CONTENTS

Live attenuated yellow fever virus (avian leucosis-free 17D strain).

PRESENTATION

Vial 1 dose (freeze-dried) + syringe 0.5 mL (diluent) x 1's.

DESCRIPTION

Each dose contains a heat stable freeze-dried suspension of live attenuated yellow fever virus (avian leucosis-free 17D strain) propagated in leucosis-free, chick embryos 1000 mouse LD50 (mini) and special diluent 0.5 mL.

ACTIONS

The vaccine is obtained, according to the WHO standards, by propagating leucosis-free attenuated yellow fever 17D virus (Rockefeller Foundation) in avian leucosis-free chick embryos.

The vaccination certificate will be valid for 10 years, starting 10 days from the vaccination date.

INDICATIONS

Active immunization against yellow fever in persons: Travelling to, passing through or living in an endemic area.

Travelling to any country that requires an International Certificate of Vaccination (ICV) for entry (which may or may not depend on the previous itinerary).

Handling potentially infectious materials (eg, laboratory personnel).

For the minimum age for vaccination of children under special circumstances and guidance for vaccination and other specific patient populations (see Dosage & Administration, Contraindication and Precautions).

In order to comply with vaccine regulations and to be officially recognized, yellow fever vaccines must be administered in an approved World Health Organization (WHO) vaccination center and registered on an ICV. This certificate is valid for 10 years from the 10th day after vaccination and immediately after revaccination.

DOSAGE & ADMINISTRATION

Dosage: Primary Vaccination: Adults and Children >9 months: 0.5 mL of reconstituted vaccine administered as a single dose.

Children <9 months: The vaccine must not be given to children <6 months. Vaccination against yellow fever is not usually recommended in children aged from 6 months up to 9 months except in specific circumstances and in accordance with available official recommendations, in which case, the dose is the same as in older children and adults.

The vaccine should be given at least 10 days before entering an endemic area since protective immunity may not be achieved until at least this time has elapsed.

Elderly: The dose is the same as for adults. However, due to a higher risk of yellow fever vaccine-associated severe and potentially fatal disease in persons from 60 years of age, the vaccine should only be given when it is considered that there is a considerable and unavoidable risk of acquiring yellow fever infection.

Re-Vaccination: Re-vaccination with 1 dose of 0.5 mL is recommended every 10 years in persons considered to be at risk of exposure. International Health Regulations (IHR) require re-vaccination, using the same dose as for primary vaccination, at intervals of 10 years in order to retain a valid certificate.

Administration: It is preferable that the vaccine is injected by the SC route.

IM injection may be performed if this is in accordance with applicable official recommendations.

For IM use, the recommended injection sites are the anterolateral aspect of the thigh in the infants and toddlers (6 months up to 2 years of age) and the deltoid muscle in older children and adults.

Note: Do not inject intravascularly.

CONTRAINDICATIONS

Hypersensitivity reaction to eggs, chicken proteins or to any component of Stamaril.

Serious hypersensitivity reactions (eg, anaphylaxis) after a previous dose of any yellow fever vaccine.

Immunosuppression, whether congenital, idiopathic or as a result of treatment with systemic steroids (greater than the standard dose of topical or inhaled steroids), radiotherapy or cytotoxic drugs.

History of thymus dysfunction (including thymoma, thymectomy).

Symptomatic HIV infection.

Asymptomatic HIV infection when accompanied by evidence of impaired immune function (see Precautions).

Age <6 months (see Dosage & Administration and Precautions).

Current severe febrile illness.

PRECAUTIONS

As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of anaphylaxis or other severe hypersensitivity reaction following administration of the vaccine.

Stamaril should be administered only to persons who are or will be at risk of infection with yellow fever virus or who must be vaccinated to comply with IHR. Before considering administration of yellow fever vaccine, care should be taken to identify those which might be at risk of adverse reactions following vaccination.

Yellow Fever Vaccine-Associated Neurotropic Disease (YEL-AND): Very rarely, YEL-AND has been reported following vaccination, with sequelae or with fatal outcome in some cases. Clinical features have appeared within 1 month of vaccination and include high fever with headache that may progress to include 1 or more of the following: Confusion, encephalitis or encephalopathy, meningitis, focal neurological deficits or Guillain-Barré syndrome. To date, those affected have been primary vaccinees. The risk appears to be higher in those >60 years, although cases have been also reported in younger persons.

Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD): Very rarely, YEL-AVD resembling fulminant infection by wild-type virus has been reported following vaccination. The clinical presentation may include fever, fatigue, myalgia, headache, hypotension, progressing to 1 or more of metabolic acidosis, muscle and liver cytolysis, lymphocytopenia and thrombocytopenia, renal failure and respiratory failure. The mortality rate has been around 60%. To date, all cases of YEL-AVD have been in primary vaccinees with onset within 10 days of vaccination. The risk appears to be higher in those >60 years although cases have also been reported in younger persons. Disease of the thymus gland has also been recognized as a potential risk factor.

Immunosuppressed Persons: Stamaril must not be administered to immunosuppressed persons.If the immunosuppression is temporary, vaccination should be delayed until the immune function has recovered. In patients who have received systemic corticosteroids for >14 days, it is advisable to delay vaccination until at least 1 month after completing the course.

