Introduction

Nucleoside-modified mRNA (modRNA) vaccine used to stimulate active immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Uses for COVID-19 Vaccine (Pfizer-BioNTech)

Prevention of Coronavirus Disease 2019 (COVID-19)

COVID-19 vaccine, mRNA (Comirnaty) is used for prevention of COVID-19 caused by SARS-CoV-2 in individuals ≥12 years of age as a 2-dose primary vaccination series. Comirnaty is the FDA-approved monovalent Pfizer-BioNTech COVID-19 vaccine labeled for prevention of COVID-19 in individuals ≥12 years of age.

Although efficacy and safety have not been established, the Pfizer-BioNTech COVID-19 vaccine is also available under an FDA emergency use authorization (EUA) for active immunization to prevent COVID-19 in individuals 6 months of age or older as the bivalent vaccine (Pfizer-BioNTech COVID-19 vaccine, bivalent).

There are 2 formulations of the Pfizer BioNTech COVID-19 vaccine, a monovalent vaccine (Pfizer BioNTech COVID-19 vaccine/Comirnaty) and a bivalent vaccine (Pfizer BioNTech COVID-19 vaccine, bivalent). The monovalent form was the initial vaccine presentation; a bivalent vaccine was later authorized for improving protection against the circulating Omicron variant of SARS-CoV-2.

On April 18, 2023, FDA amended the EUA of Pfizer-BioNTech COVID-19 vaccine, bivalent to simplify the vaccination schedule. Current EUA authorizes use of the bivalent vaccine for all doses administered to individuals ≥6 months of age. The monovalent Pfizer-BioNTech COVID-19 vaccine is no longer authorized for use in the US.

Consult the CDC's Advisory Committee on Immunization Practices (ACIP) interim recommendations and clinical considerations for use of COVID-19 vaccines, including dosage and administration, specific populations and situations, and cautionary information.

COVID-19 Vaccine (Pfizer-BioNTech) Dosage and Administration

General

Pretreatment Screening

• Screen all individuals for contraindications and precautions to vaccination.

Patient Monitoring

• Monitor all individuals who receive a COVID-19 vaccine for immediate adverse reactions according to CDC (ACIP) guidelines. ACIP states that vaccination providers should consider observing the following individuals for 30 minutes after receiving the vaccine: those with a history of anaphylaxis to a non-COVID-19 vaccine or injectable therapy; those with an allergy-related contraindication to a different type of COVID-19 vaccine; those with a history of a non-severe, immediate (onset within 4 hours) allergic reaction to a previous dose of COVID-19 vaccine. Vaccination providers should consider observing all other individuals for 15 minutes because of the risk of syncope.

Premedication and Prophylaxis

• Antipyretics or analgesics (e.g., acetaminophen, nonsteroidal anti-inflammatory agents) may be taken for the treatment of postvaccination local or systemic symptoms, if medically appropriate. However, these medications should not be used prophylactically for the purposes of prevention of post-vaccination symptoms.

• Premedication with antihistamines prior to vaccination to prevent allergic reactions is generally not recommended; however, while antihistamines will not prevent anaphylaxis, some experts advise antihistamine use as a means of preventing milder allergic reactions in patients who might be at higher risk for allergic reactions.

Dispensing and Administration Precautions

• Appropriate medications and supplies for managing immediate allergic reactions must be immediately available in the event that an acute anaphylactic reaction occurs following administration of COVID-19 vaccines.

• Syncope may occur following administration of parenteral vaccines, especially in adolescents. Patients should be seated or lying down during vaccination. Vaccination providers should consider observing vaccine recipients (especially adolescents) for 15 minutes after vaccination. If syncope develops, patients should be observed until symptoms resolve.

Administration

IM Administration

Administer only by IM injection into the deltoid muscle in the upper arm for individuals 3 years of age and older. Administer by IM injection in the vastus muscle in the anterolateral thigh for children 6 months through 2 years of age. Confirm dosing volume prior to administration based on age of the recipient, product used, and whether a primary series dose or a booster dose.

