Japanese encephalitis virus vaccine is a parenteral viral vaccine that works by inducing antibodies that neutralize live virus. The arboviral Flavivirus is spread by mosquitos and is the leading cause of viral encephalitis in Asia. Two inactivated vaccines are licensed for use in the United States: JE-VAX and Ixiaro. JE-VAX was prepared by inoculating mice intracerebrally with the virus and harvesting the brains whereas Ixiaro is prepared by propagating a viral strain in Vero cells. Ixiaro, FDA approved in March 2009, is now the only vaccine commercially available in the US to help prevent Japanese encephalitis. The Research Foundation for Microbial Diseases of Osaka University, the manufacturer of JE-VAX vaccine, has discontinued production of JE-VAX.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Epinephrine 1:1000 must be immediately available in the event of an anaphylactic reaction. Interview the potential vaccine recipient before administration. A severe allergic reaction after a previous Japanese encephalitis virus vaccine dose is a contraindication to Ixiaro administration.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intramuscular Administration
-Shake the syringe well to obtain a white, opaque, homogeneous suspension. Do not administer if particulate matter is present after shaking or if discoloration is observed.
-With a careful twist, remove the syringe tip cap; do not attempt to snap or pull off the tip cap as this may damage the syringe.
-Attach a safety needle to the syringe.
-For adults and pediatric patients >= 3 years:-Administer the full 0.5 mL by intramuscular injection into the deltoid muscle.
-For pediatric patients 2 months to < 3 years:-Hold the syringe upright, uncap the needle, and slowly push the plunger up to the edge of the red line on the syringe barrel. Discard the expelled volume in a medical waste container. If the plunger stopper is pushed beyond the line, the entire syringe must be wasted and the process repeated with a new pre-filled syringe.
-Once the plunger stopper is at the edge of the red line, lock the needle safety shield and remove the needle.
-Attach a new sterile needle and inject the remaining 0.25 mL volume by intramuscular injection into the anterolateral aspect of the thigh. Alternatively, the deltoid muscle may be used for children ages 1 to < 3 years if muscle mass is adequate.
-Do not mix with any other vaccine in the same syringe or vial.
The US Department of Health and Human Services has established a Vaccine Adverse Event Reporting System (VAERS) to accept all reports of suspected adverse events after the administration of any vaccine, including the Japanese encephalitis virus vaccine. This includes, but is not limited to, the reporting of events required by the National Childhood Vaccine Injury Act of 1986. The toll-free number for VAERS is (800) 822-7967.
In clinical trials of the Japanese encephalitis virus vaccine, the most common systemic adverse reactions among vaccine recipients were headache (11.1% to 30.4%), anorexia (16.1%), myalgia (15.6% to 16.1%), fatigue (11.3% to 33.9%), influenza-like illness (11.7% to 12.3%), nausea (6.6% to 14.3%), arthralgia (5.4%), naso-pharyngitis (4.7% to 15.2%), and fever (3.2%). Other adverse reactions that were noted in a similar percentage of Japanese encephalitis virus vaccine and control recipients include rhinitis (1.4% both groups), upper respiratory tract infection (1.7% vs. 2%), back pain (1.3% vs. 1.1%), pharyngolaryngeal pain (1.6% vs. 1.4%), rash (1.3% vs. 1.5%), diarrhea (1.5% vs. 1.1%), cough (1.2% both groups), and vomiting (1.4% vs. 1.7%).
In clinical trials, about half of the Japanese encephalitis virus vaccine or control recipients had an injection site reaction after either dose 1 or 2. Tenderness and pain (12.8% to 53.6%), erythema (9.6% to 19.6%), induration (7.5% to 14.3%), edema (4.2%), and pruritus (3.8%) were noted during clinical trials. Any injection reaction was reported by fewer patients after dose 2 (32.6% of 1,951) as compared with after dose 1 (48.5% of 1,963). In a study of 198 adults who received booster vaccination with Japanese encephalitis virus vaccine, 30.8% reported having an injection site reaction after the booster dose. In a study, at least 1 severe local symptom was noted by 9 of 421 vaccine recipients. In this study, hardening, swelling, and erythema were the most common severe, local symptoms.
The Japanese encephalitis virus vaccine (Ixiaro) contains protamine sulfate, which is a compound known to cause hypersensitivity reactions in some individuals. Instruct patients to immediately report dyspnea, hoarseness or wheezing, urticaria, dizziness, weakness, or sinus tachycardia, as these may be signs of an allergic reaction. Pruritus may also be a symptom of a hypersensitivity reaction, although it may also just be a local reaction to the vaccine if it occurs at the injection site. Have appropriate medical care readily available in case of anaphylactoid reactions including anaphylactic shock.
