between 2 and 8 °C (36 and 46 °F). Each package of vaccine shows an expiration date. This expiration date is valid only if the product has been maintained at 2 to 8 °C (36 to 46 °F) {10}.

Auxiliary labeling:
   • Keep refrigerated at all times {10}.
   • Swallow capsules whole {10}.



Revised: 02/26/1997



References
  1. Epinephrine Injection USP, part of Bronchodilators, Adrenergic (Systemic):

    DI 90, p 679.

    DI 91, p 668, no changes.
  1. New Drugs & Devices. Live oral typhoid vaccine. American Pharmacy 1990 Nov; 30(11): 23.
  1. Germanier R, Cryz SJ Jr. Attenuated oral typhoid vaccine Ty 21a. Progress in Vaccinology. Volume 2. New York: Springer-Verlag, 1989. Chapter 13.
  1. Cryz SJ Jr. Attenuated, live, oral typhoid vaccine. Drugs of Today 1988; 24(5): 349-53.
  1. Levine MM, et al. Large-scale field trial of Ty 21a live oral typhoid vaccine in enteric-coated capsule formulation. Lancet 1987 May 9: 1049-52.
  1. Woodruff BA, et al. A new look at typhoid vaccination. Information for the practicing physician. JAMA 1991 Feb 13; 265(6): 756-9.
  1. FDA. News Release. New oral typhoid vaccine approved. January 8, 1990.
  1. Wolfe MS. Precautions with oral live typhoid (Ty 21a) vaccine. Lancet 1990 Sept 8; 336: 631-2.
  1. Centers for Disease Control and Prevention. Epidemiologic Notes and Reports. Typhoid fever-Skagit County, Washington. MMWR Morb Mortal Wkly Rep 1990; 39(42): 749-51.
  1. PI - (US) Vivotif Berna, Berna, received 12/90.
  1. PPI - (US) Vivotif Berna, Berna, received 12/90 with PI.
  1. Centers for Disease Control and Prevention. Typhoid Immunization: Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 1990; 39(RR-10): 1-5.
  1. CPS-91. Drug not listed.
  1. USAN-92.
  1. Centers for Disease Control and Prevention. Health information for international travel—1990. Atlanta, Georgia: CDC, 1990; HHS Publication no. (CDC)90-8280, p 68-71, 81.
  1. Panel comments, sent 3/27/92, due 4/17/92, processed 5/22/92.
  1. Vivotif Berna package insert (Swiss Serum—Canada), Rec 9/96.
  1. Centers for Disease Control and Prevention. Update on adult immunization. Recommendation of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1991; 40(RR-12): 44-59.
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