Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: AstraZeneca AB, SE-151 85 Södertälje, Sweden
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Individuals who have experienced thrombosis with thrombocytopenia syndrome (TTS) following vaccination with Vaxzevria (see section 4.2).
Individuals who have previously experienced episodes of capillary leak syndrome (see also section 4.4).
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Events of anaphylaxis have been reported. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine. Close observation for at least 15 minutes is recommended following vaccination. An additional dose of the vaccine should not be given to those who have experienced anaphylaxis to a previous dose of Vaxzevria.
Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress-related reactions may occur in association with vaccination as a psychogenic response to the needle injection. It is important that precautions are in place to avoid injury from fainting.
Vaccination should be postponed in individuals suffering from an acute severe febrile illness or acute infection. However, the presence of a minor infection and/or low-grade fever should not delay vaccination.
Healthcare professionals should be alert to the signs and symptoms of thromboembolism and/or thrombocytopenia. Those vaccinated should be instructed to seek immediate medical attention if they develop symptoms such as shortness of breath, chest pain, leg swelling, leg pain, persistent abdominal pain following vaccination. Additionally, anyone with neurological symptoms including severe or persistent headaches, blurred vision, confusion or seizures after vaccination, or who experiences spontaneous bleeding, skin bruising (petechia) beyond the site of vaccination after a few days, should seek prompt medical attention.
Individuals diagnosed with thrombocytopenia within three weeks after vaccination with Vaxzevria, should be actively investigated for signs of thrombosis. Similarly, individuals who present with thrombosis within three weeks of vaccination should be evaluated for thrombocytopenia.
As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals.
Very rare cases of capillary leak syndrome (CLS) have been reported in the first days after vaccination with Vaxzevria. A history of CLS was apparent in some of the cases. Fatal outcome has been reported. CLS is a rare disorder characterised by acute episodes of oedema mainly affecting the limbs, hypotension, haemoconcentration and hypoalbuminaemia. Patients with an acute episode of CLS following vaccination require prompt recognition and treatment. Intensive supportive therapy is usually warranted. Individuals with a known history of CLS should not be vaccinated with this vaccine. See also section 4.3.
Guillain-Barré syndrome (GBS) and transverse myelitis ™ have been reported very rarely following vaccination with Vaxzevria. Healthcare professionals should be alert of GBS and TM signs and symptoms to ensure correct diagnosis, in order to initiate adequate supportive care and treatment, and to rule out other causes.
The risk of very rare events (such as coagulation disorders including thrombosis with thrombocytopenia syndrome, CLS, GBS and TM) after a booster dose of Vaxzevria has not yet been characterised.
The efficacy, safety and immunogenicity of the vaccine have not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of Vaxzevria may be lower in immunosuppressed individuals.
The duration of protection afforded by the vaccine is unknown as it is still being determined by ongoing clinical trials.
Protection starts from approximately 3 weeks after the first dose of Vaxzevria. Individuals may not be fully protected until 15 days after the second dose is administered. As with all vaccines, vaccination with Vaxzevria may not protect all vaccine recipients (see section 5.1).
This medicinal product contains less than 1 mmol sodium (23 mg) per 0.5 ml dose, that is to say essentially “sodium-free”.
This medicinal product contains 2 mg of alcohol (ethanol) per 0.5 ml dose. The small amount of alcohol in this medicinal product will not have any noticeable effects.
No interaction studies have been performed.
Concomitant administration of Vaxzevria with other vaccines has not been studied.
There is limited experience with use of Vaxzevria in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or post-natal development (see section 5.3).
Administration of Vaxzevria during pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.
It is unknown whether Vaxzevria is excreted in human milk.
In animal studies, lactational transfer of anti-SARS-CoV-2 S antibodies from maternal female mice to pups was observed (see section 5.3).
Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).
Vaxzevria has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions mentioned under section 4.8 may temporarily affect the ability to drive or use machines.
The overall safety of Vaxzevria is based on an analysis of pooled data from four clinical studies phase I/II, II/III and III conducted in the United Kingdom, Brazil, and South Africa, and of data from an additional phase III clinical study conducted in the United States, Peru and Chile. At the time of the analysis, a total of 56,124 participants ≥18 years old had been randomised and of these, 33,869 received at least one dose of Vaxzevria and 31,217 received two doses.
The most frequently reported adverse reactions are injection site tenderness (68%), injection site pain (58%), headache (53%), fatigue (53%), myalgia (44%), malaise (44%), pyrexia (includes feverishness [33%] and fever ≥38°C [8%]), chills (32%), arthralgia (27%) and nausea (22%). The majority of these adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination.
Very rare cases of thrombosis with thrombocytopenia syndrome have been reported post-marketing within the first three weeks following vaccination (see section 4.4).
