Stamaril

Yellow fever virus (produced in specified pathogen-free chick embryos) 17 D-204 strain (live, attenuated).

After reconstitution, 1 dose (0.5 ml) contains: Yellow fever virus¹, 17D-204 strain (live, attenuated) not less than 1000 IU.
¹produced in specified pathogen-free chick embryos.
Excipient with known effect: This product contains about 8 mg of sorbitol (E420) per dose.
Excipients/Inactive Ingredients: Powder: Lactose, Sorbitol E420, L-Histidine hydrochloride, L-Alanine, Sodium chloride, Potassium chloride, Disodium phosphate dihydrate, Potassium dihydrogen phosphate, Calcium chloride, Magnesium sulphate.
Solvent: Sodium chloride, Water for injections.

Pharmacotherapeutic group: Yellow Fever Vaccine (Live). ATC code: J07B-L01.
Pharmacology: Pharmacodynamics: STAMARIL is a live attenuated yellow fever virus vaccine. As with other live attenuated viral vaccines, there is a sub-clinical infection in healthy recipients that results in the production of specific B and T cells and the appearance of specific circulating antibody. A neutralising antibody titre of 1:10 is assumed to correlate with protection.
Protective immunity appears from about 10 days after vaccination, lasts 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 seroconversion rates of 93% and 100% were obtained.
Paediatric Population: In a clinical study conducted in 337 toddlers aged 12 to 13 months the yellow fever seropositivity rates 28 days post injection of STAMARIL were 99.7% (98.5; 100.0) and the Geometric Mean Titres were 423 (375; 478). In another clinical study conducted in 30 children and adolescents aged 2 to 17 years a seroconversion rate of 90 to 100% was observed, confirming results observed in earlier clinical studies.
Pharmacokinetics: No pharmacokinetic studies have been performed.
Toxicology: Preclinical Safety Data: No non-clinical studies have been performed.

STAMARIL is indicated for active immunization against yellow fever in persons: travelling to, passing through or living in an area where there is a persisting or periodical risk of yellow fever transmission; travelling to any country that requires an International Certificate of Vaccination for entry (which may or may not depend on the previous itinerary); handling potentially infectious materials (e.g., laboratory personnel).
See Dosage & Administration, Contraindications and Precautions regarding the minimum age for vaccination of children under special circumstances and guidance for vaccination of other specific patient populations.
See the regular updates related to obligations and recommendations for yellow fever vaccination on the dedicated site of the World Health Organisation (WHO) or on the official sites of local health authorities.
In order to comply with vaccine regulations and to be officially recognised, yellow fever vaccines must be administered by a qualified and trained health professional in an approved WHO vaccination centre and registered on an International Certificate of Vaccination. The validity period of this Certificate is established according to International Health Regulations (IHR) recommendations, and starts 10 days after primary vaccination and immediately after re-vaccination (See Dosage & 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: a single dose of 0.5 ml of the reconstituted vaccine.
Persons aged 60 years and older: The dose is the same as for adults. However due to a potentially 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 significant and unavoidable risk of acquiring yellow fever infection, such as in case of travel in an area where there is persisting or periodical risk of yellow fever transmission (see Precautions and Adverse Reactions).
Paediatric population: Children aged 9 months and older: a single dose of 0.5 ml of the reconstituted vaccine.
Children from 6 to 9 months of age: vaccination against yellow fever is not recommended in children aged from 6 months up to 9 months except in specific circumstances and in accordance with available official recommendations (see Precautions), in which case the dose is the same as in children aged 9 months and older.
Children under 6 months of age: STAMARIL is contraindicated in children less than 6 months of age (see Contraindications).
Re-vaccination: The duration of protection following administration of one single 0.5 ml dose of STAMARIL is expected to be at least 10 years and may be life-long.
According to the recommendations of WHO and International Health Regulations, a yellow fever vaccination certificate is valid for the entire life of the vaccinated person. However, re-vaccination with one dose of 0.5 mL may be needed in subjects who had an insufficient immune response after their primary vaccination and are still at risk of infection with the yellow fever virus. Re-vaccination may also be required according to official recommendations of local Health Authorities.
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 anterolateral 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 INTRAVASCULARLY.
Precautions to be taken before handling or administering the medicinal product.
For instructions on reconstitution of the medicinal product before administration, see Special Precautions for Disposal and Other Handling under Cautions for Usage.

