Yellow Fever vaccine (English)

MINISTRY of health and welfare of the Russian Federation

INSTRUCTION*

on application of Yellow Fever Vaccine, live freeze-dried,

lyophilizate for preparing the solution for intramuscular/subcutaneous injections

The vaccine is freeze-dried virus-containing suspension of SPF (specific pathogen free) chick embryo tissues, infected with attenuated Yellow Fever virus, strain 17D. The final form of the vaccine is a hygroscopic porous tablet of light pink color. The vaccine meets WHO requirements (WHO, TRS No. 872, Geneva 1998).

A single dose of the vaccine contains:
Volume	0.5 ml
Yellow Fever Virus	no less than 1,000 LD₅₀ or 1,600 PFU
Lactose	20 mg
Sorbitol	10 mg
L-hystidin	1.2 mg
L-alanin	0.7 mg
The vaccine contains neither preservatives nor antibiotics

Diluent composition: water for injection

Immune & biological properties

The vaccine injected stimulates immunity against Yellow Fever virus within the period of no less than 10 years.

Purpose

Prophylaxis of yellow fever in children since nine (9) months of age and in adults visiting regions enzootic for yellow fever or persons dealing with live causative agent of the disease.

Administration and Immunization Schedule

Application method and dosage

The vaccine is injected with a syringe preferably through intramuscular administration, although, subcutaneous route is an alternative, under an outer angle of a shoulder blade or into deltoid muscle in a dose of 0.5 ml to all age groups since nine (9) months onwards and not later than 10 days before their departure to the endemic region.

If necessary, the repeated vaccination is carried out with the same dose 10 years after the first inoculation.

The vaccine contained in cracked ampoules, in ampoules with damaged label, and/or in the case of alteration of physical properties (deformation of the tablet: the porous mass of light pinky colour becomes half-transparent, melted and showing a sharp volume reduction; non-homogeneity of the preparation reconstituted, etc.), expired shelf life, stored or shipped under wrong storage conditions is forbidden for use and has to be discarded.

Unsealing the ampoules as well as vaccination procedure has to be carried out under strict aseptic conditions.

Full contents of the ampoule with the diluent are added into the ampoule with freeze-dried vaccine in order to reconstitute the vaccine. The vaccine should be completely dissolved within 5 minutes after adding the diluent. The dissolved vaccine is a homogeneous opaque liquid of yellowish-pink color. Ten to fifteen minutes later the ampoule is shaken thoroughly and a single immunizing dose of the vaccine is gathered into a syringe.

Because of sensitivity to ultraviolet light, the vaccine must be protected from sunlight. Once the vaccine has been reconstituted, it should be used the same day (preferably immediately but by no means beyond six hours after reconstitution), and only then if the vaccine in the ampoule has been maintained at 2-8°C in the place protected from sunlight. If not used immediately after reconstitution, the vaccine should be kept on ice to maintain its temperature between 2-8°C. Any opened ampoule containing the rest of vaccine reconstituted at the end of a session (six hours after reconstitution) should be discarded.

The inoculation of the vaccine is to be registered in special registration form bearing name of the preparation, date of inoculation, dosage, manufacturer's name, vaccine lot number, short description of adverse reaction(s) after the inoculation (if any).

The diluent supplied by the manufacturer is specially designed for use with this vaccine. Only this diluent should be used in order to reconstitute the vaccine. Do not use diluents supplied with other vaccines or those produced by other manufacturers. Using an incorrect diluent may result in damage to the vaccine's properties and/or serious adverse reactions in vaccinee(s). The diluent is not allowed to be frozen but should be cooled up to 2-8°C before reconstitution of the vaccine. The vaccine should not be reconstituted using another (liquid) vaccine as a solvent.

Adverse reactions

Occasionally, local and/or generalized adverse reactions could be observed after the vaccine inoculation.

The local reactions such as hyperemia and oedema (no more than 2.5 cm in diameter) may appear within 12-24 hours and disappear 2-3 day after the injection. In extremely rare cases a gelosis of cellular tissue accompanying with itchiness and enlargement of lymph nodes may be observed.

The generalized adverse reaction such as increase of the body temperature up to 38.5ºC, indisposition, giddiness, headache, chilly sensation can be observed within the period of 4 to 10 days after the inoculation. As a rule, the duration of general reaction does not exceed three days.

Occasionally, the complications of allergic character are possible. In this regard, any vaccination station should be equipped with anti-shock medicines & equipment, and each the vaccinee is obliged to be under medical observation for no less than 30 minutes after injection.