Postmarketing, paresthesias and neuritis were noted with the Japanese encephalitis virus vaccine (Ixiaro). Several reports exist of possible acute disseminated encephalomyelitis after vaccination with JE-VAX, which is a vaccine that was once marketed in the United States. In 3 adults, symptoms developed within a month of a dose and included headache, neck stiffness, fatigue, cognitive dysfunction (confusion), paresthesias, double vision (visual impairment), gait instability, oculogyral instability, and dysarthria. These effects have not been reported with the Ixiaro product.
Syncope has been noted with postmarketing use of the Japanese encephalitis virus vaccine. Health care professionals are advised to have procedures in place to avoid falling injury and to restore cerebral perfusion after syncope.
Ixiaro is contraindicated for use by patients with a previous severe allergic reaction, such as anaphylaxis, to the vaccine. Because of differing vaccine components, individuals with a history of severe allergic reactions to another Japanese encephalitis vaccine should be referred to an allergist for evaluation. Ixiaro contains protamine sulfate, which may cause a hypersensitivity reaction. It also contains sodium metabisulfite and bovine serum albumin and may be inappropriate for use by patients with either sulfite hypersensitivity or albumin hypersensitivity. Review the patient's immunization history for possible vaccine sensitivity and previous vaccination-related adverse reactions. As with any biologic product, precautions should be taken to prevent allergic reactions. The health care professional should have immediate availability of epinephrine (1:1000) injection and other agents used in the treatment of severe anaphylaxis in the event of a serious allergic reaction to the vaccine.
Ixiaro is only given intramuscularly and may be inappropriate for patients with thrombocytopenia, vitamin K deficiency, or coagulopathy such as hemophilia. Patients taking anticoagulant therapy also may not be appropriate candidates for Ixiaro receipt.
Patients with immunosuppression may not have an adequate antibody response to vaccination with the Japanese encephalitis virus vaccine. No safety or efficacy data exist regarding use in immunocompromised individuals. Consider the patient's degree of altered immunocompetence. Inactivated vaccines administered during the period of altered immunocompetence might need to be repeated after immune function has improved.
No adequate and well-controlled studies have been conducted in pregnant women and the ability of the vaccine to cause fetal harm or affect reproductive capacity is unknown. During a developmental toxicity study preformed in rats, there was no evidence of fetal harm. According to the Advisory Committee on Immunization Practices (ACIP), administration of inactivated virus vaccines to pregnant women have not resulted in adverse effects in the fetus. The ACIP recommends vaccination during pregnancy when the likelihood of disease exposure is high, potential infection would cause harm to mother or fetus, and when the vaccine is unlikely to cause harm. Infection with the Japanese encephalitis virus during pregnancy may cause intrauterine infection and fetal death. Health professionals caring for patients who receive the Japanese encephalitis virus vaccine during pregnancy are encouraged to contact Valneva USA, Inc by telephone at 844-349-4276.
Safety and efficacy of Ixiaro have not been established in neonates and infants less than 2 months of age.
Data are limited regarding use of the Japanese encephalitis virus vaccine during breast feeding and its' excretion in human milk is unknown. The manufacturer recommends caution when administering to nursing mothers; however according to the Advisory Committee on Immunization Practices (ACIP), inactivated vaccines pose no risk to breast-feeding mothers or their infants. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Limited data indicate that geriatric patients have a similar response to Ixiaro. Among 24 patients at least 65 years of age, 95.8% seroconverted. Vaccination may be desirable, as advanced age may be a risk factor for developing symptomatic illness after infection.
General Dosing Information
-Advise patients to take personal precautions to reduce exposure to mosquito bites. Protective clothing, insect repellents, and outdoor activity avoidance, especially during twilight periods and at night may be appropriate.
-Immunization is advised for all laboratory workers with potential exposure to infectious Japanese encephalitis (JE) virus. Infection may occur via inhalation of aerosolized virus or via percutaneous delivery such as from a needle stick. Vaccine-derived immunity from such exposures is not established but is presumed for percutaneous exposure.
-Consider immunization for persons planning to reside in areas where JE is endemic or epidemic, longer-term (greater than 1 month) travelers to JE-endemic areas, and frequent travelers to JE-endemic areas. Consider the JE vaccine for shorter-term (less than 1 month) travelers with an increased risk for JE based on planned travel duration, season, location, activities, and accommodations.