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

Hypersensitivity to the active substance or to any of the excipients listed in Description or to eggs or chicken proteins.
Severe hypersensitivity reactions (e.g., anaphylaxis) after a previous dose of any yellow fever vaccine.
Age less than 6 months (see Dosage & Administration and Precautions).
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 (see Precautions).
Moderate or severe febrile illness or acute illness.

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch name of the administered product should be clearly registered.
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.
Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. Procedures should be in place to prevent injury from faints and manage syncopal reactions.
DO NOT INJECT INTRAVASCULARLY.
Because intramuscular injection can cause injection site haematoma, STAMARIL 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.
STAMARIL 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. Before considering administration of yellow fever vaccine, care should be taken to identify those who might be at increased risk of adverse reactions following vaccination (see Contraindications and as follows).
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 (see Adverse Reactions). To date, most of cases of YEL-AND have been reported in primary vaccinees with an onset within 30 days of vaccination. The risk appears to be higher in those aged over 60 years and below 9 months of age (including infants exposed to vaccine through breast-feeding), although cases have been also reported in other age groups. Congenital or acquired immunodeficiency has also been recognised as a predisposing factor (see Contraindication). 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 the patient feels, after vaccination, any symptoms indicative of YEL-AND such as high fever together with headache or confusion, personality change, or if the patient feels extreme fatigue, neck stiffness, seizures, loss of movement or feeling in part or all of the body. Vaccinated persons should also be reminded to inform their health care provider that they received a yellow fever vaccine (see Adverse Reactions).
Yellow fever vaccine-associated viscerotropic disease (YEL-AVD): Very rarely, YEL-AVD resembling fulminant infection by wild-type virus has been reported following vaccination (see Adverse Reactions). The mortality rate has been around 60%. To date, most of cases of YEL-AVD have been reported in primary vaccinees 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 recognised as a predisposing factor (see Contraindications). 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 the patient feels 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. Vaccinated persons should also be reminded to inform their health care provider that the patient received a yellow fever vaccine (see Adverse Reactions).
Immunosuppressed persons: STAMARIL must not be administered to immunosuppressed persons (see Contraindications).
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 or more, it is advisable to delay vaccination until at least one month after completing the course.
HIV infection: STAMARIL must not be administered to persons with symptomatic HIV infection or with asymptomatic HIV infection when accompanied by evidence of impaired immune function (see Contraindications). 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 an 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 (see Dosage & Administration and Contraindications and as follows) 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: Paediatric population: children less than 9 months of age: Children aged from 6 months up to 9 months should only be vaccinated under special circumstances (e.g., during major outbreaks) and on the basis of current official advice.
STAMARIL is contraindicated in children less than 6 months of age (see Contraindications).
Older people: persons aged 60 years and older: 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. The countries designated by WHO, where vaccination is not recommended generally, or not recommended, should be considered as not presenting an inevitable significant risk (refer to the list of countries with yellow fever infection risk updated by WHO) (see as previously mentioned and Adverse Reactions).
Transmission: There are very 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 YEL-AND from which the infants recover (see Use in Pregnancy & Lactation).
As with any vaccine, vaccination with STAMARIL may not protect 100% of vaccinated individuals.
Latex: The tip-caps of the prefilled syringes contain a natural latex derivative that could cause allergic reaction in people sensitive to latex.
Excipients with a known effect: STAMARIL contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially "sodium-free."
STAMARIL contains less than 1 mmol (39 mg) of potassium per dose, i.e. it is essentially "potassium-free".
STAMARIL contains about 8 mg of sorbitol (E420) per dose.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive or use machines have been performed.
Use in Pregnancy & Lactation: STAMARIL should not be used in pregnant and breast-feeding woman unless when clearly needed and following an assessment of the risks and benefits (see Use in Pregnancy & Lactation).

Pregnancy: No animal developmental and reproductive studies have been conducted with STAMARIL and the potential risk for humans is unknown. Data on a limited number of exposed pregnancies indicate no adverse effects of STAMARIL on pregnancy or the health of the foetus/newborn child. Nevertheless, STAMARIL is a live attenuated vaccine, it should not be used during pregnancy unless clearly needed and only after careful consideration of the potential risks and benefits. Pregnancy should be avoided in the month after the vaccination.
Breast-feeding: As there is a probable risk of transmission of the vaccine virus strain to the infants from breastfeeding mothers, STAMARIL should not be given to nursing mothers unless when clearly needed such as during an outbreak and only if the potential benefits to the mother are higher than the potential risks, including those for the breastfed child (see Precautions). 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 and no fertility data are available in humans.

