Japanese Encephalitis Virus Vaccine (Systemic )


VA CLASSIFICATION
Primary: IM100

Commonly used brand name(s): Je-Vax.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Immunizing agent (active)—

Indications

Accepted

Japanese encephalitis (prophylaxis)—Japanese encephalitis virus vaccine (JE vaccine) is indicated for immunization against Japanese encephalitis (JE).
—Immunization with JE vaccine should be considered for adults and children one year of age and older who plan to reside in or travel to areas where JE is endemic or epidemic during a transmission season. JE vaccine is not recommended for all persons traveling to or residing in Asia. The incidence of JE in the location of intended stay, the conditions of housing, the nature of activities, the duration of stay, and the possibility of unexpected travel to high-risk areas are factors that should be considered in the decision to administer JE vaccine. In general, JE vaccine should be considered for use in persons spending a month or longer in epidemic or endemic areas during the transmission season, especially if travel will include rural areas. Depending on the epidemic circumstances, JE vaccine should also be considered for persons spending less than 30 days if their activities, such as extensive outdoor activities in rural areas, place them at particularly high risk for exposure. Immunization with JE vaccine is not intended to take the place of the usual precautions to reduce exposure to mosquito bites.
—Immunization with JE vaccine also is recommended for all laboratory workers who may be exposed to infectious JE virus. {01} {02}


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Following subcutaneous administration, JE vaccine induces the formation of protective neutralizing antibodies. {01} {02}


Protective effect

The precise relationship between antibody level and efficacy has not been established. {01}

In a U.S. Army study using 538 volunteers, 100% of recipients demonstrated neutralizing antibodies 2 months after immunization with 3 doses of JE vaccine. {01} In another study, substantial neutralizing antibody titers were elicited by 3 doses of JE vaccine in more than 90% of U.S. travelers without a history of prior JE immunization or prior exposure to JE. {01} However, less than 80% of U.S. travelers receiving 2 doses of JE vaccine demonstrated neutralizing antibodies, and the neutralizing antibody levels declined substantially in most of these recipients within 6 months. {01} {02}


Time to protective effect

An immune response is thought to occur within 10 days. {01} {02}


Duration of protective effect

At least 2 years in persons receiving 3 doses of JE vaccine. Protection for longer than 2 years has not yet been determined. {01} {02}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to thimerosal, formaldehyde, gelatin, or rodent protein or neural products may be sensitive to JE vaccine also, since these products are used in the production of JE vaccine. {01} {02}

Carcinogenicity/Mutagenicity

No studies have been performed. {01}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans. It is not known whether JE vaccine can cause fetal harm when administered to a pregnant woman. However, JE infection acquired during the first or second trimester of pregnancy may cause intrauterine infection and miscarriage. JE infection acquired during the third trimester of pregnancy has not been associated with adverse effects in neonates. Pregnant women who must travel to an area where the risk of JE infection is high should be immunized only when the risk of infection outweighs the unknown risks to the fetus of immunization with JE vaccine. {01} {02}

Studies have not been done in animals.

FDA Pregnancy Category C {01}.

Breast-feeding

It is not known whether JE vaccine is distributed into breast milk. {01}

Pediatrics

Appropriate studies on the relationship of age to the effects of JE vaccine have not been performed in infants up to 1 year of age. Safety and efficacy have not been established. {01}


Geriatrics


No information is available on the relationship of age to the effects of JE vaccine in geriatric patients; {01} however, advanced age may be a risk factor for the development of symptomatic illness following infection with JE. {01} {02}

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Hypersensitivity to rodent protein or neural products    (JE vaccine is produced from infected mouse brains {01} {02} {03})


» Hypersensitivity to thimerosal{01}{02}
Risk-benefit should be considered when the following medical problem exists
» Urticaria, history of    (persons with this condition appear to have a greater risk of adverse reactions following immunization with JE vaccine and should be cautioned and monitored appropriately {01} {02})




