STAMARIL PASTEUR

Abbreviated Prescribing Information

See local Prescribing Information for full details prior to prescribing

1. TRADE NAME OF THE MEDICINAL PRODUCT AND PRESENTATION

Stamaril Pasteur is a powder with solvent for single-dose suspension for injection (0.5 mL), contains attenuated yellow fever virus, 17 D-204 strain, cultured on chick embryos. The other components for the powder are stabilizer medium containing lactose, sorbitol E420, L-histidine hydrochloride, L-alanine, sodium chloride, potassium chloride, disodium phosphate dihydrate, Potassium dihydrogen phosphate, Calcium chloride, Magnesium sulphate, The component for Solvent: Sodium chloride, Water for injection

2. THERAPEUTIC INDICATIONS

This medicine is indicated in the prevention of yellow fever for travelers to area where there is a persisting or periodical risk of yellow fever transmission. Yellow fever vaccination should not be prescribed for individuals who are not risk of exposure to infection.

3. POSOLOGY AND METHOD OF ADMINISTRATION

Posology

Primary vaccination

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.

Adults and children aged 9 months and over. A single dose of 0.5 ml of reconstituted vaccine.

Re-vaccination:

The duration of protection is expected to be at least 10 years and may be a life-long protection.

In accordance with WHO recommendations, the validity of a certificate of vaccination against yellow fever shall extend for the life of the person vaccinated. However, re-vaccination may be needed in some individuals who had an insufficient immune response after their primary vaccination if they continue to be at risk for yellow fever virus infection, or in certain travellers to high risk areas of yellow fever virus infection.

Method of administration

It is preferable that the vaccine is injected by the subcutaneous route. Intramuscular injection may be performed if this is in accordance with applicable official recommendations.

For intramuscular use the recommended injection sites are the ac aspect of the thigh in children less than 12 months of age, the anterolateral aspect of the thigh (or the deltoid muscle if muscle mass is adequate) in children 12 months through 35 months of age or the deltoid muscle in children from 36 months of age onwards and adults.

DO NOT INJECT INTRAVASCULARY.

4. CONTRA-INDICATIONS

- Hypersensitivity reaction to eggs, chicken proteins or to any component of STAMARIL PASTEUR

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

- Immunosuppression, whether congenital, idiopathic or acquired. This includes individuals receiving immunosuppressive therapies, such as treatment with high-dose systemic steroids (for example, a daily dose of 20 mg or 2 mg/kg body weight of prednisone or the equivalent for 2 weeks or more or a daily dose of 40 mg or more of prednisone for more than one week), any other medicinal product including biological products with known immunosuppressive properties, radiotherapy, cytotoxic drugs or any other situation that may cause immunodepression.

- History of thymus dysfunction (including myasthenia gravis, thymoma)

- Thymectomy (regardless of cause).

- Symptomatic HIV infection

- Asymptomatic HIV infection when accompanied by evidence of impaired immune function

- Age less than 9 months

- Moderate severe febrile illness or acute illness.

5. SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE

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 PASTEUR should be administered only to persons who are/will be at risk of infection with yellow fever virus or who must be vaccinated to comply with international health regulations.

Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection.

DO NOT INJECT INTRAVASCULARLY

Because intramuscular injection can cause injection site haematoma, STAMARIL PASTEUR should not be given by the intramuscular route to persons with any bleeding disorder, such as haemophilia or thrombocytopenia, or to persons on anticoagulant therapy. The subcutaneous route of administration should be used instead

Yellow fever vaccine associated neurotropic disease (YEL-AND)

Very rarely, YEL-AND has been reported following vaccination, with sequel or with fatal outcome in some cases. To date, most of cases of YEL-AND have been reported in primary vaccinees with an onset within 30 days of vaccination. The risk to be higher in those aged over 60 years and below 9 months of age. Congenital or acquired immunodeficiency has also been recognized as a predisposing risk factor. However, YEL-AND cases have also been reported in persons without identified risk factors. The vaccinated persons must be informed of the need to request a medical opinion if they feel, after vaccination, any symptoms indicative of YEL-AND such as high fever together with headache or confusion, personality change, or if they feel extreme fatigue, neck stiffness, seizures, loss of movement or feeling in part or all of the body

Yellow fever vaccine-associated viscerotropic disease (YEL-AVD)

