Primary immunization: Adults ≤65 years: IM: 0.5 mL/dose; a total of 2 doses given on days 0 and 7 to 28. Series should be completed at least 1 week prior to potential exposure (CDC/ACIP [Hills 2019]).
Booster dose: IM: 0.5 mL/dose; given ≥1 year after completion of the primary immunization series if exposure to Japanese encephalitis is ongoing or expected (CDC/ACIP [Hills 2019]).
Note: If the second dose is missed, limited data from one clinical trial in adults demonstrated a 99% seroconversion rate when the second dose was administered 11 months after the initial dose (CDC/ACIP [Hills 2019]).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Japanese encephalitis virus vaccine (inactivated): Pediatric drug information")
Primary immunization: Note: Series should be completed at least 1 week prior to potential exposure.
ACIP/CDC Recommendations (CDC/ACIP [Hills 2019]):
Infants 2 months to Children ≤35 months: IM: 0.25 mL/dose on days 0 and 28 for a total of 2 doses.
Children ≥3 years (36 months) and Adolescents ≤17 years: IM: 0.5 mL/dose on days 0 and 28 for a total of 2 doses.
Adolescents ≥18 years: IM: 0.5 mL/dose with dose 1 administered on day 0 and dose 2 administered any time between days 7 to 28 for a total of 2 doses; second doses can be administered as early as 7 days after the first dose.
Booster dose, for patients with ongoing or expected reexposure (CDC/ACIP [Hills 2019]):
Children <3 years: IM: 0.25 mL/dose administered ≥1 year after primary immunization series completed; there is no efficacy data on booster doses administered >2 years after series completion.
Children ≥3 years and Adolescents: IM: 0.5 mL/dose administered ≥1 year after primary immunization series completed; there is no efficacy data on booster doses administered >2 years after series completion.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Primary immunization: Adults >65 years: IM: 0.5 mL/dose; a total of 2 doses given on days 0 and 28. Series should be completed at least 1 week prior to potential exposure.
Booster dose: Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intramuscular [preservative free]:
Ixiaro: (0.5 mL) [latex free; contains albumin bovine, protamine sulfate, sodium metabisulfite]
No
In the US, the appropriate 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/je-ixiaro.html.
IM: For IM injection. Do not inject IV, SubQ, or intradermally. Shake well prior to use to form a homogeneous suspension. Do not use if discolored or if particulate matter remains. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Kroger 2021]).
The preferred site for administration is the deltoid muscle. To prevent syncope related injuries, patients should be vaccinated while seated or lying down (ACIP [Kroger 2021]).
Canadian labeling recommends avoiding IM administration in patients with bleeding disorders (eg, thrombocytopenia, hemophilia) and suggests that SubQ administration may be considered in these patients. Clinical efficacy data regarding this route is lacking and the US labeling does not recommend SubQ administration. 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 (ACIP [Kroger 2021]). If purchased under CDC 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.
For IM injection; do not inject IV, SubQ, or intradermally. Shake well prior to use to form a homogeneous suspension. Do not use if discolored or if particulate matter remains. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Kroger 2021]).
Ixiaro is available only in a prefilled syringe containing 0.5 mL. In order to administer a 0.25 mL dose in children 2 months to <3 years, first shake the syringe to form a homogenous suspension. Attach a sterile needle to the prefilled syringe and while holding the syringe upright, expel and discard 0.25 mL (half of the volume) of the suspension (CDC/ACIP [Hills 2019]). Attach a new sterile needle prior to administration. To prevent syncope-related injuries, adolescents should be vaccinated while seated or lying down (ACIP [Kroger 2021]).
Administration site (preferred):
Infants 2 to <12 months: Anterolateral aspect of the thigh
Children 1 to <3 years: Anterolateral aspect of the thigh or deltoid muscle may be used (if mass is adequate)
Children ≥3 years and Adolescents: Deltoid muscle
If purchased under CDC 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.
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) should be used for the vaccination and firm pressure on 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 (ACIP [Kroger 2021]).
Japanese encephalitis prevention: Active immunization against Japanese encephalitis (JE) for persons ≥2 months of age.