Side/Adverse Effects

Note: Adverse reactions to JE vaccine manifesting as generalized urticaria or angioedema may occur within minutes following immunization. A possibly related reaction has occurred as late as 17 days after immunization. Most reactions occur within 10 days after immunization with the majority occurring within 48 hours. There is no increase in the number or severity of adverse reactions after 1, 2, or 3 doses of JE vaccine. {01} {02} Continued use of this medication is contraindicated when angioedema or generalized urticaria occurs following a dose of JE vaccine. {01} {02}The following serious adverse events have been reported following immunization with JE vaccine; however the etiology of these adverse events is unknown:

   • One case of Guillain-Barré syndrome has been reported in the U.S. since 1984; however, the patient was diagnosed as having mononucleosis 3 weeks before the onset of weakness. {01} {02}
   • One case of urticaria, hepatitis, and respiratory failure occurred one week after dose 2 (the patient had eosinophilia and showed effusion and infiltrates on the chest x-ray). {01}
   • One case of respiratory and renal failure occurred 1 week after a dose of JE vaccine (the patient, a 26-month-old male, had infiltrates on chest x-ray and acid-fast bacilli in sputum). {01}
   • One case of newly diagnosed hypertension occurred in a young adult male presenting with headache several hours after receiving the first dose. {01}
   • Sudden death occurred in a 21-year-old U.S. military person approximately 60 hours after the person received the first dose of JE vaccine. The person had a history of recurrent hypersensitivity and a previous episode of possible anaphylaxis. The person also had received the third dose of plague vaccine approximately 12 to 15 hours prior to death. There was no evidence of urticaria or angioedema. The cause of death was not established during autopsy. {01} {02}
Because of the severity of some of the adverse reactions to JE vaccine, patients should be encouraged to seek medical attention immediately upon onset of any adverse reaction. {01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
angioedema of the face (especially lips), oropharynx, or extremities {01}{02}(swelling of face, lips, eyelids, throat, tongue, hands, or feet)
    
hypotension, severe {01}{02}(severe, unusual tiredness or weakness)
    
urticaria {01}{02}(hives)
    
wheezing or troubled breathing{01}{02}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
tenderness, soreness, redness, or swelling at injection site{01}{02}

Incidence less frequent
    
abdominal pain {01}{02}
    
chills {01}{02}
    
dizziness {01}{02}
    
fever {01}{02}
    
headache {01}{02}
    
itching or skin rash {01}{02}
    
malaise {01}{02}(general feeling of discomfort or illness)
    
myalgia {01}{02}(aches or pains in muscles)
    
nausea or vomiting {01}{02}

Incidence rare
    
erythema multiforme (skin rash)
    
erythema nodosum (skin rash)
    
{01}{02} joint swelling{01}{02}





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Japanese Encephalitis Virus Vaccine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this vaccine
»   Conditions affecting use, especially:
Sensitivity to thimerosal, formaldehyde, gelatin, or rodent protein or neural products





Use in children—Not recommended for use in infants under 1 year of age

Other medical problems, especially a history of urticaria

Proper use of this vaccine
» Importance of receiving all 3 doses of vaccine

» Importance of not traveling out of the country for at least 10 days following the last dose of vaccine

» Proper dosing

Precautions after receiving this vaccine
» Importance of using precautions against mosquito bites


Side/adverse effects
Patients are encouraged to seek medical attention for any side effect that occurs, since a mild-appearing side effect may portend a more serious one

Importance of telling physician about any side effect that occurs after a dose of vaccine; may mean that patient should not receive any more doses of vaccine

Signs of potential side effects, especially angioedema of the face (especially lips), oropharynx, or extremities; severe hypotension; urticaria; or wheezing or troubled breathing


General Dosing Information
Patients should be observed for 30 minutes after immunization with JE vaccine and warned about the possibility of delayed generalized urticaria, often in a generalized distribution, or angioedema of the face (especially lips), oropharynx, or extremities. {01} {02}

Continued use of JE vaccine is contraindicated if angioedema or generalized urticaria occurs following a dose. {01} {02}

The final dose of the immunization series should be administered at least 10 days before international travel, to ensure an adequate immune response and access to medical care in the event of delayed adverse reactions. In addition, patients should be advised to remain in areas where they have ready access to medical care for 10 days after receiving a dose of JE vaccine. Patients should be instructed to seek medical attention immediately upon onset of any reaction. {01} {02}