Following vaccination with Vaxzevria, recipients may experience multiple adverse reactions occurring at the same time (for example, myalgia/arthralgia, headache, chills, pyrexia and malaise).
When compared with the first dose, adverse reactions reported after the second dose were milder and less frequent.
Reactogenicity was generally milder and reported less frequently in the population of older adults (≥65 years old).
The safety profile was consistent across participants with or without prior evidence of SARS-CoV-2 infection at baseline.
The safety profile observed in individuals who received a booster dose (third dose) was consistent with the known safety profile of Vaxzevria. No new safety concerns, as compared with adverse reactions reported for the primary vaccination course with Vaxzevria, have been identified in individuals receiving a booster dose of Vaxzevria.
In study D7220C00001, 367 participants who had previously received a 2-dose primary vaccination course with Vaxzevria received a single booster dose (third dose) of Vaxzevria. Median time between the second dose and the booster dose was 8.6 months (263 days).
The most frequently reported adverse reactions in previously Vaxzevria vaccinated participants were injection site tenderness (54%), fatigue (43%), injection site pain (38%), headache (34%), myalgia (23%), and malaise (22%). The majority of these adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination.
In study D7220C00001, 322 participants who had previously received a 2-dose primary vaccination course with an mRNA COVID-19 vaccine received a single booster dose (third dose) of Vaxzevria. Median time between the second dose and the booster dose was 3.9 months (119 days).
The most frequently reported adverse reactions in previously mRNA vaccinated participants were injection site tenderness (71%), fatigue (58%), headache (52%), injection site pain (50%), myalgia (47%), malaise (42%), chills (31%), and nausea (21%). The majority of these adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination.
The safety profile presented below is based on an analysis of data from five clinical studies which included participants ≥18 years old (pooled data from four clinical studies conducted in the United Kingdom, Brazil and South Africa, and data from one clinical study conducted in the United States, Peru and Chile) and on data from post-authorisation experience.
Adverse drug reactions (ADRs) are organised by MedDRA System Organ Class (SOC). Frequencies of occurrence of adverse reactions are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000) and not known (cannot be estimated from available data); within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness.
Table 1. Adverse drug reactions:
| MedDRA SOC | Frequency | Adverse Reactions |
|---|---|---|
| Blood and lymphatic system disorders | Common | Thrombocytopeniaa |
| Uncommon | Lymphadenopathy | |
| Not known | Immune thrombocytopeniab | |
| Immune system disorders | Not known | Anaphylaxis Hypersensitivity |
| Metabolism and nutrition disorders | Uncommon | Decreased appetite |
| Nervous system disorders | Very common | Headachec |
| Uncommon | Dizziness Somnolence Lethargy | |
| Rare | Facial paralysisd | |
| Very rare | Guillain-Barré syndrome | |
| Not known | Transverse myelitis | |
| Ear and labyrinth disorders | Uncommon | Tinnitus |
| Vascular disorders | Very rare | Thrombosis with thrombocytopenia syndromee |
| Not known | Capillary leak syndrome Cerebrovascular venous and sinus thrombosisb | |
| Gastrointestinal disorders | Very common | Nausea |
| Common | Vomiting Diarrhoea | |
| Skin and subcutaneous tissue disorders | Uncommon | Hyperhidrosis Pruritus Rash Urticaria |
| Not known | Angioedema | |
| Musculoskeletal and connective tissue disorders | Very common | Myalgia Arthralgia |
| Common | Pain in extremity | |
| Uncommon | Muscle spasms | |
| General disorders and administration site conditions | Very common | Injection site tenderness, pain, warmth, pruritus, bruisingf Fatigue Malaise Feverishness Chills |
| Common | Injection site swelling, erythema Feverg Influenza-like illness Asthenia |
a In clinical trials, transient mild thrombocytopenia was commonly reported (see section 4.4).
b Cases have been reported post-marketing (see also section 4.4).
c Headache includes migraine (uncommon).
d Based on data from the clinical trial conducted in the United States, Peru and Chile. Through the safety followup period to 05 March 2021, facial paralysis (or palsy) was reported by five participants in the Vaxzevria group. Onset was 8 and 15 days after first dose and 4, 17, and 25 days after the second dose. All events were reported to be non-serious. No cases of facial paralysis were reported in the placebo group.
e Severe and very rare cases of thrombosis with thrombocytopenia syndrome have been reported post-marketing. These included venous thrombosis such as cerebral venous sinus thrombosis, splanchnic vein thrombosis, as well as arterial thrombosis (see section 4.4).
f Injection site bruising includes injection site haematoma (uncommon).
g Measured fever ≥38°C.
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 suspectedadverse reactions via the national reporting system listed in Appendix V and include batch/Lot number if available.
This medicinal product must not be mixed with other medicinal products or diluted.
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