-Immunization is not recommended for short-term travelers whose visit is restricted to urban areas or times outside of a well-defined JE virus transmission season.
For Japanese encephalitis prophylaxis:
Intramuscular dosage (Ixiaro):
NOTE: Receipt of only 1 dose may lead to a suboptimal response. Also, receipt of both doses may not protect 100% of patients and will not protect against encephalitis caused by viruses or pathogens other than the Japanese encephalitis virus.
Geriatric: 0.5 mL IM, followed by a second 0.5 mL IM injection administered 28 days later. Administer the second dose at least 1 week before potential exposure to the Japanese encephalitis virus. Individuals with ongoing or repeated exposure may receive a 0.5 mL IM booster injection (3rd dose) if more than 11 months have elapsed since completion of the primary 2 dose series. Data is not available on the response to a booster dose administered more than 2 years after the primary series. Clinical trial data show high rates of seroprotection for at least 6 years after a booster dose; no longer-term study data are available.
Adults 18 to 65 years of age: 0.5 mL IM, followed by a second 0.5 mL IM injection administered either 7 or 28 days later. Administer the second dose at least 1 week before potential exposure to the Japanese encephalitis virus. Individuals with ongoing or repeated exposure may receive a 0.5 mL IM booster injection (3rd dose) if more than 11 months have elapsed since completion of the primary 2 dose series. Data is not available on the response to a booster dose administered more than 2 years after the primary series. Clinical trial data show high rates of seroprotection for at least 6 years after a booster dose; no longer-term study data are available.
Children and Adolescents 3 to 17 years: 0.5 mL IM, followed by a second 0.5 mL IM injection administered 28 days later. Administer the second dose at least 1 week before potential exposure to the Japanese encephalitis virus. Individuals with ongoing or repeated exposure may receive a 0.5 mL IM booster injection (3rd dose) if more than 11 months have elapsed since completion of the primary 2 dose series. Data is not available on the response to a booster dose administered more than 2 years after the primary series. Clinical trial data show high rates of seroprotection for at least 6 years after a booster dose; no longer-term study data are available.
Children 14 months to 2 years: 0.25 mL IM, followed by a second 0.25 mL IM injection administered 28 days later. Administer the second dose at least 1 week before potential exposure to the Japanese encephalitis virus. Individuals with ongoing or repeated exposure may receive a 0.25 mL IM booster injection (3rd dose) if more than 11 months have elapsed since completion of the primary 2 dose series. Data is not available on the response to a booster dose administered more than 2 years after the primary series. Clinical trial data show high rates of seroprotection for at least 6 years after a booster dose; no longer-term study data are available.
Infants and Children 2 to 13 months: 0.25 mL IM, followed by a second 0.25 mL IM injection administered 28 days later. Administer the second dose at least 1 week before potential exposure to the Japanese encephalitis virus. Safety and immunogenicity of a booster dose have not been established.
Maximum Dosage Limits:
-Adults
0.5 mL/dose IM.
-Geriatric
0.5 mL/dose IM.
-Adolescents
0.5 mL/dose IM.
-Children
>= 3 years: 0.5 mL/dose IM.
1-2 years: 0.25 mL/dose IM.
-Infants
2-11 months: 0.25 mL/dose IM.
< 2 months: Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Albuterol; Budesonide: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Betamethasone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Bimekizumab: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to vaccines. When feasible, administer indicated vaccines at least two weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Budesonide: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Budesonide; Formoterol: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Corticosteroids (systemic): (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Corticotropin, ACTH: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Cortisone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Deflazacort: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Deucravacitinib: (Moderate) Patients receiving immunosuppressant medications may have a diminished vaccine response. When feasible, administer indicated vaccines at least two weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dexamethasone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Elivaldogene Autotemcel: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to non-live vaccines. When feasible, administer indicated vaccines at least six weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Hydrocortisone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Methylprednisolone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ocrelizumab: (Moderate) Administer all non-live vaccines at least 2 weeks before ocrelizumab initiation, whenever possible. Ocrelizumab may interfere with the effectiveness of non-live virus vaccines. Attenuated antibody responses to tetanus toxoid-containing vaccine, pneumococcal polysaccharide and pneumococcal conjugate vaccines, and seasonal influenza vaccine were observed in patients exposed to ocrelizumab at the time of vaccination during an open-label study. Infants born to mothers exposed to ocrelizumab during pregnancy may receive non-live vaccines as indicated before B-cell recovery; however, consider assessing the immune response to the vaccine. ACIP recommends that patients receiving any vaccination during immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated a minimum of 3 months after discontinuation of therapy. Passive immunoprophylaxis with immune globulins may be indicated for immunocompromised persons instead of, or in addition to, vaccination.
