VA Class:IM100
ATC Class:J07BA01
Japanese encephalitis vaccine stimulates active immunity to Japanese encephalitis virus and is commercially available in the US as Japanese encephalitis vaccine inactivated adsorbed, an inactivated Vero cell culture-derived vaccine (JE-VC; Ixiaro®).1, 2, 3, 115 Other inactivated Japanese encephalitis vaccines (e.g., inactivated mouse brain-derived vaccine; JE-MB) and live, attenuated or live, chimeric Japanese encephalitis vaccines may be available in Asia or elsewhere.2, 5, 7, 8, 115
Prevention of Disease Caused by Japanese Encephalitis Virus
Japanese encephalitis vaccine inactivated adsorbed (JE-VC) is used in adults, adolescents, and children 2 months of age or older for prevention of disease caused by Japanese encephalitis virus.1, 2, 3
Japanese encephalitis virus is a Flavivirus closely related to West Nile virus (WNV), St. Louis and Murray Valley encephalitis viruses, yellow fever virus, and dengue virus.2, 7, 8, 115 Japanese encephalitis virus is transmitted to humans through the bite of infected mosquitoes that acquired the virus by biting infected vertebrate hosts (usually pigs or wading birds).2, 8, 115 Humans are incidental or dead-end hosts for Japanese encephalitis virus since the level or duration of viremia usually is insufficient to infect mosquitoes.8, 115 Direct person-to-person transmission of Japanese encephalitis virus does not occur; however, intrauterine transmission of the virus from mother to child during pregnancy can occur and transmission of the virus through blood products or transplanted organs theoretically could occur since it has been reported with similar Flaviruses .2
Japanese encephalitis virus is the most common vaccine-preventable cause of encephalitis in Asia, and endemic transmission of the virus has been reported in at least 24 countries in Southeast Asia and the Western Pacific.2, 8 Although Japanese encephalitis virus infection usually is asymptomatic or associated with mild disease (fever, headache, aseptic meningitis),2, 8, 115 1 out of every 200-250 infections results in severe disease (rapid onset of high fever, headache, vomiting, generalized weakness, neck stiffness, disorientation, seizures, spastic paralysis, coma, death).2, 8 Approximately 30,000-68,000 cases of Japanese encephalitis are reported annually in areas where Japanese encephalitis virus is endemic;2, 8 the case fatality rate is approximately 20-30% and 30-50% of survivors have permanent neurologic or psychiatric sequelae.2, 8, 115 Most cases of Japanese encephalitis in populations residing in endemic areas occur in children younger than 15 years of age since older individuals may have developed natural immunity from prior infection with the virus.2, 8, 115 However, in endemic areas that have established childhood Japanese encephalitis vaccination programs, the overall incidence of Japanese encephalitis is decreasing and similar numbers of cases are reported in children and adults.2 Because unvaccinated travelers from nonendemic countries usually have had no prior exposure to the virus, travel-associated Japanese encephalitis can occur in travelers of any age.2, 115 (See Travelers under Uses: Prevention of Disease Caused by Japanese Encephalitis Virus.)
