Version May 2024
Typhoid fever prevention:
Oral:
Primary immunization: One capsule on alternate days (day 1, 3, 5, and 7) for a total of 4 doses; all doses should be complete at least 1 week prior to potential exposure
Reimmunization (with repeated or continued exposure to typhoid fever): Repeat full course of primary immunization every 5 years. Alternatively, in Canada, it is recommended to repeat a full course of primary immunization every 7 years (Ref).
IM:
Initial: 0.5 mL given at least 2 weeks prior to expected exposure
Reimmunization (with repeated or continued exposure to typhoid fever):
Typhim Vi: 0.5 mL every 2 years (US labeling) or every 3 years (Canadian labeling)
Typherix [Canadian product]: 0.5 mL every 3 years
There are no dosage adjustments provided in manufacturer's labeling.
There are no dosage adjustments provided in manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Typhoid vaccine: Pediatric drug information")
Typhoid fever prevention (immunization):
Oral:
Vivotif: Children ≥6 years and Adolescents: Primary immunization: Oral: One capsule (viable S. typhi Ty21a 2-10 × 109 colony-forming units) every other day for 4 doses (ie, days 1, 3, 5, and 7); all doses should be completed at least 1 week prior to potential exposure. Note: Optimal booster schedule has not been established; in trials, efficacy has been observed for at least 5 years. It is recommended to repeat primary immunization (all 4 doses) every 5 years for repeated or continued exposure. Canadian labeling allows use in children ≥5 years of age and recommends re-immunization every 7 years.
IM:
Typhim Vi: Children ≥2 years and Adolescents: Primary immunization: IM: 0.5 mL administered at least 2 weeks prior to expected exposure. Note: Optimal booster schedule has not been established; in trials, efficacy was reported for the 3-year trial duration. It is recommended to repeat primary immunization every 2 years if exposure is repeated or continued. Canadian labeling recommends re-immunization every 3 years.
There are no dosage adjustments provided in manufacturer's labeling.
There are no dosage adjustments provided in manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
In the US, all serious adverse reactions must be reported to the Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS) 1-800-822-7967 or online at https://vaers.hhs.gov/esub/index. In Canada, adverse reactions may be reported to local provincial/territorial health agencies or to the Vaccine Safety Section at Public Health Agency of Canada (1-866-844-0018).
Injection (incidence may vary based on age and/or product used):
>10%:
Central nervous system: Malaise (4% to 24%), headache (16% to 20%), generalized ache (1% to 13%)
Local: Tenderness at injection site (97% to 98%), pain at injection site (27% to 41%), induration at injection site (5% to 15%)
Neuromuscular & skeletal: Muscle tenderness (≤16%)
Miscellaneous: Fever (undefined 2% to 32%)
1% to 10%:
Dermatologic: Pruritus (≤8%)
Gastrointestinal: Nausea (≤8%), vomiting (2%)
Local: Injection site: Erythema at injection site (≤5%), swelling at injection site (≤4%)
Neuromuscular & skeletal: Myalgia (3% to 7%)
Miscellaneous: Fever greater than 100 to 101 degrees (2%)
Postmarketing and/or case reports: Abdominal pain, anaphylaxis, angioedema, arthralgia, asthma, diarrhea, dizziness, flu-like symptoms, Guillain-Barré syndrome, hypersensitivity reaction, hypotension, inflammation at injection site (including angioedema and urticaria), intestinal perforation (jejunum), loss of consciousness, lymphadenopathy, malaise, neck pain, serum sickness, skin rash, syncope (with and without convulsions), tremor, urticaria, vasodilation, weakness
Oral:
1% to 10%:
Central nervous system: Headache (5%)
Dermatologic: Skin rash (1%)
Gastrointestinal: Abdominal pain (6%), nausea (6%), diarrhea (3%), vomiting (2%)
Miscellaneous: Fever (3%)
Postmarketing and/or case reports: Anaphylaxis, demyelinating disease, myalgia, pain, rheumatoid arthritis, sepsis, urticaria, weakness
Hypersensitivity to any component of the vaccine. In addition, the oral vaccine is contraindicated with congenital or acquired immunodeficient state, acute febrile illness.
Note: Canadian immunization guidelines also contraindicate oral typhoid vaccine in acute gastrointestinal conditions.
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Injection: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Kroger 2023]).
• Shoulder injury related to vaccine administration: Vaccine administration that is too high on the upper arm may cause shoulder injury (eg, shoulder bursitis, tendinopathy) resulting in shoulder pain and reduced range of motion following injection. Use proper injection technique for vaccines administered in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).
• Syncope: Injection: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2023]).
Disease-related concerns:
• Acute illness: Injection: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Postpone administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (ACIP [Kroger 2023]). Do not administer oral formulation during acute GI illness; vaccination may be deferred with persistent diarrhea or vomiting.
• Bleeding disorders: Injection: Use with caution in patients with bleeding disorders (including thrombocytopenia); bleeding/hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2023]).
• Typhoid fever: Should not be used to treat typhoid fever or a chronic typhoid carrier. Not all recipients of typhoid vaccine will be fully protected against typhoid fever. Travelers should take all necessary precautions to avoid contact or ingestion of potentially contaminated food or water sources.
