COVID‑19 Vaccine – Uses, Dosage, Side Effects, Interactions

An efficacious parenterally administered modified live Canine Coronavirus vaccine? which provides systemic?, humoral protection and also protection of the intestinal tract in dogs from infection? by virulent Canine Coronavirus is produced. A method for propagation of the Canine Coronavirus and its attenuation and a method of evaluating the effectiveness of a Canine Coronavirus vaccine in canines is also disclosed.

Types  of COVID‑19 Vaccine?

This medicinal product has been given authorization for temporary supply by the UK Department of Health and Social Care and the Medicines and Healthcare products Regulatory Agency. It does not have a marketing authorization, but this temporary authorization grants permission for the medicine to be used for active immunization of individuals aged 18 years and older for the prevention of coronavirus disease 2019 (COVID-19).

As with any new medicine in the UK, this product will be closely monitored to allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Nature and contents of the container

Chemical ingredient of Vaccine?

• L-Histidine
• L-Histidine hydrochloride monohydrate
• Magnesium chloride hexahydrate
• Polysorbate 80
• Ethanol
• Sucrose
• Sodium chloride
• Disodium edetate dihydrate
• Water for injections
• Solution for injection.
• The solution is colorless to slightly brown, clear to slightly opaque, and particle-free with a pH of 6.6.

Indications of COVID‑19 Vaccine?

• At First all population in the country those who are 18 to the 65-year-old adult population.
• COVID-19 Vaccine? AstraZeneca is indicated for active immunization of individuals ≥18 years old for the prevention of coronavirus disease 2019 (COVID-19).
• The use of COVID-19 Vaccine? AstraZeneca should be in accordance with official guidance.
• provides summary tables of COVID-19 vaccine? candidates in both clinical and pre-clinical development;
• provides analysis and visualization for several COVID-19 vaccine? candidate categories;
• tracks the progress of each vaccine? from pre-clinical, Phase 1, Phase 2 through to Phase 3 efficacy studies,
• provides links to published reports on safety, immunogenicity, and efficacy data of the vaccine? candidates;
• includes information on key attributes of each vaccine? candidate; and
• allows users to search for COVID-19 vaccines through various criteria such as vaccine? platform, dosage?, schedule of vaccination, route of administration, developer, trial phase, and clinical endpoints being measured in Phase 3.

Contraindications of COVID‑19 Vaccine?

• Hypersensitivity to the active substance or to any of the excipients listed

Special warnings and precautions for use

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Hypersensitivity

• 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?.

Concurrent illness

• As with other vaccines, administration of COVID-19 Vaccine? AstraZeneca should be postponed in individuals suffering from an acute? severe febrile illness. However, the presence of a minor infection?, such as cold, and/or low-grade fever? should not delay vaccination.

platelet? count, which can increase bleeding risk. সহজ বাংলা: প্লাটিলেট কম।" data-rx-term="thrombocytopenia" data-rx-definition="Thrombocytopenia means low platelet count, which can increase bleeding risk. সহজ বাংলা: প্লাটিলেট কম।">Thrombocytopenia? and coagulation disorders

• As with other intramuscular injections, COVID-19 Vaccine? AstraZeneca should be given with caution to individuals with platelet? count, which can increase bleeding risk. সহজ বাংলা: প্লাটিলেট কম।" data-rx-term="thrombocytopenia" data-rx-definition="Thrombocytopenia means low platelet count, which can increase bleeding risk. সহজ বাংলা: প্লাটিলেট কম।">thrombocytopenia?, any coagulation disorder, or to persons on anticoagulation therapy, because bleeding or bruising may occur following an intramuscular administration in these individuals.

Immunocompromised individuals

• It is not known whether individuals with impaired immune responsiveness, including individuals receiving immunosuppressant therapy, will elicit the same response as immunocompetent individuals to the vaccine? regimen.

Duration and level of protection

• The duration of protection has not yet been established. As with any vaccine?, vaccination with COVID-19 Vaccine AstraZeneca may not protect all vaccine recipients.

Interchangeability

• No data are available on the use of COVID-19 Vaccine? AstraZeneca in persons that have previously received a full or partial vaccine series with another COVID-19 vaccine.

Sodium

• This medicinal product contains less than 1 mmol sodium (23 mg) per dose and is considered to be essentially sodium-free.

Dosage of COVID‑19 Vaccine

Posology and method of administration

Posology

• The COVID-19 Vaccine AstraZeneca vaccination course consists of two separate doses of 0.5 ml each. The second dose should be administered between 4 and 12 weeks after the first dose (see section 5.1).
• It is recommended that individuals who receive the first dose of COVID-19 Vaccine AstraZeneca complete the vaccination course with COVID-19 Vaccine AstraZeneca.