The Advisory Committee on Immunization Practices (ACIP) recommends vaccination for (CDC/ACIP [Hills 2019]):
- Persons moving to or frequently traveling to JE-endemic areas
- Persons spending ≥1 month in endemic areas
- Laboratory workers who may be exposed to the JE virus other than SA14-14-2 JE vaccine virus. For those working with SA14-14-2 JE virus, vaccination should be considered for those working with high concentrations or volumes or passaging virus. Note: Vaccination not required for workers handling routine clinical samples.
- Persons traveling for shorter periods of time (eg, <1 month) who are at increased risk for JE based on travel duration, season, location, activities, accommodations or those with uncertain travel itineraries should consider vaccination. Note: Not recommended for very low-risk travelers (eg, those traveling for shorter terms and only to urban areas or periods outside of the well-defined JE virus transmission season).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentage of adverse reactions reported over days 0 to 56 in adults and 0 to 7 in pediatric patients. In general, incidence decreased with subsequent dosing.
>10%:
Central nervous system: Headache (adults: 13% to 28%; children & adolescents: 1% to 5%), irritability (infants & children: ≤15%; adolescents: 2%), fatigue (≤11%)
Gastrointestinal: Diarrhea (infants, children, & adolescents: ≤17%; adults: ≤2%)
Local: Injection site reaction (adults: 33% to 55%), tenderness at injection site (infants, children, & adolescents: ≤50%; adults: 23% to 29%), pain at injection site (2% to 28%), erythema at injection site (infants, children, & adolescents: ≤25%; adults: 5% to 7%)
Neuromuscular & skeletal: Myalgia (infants, children, & adolescents: ≤31%; adults: 6% to 16%)
Miscellaneous: Fever (infants & children: ≤24%; adolescents & adults: ≤5%)
1% to 10%:
Central nervous system: Migraine (adults: ≥1%)
Dermatologic: Skin rash (infants & children: 1% to 8%; adolescents & adults: ≤1%)
Gastrointestinal: Vomiting (infants & children: ≤8%; adolescents & adults: ≤1%), anorexia (infants & children: 1% to 6%; adolescents: ≤2%), nausea (≤7%)
Infection: Influenza (adults: ≥1%)
Local: Induration at injection site (adults: 4% to 5%; children & adolescents: ≤1%), itching at injection site (adults: 2% to 3%; infants, children, & adolescents: ≤1%), swelling at injection site (≤2%)
Neuromuscular & skeletal: Back pain (adults: ≤1%)
Respiratory: Flu-like symptoms (≤12%), nasopharyngitis (adults: 2% to ≤5%), cough (adults: ≤1%), pharyngolaryngeal pain (adults: ≤2%), sinusitis (adults: ≥1%), upper respiratory tract infection (adults: ≤2%), rhinitis (adults: ≤1%)
Miscellaneous: Febrile seizures (children: 1%)
<1%, postmarketing, and/or case reports: Bacterial meningitis, myocardial infarction, neuritis, paresthesia, syncope
Severe allergic reaction to a previous dose of the vaccine, any other Japanese encephalitis virus vaccine, or any component of the vaccine, including protamine sulfate.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to a previous dose of the vaccine or to any component of the formulation; acute severe febrile conditions
Concerns related to adverse effects:
• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Kroger 2021]).
• 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: 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 2021]).
Disease-related concerns:
• Acute illness: 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. Defer 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 2021]).
• Bleeding disorders: 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 2021]). Canadian labeling recommends avoiding IM administration in patients with bleeding disorders (eg, thrombocytopenia, hemophilia) and suggests that SubQ administration may be considered in these patients. Clinical efficacy data regarding this route is lacking and the US labeling does not recommend SubQ administration.
Concurrent drug therapy issues:
• Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2021]).
• Vaccines: In order to maximize vaccination rates, the Advisory Committee on Immunization Practices recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist (ACIP [Kroger 2021]).
Special populations:
• Altered immunocompetence: Consider deferring immunization during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy or other immunosuppressive therapy [including high dose corticosteroids]); may have a reduced response to vaccination. In general, household and close contacts of persons with altered immunocompetence may receive all age appropriate vaccines. Inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; inactivated vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Kroger 2021]; Rubin 2014).