Summary of the safety profile: Cases of serious adverse events such as severe hypersensitivity or anaphylactic reactions, neurotropic or viscerotropic disease (YEL-AND; YEL-AVD) have been reported from post-marketing experience (see Tabulated list of adverse reactions and Description of selected adverse reactions as follows).
In all clinical studies, 4896 subjects (all ages) received STAMARIL.
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.
Tabulated list of adverse reactions: The table as follows summarises the frequencies of the adverse reactions that were recorded following vaccination with STAMARIL during clinical studies and worldwide post-marketing experience.
The adverse reactions are ranked under headings of frequency, using the following convention: Very common: (≥ 1/10); Common: (≥ 1/100 to < 1/10); Uncommon: (≥ 1/1000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (cannot be estimated from available data). Adverse reactions in each frequency group are presented in the decreasing order of severity. (See table.)

Click on icon to see table/diagram/image

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, and other yellow fever vaccines. YEL-AND may manifest either as an encephalitis (with or without demyelination), or as 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 (for example confusion, lethary, personality change for more than 24h, focal neurological deficits, cerebellar dysfunction or seizures. 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 (see Precautions).
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. These cases are generally of mild or moderate severity and resolve spontaneously.
Cases of viscerotropic disease (known as YEL-AVD and formerly described as "Febrile Multiple Organ-System Failure") have been reported following vaccination with STAMARIL, 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 (see Precautions).
Paediatric population: The safety of STAMARIL in paediatric population has been studied through a clinical study performed in 393 toddlers aged 12 to 13 months who received STAMARIL and placebo concomitantly.
The safety profile was assessed during the first 4 weeks following vaccination.
The following most frequently reported adverse reactions specific to the paediatric 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. Fever and vomiting were more frequently reported than in general population (see Tabulated summary of adverse reactions as previously mentioned).
Injection site erythema (9.8%) and injection site swelling (4.4%) were reported as "common" in toddlers, like in general population, however with significantly higher frequencies compared to general population.
Other special population: Congenital or acquired immunodeficiency has been recognised as a potential risk factor for serious adverse events, including YEL-AND (see Contraindications and Precautions).
Age of more than 60 years (see Precautions) has been recognised as a potential risk factor for YEL-AVD and YEL-AND.
Age below 9 months (including infants exposed to vaccine through breast-feeding) (see Precautions) has been recognised as a potential risk factor for YEL-AND.
A medical history of thymus dysfunction (see Contraindications and Precautions) has been recognised as a potential risk factor for YEL-AVD.
Reporting of Suspected Adverse Reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

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).
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.
It must not be administered to persons who are receiving immunosuppressant 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 (see Contraindications). In case of uncertainty regarding the degree of immunosuppression, vaccination should be suspended and the opinion of a specialist should be requested.
It can induce false positive results with laboratory and/or diagnostic tests for other flavivirus related diseases such as dengue or Japanese encephalitis.

Special precautions for disposal and other handling: For syringe without attached needle only: after removing the syringe tip cap, a needle should be firmly placed on the tip of the syringe and secured by rotating a quarter of a turn (90°).
The vaccine is reconstituted by adding the solvent provided in the pre-filled syringe to the vial of powder. The vial is shaken and, after complete dissolution, the suspension obtained is withdrawn into the same syringe for injection.
Before administration, the reconstituted vaccine should be vigorously shaken.
Use immediately after reconstitution.
After reconstitution the suspension is beige to pink beige, more or less opalescent.
Contact with disinfectants is to be avoided since they may inactivate the virus.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.

Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the vial of powder and the syringe of solvent in the outer carton in order to protect from light.
For storage conditions after reconstitution of the medicinal product, see Shelf-Life as follows.
Shelf life: 3 years.
After reconstitution, the medicinal product must be used immediately.

Vaccines, Antisera & Immunologicals

J07BL01 - yellow fever, live attenuated ; Belongs to the class of yellow fever viral vaccines.

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