Elderly population

• Efficacy and safety data are currently limited in individuals ≥65 years of age. No dosage adjustment is required.

Pediatric population

• The safety and efficacy of COVID-19 Vaccine AstraZeneca in children and adolescents (aged <18 years old) have not yet been established. No data are available.

Method of administration

• COVID-19 Vaccine AstraZeneca is for intramuscular (IM) injection only, preferably in the deltoid muscle.

Multidose vial

• 5 ml of solution in a 10-dose vial (clear type I glass) with a halobutyl rubber stopper and an aluminum overseal with a plastic flip-off cap. Packs of 10 vials.
• 4 ml of solution in an 8-dose vial (clear type I glass) with a halobutyl rubber stopper and an aluminum overseal with a plastic flip-off cap. Packs of 10 vials.

Overdose

• Experience of overdose is limited.
• There is no specific treatment for an overdose with COVID-19 Vaccine AstraZeneca. In the event of an overdose, the individual should be monitored and provided with symptomatic treatment as appropriate.

Special precautions for disposal and another handling

Administration

COVID-19 Vaccine AstraZeneca is colorless to slightly brown, clear to the slightly opaque solution. The vaccine should be inspected visually prior to administration and discarded if particulate matter or differences in the described appearance are observed. Do not shake the vial.

Each vaccine dose of 0.5 ml is withdrawn into a syringe for an injection to be administered intramuscularly. Use a separate sterile needle and syringe for each individual. Each vial contains at least the number of doses stated. It is normal for the liquid to remain in the vial after withdrawing the final dose. When low dead volume syringes and/or needles are used, the amount remaining in the vial may be sufficient for an additional dose. Care should be taken to ensure a full 0.5 ml dose is administered. Where a full 0.5 ml dose cannot be extracted, the remaining volume should be discarded.

The vaccine does not contain any preservatives. Aseptic technique should be used for withdrawing the dose for administration.

After first dose withdrawal, use the vial as soon as practically possible and within 6 hours (stored at 2°C to 25°C). Discard any unused vaccine.

To facilitate the traceability of the vaccine, the name and the batch number of the administered product should be clearly recorded for each recipient.

Qualitative and quantitative composition

• One dose (0.5 ml) contains:
• COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 × 10^10 viral particles (vp)

*Recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS CoV 2 Spike (S) glycoprotein. Produced in genetically modified human embryonic kidney (HEK) 293 cells.

This product contains genetically modified organisms (GMOs).

Incompatibilities

In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.

Shelf life

Unopened multidose vial

6 months

After first use

Use as soon as practically possible and within 6 hours. The vaccine may be stored between 2°C and 25°C during the in-use period.

Special precautions for storage

• Unopened multidose vial
• Store in a refrigerator (2 to 8°C).
• Do not freeze.
• Keep vials in the outer carton to protect from light.

After first use

For storage conditions after the first use of the medicinal product,

Side Effects of COVID‑19 Vaccine

MedDRA SOC: Blood and lymphatic system disorders

• Frequency: Uncommon
• Adverse reactions: Lymphadenopathy (a)

MedDRA SOC: Metabolism and nutrition disorders

• Frequency: Uncommon
• Adverse reactions: Decreased appetite (a)

MedDRA SOC: Nervous system disorders

• Frequency: Very common
• Adverse reactions: Headache

MedDRA SOC: Nervous system disorders

• Frequency: Uncommon
• Adverse reactions: Dizziness (a)

MedDRA SOC: Gastrointestinal disorders

• Frequency: Very common
• Adverse reactions: Nausea

MedDRA SOC: Gastrointestinal disorders

• Frequency: Common
• Adverse reactions: Vomiting

MedDRA SOC: Gastrointestinal disorders

• Frequency: Uncommon
• Adverse reactions: Abdominal pain (a)

MedDRA SOC: Skin and subcutaneous tissue disorders

• Frequency: Uncommon
• Adverse reactions: Hyperhidrosis (a), pruritus (a), rash (a)

MedDRA SOC: Musculoskeletal and connective tissue disorders

• Frequency: Very common
• Adverse reactions: Myalgia, arthralgia

MedDRA SOC: General disorders and administration site conditions

• Frequency: Very common
• Adverse reactions: Injection site tenderness, injection site pain, injection site warmth, injection site erythema, injection site pruritus, injection site swelling, injection site bruising (b), fatigue, malaise, pyrexia (c), chills

MedDRA SOC: General disorders and administration site conditions

• Frequency: Common
• Adverse reactions: Injection site induration, influenza-like illness (a)

(a) Unsolicited adverse reaction

(b) Injection site bruising includes injection site hematoma (uncommon, unsolicited adverse reaction)

(c) Pyrexia includes feverishness (very common) and fever ≥38°C (common)

Very rare events of neuroinflammatory disorders have been reported following vaccination with COVID-19 Vaccine AstraZeneca. A causal relationship has not been established.

