Pharmaceutical Name

Trade (marketing or proprietary) name: Vivotif®, TYPHIM VI®

Generic (nonproprietary or active ingredient) name: Typhoid Vaccine Live Oral Ty21a, TYPHOID VI POLYSACCHARIDE VACCINE

Indication and Usage

Reason the product has been approved for sale on the market.

Vivotif (Typhoid Vaccine Live Oral Ty21a) is indicated for immunization of adults and children greater than 6 years of age against disease caused by Salmonella typhi. Typhim Vi vaccine is indicated for active immunization for the prevention of typhoid fever caused by S typhi and is approved for use in persons two years of age or older.

There is no evidence to support the use of typhoid vaccine to control common source outbreaks, disease following natural disasters or in persons attending rural summer camps. 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. The vaccine will not afford protection against species of Salmonella other than Salmonella typhi or other bacteria that cause enteric disease. The vaccine is not suitable for treatment of acute infections with S. typhi. Typhim Vi vaccine should not be used to treat a patient with typhoid fever or a chronic typhoid carrier.

Manufacturer Insert

Ingredients

Also known as “excipients” for vaccines.

Vivotif (Typhoid Vaccine Live Oral Ty21a) is a live attenuated vaccine for oral administration only. The vaccine contains the attenuated strain Salmonella typhi Ty21a. Vivotif is manufactured by the Crucell Switzerland LTD. The vaccine strain is grown in fermentors under controlled conditions in medium containing a digest of yeast extract, an acid digest of casein, dextrose and galactose. The bacteria are collected by centrifugation, mixed with a stabilizer containing sucrose, ascorbic acid and amino acids, and lyophilized. The lyophilized bacteria are mixed with lactose and magnesium stearate and filled into gelatin capsules which are coated with an organic solution to render them resistant to dissolution in stomach acid. The enteric-coated, salmon/white capsules are then packaged in 4-capsule blisters for distribution.

Typhim Vi®, Typhoid Vi Polysaccharide Vaccine, produced by Sanofi Pasteur SA, for
intramuscular use, is a sterile solution containing the cell surface Vi polysaccharide extracted from Salmonella enterica serovar Typhi, S typhi Ty2 strain. The organism is grown in a semisynthetic medium. Casein derived raw materials are used early in manufacturing during the fermentation process. The capsular polysaccharide is precipitated from the concentrated culture supernatant by the addition of hexadecyltrimethylammonium bromide, and the product is purified by differential centrifugation and precipitation. Each 0.5 mL dose may contain residual amounts of formaldehyde (not more than 100 mcg) used for the inactivation of the bacterial culture. The potency of the purified polysaccharide is assessed by molecular size and O-acetyl content. Phenol, 0.25%, is added as a preservative. The vaccine contains residual polydimethylsiloxane or fatty-acid ester-based antifoam. The vaccine is a clear, colorless solution. Each dose of 0.5 mL is formulated to contain 25 mcg of purified Vi polysaccharide in a colorless isotonic phosphate buffered saline (pH 7 ± 0.3), 4.150 mg of Sodium Chloride, 0.065 mg of Disodium Phosphate, 0.023 mg of Monosodium Phosphate, and 0.5 mL of Sterile Water for Injection.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

Vivotif

Hypersensitivity to any component of the vaccine or the enteric-coated capsule. The vaccine should not be administered to persons during an acute febrile illness. Safety of the vaccine has not been demonstrated in persons deficient in their ability to mount a humoral or cell mediated immune response, due to either a congenital or acquired immunodeficient state including treatment with immunosuppressive or antimitotic drugs. The vaccine should not be administered to these persons regardless of benefits.

Typhim Vi®

Typhim Vi vaccine is contraindicated in patients with a history of hypersensitivity to any
component of this vaccine.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

Vivotif

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.

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.

Typhim Vi®

Allergic reactions have been reported rarely in the post-marketing experience. 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.

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

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.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

Vivotif can cause: Abdominal pain, Nausea, Headache, Fever, Diarrhea, Vomiting, Skin rash, Urticaria (hives), Anaphylactic reaction.

Typhim Vi can cause: Syncope (fainting) with or without convulsions, Nausea, Vomiting, Diarrhea, Abdominal pain, Injection site pain, Lymphadenopathy, Fever, Asthenia, Malaise, Flu-like episode, Anaphylaxis, Pruritus (itchy skin), Rash, Urticaria (hives), Angioedema (swelling), Difficulty breathing, Hypotension, Serum sickness, Myalgia (muscle pain), Arthralgia (joint pain), Cervical pain, Headache, Loss of consciousness, Tremor, Asthma, Neutropenia, Bilateral retinitis, Polyneuritis (nerve damage), Glomerulonephritis (kidney disease).

Specific Populations

Pregnancy

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

Breastfeeding

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

Fertility

Long-term studies in animals with Vivotif have not been performed to evaluate carcinogenic potential, mutagenic potential or impairment of fertility.

Typhim Vi vaccine has not been evaluated for its carcinogenic potential, mutagenic potential or impairment of fertility.

Pediatric

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.

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

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

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.

Typhim Vi®: Because of the low incidence of typhoid fever, efficacy studies were not feasible in a US population. Controlled comparative efficacy studies of Typhim Vi vaccine and other types of typhoid vaccines have not been performed. An increase in serum anti-capsular antibodies is thought to be the basis of protection provided by Typhim Vi vaccine. However, a specific correlation of post-vaccination antibody levels with subsequent protection is not available, and the level of Vi antibody that will provide protection has not been determined. Also, limitations exist for comparing immunogenicity results from subjects in endemic areas, where some subjects have baseline serological evidence of prior S typhi exposure, to naive populations such as most American travelers.

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).

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