The Pfizer-BioNTech COVID-19 vaccine is supplied in various formulations and vial presentations. There are important differences between these formulations such as method of preparation, requirement for dilution, dose volume, and storage requirements; consult the manufacturer's labeling (for the Comirnaty product) or the FDA EUA Fact Sheets for the Pfizer-BioNTech COVID-19 vaccine authorized for use under an EUA for specific instructions on each formulation. The various formulations and vial presentations are distinguished by different color vial caps and labels. As of April 18, 2023, the monovalent Pfizer-BioNTech COVID-19 vaccine is no longer authorized for use in US.

There are 4 presentations of Pfizer-BioNTech COVID-19 vaccine, bivalent. The bivalent vaccine supplied in single dose and multiple dose vials with a gray cap and label with a gray border is authorized for use in individuals ≥12 years of age; this formulation must not be diluted prior to use. The bivalent vaccine supplied in a multiple dose vial with an orange cap and label with an orange border is authorized for use in individuals 5 through 11 years of age; this formulation must be diluted prior to use. The bivalent vaccine supplied in a multiple dose vial with a maroon cap and label with a maroon border is authorized for use in individuals 6 months through 4 years of age; this formulation must be diluted prior to use.

Comirnaty Vials with Purple Caps

The Pfizer-BioNTech COVID-19 vaccine labeled as Comirnaty with a purple cap must be diluted with 0.9% sodium chloride injection prior to use; the vaccine is supplied as a frozen suspension in multiple-dose vials that must be thawed prior to dilution. See manufacturer's prescribing information for specific instructions for thawing.

Prior to dilution, gently invert vial 10 times; do not shake. Using aseptic technique, withdraw 1.8 mL of 0.9% sodium chloride injection into a 3- or 5-mL transfer syringe (21-gauge or narrower needle) and inject into vial of thawed vaccine suspension.

To equalize vial pressure, withdraw 1.8 mL of air into empty diluent syringe before removing the needle from the vial. Gently invert vial 10 times to mix; do not shake.

Following dilution, the Pfizer-BioNTech COVID-19 vaccine should appear as an off-white suspension; do not use if it is discolored or contains particulates.

May store vials containing diluted Pfizer-BioNTech COVID-19 vaccine between 2–25°C, but must use within 6 hours after dilution (regardless of storage temperature). Discard any unused diluted vaccine remaining in vials if not used within 6 hours after dilution.

To administer a dose, withdraw 0.3 mL of the diluted vaccine from the vial using aseptic technique and an appropriate syringe and needle, and administer immediately.

A low dead-volume syringe and needle is preferred for administration of the vaccine.

Each multiple-dose vial of thawed and diluted vaccine provides six 0.3-mL doses when low dead-volume syringes and needles are used. If standard syringes and needles are used, remaining volume of vaccine may be insufficient to extract a sixth dose from the vial. Irrespective of the type of syringe and needle used, each dose must contain 0.3 mL of vaccine.

Discard any vaccine remaining in the vial that does not constitute a full 0.3-mL dose; do not pool with vaccine from other vials to obtain a dose.

Comirnaty Vials with Gray Cap

The COVID-19 vaccine (Pfizer-BioNTech) labeled as Comirnaty with a gray cap must NOT be diluted prior to use; the vaccine is supplied as a frozen suspension in multiple-dose vials that must be thawed prior to administration. See manufacturer's prescribing information for specific instructions for thawing.

Prior to use, gently invert the vial 10 times; do not shake. After gently inverting the vial, the vaccine should appear as a white to off-white suspension with no visible particulates. Do not use if the liquid is discolored or if particles are observed.

To administer a dose, withdraw 0.3 mL of the vaccine from the vial using aseptic technique and an appropriate syringe and needle, and administer immediately. A low dead-volume syringe and needle is preferred for administration of the vaccine; however, a standard 1-mL syringe can be used if a low dead-volume syringe is not available.