Persons susceptible to allergic reactions are recommended to be treated with oral anti-histamine preparations in doses depending upon their age 2-4 days prior to the vaccination and within further 2-4 days.

Contraindications

· Allergic response to chicken proteins in anamnesis.

· Primary (inherent) immune deficiency.

· Immune deficiency of an infectious nature. Yellow Fever vaccine can be given to asymptomatic HIV-infected patients, but should not be given to symptomatic HIV-infected persons. This advice may be modified if the risk from yellow fever infection is greater than from the theoretical risk of the vaccine.

· Secondary (adventitious) immune deficiency induced by immune suppressing therapy, anti-metabolites, X-ray therapy. In such cases the vaccination should be carried out not earlier than 12 months after the patient’s recovery (finishing the treatment).

· Acute infectious and non-infectious diseases or flare-up of chronic diseases. In such cases the vaccination should be carried out not earlier than 1 month after the patient’s recovery (remission).

· Pregnancy (for persons leaving for endemic regions).

· The vaccine is contraindicated in children aged under 6 months and is not recommended for those aged 6 to 9 months, except during epidemics when the risk of YF virus transmission may be very high and the risk of disease would outweigh the small theoretical safety risk from immunization.

In order to reveal possible contraindications the physician interviews and surveys each vaccinee with thermometry at the day of an immunization. The final decision on need for vaccination to certain resident groups (pregnant women; patients afflicted with chronic diseases, malignant illnesses of blood as well as tumors, etc.), inhabiting YF endemic region depends upon the rate of risk of being infected.

Interaction with another vaccines and biologicals

The yellow fever vaccine can be given to children since 9 months of age safely and effectively at the same visit as measles vaccine, DT, Td, TT, BCG, polio (OPV or IPV), hepatitis B, and Haemophilus influenzae type b vaccines and vitamin A supplementation.

However, in order to maximize the protective effect for children before 15 years old it is recommended to observe, if possible an interval of no less than 2 months between vaccination against yellow fever, and previous vaccinations against other diseases. For those aged over 15 years old it is allowed to combine (within the same day) administration of the Yellow Fever vaccine with another vaccines included to the National Calendar of Preventive Vaccination, provided that inoculation of the vaccines is carried out into different parts of the body. However, it has to be taken into consideration that in such situation the immune response to one or more of the antigens inoculated may be reduced.

It is not recommended to inoculate the Yellow Fever vaccine at the same day with the vaccines used to prevent cholera and/or paratyphoid (type A and B). In such a case, the observance of 3-month interval between those vaccinations is recommended for maximum protective efficacy.

Production form

The vaccine is supplied in ampoules in a set with the diluent together with the leaflet. Two packaging forms are available:

Form 1. The vaccine and diluent are packed into two different packages: the vaccine in ampoules containing 2, 5 or 10 doses each, 10 ampoules in cardboard box; the diluent (water for injection) in ampoules containing 1.25 ml, 3.0 ml or 6.0 ml each respectively, 10 ampoules in box.

Form 2. The vaccine and diluent are packed together into single package: the vaccine in ampoules containing 2, 5 or 10 doses, the diluent (water for injection) in ampoules containing 1.25 ml, 3.0 ml or 6.0 ml respectively; 5 ampoules of the vaccine plus 5 ampoules of the diluent in cardboard box.

Conditions of storage and transportation

Transportation by all types of transport at the temperature of 2-8°C is allowed (as per the “Guidelines on international packaging and shipping of vaccines”, WHO/IVB/05.23., and Sanitary Regulations 3.3.2.1248-03). Long-distance transportation of the vaccine packed into insulated boxes equipped with ice-packs is allowed within 48 hours.

The vaccine is to be stored at the temperature of 2-8°C in the place inaccessible for children.

The diluent can be stored either in refrigerator (2-8°C) or at room temperature (20-25°C) if packed separately from the vaccine. If stored at 20-25°C the diluent has to be cooled to 2-8°C before reconstitution of the vaccine. The freezing of the diluent is not allowed.

Shelf life is 2 years if stored at the temperature of 2-8 C°. Use of the expired vaccine is forbidden!

Condition of distribution: to be shipped to medical & prophylactic institutions only!

Any case of an adverse reaction appearance after inoculation of the vaccine as well as any case of increased reactogenicity is to be reported urgently to the National research institute for Standardization and Control of Medical Biological Preparations named after L. А. Tarasevich of Ministry of Health and Welfare of the Russian Federation (41, Sivtsev-Vrazhek Street, Moscow 121002, Russia, phone: +495-2413922) and/or to the manufacturer with consequent submission of the medical documentation.