Concurrent drug therapy issues:
• Anticoagulant therapy: Use with caution in receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2023]).
• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or nonlive) for which a person is eligible at a single visit, unless contraindications exist (ACIP [Kroger 2023]).
Special populations:
• Altered immunocompetence: Postpone vaccination with the inactive vaccine during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high-dose corticosteroids]) if appropriate; may have a reduced response to vaccination or may have an adverse event secondary to replication. Live vaccine should generally not be administered. Household and close contacts of persons with altered immunocompetence may receive most age-appropriate vaccines (ACIP [Kroger 2023]; IDSA [Rubin 2014]). Nonlive vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; nonlive vaccines administered during chemotherapy should be readministered after immune competence is regained. Live vaccines should be administered ≥4 weeks prior to planned immunosuppression and avoided within 2 weeks of immunosuppression when feasible; live vaccines should not be administered for at least 3 months after immunosuppressive therapy (ACIP [Kroger 2023]; IDSA [Rubin 2014]).
Other warnings/precautions:
• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Kroger 2023]). One study reported that routine prophylactic administration of acetaminophen prior to vaccination to prevent fever decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).
• Appropriate use: Specific recommendations for vaccination in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions as well as contacts of immunocompromised patients are available from the IDSA (Rubin 2014).
• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval (ACIP [Kroger 2023]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, enteric coated, Oral [live]:
Vivotif: Viable S. typhi Ty21a 2-10 x 109 colony-forming units [contains lactose 180-200 mg/capsule and sucrose 3.3-34.2 mg/capsule]
Injection, solution [inactivated]:
Typhim Vi: Purified Vi capsular polysaccharide 25 mcg/0.5 mL (0.5 mL, 10 mL) [derived from S. typhi Ty2 strain]
No
Solution (Typhim VI Intramuscular)
25 mcg/0.5 mL (per mL): $220.55
Solution Prefilled Syringe (Typhim VI Intramuscular)
25 mcg/0.5 mL (per 0.5 mL): $159.53
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, enteric coated, Oral [live]:
Vivotif: Viable S. typhi Ty21a 2-10 x 109 colony-forming units [contains lactose 180-200 mg/capsule and sucrose 3.3-34.2 mg/capsule]
Injection, solution:
Typhim Vi: Vi capsular polysaccharide 25 mcg/0.5 mL (0.5 mL) [dreived from S. typhi Ty2 strain]
IM: For IM administration. Administer as a single 0.5 mL (25 mcg) injection into the deltoid muscle. Use proper injection technique in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013). Not for gluteal administration. Do not administer Typhim Vi or Typherix [Canadian product] intravascularly. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. To prevent syncope-related injuries, patients should be vaccinated while seated or lying down (Ref). Note: For patients at risk of hemorrhage following intramuscular injection, the vaccine should be administered intramuscularly if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, intramuscular vaccination can be scheduled shortly after such therapy is administered. A fine needle (23-gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (Ref). If purchased under Centers for Disease Control and Prevention contract, US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, Vaccine Information Statement (VIS) edition date and date it was provided, and the administering person's name, title, and address be recorded.
Oral: Swallow capsule whole soon after placing into mouth; do not chew or open capsule. Capsule should be taken with a cold or lukewarm beverage (≤37°C/98.6°F). Take 1 hour prior to a meal. Avoid alcohol 1 hour before or 2 hours after administration; alcohol may disrupt the enteric coating.
Oral: Administer oral capsule 1 hour before a meal with a cold or lukewarm drink on alternate days; swallow capsule whole as soon as possible after placing in the mouth; do not open or chew capsule.
Parenteral: IM: Administer by IM injection into the anterolateral aspect of the thigh (children) or into the deltoid muscle; not for IV or SUBQ administration. If injecting in the deltoid muscle, use proper injection technique (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Ref). Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. To prevent syncope-related injuries, adolescents should be vaccinated while seated or lying down (Ref). Note: For patients at risk of hemorrhage following intramuscular injection, the vaccine should be administered intramuscularly if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, intramuscular vaccination can be scheduled shortly after such therapy is administered. A fine needle (23-gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (Ref).
If purchased under Centers for Disease Control and Prevention contract, US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, Vaccine Information Statement (VIS) edition date and date it was provided, and the administering person's name, title, and address be recorded.
In the United States, the appropriate Centers for Disease Control and Prevention (CDC)-approved Vaccine Information Statement (VIS) should be provided to the patient/caregiver before administering each dose of this vaccine. If purchased under CDC contract, the VIS must be provided and the VIS edition date and date it was provided to the patient/caregiver should be recorded. VIS is available at http://www.cdc.gov/vaccines/hcp/vis/vis-statements/typhoid.html.
Typhoid fever prevention: Active immunization against typhoid fever caused by Salmonella typhi:
Oral: Immunization of adults and children >6 years of age; complete the vaccine regimen at least 1 week before potential exposure to typhoid bacteria.