When time constraints prevent the use of one of the recommended 3-dose schedules, 2 doses, administered 1 week apart, may be used. However, a 2-dose regimen will induce antibody formation in only approximately 80% of recipients, and therefore this regimen should be used only under unusual circumstances. {01} {02}

There are no data supporting the efficacy of prophylactic antihistamines or steroids in preventing JE vaccine–related allergic reactions. {01} {02}

The decision to administer JE vaccine should take into consideration the chance of exposure to the virus and of developing illness, the availability and acceptability of repellents and other alternative protective measures, and the side effects of immunization. {01} {02}

Limited data suggest that diphtheria and tetanus toxoids and pertussis vaccine (DTP and DTaP) may be administered concurrently with JE vaccine. {02} There are no data on the effect of concurrent administration of other vaccines, medications (e.g., chloroquine, mefloquine), or biologicals on the safety and immunogenicity of JE vaccine. {01} {02} In the event that JE vaccine and other vaccines are given concurrently, separate syringes and separate sites should be used. {01}

For treatment of adverse effects
Recommended treatment includes

   • For mild hypersensitivity reaction—Administering antihistamines and, if necessary, glucocorticoids.
   • For severe hypersensitivity or anaphylactic reaction—Administering epinephrine. Antihistamines and/or glucocorticoids may also be administered as required. {02}


Parenteral Dosage Forms

JAPANESE ENCEPHALITIS VIRUS VACCINE INACTIVATED FOR INJECTION

Usual adult and adolescent dose
Japanese encephalitis (prophylaxis)
Subcutaneous, 1 mL, administered on days zero, seven, and thirty. If there are time constraints, an abbreviated schedule of days zero, seven, and fourteen may be used instead. {01} {02} {04} A booster dose of 1 mL may be administered two years after the initial immunization series. {02} {04}


Usual pediatric dose
Japanese encephalitis (prophylaxis)
Infants up to 1 year of age: Safety and efficacy have not been established. {01} {02} {04}

Children 1 to 3 years of age: Subcutaneous, 0.5 mL, administered on days zero, seven, and thirty. If there are time constraints, an abbreviated schedule of days zero, seven, and fourteen may be used instead. {01} {02} {04} A booster dose of 0.5 mL may be administered two years after the initial immunization series. {02} {04}

Children 3 years of age and over: See Usual adult and adolescent dose.{01}{02}{04}


Strength(s) usually available
U.S.—


Less than 50 nanograms of mouse serum protein per 1-mL dose (Rx) [Je-Vax (thimerosal 0.007%, formaldehyde 100 mcg)]{01}

Canada—


Less than 50 nanograms of mouse serum protein per 1-mL dose (Rx) [Je-Vax (thimerosal 0.007%, formaldehyde 100 mcg)]{04}

Packaging and storage:
Store the lyophilized form of the vaccine and the reconstituted form of the vaccine between 2 and 8 °C (36 and 46 °F), unless otherwise specified by manufacturer. Protect from freezing. {01}

Preparation of dosage form:
To reconstitute, use only the diluent provided by the manufacturer. {01}

The entire volume of diluent should be withdrawn into the syringe. All the diluent in the syringe should be injected into the vial of lyophilized vaccine and the vial should be shaken thoroughly. Immediately before withdrawing each dose, the vial should be shaken thoroughly. {01}

Stability:
The reconstituted vaccine should be used within 8 hours. {01}

Auxiliary labeling:
   • Store in refrigerator. {01}
   • Protect from freezing. {01}
   • Discard reconstituted solution if not used within 8 hours. {01}

Note: The date and time of reconstitution should be indicated on the vial if the reconstituted vaccine is not used at once.




Revised: 06/27/1995



References
  1. Je-Vax package insert (Connaught—US), Rev 12/92, Rec 2/93.
  1. Centers for Disease Control and Prevention. Inactivated Japanese encephalitis virus vaccine. Recommendations of the advisory committee on immunization practices (ACIP). MMWR 1993 Jan 8; 42 (RR-1): 1-15.
  1. Panel comment, 5/4/93.
  1. Je-Vax (Connaught). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 30th ed. Ottawa: Canadian Pharmaceutical Association, 1995: 654.
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