Safety and efficacy of a 2-dose primary vaccination series of JE-VC have been evaluated in studies involving adults, adolescents, and children 2 months of age or older residing in countries where Japanese encephalitis virus is endemic (e.g., Philippines) or residing in countries where the disease is not epidemic (e.g., US, Europe, Australia).1 In one randomized, observer-blinded study evaluating use of JE-VC in adults 18 years of age or older residing in nonendemic countries, only 21% of vaccinees in the per-protocol population had protective immunity (i.e., Japanese encephalitis virus-neutralizing antibody titers of 1:10 or greater) 10 days after the first dose of JE-VC, but 97% had protective immunity 7 days after the second dose of JE-VC and still had protective immunity 28 days after the second dose.1 In a study in adults residing in nonendemic countries who received the 2-dose primary vaccination series of JE-VC, protective immunity persisted for 6, 12, 24, and 36 months after initiation of the primary series in 95, 83, 82, and 85%, respectively, of these adults.1 However, in another study in adults residing in nonendemic countries (western and northern Europe) who received the 2-dose primary series, only 83, 58, and 48% of vaccinees had protective immunity 6, 12, and 24 months, respectively, after initiation of the primary series.1, 2
In an uncontrolled, open-label study evaluating JE-VC in children 2 months through 17 years of age residing in nonendemic countries who received an age-appropriate 2-dose primary series of the vaccine, 100% had protective immunity when evaluated 56 days and 7 months later.1 In a randomized, controlled, open-label study evaluating JE-VC in children 2 months of age or older residing in the Philippines where Japanese encephalitis is endemic, 0-30% of those 2 months to 1 year of age and 3-46% of those 1 through 17 years of age already had protective immunity prior to administration of JE-VC;1 99-100% of these children had protective immunity 28 days after the second age-appropriate dose of JE-VC and 86-100% still had protective immunity 6 months after the second dose.1
There is evidence from several studies in adults that administration of a single booster dose of JE-VC given 14-24 months after completion of the 2-dose primary vaccination series of JE-VC elicits a booster response and increases Japanese encephalitis virus-neutralizing antibody titers.1, 6 In an uncontrolled, open-label, phase 3 study in adults residing in nonendemic countries who received a single booster dose of JE-VC 14 months after completion of the 2-dose primary series, the proportion of these adults with protective immunity increased from 69% immediately prior to the booster dose to 100% at 28 days after the booster dose and 99% still had protective immunity 12 months after the booster dose.1 Data are not available regarding the immune response in adults who receive a booster dose of JE-VC more than 2 years after completion of the 2-dose primary vaccination series.6 In addition, safety and immunogenicity of booster doses of JE-VC have not been evaluated in children 2 months through 16 years of age previously vaccinated with the age-appropriate 2-dose primary series of JE-VC.1, 3
Data from several limited studies indicate that administration of a single dose of JE-VC in adults who previously received primary vaccination with inactivated mouse brain-derived Japanese encephalitis vaccine (JE-MB; no longer available in the US but may be available in other countries) results in a booster response.9, 10 In a single-blind, prospective, nonrandomized study that included adults who had received 2 or 3 doses of JE-MB given 1-21 years (median 5 years) previously, a single dose of JE-VC boosted antibody levels in 95-98% of these individuals.9 However, until further data become available, the US Public Health Service Advisory Committee on Immunization Practices (ACIP) and US Centers for Disease Control and Prevention (CDC) recommend that adults 17 years of age or older who previously received JE-MB be revaccinated with the usually recommended 2-dose primary series of JE-VC if they are at continued risk of exposure to Japanese encephalitis virus or if reexposure to the virus is expected.6, 115
For most travelers to Asia, the risk of acquiring Japanese encephalitis virus is very low, but varies depending on the location and duration of travel, season, and the traveler's expected activities.2, 115 The overall incidence of Japanese encephalitis among individuals from nonendemic countries traveling in Asia is estimated to be less than 1 case per 1 million travelers.2, 115 The risk for Japanese encephalitis is considered minimal for most short-term travelers (traveling for less than 1 month) who only visit urban areas in Asia.2, 115 However, travelers who stay for prolonged periods in rural areas where active transmission of Japanese encephalitis virus is occurring and short-term or recurrent travelers who have extensive outdoor or nighttime exposure in rural areas during periods of active transmission of the virus probably have the same level of risk for Japanese encephalitis as susceptible resident populations.2, 115
The risk of transmission of Japanese encephalitis virus is greatest in rural agricultural areas where the virus is endemic2, 8, 115 and often is related to rice production and flooding irrigation, which results in large numbers of vector mosquitoes breeding in close proximity to amplifying vertebrate hosts.2, 115 In temperate areas of Asia, Japanese encephalitis virus is transmitted seasonally (usually peaking in the summer and fall) and large seasonal epidemics can occur.2, 8, 115 In tropical and subtropical areas, transmission of the virus can be sporadic or occur all year, but often peaks during the rainy season.2, 8, 115
