Ixiaro

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Ixiaro

Classes

Japanese Encephalitis Vaccines

Administration

 
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.

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.

Adverse Reactions
Severe

anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

Moderate

erythema / Early / 9.6-19.6
edema / Delayed / 4.2-4.2
wheezing / Rapid / Incidence not known
dyspnea / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
neuritis / Delayed / Incidence not known

Mild

injection site reaction / Rapid / 32.6-48.5
fatigue / Early / 11.3-33.9
headache / Early / 11.1-30.4
anorexia / Delayed / 16.1-16.1
myalgia / Early / 15.6-16.1
pharyngitis / Delayed / 4.7-15.2
nausea / Early / 6.6-14.3
arthralgia / Delayed / 5.4-5.4
pruritus / Rapid / 3.8-3.8
fever / Early / 3.2-3.2
infection / Delayed / 1.7-1.7
diarrhea / Early / 1.5-1.5
rhinitis / Early / 1.4-1.4
vomiting / Early / 1.4-1.4
rash / Early / 1.3-1.3
back pain / Delayed / 1.3-1.3
cough / Delayed / 1.2-1.2
weakness / Early / Incidence not known
dizziness / Early / Incidence not known
urticaria / Rapid / Incidence not known
paresthesias / Delayed / Incidence not known
syncope / Early / Incidence not known

Common Brand Names

Ixiaro

Dea Class

Rx

Description

Inactivated viral vaccine that induces antibodies that neutralize live virus
Used for prevention of Japanese encephalitis
Ixiaro is only vaccine available in the US to help prevent Japanese encephalitis

Dosage And Indications
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.[48500] 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.[64479]

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.[48500] 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.[64479]

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.[48500] 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.[64479]

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.[48500] 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.[64479]

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.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

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.
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.
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.
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.
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.

How Supplied

Ixiaro Intramuscular Inj Susp: 1dose, 6mcg

Maximum Dosage
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.

Mechanism Of Action

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.

Pharmacokinetics

The Japanese encephalitis virus vaccine (Ixiaro) is administered intramuscularly.

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.

Pregnancy And Lactation
Pregnancy

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.

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.