Reporting of suspected adverse reactions

If you are concerned about an adverse event, it should be reported on a Yellow Card. Reporting forms and information can be found at the Coronavirus Yellow Card reporting site search for MHRA Yellow Card in the Google Play or Apple App Store and include the vaccine brand and batch/Lot number if available.

Alternatively, adverse events of concern in association with COVID-19 Vaccine AstraZeneca can be reported to AstraZeneca on 08000541028 or via the AstraZeneca website.

Please do not report the same adverse event(s) to both systems as all reports will be shared between AstraZeneca and the MHRA (in an anonymized form) and dual reporting will create unnecessary duplicates.

Drugs Interaction

View interaction reports for Pfizer-BioNTech COVID-19 Vaccine (sars-cov-2 (covid-19) mrna bnt-162b2 vaccine) and the medicines listed below.

• albuterol
• amlodipine
• aspirin
• atorvastatin
• cetirizine
• famotidine
• gabapentin
• levothyroxine
• lisinopril
• melatonin
• metformin
• Moderna COVID-19 Vaccine (sars-cov-2 (covid-19) mrna-1273 vaccine)
• omeprazole
• pantoprazole
• prednisone
• Tylenol (acetaminophen)
• venlafaxine
• Vitamin B12 (cyanocobalamin)
• Vitamin D3 (cholecalciferol)
• Xanax (alprazolam)

Pregnancy, and Lactation

Pregnancy

There is limited experience with the use of COVID-19 Vaccine AstraZeneca in pregnant women.

Preliminary animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryofetal development, parturition, or postnatal development; definitive animal studies have not been completed yet. The full relevance of animal studies to human risk with vaccines for COVID-19 remains to be established.

Pregnancy and women who are breastfeeding – the vaccine should only be considered for use in pregnancy when the potential benefits outweigh any potential risks for the mother and baby. Women should discuss the benefits and risks of having the vaccine with their healthcare professional and reach a joint decision based on individual circumstances. Women who are breastfeeding can also be given the vaccine. This advice is in line with pregnancy and breastfeeding advice for the Oxford University/AstraZeneca vaccine

Administration of COVID-19 Vaccine AstraZeneca in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus.

Breastfeeding

It is unknown whether COVID-19 Vaccine AstraZeneca is excreted in human milk.

Fertility

Preliminary animal studies do not indicate direct or indirect harmful effects with respect to fertility.

Women who are pregnant

There is no known risk associated with giving non-live vaccines during pregnancy. These vaccines cannot replicate, so they cannot cause infection in either the woman or the unborn child.

Although the available data do not indicate any safety concern or harm to pregnancy, there is insufficient evidence to recommend routine use of COVID-19 vaccines during pregnancy.

JCVI advises that, for women who are offered vaccination with the Pfizer-BioNTech or AstraZeneca COVID-19 vaccines, vaccination in pregnancy should be considered where the risk of exposure to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV2) infection is high and cannot be avoided, or where the woman has underlying conditions that put them at very high risk of serious complications of COVID-19. In these circumstances, clinicians should discuss the risks and benefits of vaccination with the woman, who should be told about the absence of safety data for the vaccine in pregnant women.

JCVI does not advise routine pregnancy testing before receipt of a COVID-19 vaccine. Those who are trying to become pregnant do not need to avoid pregnancy after vaccination.

Women who are breastfeeding

There is no known risk associated with giving non-live vaccines whilst breastfeeding. JCVI advises that breastfeeding women may be offered vaccination with the Pfizer-BioNTech or AstraZeneca COVID-19 vaccines.

The developmental and health benefits of breastfeeding should be considered along with the woman’s clinical need for immunization against COVID-19, and the woman should be informed about the absence of safety data for the vaccine in breastfeeding women.

The CHM (Commission on Human Medicines) has also reviewed further data for the Pfizer/BioNTech vaccine as it has become available and has recommended the following changes:

• Pregnancy and women who are breastfeeding – the vaccine should only be considered for use in pregnancy when the potential benefits outweigh any potential risks for the mother and baby. Women should discuss the benefits and risks of having the vaccine with their healthcare professional and reach a joint decision based on individual circumstances. Women who are breastfeeding can also be given the vaccine. This advice is in line with pregnancy and breastfeeding advice for the Oxford University/AstraZeneca vaccine.