When making recommendations regarding vaccination against Japanese encephalitis virus for travelers, health-care providers should weigh the overall low risk for travel-associated Japanese encephalitis virus disease, the high morbidity and mortality associated with Japanese encephalitis, the low probability of serious adverse effects following vaccination, and the cost of the vaccine.2, 115 The planned itinerary, including destinations, duration of travel, season, accommodations, and activities, should be considered as well as the possibility of unexpected travel to high-risk areas.2, 115
JE-VC vaccination is not recommended for short-term travelers (traveling for less than 1 month) to Asia when the visit will be restricted to urban areas or times outside a well-defined Japanese encephalitis virus transmission season.2, 115
ACIP and CDC state that vaccination with JE-VC is recommended for travelers who plan to spend 1 month or longer in endemic areas during the Japanese encephalitis virus transmission season.2, 115 This includes long-term travelers, recurrent travelers, or expatriates who will be based in urban areas but are likely to visit endemic rural or agricultural areas during a high-risk period of Japanese encephalitis virus transmission.2, 115
ACIP and CDC state that vaccination with JE-VC should be considered for short-term travelers (traveling for less than 1 month) to endemic areas during the Japanese encephalitis virus transmission season if they are planning to travel outside of urban areas or participate in activities associated with increased exposure.2, 115 This includes those who will spend substantial time outdoors in rural or agricultural areas (especially during the evening or nighttime), those who will participate in extensive outdoor activities (e.g., camping, hiking, trekking, biking, fishing, hunting, farming), and those staying in accommodations without air conditioning, screens, or bed nets.2, 115
These experts also state that vaccination with JE-VC should be considered for travelers to areas with an ongoing Japanese encephalitis outbreak and travelers to endemic areas who are uncertain of specific destinations, activities, or duration of travel.2, 115
If a decision is made to administer JE-VC to travelers, clinicians should consider that the primary vaccination series includes 2 doses given 28 days apart and that the series should be completed at least 1 week prior to potential exposure to Japanese encephalitis virus.1, 2, 115 (See Dosage and Administration: Dosage.)
Regardless of vaccination or the circumstances and timing of travel, all travelers to Asia should be advised to take precautions to avoid mosquito bites to reduce the risk of exposure to Japanese encephalitis virus and other vector-borne infectious diseases.1, 2, 115 Such precautions include the use of insect repellant and protective clothing; staying in accommodations with air conditioning, screens, or bed nets; and avoidance of extensive outdoor activities, especially during the evening and nighttime.1, 2, 115
Because the risk of infection with Japanese encephalitis virus is highly variable within endemic regions and varies from year to year within a given region,2 current CDC recommendations for international travel should be consulted for information concerning the geographic areas where transmission of Japanese encephalitis virus is being reported.2 Information on the risk of Japanese encephalitis in specific countries, information on mosquito avoidance and protective measures against mosquito bites, and additional information regarding the benefits and risks of JE-VC vaccination in travelers is available from CDC at [Web] and [Web].115
ACIP recommends that all laboratory personnel at risk of exposure to infectious Japanese encephalitis virus be vaccinated with JE-VC.2
Laboratory-acquired Japanese encephalitis has been reported.2 In laboratory settings, Japanese encephalitis virus may be transmitted through needlestick injuries or, theoretically, through mucosal or inhalational exposures.2 Although vaccine-induced immunity is presumed to provide protection against percutaneous exposures, it is not known whether vaccine-induced immunity would provide protection against aerosolized Japanese encephalitis virus (especially exposures involving high concentrations of the virus) that may occur during viral purification procedures and may lead to infection through mucous membranes with direct CNS exposure (e.g., olfactory epithelium).2
Japanese encephalitis vaccine inactivated adsorbed (JE-VC) is administered by IM injection.1 The vaccine should not be given IV, intradermally, or subcutaneously.1
Depending on patient age, IM injections of JE-VC should be made into the anterolateral muscles of the thigh or deltoid muscle of the arm.1, 134 In infants and children 2 months through 2 years of age, IM injections should preferably be made into the anterolateral thigh;1, 134 alternatively, the deltoid muscle can be used in those 1 through 2 years of age if muscle mass is adequate.1, 134 In adults, adolescents, and children 3 years of age or older, IM injections should preferably be made into the deltoid muscle.1, 134
To ensure delivery into muscle, IM injections should be made at a 90° angle to the skin using a needle length appropriate for the individual's age and body mass, thickness of adipose tissue and muscle at the injection site, and injection technique.134
IM injections should not be made into the gluteal area or any area where there may be a major nerve trunk.134 If the gluteal muscle is chosen for infants younger than 12 months of age because of special circumstances (e.g., physical obstruction of other sites), it is essential that the clinician identify anatomic landmarks prior to injection.134
