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Comirnaty復必泰

Comirnaty

Manufacturer:

BioNTech

Distributor:

Pharmason

Marketer:

Fosun Pharma
Full Prescribing Info
Contents
COVID-19 mRNA vaccine (BNT162b2) (embedded in lipid nanoparticles).
Description
This is a multidose vial and must be diluted before use.
One vial (0.45 mL) contains 5 doses of 0.3 mL after dilution.
1 dose (0.3 mL) contains 30 micrograms of COVID-19 mRNA Vaccine (embedded in lipid nanoparticles).
Single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2.
pH: 6.9-7.9.
Excipients/Inactive Ingredients: (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315); 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159); 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC); Cholesterol; Potassium chloride; Potassium dihydrogen phosphate; Sodium chloride; Disodium hydrogen phosphate dihydrate; Sucrose; Water for injections.
Action
Pharmacotherapeutic group: vaccines. ATC code: J07BX.
Pharmacology: Pharmacodynamics: Mechanism of action: The nucleoside-modified messenger RNA in COMIRNATY is formulated in lipid nanoparticles, which enable delivery of the non replicating RNA into host cells to direct transient expression of the SARS-CoV-2 S antigen. The mRNA codes for membrane-anchored, full-length S with two point mutations within the central helix. Mutation of these two amino acids to proline locks S in an antigenically preferred prefusion conformation. The vaccine elicits both neutralizing antibody and cellular immune responses to the spike (S) antigen, which may contribute to protection against COVID-19.
Efficacy: Study 2 is a multicentre, multinational, Phase 1/2/3 randomised, placebo-controlled, observer-blind dose-finding, vaccine candidate selection and efficacy study in participants 12 years of age and older. Randomisation was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the ≥ 56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19. Participants with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrolment, were included as were participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV). At the time of the analysis of Study 2, information presented is based on participants 16 years and older.
Efficacy in participants 16 years of age and older: In the Phase 2/3 portion, approximately 44,000 participants were randomised equally and were to receive 2 doses of COVID-19 mRNA Vaccine or placebo separated by 21 days. The efficacy analyses included participants that received their second vaccination within 19 to 42 days after their first vaccination. Participants are planned to be followed for up to 24 months after Dose 2, for assessments of safety and efficacy against COVID-19. In the clinical study, participants were required to observe a minimum interval of 14 days before and after administration of an influenza vaccine in order to receive either placebo or COVID-19 mRNA Vaccine. In the clinical study, participants were required to observe a minimum interval of 60 days before or after receipt of blood/plasma products or immunoglobulins within through conclusion of the study in order to receive either placebo or COVID-19 mRNA Vaccine.
The population for the analysis of the primary efficacy endpoint included, 36,621 participants 12 years of age and older (18,242 in the COVID-19 mRNA Vaccine group and 18,379 in the placebo group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. In addition, 134 participants were between the ages of 16 to 17 years of age (66 in the COVID-19 mRNA Vaccine group and 68 in the placebo group) and 1616 participants 75 years of age and older (804 in the COVID-19 mRNA Vaccine group and 812 in the placebo group).
Efficacy against COVID-19: At the time of the primary efficacy analysis, participants had been followed for symptomatic COVID-19 for in total 2,214 person-years for the COVID-19 mRNA Vaccine and in total 2,222 person-years in the placebo group.
There were no meaningful clinical differences in overall vaccine efficacy in participants who were at risk of severe COVID-19 including those with 1 or more comorbidities that increase the risk of severe COVID-19 (e.g. asthma, body mass index (BMI) ≥ 30 kg/m2, chronic pulmonary disease, diabetes mellitus, hypertension).
The vaccine efficacy information is presented in Table 1. (See Table 1.)