• Adults ≥65 years of age: May have a reduced response to the vaccine (CDC/ACIP [Hills 2019])
• Pediatric: Apnea has occurred following IM vaccine administration in premature infants; consider clinical status implications. In general, preterm infants should be vaccinated at the same chronological age as full-term infants (ACIP [Kroger 2021]).
Dosage form specific issues:
• Protamine sulfate: May contain protamine sulfate, which may cause hypersensitivity reactions in certain individuals.
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 2021]). 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: Because of the potential for severe adverse reactions, not recommended for all persons traveling to or residing in Asia. Use is not recommended for short-term travelers (<1 month) who will not be outside of an urban area or when the visit is outside of a well-defined Japanese encephalitis (JE) virus transmission season. Risk of exposure to the JE virus may vary from year to year for a particular area. Immunization should be completed ≥1 week prior to potential exposure (CDC/ACIP [Hills 2019]).
• 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. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2021]).
• Other methods to reduce mosquito exposure: Use of vaccine should also include other means to reduce the risk of mosquito exposure (bed nets, insect repellents, permethrin-impregnated clothing, avoidance of travel in endemic areas, and avoidance of outdoor activity during twilight and evening periods) (CDC/ACIP [Hills 2019]).
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
Cladribine: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of cladribine when possible. Patients vaccinated less than 14 days before initiating or during cladribine should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Corticosteroids (Systemic): May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Administer vaccines at least 2 weeks prior to immunosuppressive corticosteroids if possible. If patients are vaccinated less than 14 days prior to or during such therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. Risk D: Consider therapy modification
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
Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Risk D: Consider therapy modification
Immunosuppressants (Cytotoxic Chemotherapy): May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification
Immunosuppressants (Miscellaneous Oncologic Agents): May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Immunosuppressants (Therapeutic Immunosuppressant Agents): May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Methotrexate: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Administer vaccines at least 2 weeks prior to methotrexate initiation, if possible. If patients are vaccinated less than 14 days prior to or during methotrexate therapy, repeat vaccination at least 3 months after therapy if immunocompetence restored. 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
RiTUXimab: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of rituximab when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 6 months after therapy is complete. Risk D: Consider therapy modification
Siponimod: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Avoid administration of vaccines (inactivated) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Risk D: Consider therapy modification
Teplizumab: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Vaccination with inactivated or non-replicating vaccines is not recommended in the 2 weeks prior to teplizumab therapy, during treatment, or for 6 weeks following completion of therapy. Risk D: Consider therapy modification
Outcome information following inadvertent use of the Japanese encephalitis (JE) virus vaccine during pregnancy is limited (WHO 2015).
In general, vaccination should be deferred during pregnancy. However, use may be considered in pregnant women at high risk for infection. Intrauterine transmission of the JE virus has been reported; miscarriages have occurred in women infected during the first or second trimester of pregnancy (CDC/ACIP [Hills 2019]).
To report inadvertent use of Ixiaro during pregnancy, contact Valneva USA, Inc (1-844-349-4276).
It is not known if the vaccine is present in breast milk.
According to the manufacturer, the decision to continue or discontinue breastfeeding following immunization should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. However, inactivated vaccines are not expected to affect the safety of breastfeeding for the mother or the infant (CDC/ACIP [Hills 2019]).
Observe for anaphylaxis and syncope for 15 minutes following administration (ACIP [Kroger 2021]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
This vaccine induces antibodies to neutralize the Japanese encephalitis virus. Antibody response is measured using a 50% plaque-reduction neutralization antibody test (PRNT50); a threshold of ≥1:10 is considered protective immunity.
Onset: Protective immunity was observed in ≥95% of children and adults (<65 years of age) 28 days after the second vaccine dose.
Duration: Protective immunity was observed in ~80% to 85% of adults 12 to 36 months after the initiation of the two-dose series. In 96% of adults, seroprotection was shown to last ≥6 years after a booster dose administered 15 months after the first dose of a two-dose primary series. In children, 100% were reported to be seroprotective up to 24 months after the booster dose; pharmacodynamic modeling suggest median duration of seroprotection of 9 years in children (CDC/ACIP [Hills 2019]).