JE-VC is commercially available in prefilled single-dose glass syringes containing 0.5 mL of the vaccine.1
During storage, JE-VC appears as a clear liquid with a white precipitate.1 Immediately prior to administration, the syringe containing JE-VC should be shaken well to obtain a white, opaque, homogeneous suspension.1 The vaccine should not be administered if it is discolored or contains particulate matter.1
After shaking, a sterile needle should be attached to the prefilled syringe.1 For adults, adolescents, and children 3 years of age or older, the entire contents of the syringe (0.5 mL) should be administered IM.1 To provide the appropriate dose for children 2 months through 2 years of age (0.25 mL), the indicated portion of the syringe contents should be expelled through the needle into a medical waste container according to the manufacturer's directions;1 the needle should then be replaced with a new sterile needle and the remaining 0.25 mL of vaccine in the syringe should be administered IM to the child.1
JE-VC should not be mixed with any other vaccine.1
When multiple parenteral vaccines are administered during a single health-care visit, each vaccine should be given with a different syringe and at different injection sites.134 Injection sites should be separated by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.134
Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;134 such reactions occur most frequently in adolescents and young adults.134 Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after the vaccination.134 If syncope occurs, the patient should be observed until symptoms resolve.134
Prevention of Disease Caused by Japanese Encephalitis Virus
Children 2 Months through 2 Years of Age
For primary immunization in children 2 months through 2 years of age, 2 doses of JE-VC should be given 28 days apart.1 Each dose consists of 0.25 mL of the vaccine (see Dosage and Administration: Administration).1 The 2-dose primary series should be completed at least 1 week prior to potential exposure to Japanese encephalitis virus.1, 2, 115
Safety and immunogenicity of booster doses of JE-VC have not been evaluated in children 2 months through 2 years of age.1, 3
Children and Adolescents 3 through 16 Years of Age
For primary immunization in children and adolescents 3 through 16 years of age, 2 doses of JE-VC should be given 28 days apart.1 Each dose consists of the entire contents (0.5 mL) of the prefilled syringe.1 The 2-dose primary series should be completed at least 1 week prior to potential exposure to Japanese encephalitis virus.1, 2, 115
Safety and immunogenicity of booster doses of JE-VC have not been evaluated in children and adolescents 3 through 16 years of age.1, 3
Adults 17 Years of Age or Older
For primary immunization in adults 17 years of age or older, 2 doses of JE-VC should be given 28 days apart.1 Each dose consists of the entire contents (0.5 mL) of the prefilled syringe.1 The 2-dose primary series should be completed at least 1 week prior to potential exposure to Japanese encephalitis virus.1, 2, 115
If administration of the second primary dose of JE-VC is delayed (incomplete primary immunization), there is some evidence from a study in adults that high seroconversion rates are attained if the second dose is administered within 11 months after the initial dose.1, 13
If the risk of exposure to Japanese encephalitis virus is ongoing or reexposure to the virus is expected, adults 17 years of age or older can receive a booster dose (0.5 mL) of JE-VC, provided it has been at least 1 year since completion of the 2-dose primary series.1, 6 Data are not available regarding the immune response in adults who receive a booster dose of JE-VC more than 2 years after completion of the 2-dose primary series of JE-VC.6 In addition, data are not available regarding the need for and timing of additional booster doses of the vaccine.6
Adults who previously received inactivated mouse brain-derived Japanese encephalitis vaccine (JE-MB; no longer available in the US but may be available in other countries) and have ongoing risk of exposure to Japanese encephalitis virus or expect reexposure to the virus should be revaccinated with the usually recommended 2-dose primary immunization series of JE-VC.6, 115
There are no special population dosage recommendations at this time.1
Japanese encephalitis vaccine inactivated adsorbed (JE-VC) is contraindicated in individuals who have had a severe allergic reaction (e.g., anaphylaxis) to a previous dose of the vaccine or any component of the vaccine (e.g., protamine sulfate).1
JE-VC also is contraindicated in individuals who have had a severe allergic reaction to any other Japanese encephalitis vaccine.1 Alternatively, because of uncertainty regarding what component of the other vaccine may have been responsible for the allergic reaction, such individuals may be referred to an allergist for evaluation to determine whether immunization with JE-VC should be considered.1
JE-VC contains protamine sulfate, a compound known to cause hypersensitivity reactions in some individuals.1
Appropriate medical care should be readily available in case an anaphylactic reaction occurs.1
Individuals with Altered Immunocompetence
Specific data are not available regarding use of JE-VC in individuals immunosuppressed as the result of disease or immunosuppressive therapy.2 Inactivated vaccines usually may be administered to individuals with altered immunocompetence;134 however, the immune response to JE-VC may be diminished or suboptimal in these individuals.1 (See Drug Interactions: Immunosuppressive Agents.)