The MHRA has also published additional updates relating to use of the Pfizer/BioNTech vaccine in pregnancy and women who are breastfeeding.

When will COVID-19 vaccines be ready for distribution?

Disposal

COVID-19 Vaccine AstraZeneca contains genetically modified organisms (GMOs). Any unused vaccine or waste material should be disposed of in accordance with local requirements. Spills should be disinfected with an appropriate antiviral disinfectant.

Effects on ability to drive and use machines

COVID-19 Vaccine AstraZeneca has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions mentioned under may temporarily affect the ability to drive or use machines.

Undesirable effects

Summary of the safety profile

The overall safety of COVID-19 Vaccine AstraZeneca is based on an interim analysis of pooled data from four clinical trials conducted in the United Kingdom, Brazil, and South Africa. At the time of analysis, 23,745 participants ≥18 years old had been randomized and received either COVID-19 Vaccine AstraZeneca or control. Out of these, 12,021 received at least one dose of COVID-19 Vaccine AstraZeneca. The median duration of follow-up in the COVID-19 Vaccine AstraZeneca group was 105 days post-dose 1, and 62 days post-dose 2.

Demographic characteristics were generally similar among participants who received COVID-19 Vaccine AstraZeneca and those who received control. Overall, among the participants who received COVID-19 Vaccine AstraZeneca, 90.3% were aged 18 to 64 years and 9.7% were 65 years of age or older. The majority of recipients were White (75.5%), 10.1% were Black and 3.5% were Asian; 55.8% were female and 44.2% male.

The most frequently reported adverse reactions were injection site tenderness (>60%); injection site pain, headache, fatigue (>50%); myalgia, malaise (>40%); pyrexia, chills (>30%); and arthralgia, nausea (>20%). The majority of adverse reactions were mild to moderate in severity and usually resolved within a few days of vaccination. By day 7 the incidence of subjects with at least one local or systemic reaction was 4% and 13% respectively. When compared with the first dose, adverse reactions reported after the second dose were milder and reported less frequently.

Adverse reactions were generally milder and reported less frequently in older adults (≥65 years old).

If required, analgesic and/or antipyretic medicinal products (e.g. paracetamol-containing products) may be used to provide symptomatic relief from post-vaccination adverse reactions.

Tabulated list of adverse reactions

Adverse drug reactions (ADRs) are organized by MedDRA System Organ Class (SOC). Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness. 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).

Pharmacodynamic properties

Pharmacodynamic properties

Pharmacotherapeutic group: Vaccine, other viral vaccines, ATC code: J07BX03

Clinical efficacy

COVID-19 Vaccine AstraZeneca has been evaluated based on an interim analysis of pooled data from four on-going randomized, blinded, controlled trials: a Phase I/II Study, COV001, in healthy adults 18 to 55 years of age in the UK; a Phase II/III Study, COV002, in adults ≥18 years of age (including the elderly) in the UK; a Phase III Study, COV003, in adults ≥18 years of age (including the elderly) in Brazil; and a Phase I/II study, COV005, in adults aged 18 to 65 years of age in South Africa. The studies excluded participants with a history of anaphylaxis or angioedema; participants with severe and/or uncontrolled cardiovascular, gastrointestinal, liver, renal, endocrine/metabolic disease, and neurological illnesses; as well as those with immunosuppression. In studies, COV001 and COV002 licensed seasonal influenza and pneumococcal vaccinations were permitted (at least 7 days before or after their study vaccine).

All participants are planned to be followed for up to 12 months, for assessments of safety and efficacy against COVID-19 disease.

Based on the pre-defined criteria for interim efficacy analysis, COV002 and COV003 exceeded the threshold of ≥5 virologically confirmed COVID-19 cases per study and therefore contributed to the efficacy analysis; COV001 and COV005 were excluded.

In the pooled analysis for efficacy (COV002 and COV003), participants ≥18 years of age received two doses of COVID-19 Vaccine AstraZeneca (N=5,807) or control (meningococcal vaccine or saline) (N=5,829). Because of logistical constraints, the interval between dose 1 and dose 2 ranged from 4 to 26 weeks.

Baseline demographics were well balanced across COVID-19 Vaccine AstraZeneca and control treatment groups. Overall, among the participants who received COVID-19 Vaccine AstraZeneca, 94.1% of participants were 18 to 64 years old (with 5.9% aged 65 or older); 60.7% of subjects were female; 82.8% were White, 4.6% were Asian, and 4.4% were Black. A total of 2,070 (35.6%) participants had at least one pre-existing comorbidity (defined as a BMI ≥30 kg/m2, cardiovascular disorder, respiratory disease or diabetes). The median follow-up time post-dose 1 and post-dose 2 was 132 days and 63 days, respectively.