Ofatumumab: (Major) Administer all needed non-live vaccines according to immunization guidelines at least 2 weeks before initiation of ofatumumab. Ofatumumab may interfere with the effectiveness of inactivated vaccines due to its actions, which cause B-cell depletion.
Prednisolone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Prednisone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Satralizumab: (Major) Administer all non-live vaccines according to immunization guidelines at least 2 weeks before initiation of satralizumab.
Siponimod: (Moderate) Administer all non-live vaccines at least 2 weeks before siponimod initiation, whenever possible. Vaccines may be less effective if given during siponimod treatment. Patients should be considered unimmunized if vaccinated within a 14-day period before starting immunosuppresive therapy or during immunosuppressive therapy, and should they be revaccinated at least 3 months after therapy is discontinued if immune competence is restored.
Triamcinolone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ublituximab: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to non-live vaccines. When feasible, administer indicated vaccines at least two weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Vamorolone: (Moderate) Patients receiving high-dose corticosteroid therapy may have a diminished response to vaccines. High-dose corticosteroid therapy is generally defined as a dose of at least 20 mg/day of prednisone or equivalent (or 2 mg/kg/day for patients weighing less than 10 kg) for at least 14 consecutive days. When feasible, administer indicated vaccines at least 4 weeks before planned high-dose corticosteroid therapy or wait at least 2 weeks after discontinuation. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving high-dose corticosteroids about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Receipt of the Japanese encephalitis virus vaccine induces antibody production. The antibodies neutralize live Japanese encephalitis virus. Neutralizing antibodies are measured by a 50% plaque reduction neutralization test (PRNT50), with a PRNT50 titer of at least 1:10 being a reasonable correlate for protection. As determined 28 days after the last dose, a titer of at least 1:10 (seroconversion) was obtained by 96.4% of adult Ixiaro recipients and 99.2-100% of pediatric recipients (depending on age). Two doses are required for most patients; 28 days after the first dose, only 39.8% of adults had seroconverted whereas 97.3% seroconverted 7 days and 28 days after dose 2.
In most patients, neutralizing antibodies persist for at least 6 months after completion of the 2-dose Ixiaro series. In one study, the percentage of adults who maintained the titer threshold was 95% at 6 months, 83.4% at 12 months, 81.8% at 24 months, and 84.9% at 36 months. In another study the results were not as favorable, with only 58.3% and 48.3% of adults maintaining a titer of at least 1:10 at 11 and 23 months, respectively, after completion of the primary series. Based on this data, a booster dose is recommended for patients ages 17 years and older who have completed the primary series more than 1 year prior and who continue to be at risk of exposure; immunogenicity of the booster has not been established in patients less than 17 years of age.
The Japanese encephalitis virus vaccine (Ixiaro) is administered intramuscularly.
-Route-Specific Pharmacokinetics
Intramuscular Route
Twenty-eight days after the last dose of Ixiaro, 96.4% of recipients (352/365) achieved protective immunity as evident by a 50% plaque-reduction neutralization titer (PRNT50) >/= 1:10. The geometric mean titer at the same time point was 243.6 (95% CI, 216.4-274.1). Ixiaro was administered IM on days 0 and 28. Another study evaluated the efficacy of a single booster dose administered 14 months after completion of the primary series in 198 adults. The proportion of subjects achieving PRNT50 >/= 1:10 at time points day 0, day 28, month 6, and month 12 were 69.2%, 100%, 98.5%, and 98.5%, respectively.
-Special Populations
Pediatrics
An open-label study was conducted in the Philippines to evaluate the immunogenicity of an age-appropriate, 2-dose Ixiaro series in 396 healthy pediatric patients (0.25 ml/dose IM for ages 2 months to < 3 years; 0.5 ml/dose IM for ages 3-17 years). To determine protective immunity, 50% plaque-reduction neutralization titers (PRNT50) and geographic mean titers were measured at baseline, 28 days after the second dose (day 56), and 6 months after the second dose (month 7). The percentage of patients achieving a PRNT50 >/= 1:10 increased from 0-45.7% (depending on age) at baseline to 99.2-100% and 85.5-100% at day 56 and month 7, respectively. Geographic mean titers also increased from 5-13.1 at baseline to 175.6-687.4 at day 56 and 38.9-159.3 at month 7. Infants < 6 months had the highest geometric mean titers at day 56 and month 7, followed by infants 6 to 12 months of age.