HIV Infection: Stamaril must not be administrated to persons with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function. However, there are insufficient data at present to determine the immunological parameters that might differentiate persons who could be safely vaccinated and who might mount a protective immune response from those in whom vaccination could be both hazardous and ineffective. Therefore, if any asymptomatic HIV-infected person cannot avoid travel to an endemic area, available official guidance should be taken into account when considering the potential risks and benefits of vaccination.

Children Born to HIV Positive Mothers: Children aged at least 6 months may be vaccinated if it is confirmed that they are not infected with HIV.

HIV-infected children aged at least 6 months who are potentially in need of protection against yellow fever should be referred to a specialist paediatric team for advice on whether or not to vaccinate.

Age: Children 6-9 months: Stamaril must not be administered to children before the age of 6 months. Children aged from 6 months up to 9 months should only be vaccinated under special circumstances (eg, during major outbreaks) and on the basis of current official advice.

Sixty Years and Older: Some serious and potentially fatal adverse reactions (including systemic and neurological reactions persisting >48 hrs, YEL-AVD and YEL-AND) appear to occur at higher frequencies after the age of 60 years. Therefore, the vaccine should only be given to those who have a considerable risk of acquiring yellow fever.

Because IM injection can cause injection site haematoma, Stamaril should not be given by the IM route to persons with any bleeding disorder eg, haemophilia or thrombocytopenia, or to persons on anticoagulant therapy. The SC route of administration should be used instead.

Patients with rare hereditary problems of fructose intolerance should not take this vaccine. Use in pregnancy & lactation: Stamaril should be given to pregnant women only when clearly needed and only after careful consideration of the potential risks and benefits.

Although there have been no reports of transmission of vaccine viruses from breastfeeding mothers to infants Stamaril should not be given to nursing mothers unless this cannot be avoided.

ADVERSE REACTIONS

Data from Clinical Studies: Across clinical studies, the most common adverse reactions occurring after vaccine administration were local reactions, reported in approximately 16% of subjects.

The following adverse events are from 1 clinical study in which 106 healthy adult subjects received Stamaril.

The adverse events are ranked under headings of frequency, using the following convention: Very common: ³10%. Common: ³1% and £10%. Uncommon: ³0.1% and £1%.Nervous System Disorders: Very common: Headache.

Gastrointestinal System Disorders: Common: Nausea, diarrhoea, vomiting. Uncommon: Abdominal pain.

Musculoskeletal and Connective Tissue Disorders: Common: Myalgia. Uncommon: Arthralgia.

General Disorders and Administration Site Conditions: Very common: Local reactions (including pain, redness, hematoma, induration, swelling). Common: Pyrexia, asthenia.

Data from Post-Marketing Experience: The following additional adverse events have been reported during post-marketing experience with Stamaril. They are based on spontaneous reporting, therefore, the frequencies are unknown.

Blood and Lymphatic System Disorders: Lymphadenopathy.

Immune System Disorders: Anaphylaxis, angioedema.

Nervous System Disorders: Cases of neurotropic disease (known as YEL-AND), some of which have had a fatal outcome, have been reported following yellow fever vaccination. Yellow fever vaccine-associated neurotropic disease may manifest as high fever with headache that may be progress to include 1 or more of confusion, lethargy, encephalitis, encephalopathy and meningitis.

Other neurological signs and symptoms have been reported and include convulsion, Guillain-Barré syndrome and focal neurological deficits.

Skin and Subcutaneous Tissue Disorders: Rash, urticaria.

General Disorders and Administration Site Conditions: Cases of viscerotropic disease (known as YEL-AVD and formerly described as "Febrile Multiple Organ-System Failure") have been reported following yellow fever vaccinations some of which have been fatal. Yellow fever associated-viscerotropic disease may manifest as fever, fatigue, myalgia, headache and hypotension progressing to 1 or more of metabolic acidosis, muscle and liver cytolysis, lymphocytopenia and thrombocytopenia, renal and respiratory failure.

Additional Information on Special Population: Congenital or acquired immunodeficiency has been identified as a risk factor for neurotropic disease.

Age of >60 years has been identified as a risk factor for YEL-AVD and YEL-AND. A medical history of thymic disease has been identified as a risk factor for YEL-AVD.

INTERACTIONS

Stamaril must not be mixed with any other vaccine or medicinal product in the same syringe. If there is a need to administer another injectable vaccine(s) at the same time as Stamaril, each vaccine should be injected into a separate site (and preferably a separate limb).

Stamaril may be administered at the same time as measles vaccine if this is in accordance with official recommendations.

Stamaril may be administered at the same time as vaccines containing typhoid Vi capsular polysaccharide and/or inactivated hepatitis A virus.

Stamaril must not be administered to persons who are receiving immunosuppressant therapy (eg, cytotoxic agents, systemic steroids, greater than standard dose of topical or inhaled steroids or other agents).

CAUTIONS FOR USAGE

The reconstituted vaccine should be kept out of direct sunlight and used immediately.

STORAGE

Stamaril, a heat stable vaccine should be kept at a temperature ranging between 2°C and 8°C. Do not freeze.