Very rarely, YEL-AVD resembling fulminant infection by wild-type virus has been reported following vaccination. To date, most cases of YEL-AVD have been reported in primary vaccines with an onset within 10 days of vaccination. The risk appears to be higher in those aged over 60 years although cases have also been reported in other age groups. Thymectomy or history of thymus dysfunction has also been recognized as a predisposing risk factor. However, YEL-AVD cases have also been reported in persons without identified risk factors. The vaccinated persons must be informed of the need to request a medical opinion if they feel, after vaccination, any symptoms indicative of YEL-AVD such as fever, myalgia, fatigue, headache or hypotension, because these symptoms can potentially rapidly progress to liver dysfunction with jaundice, muscle cytolysis, thrombocytopenia and acute respiratory and renal failure.

Immunosuppressed persons

STAMARIL PASTEUR must not be administered to immunosuppressed persons. Therefore, vaccination should be delayed until the immune function has recovered. In patients who have received systemic corticosteroids for 14 days or more, it is advisable to delay vaccination until at least one month after completing the course.

HIV infection

STAMARIL PASTEUR must not administered to persons with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function.

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.

Age

Persons aged 60 years and older may have an increased risk of serious and potentially fatal adverse reactions (including systemic and neurological reactions persisting more than 48 hours, YEL-AVD and YEL-AND) when compared to other age groups. Therefore, the vaccine should only be given to those who visit areas where there is a risk of yellow fever transmission at the time of travel.

Transmission

There are few reports suggesting that transmission of Yellow Fever vaccine virus may occur from nursing mothers, who received Yellow Fever vaccine postpartum, to the infant. Following transmission, the infants may develop yellow fever vaccine associated neurotropic disease (YEL-AND) from which the infants recover. As with any vaccine, vaccination with STAMARIL PASTEUR may not protect 100% of vaccinated individuals.

6. INTERACTIONS

STAMARIL PASTEUR 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 PASTEUR, each vaccine should injected into a separate site (preferably a separate limb). This vaccine may be administered at the same time as measles vaccine if this is in accordance with official recommendations. It may be administered at the same time as vaccines containing typhoid Vi capsular polysaccharide and/or inactivated hepatitis A virus.

STAMARIL PASTEUR must not be administered to persons who are receiving immunosuppressant therapies, radiotherapy, cytotoxic agents or any other situation that may cause immunodepression. It can induce false positive results with laboratory and/or diagnostic tests for other flavivirus related diseases such as dengue or Japanese encephalitis

7. PREGNANCY AND LACTATION

Pregnancy:

There is generally no indication for vaccinating women during pregnancy. No animal reproduction studies have been conducted with STAMARIL PASTEUR and potential risk for humans is unknown. Data on a limited number of exposed pregnancies indicate no adverse effects of STAMARIL PASTEUR on pregnancy of the health of the fetus/newborn child. Nevertheless, STAMARIL PASTEUR is a live attenuated vaccine, it should not be given during pregnant women only when clearly needed and only after careful consideration of the potential risks and benefits. Pregnancy should be avoided in the month after the vaccinations.

Lactation:

As there is a probable risk of transmission of the vaccine virus strain to the infants from breast- feeding mothers, STAMARIL PASTEUR should not be given to nursing mothers unless when clearly needed such as during an outbreak control and following an assessment of the risks and benefits. and only if the potential benefits to the mother are higher than the potential risks, including those for the breastfed child. In the case where vaccination is needed, it is recommended to discontinue breast-feeding for at least 2 weeks after vaccination.

Fertility

No animal fertility studies have been conducted with STAMARIL PASTEUR and no fertility data are available in humans.

8. EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

No studies on the effects on the ability to drive or use machine have been performed.

9. UNDESIRABLE EFFECTS

a. Summary of the safety profile

In the most representative study in general population, the most frequently reported reactions (between 12% and 18% of subjects) were cephalalgia, asthenia, injection site pain and myalgia. In the most representative study in toddler population, the most frequently reported reactions (between 32% and 35% of toddlers) were irritability, crying and appetite loss. Adverse reactions usually occurred within the first three days following vaccination except fever, which occurred between Day 4 and Day 14.

These reactions usually lasted for not more than 3 days.

