Adverse reactions : תופעות לוואי

4.8     Undesirable effects
a. 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 subsections b. Tabulated list of adverse reactions and c. Description of selected adverse reactions).
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 headache, 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 pyrexia, 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 subject 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 summarizes 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 (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from available data)


Within each frequency grouping the adverse reactions are presented in the order of decreasing seriousness.

System Organ Class             Frequency                       Adverse reactions Infections and infestations       Rare                                  Rhinitis Very rare                           YEL-AVD‡
Blood and lymphatic system        Not known                         Lymphadenopathy disorders
Immune system disorders           Not known           Anaphylactoid reaction including angioedema Metabolism and nutrition          Very common                        Appetite loss* disorders
Nervous system disorders          Very common                  Drowsiness*, Headache Uncommon                           Dizziness
Very rare              YEL-AND‡, Seizure, Meningitis aseptic
Not known                         Paresthesia
Gastrointestinal disorders        Very common                       Vomiting† Common                              Nausea
Uncommon                        Abdominal pain
Rare                               Diarrhea
Skin and subcutaneous tissue      Common                               Rash disorders                         Uncommon                            Pruritus Not known                          Urticaria
Musculoskeletal and               Very common                        Myalgia connective tissue disorders       Common                            Arthralgia General disorders and             Very common           Irritability*, Crying*, Pyrexia†, Asthenia, administration site conditions                                 Injection site pain/tenderness Common              Injection site erythema/redness, Injection site
hematoma, Injection site induration; Injection site
oedema/swelling
Uncommon                          Injection site papule
Not known                         Influenza-like illness
*Specific to paediatric population, (see Section d. Paediatric population) ‡ For clinical features see Section c. Description of selected adverse reactions † Very common in toddlers (see Section d. Paediatric population), Common in general population 
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, and other yellow fever vaccines.
YEL-AND may manifest as either encephalitis (with or without demyelination), or as a neurologic disease with peripheral nervous system involvement (e.g. Guillain-Barré syndrome). Encephalitis usually starts with high fever with headache that may progress to include encephalopathy (e.g. confusion, lethargy, personality change lasting more than 24 hours), focal neurologic deficits, cerebellar dysfunction or seizures. YEL-AND with peripheral nervous system involvement usually manifests as bilateral limb weakness or peripheral cranial nerve paresis with decreased or absent tendon reflexes (see Section 4.4).
Neurologic disease not meeting the criteria for YEL-AND has been reported. Manifestations may include cases of aseptic meningitis or seizure with no associated focal neurologic symptoms. Those cases are usually 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 pyrexia, myalgia, fatigue, headache and hypotension, potentially progressing quickly to liver dysfunction with jaundice, muscle cytolysis, thrombocytopenia and acute respiratory and renal failure (see Section 4.4).
d. 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 which 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%), pyrexia (16.5%) and vomiting (17.1%) were reported as “very common” in toddlers. Pyrexia and vomiting were more frequently reported than in general population (see table in subsection b. Tabulated summary of adverse reactions).
- 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.
e. Other special population
Congenital or acquired immunodeficiency has been recognized as a potential risk factor for serious adverse events, including YEL-AND (See Sections 4.3 and 4.4).
Age of more than 60 years (see Section 4.4) has been recognized as a potential risk factor for YEL-AVD and YEL-AND.
Age below 9 months (including infants exposed to vaccine through breastfeeding) (see Section 4.4) has been recognized as a potential risk factor for YEL-AND.


Medical history of thymus dysfunction or thymectomy (see Sections 4.3 and 4.4) have been recognized as predisposing conditions for YEL-AVD.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health (www.health.gov.il) according to the National Regulation by using an online form https://sideeffects.health.gov.il