Parenteral: Immunization of adults and children ≥2 years of age; complete the vaccine regimen at least 2 weeks before potential exposure to typhoid bacteria.
Not for routine vaccination. In the United States (CDC/ACIP [Jackson 2015]) and Canada, use should be limited to:
- Travelers to areas with a recognized risk of exposure to S. typhi
- Persons with intimate exposure to a household contact with S. typhi fever or a known carrier
- Laboratory technicians with frequent exposure to S. typhi
Additional recommendations: May consider administration to travelers with achlorhydria, or receiving acid suppression therapy; anatomic or functional asplenia (Canadian Immunization Guide)
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetaminophen: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification
Antibiotics: May diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Anti-CD20 B-Cell Depleting Therapies: May enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Anti-CD20 B-Cell Depleting Therapies may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Corticosteroids (Systemic) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Non-US labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. US labeling states that safety and effectiveness of live vaccines administered with dimethyl fumarate has not been assessed. Risk C: Monitor therapy
Dupilumab: May enhance the adverse/toxic effect of Vaccines (Live). Risk X: Avoid combination
Elivaldogene Autotemcel: May enhance the adverse/toxic effect of Vaccines. Specifically, there may be a greater risk for contracting an infection from any live vaccine. Elivaldogene Autotemcel may diminish the therapeutic effect of Vaccines. Management: Administration of vaccines is not recommended in the 6 weeks before myeloablative conditioning, and until hematologic recovery after elivaldogene autotemcel treatment. Risk X: Avoid combination
Etrasimod: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Etrasimod may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Immunosuppressants (Cytotoxic Chemotherapy): May enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Immunosuppressants (Miscellaneous Oncologic Agents): May enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Immunosuppressants (Therapeutic Immunosuppressant Agents): May enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Leniolisib: May diminish the therapeutic effect of Vaccines (Live). Risk C: Monitor therapy
Methotrexate: May enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Methotrexate may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Proguanil: May diminish the therapeutic effect of Typhoid Vaccine. This applies only to the oral (live) typhoid vaccine. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with proguanil. When possible, proguanil should not be started within 10 days of the last vaccine dose. Risk D: Consider therapy modification
Propacetamol: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of propacetamol before or during vaccine administration when possible. Propacetamol is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification
Teplizumab: May enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Teplizumab may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Tezepelumab: May enhance the adverse/toxic effect of Vaccines (Live). Risk X: Avoid combination
Tildrakizumab: May enhance the adverse/toxic effect of Vaccines (Live). The risk for contracting an infection from the vaccine may be increased. Tildrakizumab may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Tralokinumab: May enhance the adverse/toxic effect of Vaccines (Live). Risk X: Avoid combination
Travelers' Diarrhea and Cholera Vaccine: Typhoid Vaccine may diminish the therapeutic effect of Travelers' Diarrhea and Cholera Vaccine. Management: Separate the dosing of encapsulated oral typhoid vaccine and the oral travelers' diarrhea and cholera vaccine by at least 8 hours. Risk D: Consider therapy modification
Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: It is preferable to administer live vaccines simultaneously with tuberculin tests. If a live vaccine has been recently administered, the tuberculin skin test should be administered 4 to 6 weeks following the administration of the vaccine. Risk D: Consider therapy modification
Vaccines (Live): May diminish the therapeutic effect of other Vaccines (Live). Management: Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 28 days (ie, 4 weeks). If not, the vaccine administered second should be repeated at least 4 week later. Risk C: Monitor therapy
Animal reproduction studies have not been conducted. The manufacturer of the Typhim Vi injection suggests delaying vaccination until the second or third trimester if possible. Untreated typhoid fever may lead to miscarriage or vertical intrauterine transmission causing neonatal typhoid (rare).
It is not known if components of this vaccine are present in breast milk. Nonlive vaccines have not been shown to affect the safety of the breastfed infant or mother. Breastfeeding infants should be vaccinated according to the recommended schedules (ACIP [Kroger 2023]).
After injection, monitor for hypersensitivity and syncope for 15 minutes following administration (ACIP [Kroger 2023]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
Virulent strains of Salmonella typhi cause disease by penetrating the intestinal mucosa and entering the systemic circulation via the lymphatic vasculature. One possible mechanism of conferring immunity may be the provocation of a local immune response in the intestinal tract induced by oral ingesting of a live strain with subsequent aborted infection. The ability of S. typhi to produce clinical disease (and to elicit an immune response) is dependent on the bacteria having a complete lipopolysaccharide. The live attenuate Ty21a strain lacks the enzyme UDP-4-galactose epimerase so that lipopolysaccharide is only synthesized under conditions that induce bacterial autolysis. Thus, the strain remains avirulent despite the production of sufficient lipopolysaccharide to evoke a protective immune response. Despite low levels of lipopolysaccharide synthesis, cells lyse before gaining a virulent phenotype due to the intracellular accumulation of metabolic intermediates.
Onset of action: Immunity to Salmonella typhi: Oral: ~1 week after completing the series; Parenteral: Antibody response develops within 2 weeks after a single dose.
Duration: Immunity: Oral: >5 years; Parenteral: Typhim Vi: ~2 years.
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