Each thawed multiple dose Comirnaty vial with a gray cap provides six 0.3-mL doses when low dead-volume syringes and needles are used to extract doses from the vial. If standard syringes and needles are used, the volume of remaining vaccine may be insufficient to extract a sixth dose from the vial.

Irrespective of the type of syringe and needle used, each dose must contain 0.3 mL of vaccine. Discard any vaccine remaining in the vial that does not constitute a full 0.3-mL dose and do not pool with vaccine from other vials to obtain a dose.

Pfizer BioNTech COVID-19 Vaccine, Bivalent (Omicron BA.4/BA.5) Vials with Gray Cap and Gray Label Border

The Pfizer-BioNTech COVID-19 vaccine, bivalent authorized for use under an FDA EUA for individuals ≥12 years of age is supplied in single and multiple dose vials with a gray cap and label.

Each 0.3-mL dose of the vaccine contains 15 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 15 mcg of modRNA encoding the S glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5).

The vaccine formulation is supplied as a frozen suspension that must be thawed prior to use; do not dilute. See manufacturer's prescribing information for specific instructions for thawing.

To administer a dose, withdraw 0.3 mL of the vaccine from the vial using aseptic technique and an appropriate syringe and needle; administer immediately.

A low dead-volume syringe and needle is preferred for administration of the vaccine.

Each multiple dose vial provides six 0.3-mL doses when low dead-volume syringes and needles are used to extract doses from the vial. If standard syringes and needles are used, the volume of remaining vaccine may be insufficient to extract a sixth dose from the vial. Irrespective of the type of syringe and needle used, each dose must contain 0.3 mL of vaccine.

Discard any vaccine remaining in the vial that does not constitute a full 0.3-mL dose; excess vaccine remaining in the vial must not be pooled from multiple vials to obtain a dose.

Pfizer BioNTech COVID-19 vaccine, Bivalent (Omicron BA.4/BA.5) Vials with Orange Cap and Orange Label Border

The Pfizer-BioNTech COVID-19 vaccine, bivalent authorized for use under an FDA EUA for individuals 5–11 years of age is supplied in multiple dose vials with a orange cap and label.

Each 0.2 mL dose of the vaccine is formulated to contain 5 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 5 mcg of modRNA encoding the S-glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5).

The vaccine formulation is supplied as a frozen suspension that must be thawed and diluted prior to use. See manufacturer's prescribing information for specific instructions for thawing.

Prior to dilution, gently invert the vial 10 times; do not shake. Using aseptic technique, withdraw 1.3 mL of 0.9% sodium chloride diluent into a transfer syringe (21-gauge or narrower needle) and add diluent to the vaccine vial. Gently invert the vial 10 times to mix; do not shake. The vaccine should appear as a white to off-white suspension with no visible particulates. Do not use the vaccine if the liquid is discolored or if particles are observed.

To administer a dose, withdraw 0.2 mL of the vaccine from the vial using aseptic technique and an appropriate syringe and needle, and administer immediately. A low dead-volume syringe and needle is preferred for administration of the vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume.

Pfizer BioNTech COVID-19 vaccine, Bivalent (Omicron BA.4/BA.5) Vials with Maroon Cap and Maroon Label Border

The Pfizer-BioNTech COVID-19 vaccine, bivalent authorized for use under an FDA EUA for individuals 6 months through 4 years of age is supplied in multiple dose vials with a maroon cap and label.

Each 0.2 mL dose is formulated to contain 1.5 mcg of modRNA encoding the S-glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 1.5 mcg of modRNA encoding the S-glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5). Each dose contains 3 mcg modRNA.

The vaccine formulation is supplied as a frozen suspension that must be thawed and diluted prior to use. See manufacturer's prescribing information for specific instructions for thawing.

Prior to dilution, gently invert the vial 10 times; do not shake. Using aseptic technique, dilute the vaccine with 2.2 mL of 0.9% sodium chloride injection. Gently invert the vial 10 times to mix; do not shake. The vaccine should appear as a white to off-white suspension with no visible particulates. Do not use the vaccine if the liquid is discolored or if particles are observed.

