Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or to rice protein listed in section 2.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Close monitoring is recommended following vaccination for the early signs of anaphylaxis or anaphylactoid reactions. As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine.
Vaccination with Ervebo may not result in protection in all vaccinees. Vaccine efficacy has been established in the period ≥10 to ≤31 days after vaccination, however the duration of protection is not known (see section 5.1). The use of other Ebola control measures should therefore not be interrupted.
Vaccination of contacts of Ebola cases should occur as soon as possible (see section 5.1).
Vaccination with Ervebo does not eliminate the necessity of standard precautions when caring for patients with known or suspected Ebola disease. All healthcare workers and other ancillary providers who have been vaccinated should not alter their practices with regard to safe injection, hygiene, and personal protective equipment (PPE) after vaccination.
Healthcare workers caring for patients with suspected or confirmed Ebola virus should apply extra infection control measures to prevent contact with the patient’s blood and body fluids and contaminated surfaces or materials such as clothing and bedding. Samples taken from humans and animals for investigation of Ebola infection should be handled by trained staff and processed in suitably equipped laboratories.
Vaccine administrators should counsel vaccinees to continue to protect themselves with adequate measures.
Safety and efficacy of Ervebo have not been assessed in immunocompromised individuals. Immunocompromised individuals may not respond as well as immunocompetent individuals to Ervebo. As a precautionary measure, it is preferable to avoid the use of Ervebo in individuals with known immunocompromised conditions or receiving immunosuppressive therapy, including the following conditions:
As a precautionary measure, it is preferable to avoid the use of Ervebo during pregnancy. See section 4.6.
Vaccine virus might be present in biological fluids such as blood, urine, saliva, semen, vaginal fluids, aqueous humor, breast milk, faeces, sweat, amniotic fluid, and placenta. Vaccine virus RNA has been detected by PCR in the plasma of most of the adult subjects. Vaccine virus RNA was mainly detected from Day 1 to Day 7. Shedding of vaccine virus has been detected by PCR in urine or saliva in 19 out of 299 adult subjects and in skin vesicles in 4 out of 10 adult subjects. The vaccine virus RNA was detected in a skin vesicle at 12 days post-vaccination in one of the four subjects.
Viral shedding was observed more frequently in children and adolescents (28/39) compared to adults.
Transmission of vaccine virus through close personal contact is accepted as a theoretical possibility. Vaccine recipients should avoid close contact with and exposure of high-risk individuals to blood and bodily fluids for at least 6 weeks following vaccination. High-risk individuals include:
Individuals who develop vesicular rash after receiving the vaccine should cover the vesicles until they heal to minimise the risk of possible transmission of vaccine virus through open vesicles. Dispose of contaminated bandages following institutional guidelines or WHO healthcare waste management policy. See section 5.3.
Inadvertent transmission of vaccine virus to animals and livestock is also theoretically possible, see below.
Individuals administered Ervebo should not donate blood for at least 6 weeks post-vaccination.
Transmission of vaccine virus through close contact with livestock is accepted as a theoretical possibility. Vaccine recipients should attempt to avoid exposure of livestock to blood and bodily fluids for at least 6 weeks following vaccination. Individuals who develop vesicular rash after receiving the vaccine should cover the vesicles until they heal. Dispose of contaminated bandages following institutional guidelines or WHO healthcare waste management policy. See section 5.3.
Vaccination should be postponed in subjects experiencing moderate or severe febrile illness. The presence of a minor infection should not result in deferral of vaccination.
The vaccine should be given with caution to individuals with thrombocytopenia or any coagulation disorder because bleeding or bruising may occur following an intramuscular administration in these individuals.
The vaccine will not prevent disease caused by Filoviruses other than Zaire Ebola virus.
Following vaccination with Ervebo, individuals may test positive for Ebola glycoprotein (GP) nucleic acids, antigens, or antibodies against Ebola GP, which are targets for certain Ebola diagnostic tests. Therefore, diagnostic testing for Ebola should target non-GP sections of the Ebola virus.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, and is considered to be essentially sodium-free.
No interaction studies have been performed.
As there are no data on co-administration of Ervebo with other vaccines, the concomitant use of Ervebo with other vaccines is not recommended.
Immune globulin (IG), blood or plasma transfusions should not be given concomitantly with Ervebo. Administration of immune globulins, blood or plasma transfusions administered 3 months before or up to 1 month after Ervebo administration may interfere with the expected immune response.
It is unknown whether concurrent administration of antiviral medication including interferons could impact vaccine virus replication and efficacy.
There are limited amount of data (less than 300 pregnancy outcomes) from the use of Ervebo in pregnant women, or women who became pregnant after receiving the vaccine. The safety of Ervebo has not been established in pregnant women.