The final determination of COVID-19 cases was made by an adjudication committee, who also assigned disease severity according to the WHO clinical progression scale. A total of 131 participants had SARS CoV 2 virologically confirmed (by nucleic acid amplification tests) COVID-19 occurring ≥15 days post-dose 2 with at least one COVID-19 symptom (objective fever (defined as ≥37.8°C), cough, shortness of breath, anosmia, or ageusia) and were without evidence of previous SARS CoV 2 infection. COVID-19 Vaccine AstraZeneca significantly decreased the incidence of COVID-19 compared to control (see Table 2).

COVID-19 Vaccine AstraZeneca efficacy against COVID-19

N = number of subjects included in each group

n = Number of subjects having a confirmed event

CI = Confidence Interval

a 95.84% CI

b WHO severity grading ≥4

c WHO severity grading ≥6

d 95% CI

e Two cases of hospitalization occurred on Days 1 and 10 post-vaccination.

The level of protection gained from a single dose of COVID-19 Vaccine AstraZeneca was assessed in an exploratory analysis that included participants who had received one dose. Participants were censored from the analysis at the earliest time point of when they received a second dose or at 12 weeks post-dose 1. In this population, vaccine efficacy from 22 days post-dose 1 was 73.00% (95% CI: 48.79; 85.76 [COVID-19 Vaccine AstraZeneca 12/7,998 vs control 44/7,982]).

Exploratory analyses showed that increased immunogenicity was associated with a longer dose interval (see Immunogenicity Table 3). Efficacy is currently demonstrated with more certainty for dose intervals from 8 to 12 weeks. Data for intervals longer than 12 weeks are limited.

Participants who had one or more comorbidities had a vaccine efficacy of 73.43% [95% CI: 48.49; 86.29]; 11 (0.53%) vs 43 (2.02%) for COVID-19 Vaccine AstraZeneca (N=2,070) and control (N=2,113), respectively; which was similar to the vaccine efficacy observed in the overall population.

The number of COVID-19 cases (2) in 660 participants ≥65 years old was too few to draw conclusions on efficacy. However, in this subpopulation, immunogenicity data are available, see below.

Immunogenicity

Following vaccination with COVID-19 Vaccine AstraZeneca, in participants who were seronegative at baseline, seroconversion (as measured by a ≥4 fold increase from baseline in S binding antibodies) was demonstrated in ≥98% of participants at 28 days after the first dose and >99% at 28 days after the second. Higher S binding antibodies were observed with increasing dose intervals (Table 3).

Generally, similar trends were observed between analyses of neutralizing antibodies and S binding antibodies. An immunological correlate of protection has not been established; therefore the level of immune response that provides protection against COVID-19 is unknown.

SARS CoV-2 S-binding antibody response to COVID-19 Vaccine AstraZeneca (a), (b)

N = Number of subjects included in each group

GMT = Geometric mean titre

CI = Confidence interval

S = Spike

a Immune response evaluated using a multiplex immunoassay

b in individuals who received two recommended doses of vaccine.

The immune response observed in participants with one or more comorbidities was consistent with the overall population.

High seroconversion rates were observed in older adults (≥65 years) after the first (97.8%; N=136) and the second recommended dose (100.0%; N=111). The increase in S binding antibodies was lower for participants ≥65 years old (28 days after second dose: GMT=20,727.02 [N=116, 95% CI: 17,646.6; 24,345.2]) when compared to participants aged 18 64 years (28 days after second dose: GMT=30,695.30 [N=703, 95% CI: 28,496.2; 33,064.1]). The majority of participants ≥65 years old had a dosing interval of <6 weeks, which may have contributed to the lower titers observed.

In participants with serological evidence of prior SARS CoV 2 infection at baseline (GMT=13,137.97 [N=29; 95% CI: 7,441.8; 23,194.1]), S antibody titres peaked 28 days after dose 1 (GMT=175,120.84 [N=28; 95% CI: 120,096.9; 255,354.8]).

Spike-specific T cell responses as measured by IFN ɣ enzyme-linked immunospot (ELISpot) assay were induced after the first dose of COVID-19 Vaccine AstraZeneca. These did not rise further after a second dose.

Pharmacokinetic properties

Not applicable.

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on a conventional study of repeat dose toxicity. Animal studies into potential toxicity to reproduction and development have not yet been completed.

References