A decision to administer or delay vaccination in an individual with a current or recent acute illness depends on the severity of symptoms and etiology of the illness.134
The US Public Health Service Advisory Committee on Immunization Practices (ACIP) states that vaccination in individuals with a moderate or severe acute illness generally should be deferred until they have recovered to avoid superimposing adverse effects of the vaccine on the underlying illness or to avoid mistakenly concluding that a manifestation of the underlying illness resulted from vaccination.134
Limitations of Vaccine Effectiveness
JE-VC may not protect all vaccine recipients against Japanese encephalitis.1
Individuals who receive only a single dose of JE-VC may not be protected against Japanese encephalitis virus;1 protection is unreliable until 7 days after the second primary dose of JE-VC.1, 2 (See Dosage and Administration: Dosage.)
JE-VC will not provide protection against encephalitis caused by other viruses or other pathogens and will not provide protection against other diseases transmitted by mosquitoes.1
The duration of immunity following vaccination with the 2-dose primary series of JE-VC has not been fully determined.1, 2, 115
Although results of one study in adults residing in nonendemic countries indicated that protective immunity (i.e., Japanese encephalitis virus-neutralizing antibody titers of 1:10 or greater) persists for 6, 12, 24, and 36 months in 95, 83, 82, and 85%, respectively, of adults who receive the 2-dose primary series of JE-VC,1 another study in adults residing in nonendemic countries indicated that only 83, 58, and 48% of vaccinees had protective immunity 6, 12, and 24 months, respectively, after initiation of the primary series.1, 2 Following an age-appropriate 2-dose primary series of JE-VC in children 2 months through 17 years of age, 100% had protective immunity 7 months later.1 (See Uses: Prevention of Disease Caused by Japanese Encephalitis Virus.)
Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune responses in vaccinees.134
JE-VC should be stored at 2-8°C and should not be frozen.1 The vaccine should be stored in the original packaging and protected from light.1 The vaccine does not contain thimerosal or any other preservatives.1, 2
All vaccines should be inspected upon delivery and monitored during storage to ensure that the appropriate temperature is maintained.134
Vaccine that has been mishandled or has not been stored at the recommended temperature should not be administered.134 If there are concerns about mishandling, the manufacturer or state or local immunization or health departments should be contacted for guidance on whether the vaccine is usable.134
Category B.1 (See Users Guide.)
JE-VC should be used during pregnancy only if clearly needed.1
There are no adequate and well-controlled studies using JE-VC in pregnant women.1 In animal studies (female rats), administration of JE-VC at dosages approximately 300-fold higher than the projected human dosage (on a mg/kg basis) did not reveal evidence of impaired fertility or harm to the fetus.1
Japanese encephalitis virus acquired during the first or second trimester of pregnancy may cause intrauterine infection and spontaneous abortion;2 there is some evidence that intrauterine transmission of the virus can occur.2
Clinicians are encouraged to report cases of inadvertent administration of JE-VC during pregnancy to 877-683-4732.1
It is not known whether JE-VC is distributed into human milk.1
JE-VC should be used with caution in nursing women.1
Safety and efficacy of JE-VC have not been established in infants younger than 2 months of age.1
Clinical studies did not include sufficient numbers of adults 65 years of age and older to determine whether they respond differently to JE-VC than younger adults.1
