Version May 2024
Primary immunization: IM: 0.5 mL per dose given as 2 doses 28 days apart. An accelerated regimen (0.5 mL per dose given as 2 doses 7 days apart) was noninferior to the standard regimen and may be considered in adults ≤65 years of age (Ref). Series should be completed at least 1 week prior to potential exposure. Note: If the second dose is missed, limited data from 1 clinical trial in adults demonstrated a 99% seroconversion rate when the second dose was administered 11 months after the initial dose (Ref).
Booster dose: IM: 0.5 mL/dose given ≥1 year after completion of the primary immunization series if exposure to Japanese encephalitis virus is ongoing or expected (Ref).
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 per dose given as 2 doses on days 0 and 28. Series should be completed at least 1 week prior to potential exposure.
Booster dose: Refer to adult dosing.
(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.
Infants ≥2 months and Children <3 years: IM: 0.25 mL/dose for 2 doses separated by 28 days (Ref).
Children ≥3 years and Adolescents: IM: 0.5 mL/dose for 2 doses separated by 28 days (Ref). Note: In adolescents ≥18 years of age, an accelerated regimen of 0.5 mL/dose for 2 doses separated by 7 days may be considered (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
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%:
Gastrointestinal: Diarrhea (infants and children: ≤12%; adolescents and adults: ≤2%)
Local: Erythema at injection site (infants: 5% to 17%; children, adolescents, and adults: ≤10%), pain at injection site (children and adolescents: 2% to 15%; adults: 18% to 33%), tenderness at injection site (infants, children, and adolescents: ≤10%; adults: 23% to 36%)
Nervous system: Fatigue (infants, children, and adolescents: ≤3%; adults: 5% to 11%), headache (children and adolescents: 1% to 5%; adults: 13% to 28%), irritability (infants and children: ≤15%; adolescents: 2%)
Neuromuscular & skeletal: Myalgia (children and adolescents: ≤3%; adults: 6% to 16%)
Respiratory: Flu-like symptoms (children and adults: ≤12%; adolescents: 1% to 3%)
Miscellaneous: Fever (infants and children: ≤24%; adolescents and adults: ≤5%)
1% to 10%:
Dermatologic: Skin rash (infants and children: 1% to 8%; adolescents and adults: ≤1%)
Gastrointestinal: Anorexia (infants and children: 1% to 6%; adolescents: ≤2%), nausea (children and adolescents: ≤2%; adults 3% to 7%), vomiting (infants and children: ≤8%; adolescents and adults: ≤1%)
Local: Induration at injection site (children and adolescents: ≤1%; adults: 4% to 8%), injection-site pruritus (children and adolescents: ≤1%; adults: 2% to 4%), swelling at injection site (infants, children, adolescents, and adults: ≤4%)
Nervous system: Febrile seizures (children: 1%)
Neuromuscular & skeletal: Back pain (adults: ≤1%)
Respiratory: Cough (adults: ≤1%), nasopharyngitis (adults: 2% to 5%), pharyngolaryngeal pain (adults: ≤2%), rhinitis (adults: ≤1%), upper respiratory tract infection (adults: ≤2%)
Postmarketing: Nervous system: Neuritis, paresthesia
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 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: 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: 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]).
• 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 2023]). 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 2023]).
• 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 nonlive) for which a person is eligible at a single visit, unless contraindications exist (ACIP [Kroger 2023]).
Special populations:
• Altered immunocompetence: Postpone vaccination 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. In general, household and close contacts of persons with altered immunocompetence may receive all age-appropriate vaccines. 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 (ACIP [Kroger 2023]; 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 (AAP [Saari 2003]; ACIP [Kroger 2023]).
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 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: 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 (ACIP [Kroger 2023]).
• 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]).
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
IM: Shake well prior to use to form a homogeneous suspension. Do not use if discolored or if particulate matter remains. For IM injection, preferably 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 (Ref). Do not inject IV, SUBQ, or intradermally. 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). If purchased under CDC contract, US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, Vaccine Information Statement edition date and date it was provided, and the administering person's name, title, and address be recorded.
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 IM injection, the vaccine should be administered IM if, in the opinion of the health care provider 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, IM 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 or family 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).
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 (Ref). To prevent syncope-related injuries, adolescents should be vaccinated while seated or lying down.
Administration volume: Ixiaro is available only in a prefilled syringe containing 0.5 mL dose. Additional manipulation of the syringe is required to administer the lower 0.25 mL dose.
Administration of the 0.25 mL dose: Infants ≥2 months and Children <3 years: Shake the syringe to form a homogenous suspension. Attach a sterile needle to the prefilled syringe and while holding the syringe upright, push the plunger stopper up to the edge of the red line on the syringe barrel to expel and discard 0.25 mL (half of the volume) of the suspension. If plunger stopper is pushed beyond the red line, do not administer and use a new syringe to start over. Attach a new sterile needle prior to administration.
Administration site (preferred): Note: If injected in 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).
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.
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 are lacking and the US labeling does not recommend SUBQ administration. For patients at risk of hemorrhage following IM injection, the vaccine should be administered IM if, in the opinion of the health care provider 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, IM 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 applied to the site (without rubbing) for at least 2 minutes. The patient or family 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).
In the United States, the appropriate CDC-approved Vaccine Information Statement (VIS) should be provided to the patient/caregiver before administering each dose of this vaccine. VIS is available at http://www.cdc.gov/vaccines/hcp/vis/vis-statements/je-ixiaro.html.
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 the following persons (CDC/ACIP [Hills 2019]):
- Persons moving to or frequently traveling to JE-endemic areas
- Persons spending ≥1 month in JE-endemic areas
- Laboratory workers who may be exposed to the JE virus other than SA14-14-2 JE vaccine virus (the viral strain this vaccine is derived from). For those working with SA14-14-2 JE virus, consider vaccination in 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, disease-transmission season, location (eg, proximity to animal reservoirs and mosquito vectors), 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 World Health Organization recommends integration of JE virus vaccination into national immunization schedules in areas suitable for JE virus transmission and recognized as a public health priority (ie, presence of animal reservoirs, ecological conditions supportive of virus transmission, proximity to other areas with known JE virus transmission).
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
Anti-CD20 B-Cell Depleting Therapies: May diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation or 6 months after anti-CD20 B-cell depleting therapies. If vaccinated prior to B cell recovery, consider assessing immune response to 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
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
Pregnancy testing is not required prior to vaccination (WHO 2015).
Outcome data following inadvertent use of the Japanese encephalitis (JE) virus vaccine during pregnancy are limited (WHO 2015).
In general, vaccination should be deferred during pregnancy. However, use may be considered in pregnant patients at high risk for infection. Intrauterine transmission of the JE virus has been reported; miscarriages have occurred in patients infected during the first or second trimester of pregnancy (CDC/ACIP [Hills 2019]). The inactivated vaccine (Ixiaro) is preferred if administration of a JE vaccine is needed in a pregnant patient (WHO 2015).
To report inadvertent use of Ixiaro during pregnancy, contact Intercell USA, Inc (1-844-349-4276).
It is not known if components of the vaccine are present in breast milk.
The manufacturer recommends caution be used if the vaccine is administered to a lactating patient; however, inactivated vaccines are not expected to affect the safety of breastfeeding for the mother or the infant (CDC/ACIP [Hills 2019]).
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.
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]).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