Click on icon to see table/diagram/image

In the second primary analysis, compared to placebo, efficacy of COVID-19 mRNA Vaccine in participants from first COVID-19 occurrence from 7 days after Dose 2 compared to participants with or without evidence of prior infection with SARS-CoV-2 was 94.6% (95% credible interval of 89.9% to 97.3%) in participants 16 years of age and older.
Additionally, subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across genders, racial and ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID-19.
Paediatric population: Further evidence is awaited.
Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of repeat dose toxicity and reproductive and developmental toxicity.
General toxicity: Rats intramuscularly administered COMIRNATY (receiving 3 full human doses once weekly, generating relatively higher levels in rats due to body weight differences) demonstrated some injection site oedema and erythema and increases in white blood cells (including basophils and eosinophils) consistent with an inflammatory response as well as vacuolation of portal hepatocytes without evidence of liver injury. All effects were reversible.
Genotoxicity/Carcinogenicity: Neither genotoxicity nor carcinogenicity studies were performed. The components of the vaccine (lipids and mRNA) are not expected to have genotoxic potential.
Reproductive toxicity: Reproductive and developmental toxicity were investigated in rats in a combined fertility and developmental toxicity study where female rats were intramuscularly administered COMIRNATY prior to mating and during gestation (receiving 4 full human doses that generate relatively higher levels in rat due to body weight differences, spanning between pre-mating day 21 and gestational day 20). SARS-CoV-2 neutralizing antibody responses were present in maternal animals from prior to mating to the end of the study on postnatal day 21 as well as in foetuses and offspring. There were no vaccine-related effects on female fertility, pregnancy, or embryo-foetal or offspring development. No COMIRNATY data are available on vaccine placental transfer or excretion in milk.
Indications/Uses
COMIRNATY is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 virus, in individuals 16 years of age and older.
The use of this vaccine should be in accordance with official recommendations.
Dosage/Direction for Use
Posology: Individuals 16 years of age and older: COMIRNATY is administered intramuscularly after dilution as a course of 2 doses (0.3 mL each) at least 21 days apart (see Pharmacology: Pharmacodynamics under Actions; Precautions).
There are no data available on the interchangeability of COMIRNATY with other COVID-19 vaccines to complete the vaccination course. Individuals who have received 1 dose of COMIRNATY should receive a second dose of COMIRNATY to complete the vaccination course.
Paediatric population: The safety and efficacy of COMIRNATY in children and adolescents aged less than 16 years of age have not yet been established. Limited data are available.
Elderly population: No dosage adjustment is required in elderly individuals ≥65 years of age.
Method of administration: COMIRNATY should be administered intramuscularly.
The preferred site is the deltoid muscle of the upper arm.
Do not inject the vaccine intravascularly, subcutaneously or intradermally.
The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products.
For precautions to be taken before administering the vaccine, see Precautions.
For instructions regarding thawing, handling and disposal of the vaccine, see Special precautions for disposal and other handling under Cautions for Usage.
Overdosage
Overdose data is available from 52 study participants included in the clinical trial that due to an error in dilution received 58 micrograms of COMIRNATY. The vaccine recipients did not report an increase in reactogenicity or adverse reactions.
In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.
Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in Description.
Special Precautions
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.
General recommendations: Hypersensitivity and anaphylaxis: Events of anaphylaxis have been reported. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine.
Close observation for at least 15 minutes is recommended following vaccination. A second dose of the vaccine should not be given to those who have experienced anaphylaxis to the first dose of COMIRNATY.
Anxiety-related reactions: 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.
Concurrent illness: Vaccination should be postponed in individuals suffering from acute severe febrile illness or acute infection. The presence of a minor infection and/or low-grade fever should not delay vaccination.
Thrombocytopenia and coagulation disorders: 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.
Immunocompromised individuals: The efficacy, safety and immunogenicity of the vaccine has not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of COMIRNATY may be lower in immunosuppressed individuals.
Duration of protection: The duration of protection afforded by the vaccine is unknown as it is still being determined by ongoing clinical trials.
Limitations of vaccine effectiveness: As with any vaccine, vaccination with COMIRNATY may not protect all vaccine recipients. Individuals may not be fully protected until 7 days after their second dose of vaccine.
Excipients: This vaccine contains less than 1 mmol potassium (39 mg) per dose, that is to say essentially 'potassium-free'.
This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium‑free'.
Effects on ability to drive and use machines: COMIRNATY has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under Adverse Reactions may temporarily affect the ability to drive or use machines.
Use In Pregnancy & Lactation
Pregnancy: There is limited experience with the use of COMIRNATY 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 Pharmacology: Toxicology: Preclinical safety data under Actions). Administration of COMIRNATY in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and foetus.
Breast-feeding: It is unknown whether COMIRNATY is excreted in human milk.
Fertility: Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Adverse Reactions
Summary of safety profile: The safety of COMIRNATY was evaluated in participants 16 years of age and older in 2 clinical studies that included 21,744 participants that have received at least one dose of COMIRNATY.
In Study 2, a total of 21,720 participants 16 years of age or older received at least 1 dose of COMIRNATY and a total of 21,728 participants 16 years of age or older received placebo (including 138 and 145 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively). A total of 20,519 participants 16 years of age or older received 2 doses of COMIRNATY.
At the time of the analysis of Study 2, a total of 19,067 (9,531 COMIRNATY and 9,536 placebo) participants 16 years of age or older were evaluated for safety for at least 2 months after the second dose of COMIRNATY. This included a total of 10,727 (5,350 COMIRNATY and 5,377 placebo) participants 16 to 55 years of age and a total of 8,340 (4,181 COMIRNATY and 4,159 placebo) participants 56 years and older.
The most frequent adverse reactions in participants 16 years of age and older were injection site pain (> 80%), fatigue (> 60%), headache (> 50%), myalgia and chills (> 30%), arthralgia (> 20%), pyrexia and injection site swelling (> 10%) and were usually mild or moderate in intensity and resolved within a few days after vaccination. A slightly lower frequency of reactogenicity events was associated with greater age.
Tabulated list of adverse reactions from clinical studies: Adverse reactions observed during clinical studies are listed as follows according to the following frequency categories: 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). (See Table 2.)