As there are limitations to available data, including the small number of cases, caution should be exercised in drawing conclusions. Lack of reliable data on background rates of pregnancy and neonatal outcomes in the affected regions also makes a contextual assessment of the data challenging.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
As a precautionary measure, it is preferable to avoid the use of Ervebo during pregnancy. Nevertheless considering the severity of EVD, vaccination should not be withheld when there is a clear risk of exposure to Ebola infection.
Pregnancy should be avoided for 2 months following vaccination. Women of child-bearing potential should use an effective contraceptive method.
It is unknown whether the vaccine virus is secreted in human milk.
A risk to the newborns/infants from breast-feeding by vaccinated mothers cannot be excluded.
Evaluation of the vaccine virus in animal milk has not been conducted. When Ervebo is administered to female rats, antibodies against the vaccine virus were detected in offspring, likely due to acquisition of maternal antibodies via placental transfer during gestation and via lactation. See section 5.3.
A decision must be made whether to discontinue breast-feeding or to abstain from Ervebo taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. In certain circumstances, where alternatives to breast-feeding are limited, the immediate need and health benefits to the infant should be taken into consideration and balanced with the mother’s need for Ervebo. Both may present compelling needs that should be considered before vaccination of the mother.
There are no data on fertility effects in humans.
Animal studies in female rats do not indicate harmful effects (see section 5.3).
No studies on the effects of Ervebo on the ability to drive and use machines have been performed.
Ervebo has no or negligible influence on the ability to drive and use machines.
Anaphylaxis was reported very rarely (0.006%) in clinical trials.
The most common injection-site adverse reactions were injection-site pain (70.3%), swelling (16.7%) and erythema (13.7%).
The most common systemic adverse reactions reported following vaccination with Ervebo were headache (36.9%), pyrexia (34.3%), myalgia (32.5%), fatigue (18.5%), arthralgia (17.1%), nausea (8.0%), chills (6.3%), arthritis (3.7%), rash (3.6%), hyperhidrosis (3.2%), and abdominal pain (1.4%). In general, these reactions were reported within 7 days after vaccination, were mild to moderate in intensity, and had short duration (less than 1 week).
Frequencies are reported as: 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 the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 1. Tabulated summary of adverse reactions considered related to vaccination:
| MedDRA-System Organ Class | Adverse Reactions | Frequency |
|---|---|---|
| Immune system disorders | Anaphylactic reaction | Very Rare |
| Nervous system disorders | Headache | Very common |
| Gastrointestinal disorders | Abdominal pain, Nausea | Common |
| Skin and subcutaneous tissue disorders | Rash§ | Common |
| Musculoskeletal and connective tissue disorders | Arthralgia§, Myalgia | Very common |
| Arthritis§ | Common | |
| General disorders and administration site conditions | Pyrexia, Fatigue, Injection site pain, Injection site erythema, Injection site swelling | Very common |
| Chills, Hyperhidrosis (sweats) | Common |
§ See description of selected adverse reactions.
Arthralgia was generally reported in the first few days following vaccination, was mild to moderate in intensity, and resolved within one week after onset. Arthritis (arthritis, joint effusion, joint swelling, osteoarthritis, monoarthritis or polyarthritis) was generally reported within the first few weeks following vaccination. In clinical trials with reports of arthritis, the median onsets were between 10 and 12 days (range from 0 to 25 days). Arthritis has been reported by subjects in clinical trials at a frequency that ranged from 0% in several protocols to 23.5% in one Phase 1 study. The majority of arthritis reactions were mild to moderate in severity. The median duration of arthritis across clinical trials in which arthritis was reported ranged from 2 days to 81.5 days (including duration of recurrent arthritis) with a maximum of 330 days. The reasons for differences in arthritis reporting across trials are not known but may be due to differences in study populations or outcome reporting. In the Phase 1 study with the highest rate of arthritis, 6 of 24 patients (25%) who reported arthritis after vaccination had persistent joint symptoms two years after vaccination. In a small number of subjects, the vaccine virus was recovered from joint effusion samples, suggestive ofa virally-mediated process postvaccination.
Rash was characterised in a variety of ways including generalised rash (2.3%), vesicular rash (0.5%), dermatitis (0.3%), or cutaneous vasculitis (0.01%) in clinical trials. In different trials, rash was reported with median onsets of 7.5 to 10.5 days (range from 0 to 47 days). The median durations reported were between 6 to 18 days. In 6 out of 18 subjects tested, the vaccine virus was detected in rashes (described as dermatitis, vesicles or cutaneous vasculitis lesions) suggesting a virally mediated process post-vaccination.
Transient decreases in counts of lymphocytes, neutrophils and total white blood cells in the first 3 days following vaccination have been observed very commonly in Phase ½ studies; these events generally resolved after the first week post-vaccination. No adverse events of infections were observed in Phase ½ trials.
Across the Phase 1 through Phase 3 trials, 234 children and adolescents 6 to 17 years of age received a dose of Ervebo.
The safety profile of Ervebo in children and adolescents 6 to17 years of age was generally similar to that observed in adults.
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 listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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