The most common adverse effects following a dose of JE-VC in infants and children 2 months through 11 years of age are fever, irritability, flu-like symptoms, diarrhea, vomiting, loss of appetite, rash, and injection site reactions (pain, tenderness, erythema).1 In adults and adolescents 12 years of age or older, the most common adverse reactions following a dose of JE-VC are headache, myalgia, fatigue, influenza-like illness, nausea, and injection site reactions (pain, tenderness, erythema, induration).1
Although specific data are not available regarding concomitant use of Japanese encephalitis vaccine inactivated adsorbed (JE-VC) and immunosuppressive therapy (e.g., radiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids used in greater than physiologic doses), such therapy may decrease the immune response to the vaccine.1, 134 If possible, vaccination should be completed at least 2 weeks prior to initiation of immunosuppressive therapy or should be deferred until at least 3 months after immunosuppressive therapy is discontinued.134 If administered during chemotherapy, the patient should be revaccinated after immune competence is regained.134
Although specific studies may not be available evaluating concurrent administration with each antigen, simultaneous administration with other age-appropriate vaccines, including live virus vaccines, toxoids, or inactivated or recombinant vaccines, during the same health-care visit is not expected to affect immunologic responses or adverse reactions to any of the antigens.1, 134 If JE-VC is administered concomitantly with another parenteral vaccine, the vaccines should be given at different injection sites using separate syringes.1
JE-VC has been administered concomitantly with hepatitis A virus vaccine inactivated (Havrix®) in a randomized, controlled, phase 3 study in healthy adults 18 years of age or older.1, 11 Concomitant administration did not affect the immune response to either vaccine.1, 11
Japanese encephalitis vaccine inactivated adsorbed (JE-VC) is a sterile suspension of purified, inactivated Japanese encephalitis virus proteins adsorbed onto aluminum hydroxide and is used to stimulate active immunity to Japanese encephalitis virus.1
JE-VC promotes production of antibodies that neutralize live Japanese encephalitis virus.1 Data from animal studies, clinical trials of other Japanese encephalitis vaccines, and epidemiologic studies in humans suggest that a Japanese encephalitis virus-specific neutralizing antibody titer (as measured in vitro in a 50% plaque reduction neutralization test [PRNT50]) of 1:10 correlates with protective immunity against Japanese encephalitis virus infection in humans.1, 2, 3, 6
Following vaccination with a 2-dose primary series of JE-VC in adults 18 years of age or older residing in countries where Japanese encephalitis virus is not endemic, 97% have Japanese encephalitis virus-neutralizing antibody titers of 1:10 or greater 7 days after the second vaccine dose and still have protective levels of antibody at 28 days after the second dose.1 There is evidence from a study in adults residing in nonendemic countries that protective levels of antibody persist for 6, 12, 24, and 36 months in 95, 83, 82, and 85%, respectively, of those who receive a 2-dose primary series of JE-VC.1 Data indicate that a single booster dose of JE-VC given 14-24 months after completion of the 2-dose primary series elicits a booster response in adults.1, 6 In one study following vaccination with an age-appropriate 2-dose primary series of JE-VC in infants and children 2 months through 17 years of age residing in nonendemic countries, all vaccinees had Japanese encephalitis virus-neutralizing antibody titers of 1:10 or greater when evaluated 56 days and 7 months later.1 (See Uses: Prevention of Disease Caused by Japanese Encephalitis Virus.)