Click on icon to see table/diagram/image

The safety profile in 545 subjects receiving COMIRNATY, that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.
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 to local regulatory authorities per local requirements.
Alternatively, healthcare professionals can also contact respective company representatives of local suppliers/distributors for assistance in such reporting.
Drug Interactions
No interaction studies have been performed.
Concomitant administration of COMIRNATY with other vaccines has not been studied.
Caution For Usage
Special precautions for disposal and other handling: Handling instructions: COMIRNATY should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared dispersion.
Thawing prior to dilution: The multidose vial is stored frozen and must be thawed prior to dilution. Frozen vials should be transferred to an environment of 2 °C to 8 °C to thaw; a 195-vial pack may take 3 hours to thaw. Alternatively, frozen vials may also be thawed for 30 minutes at temperatures up to 30 °C for immediate use.
Allow the thawed vial to come to room temperature and gently invert it 10 times prior to dilution. Do not shake.
Prior to dilution, the thawed dispersion may contain white to off-white opaque amorphous particles.
Dilution: The thawed vaccine must be diluted in its original vial with 1.8 mL sodium chloride 9 mg/mL (0.9%) solution for injection, using a 21 gauge or narrower needle and aseptic techniques.
Equalise vial pressure before removing the needle from the vial stopper by withdrawing 1.8 mL air into the empty diluent syringe.
Gently invert the diluted dispersion 10 times. Do not shake.
The diluted vaccine should present as an off-white dispersion with no particulates visible. Discard the diluted vaccine if particulates or discolouration are present.
The diluted vials should be marked with the appropriate date and time.
Do not freeze or shake the diluted dispersion. If refrigerated, allow the diluted dispersion to come to room temperature prior to use.
Preparation of individual 0.3-mL doses of COMIRNATY: After dilution, the vial contains 2.25 mL corresponding to 5 doses of 0.3 mL. Withdraw the required 0.3-mL dose of diluted vaccine using a sterile needle.
Discard any unused vaccine within 6 hours after dilution.
Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those previously mentioned in Special precautions for disposal and other handling.
Storage
Store at -90°C to -60°C.
Store in the original package in order to protect from light.
During storage, minimise exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
Thawed vials can be handled in room light conditions.
When ready to thaw or use the vaccine: Open-lid vial trays, or vial trays containing less than 195 vials removed from frozen storage (< -60 °C) may be at room temperature (< 25 °C) for up to 3 minutes to remove vials or for transfer between ultra-low-temperature environments.
Once a vial is removed from the vial tray, it should be thawed for use.
After vial trays are returned to frozen storage following room temperature exposure, they must remain in frozen storage for at least 2 hours before they can be removed again.
For storage conditions after thawing and dilution of the medicinal product, see Shelf life as follows.
Shelf life: Unopened vial: 6 months at -90 °C to -60 °C.
Once removed from the freezer, the unopened vaccine can be stored for up to 5 days at 2 °C to 8 °C, and up to 2 hours at temperatures up to 30 °C, prior to use.
Once thawed, the vaccine should not be re-frozen.
Closed-lid vial trays containing 195 vials removed from frozen storage (< -60 °C) may be at room temperature (< 25 °C) for up to 5 minutes for transfer between ultra-low-temperature environments. After vial trays are returned to frozen storage following room temperature exposure, they must remain in frozen storage for at least 2 hours before they can be removed again.
Diluted medicinal product: Chemical and physical in-use stability has been demonstrated for 6 hours at 2 ºC to 30 ºC after dilution in sodium chloride 9 mg/mL (0.9%) solution for injection. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.
ATC Classification
J07BX - Other viral vaccines ; Used for active immunizations.
Presentation/Packing
Concentrate for dispersion for inj (vial) 30 mcg (0.3 mL)/dose (sterile concentrate; white to off-white frozen dispersion) x 5 doses.
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