Both local and systemic reactions were usually of mild intensity; however at least one severe injection site reaction was reported in 0.8% of subjects in general population and in 0.3% of toddlers and at least one severe systemic reaction was reported in 1.4% of subjects in general population and 4.9% in toddlers.

b. Tabulated list of adverse reactions

The table below summarises the frequencies of the adverse reactions that were recorded following vaccination with STAMARIL during clinical studies and worldwide post-marketing experience

Metabolism and nutrition disorders

Very common: Appetite loss

Nervous System Disorders

Very Common: Drowsiness, Cephalalgia

Gastrointestinal disorders

Very common : vomiting

Common : nausea

Skin and Subcutaneous tissue Disorders

Common : rash

Musculoskeletal and Connective Tissue Disorders

Very common : Myalgia

Common : Arthralgia

General Disorders and Administration Site Conditions

Very common : Irritability, Crying, Fever†, Asthenia, Injection site pain/tenderness

Common : Injection site erythema/redness, Injection site haematoma, Injection site induration; Injection site oedema/swelling

For uncommon, rare and very rare side effects see full prescribing information

c. Description of selected adverse reactions

Cases of neurotropic disease (known as YEL- AND), some of which have had a fatal outcome, have been reported to occur within 30 days following vaccination with STAMARIL PASTEUR, and other yellow fever vaccines. YEL-AND may manifest either as an encephalitis (with or without demyelination), or as a neurobiological disease affecting the peripheral nervous system (for example Guillain-Barré syndrome). Encephalitis usually starts with high fever with cephalalgia that may progress to encephalopathy. YEL-AND affecting the peripheral nervous system manifests generally with bilateral weakness of the limbs, or peripheral paresis of the cranial nerves with reduction or disappearance of tendon reflexes. Neurological diseases not fulfilling the YEL-AND criteria have been reported. The manifestations may include cases of aseptic meningitis or seizures not associated with focal neurological signs.

Cases of viscerotropic disease (known as YEL- AVD and formerly described as “Febrile Multiple Organ-System Failure”) have been reported following vaccination with STAMARIL PASTEUR, and other yellow fever vaccines, some of which have been fatal. In the majority of cases reported, the onset of signs and symptoms was within 10 days after the vaccination. Initial signs and symptoms are non-specific and may include fever, myalgia, fatigue, cephalalgia and hypotension, potentially progressing quickly to liver dysfunction with jaundice, muscle cytolysis, thrombocytopenia and acute respiratory and renal failure .

d. Paediatric population

The safety of STAMARIL PASTEUR in pediatric population has been studied through a clinical study. The following most frequently reported adverse reactions specific to the pediatric population were reported as “very common”: irritability (34.7%), appetite loss (33.7%), crying (32.1%) and drowsiness (22%).

The other adverse reactions reported in toddlers were also reported from studies in general population:

• Injection site pain (17.6%), fever (16.5%) and vomiting (17.1%) were reported as “very common” in toddlers.

• Injection site erythema (9.8%) and injection site swelling (4.4%) were reported as “common” in toddlers

e. Additional information on special population

Congenital or acquired immunodeficiency has been recognized as a potential risk factor for serious adverse events, including YEL-AND

Age of more than 60 years has been recognized as a potential risk factor for YEL- AVD and YEL-AND.

Age below 9 months (including infants exposed to vaccine through breast-feeding) has been recognized as a potential risk factor for YEL-AND.

A medical history of thymus dysfunction or thymectomy or have been recognized as a predisposing factor for YEL- AVD.

10. OVERDOSE

Cases of administration of more than the recommended dose (overdose) have been reported with STAMARIL PASTEUR. When adverse reactions were reported, the information was consistent with the known safety profile of STAMARIL PASTEUR described in section Undesirable effects.

11. PHARMACOLOGICAL PROPERTIES

Protective immunity appears from about 10 days after vaccination, is expected to be at least 10 years and may be life-long.

In clinical studies in adults, it has been shown that 28 days following vaccination with STAMARIL PASTEUR seroconversion rates of 93% and 100% were obtained.

In a clinical study involving 337 toddlers aged 12 to 13 months the yellow fever seropositivity rates 28 days post injection of STAMARIL PASTEUR were 99.7% (98.5; 100.0) and the Geometric Mean Titres were 423 (375; 478).

ATC Code: J07BL01.

Presentation: 1 box, 1 vial of powder + 1 pre-filled syringe 0.5 ml of solvent

(DKI1059702744A1)

This information is intended for Health Care Professional only. See local product information for full details information