JE-VC is prepared by propagating Japanese encephalitis virus strain SA14-14-2 in Vero cells.1 After the virus is harvested, pooled, clarified, and concentrated, the virus suspension is treated with protamine sulfate to remove contaminating DNA and proteins and the partially purified virus is then processed through a sucrose density gradient centrifugation step and fractionated.1 Each fraction is analyzed for the presence of the virus;1 fractions with the highest virus activity are pooled to give a purified virus suspension.1 After the purified virus is inactivated with formaldehyde, the preparation is adjusted to a specified protein concentration and formulated by adding an aluminum hydroxide adjuvant.1
Each 0.5-mL dose of JE-VC contains 6 mcg of purified, inactivated Japanese encephalitis virus proteins and 250 mcg of aluminum hydroxide.1 Each 0.5-mL dose of the vaccine also contains formaldehyde (not exceeding 200 ppm), bovine serum albumin (not exceeding 100 ng/mL), host cell DNA (not exceeding 200 pg/mL), sodium metabisulfite (not exceeding 200 ppm), host cell proteins (not exceeding 300 ng/6 mcg of protein), and protamine sulfate (not exceeding 1 mcg/mL) from the manufacturing process.1
Prior to administration of each dose of Japanese encephalitis vaccine inactivated adsorbed (JE-VC), provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient's legal representative (VISs are available at [Web]).1, 4
Advise patient and/or patient's parent or guardian of the risks and benefits of vaccination against Japanese encephalitis virus.1
Importance of consulting current US and international advisories regarding the prevalence of Japanese encephalitis in specific locations prior to travel.1, 115 Information is available from CDC at [Web] and [Web].115
Importance of completing the 2-dose primary vaccination series of JE-VC at least 1 week prior to potential exposure to Japanese encephalitis virus.1, 2, 115
Advise patient and/or patient's parent or guardian that JE-VC may not fully protect everyone who receives the vaccine,1 and that travelers to areas with Japanese encephalitis virus should take precautions to avoid mosquito bites (e.g., use insect repellant, wear protective clothing, stay in accommodations with air conditioning, screens, or bed nets).1, 2, 115
Importance of informing clinicians of any reactions to a previous dose of JE-VC or to any other vaccines.1
Importance of informing clinicians of any signs and/or symptoms of severe adverse reactions or anaphylaxis (e.g., difficulty breathing, wheezing, weakness or fast heart beat, hives) that occur after administration of JE-VC.1 Clinicians or individuals can report any adverse reactions that occur following vaccination to Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or [Web].1, 4
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions June 22, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Intercell Biomedical Ltd. Ixiaro® (Japanese encephalitis vaccine, inactivated, adsorbed) suspension for intramuscular injection prescribing information. Livingston, UK; 2013 May.
2. Fischer M, Lindsey N, Staples JE et al. Japanese encephalitis vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep . 2010; 59(RR-1):1-27.
3. Centers for Disease Control and Prevention (CDC). Use of Japanese encephalitis vaccine in children: recommendations of the advisory committee on immunization practices, 2013. MMWR Morb Mortal Wkly Rep . 2013; 62:898-900. [PubMedCentral][PubMed 24226626]
4. Centers for Disease Control and Prevention. Japanese encephalitis vaccine information statement. 2014 Dec 24. From CDC website. [Web]
5. Centers for Disease Control and Prevention (CDC). Update on Japanese encephalitis vaccine for children: United States, May 2011. MMWR Morb Mortal Wkly Rep . 2011; 60:664-5. [PubMed 21617633]
6. Centers for Disease Control and Prevention (CDC). Recommendations for use of a booster dose of inactivated vero cell culture-derived Japanese encephalitis vaccine: advisory committee on immunization practices, 2011. MMWR Morb Mortal Wkly Rep . 2011; 60:661-3. [PubMed 21617632]
7. McArthur MA, Holbrook MR. Japanese Encephalitis Vaccines. J Bioterror Biodef . 2011; S1:2. [PubMed 23125946]
8. World Health Organization. Japanese encephalitis. From WHO website. Accessed 2015 Mar 12. [Web]
9. Erra EO, Askling HH, Rombo L et al. A single dose of vero cell-derived Japanese encephalitis (JE) vaccine (Ixiaro) effectively boosts immunity in travelers primed with mouse brain-derived JE vaccines. Clin Infect Dis . 2012; 55:825-34. [PubMedCentral][PubMed 22696017]
10. Woolpert T, Staples JE, Faix DJ et al. Immunogenicity of one dose of Vero cell culture-derived Japanese encephalitis (JE) vaccine in adults previously vaccinated with mouse brain-derived JE vaccine. Vaccine . 2012; 30:3090-6. [PubMed 22406277]
11. Kaltenböck A, Dubischar-Kastner K, Eder G et al. Safety and immunogenicity of concomitant vaccination with the cell-culture based Japanese Encephalitis vaccine IC51 and the hepatitis A vaccine HAVRIX1440 in healthy subjects: A single-blind, randomized, controlled Phase 3 study. Vaccine . 2009; 27:4483-9. [PubMed 19486955]
13. Dubischar-Kastner K, Eder S, Buerger V et al. Long-term immunity and immune response to a booster dose following vaccination with the inactivated Japanese encephalitis vaccine IXIARO, IC51. Vaccine . 2010; 28:5197-202. [PubMed 20541581]
115. Centers for Disease Control and Prevention. CDC health information for international travel, 2014. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website. [Web]
134. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep . 2011; 60:1-64.