To administer a dose, withdraw 0.2 mL of the vaccine from the vial using aseptic technique and an appropriate syringe and needle, and administer immediately. A low dead-volume syringe and needle is preferred for administration of the vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume.

Dosage

Pfizer-BioNTech COVID-19 vaccine is available in various formulations and vial presentations. Ensure the correct age-appropriate formulation is selected for administration. The monovalent Pfizer-BioNTech COVID-19 vaccine is no longer authorized for use in US; therefore, dosing recommendations are provided only for the bivalent vaccine below.

See the following tables for recommended doses and dosing intervals for the Pfizer-BioNTech COVID-19 vaccine, bivalent.

In certain immunocompromised individuals ≥5 years of age, a single additional age-appropriate dose of Pfizer-BioNTech COVID-19 vaccine, bivalent may be administered at least 2 months following the initial bivalent vaccine dose; additional doses may be administered at clinician discretion.

Contraindications

• Known history of severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine.

ACIP considers the following to be contraindications to vaccination with both mRNA COVID-19 vaccines (Pfizer BioNTech COVID-19 vaccine and Moderna COVID-19 vaccine):

• Severe allergic reaction (e.g., anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or severe allergic reaction to a component of the vaccine (e.g., polyethylene glycol [PEG]).

• Known (diagnosed) allergy to a component of the vaccine (e.g., PEG).

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Severe allergic reactions, including anaphylaxis, reported rarely following administration of mRNA COVID-19 vaccines outside of clinical trials.

Following issuance of the FDA EUA for the Pfizer-BioNTech COVID-19 vaccine, safety monitoring data identified 21 cases of anaphylaxis occurring between December 14–23, 2020 among 1,893,360 individuals in the US who received the first dose of the vaccine (11.1 cases per million vaccine doses administered).

Delayed-onset local reactions (e.g., erythema, induration, pruritus, tenderness) around the injection site area reported in some vaccine recipients, after first dose of an mRNA COVID-19 vaccine. ACIP states that delayed-onset local reaction after the first dose of an mRNA COVID-19 vaccine is not a contraindication or precaution to administration of the second vaccine dose.

If a hypersensitivity reaction, including anaphylaxis, occurs following COVID-19 vaccination, report the case to VAERS. (See EUA Requirements for Postvaccination Monitoring and Mandatory Vaccine Adverse Event Reporting under Cautions.)

Because anaphylactic reactions have been reported rarely following administration of COVID-19 vaccines, ACIP issued interim guidance with contraindications and precautions for use of COVID-19 vaccines pending further investigation.

History of severe allergic reaction (e.g., anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components (e.g., PEG): ACIP considers this a contraindication to vaccination with the mRNA COVID-19 vaccines. ACIP states may consider using an alternative COVID-19 vaccine (Janssen COVID-19 vaccine) in such individuals. However, because of potential cross-reactive hypersensitivity between ingredients in mRNA COVID-19 vaccines and the Janssen COVID-19 vaccine (including PEG and polysorbate 80, respectively), consider consultation with an allergist-immunologist to help determine if the individual can safely receive the Janssen COVID-19 vaccine.

Known (diagnosed) allergy to a component of the vaccine (e.g., PEG): ACIP considers this a contraindication to vaccination with the mRNA COVID-19 vaccines. ACIP states may consider using an alternative COVID-19 vaccine (Janssen COVID-19 vaccine) in such individuals. However, because of potential cross-reactive hypersensitivity between ingredients in mRNA COVID-19 vaccines and the Janssen COVID-19 vaccine (including PEG and polysorbate 80, respectively), consider consultation with an allergist-immunologist to help determine if the individual can safely receive the Janssen COVID-19 vaccine.

History of any immediate allergic reaction to any other vaccine or injectable therapy (i.e., IM, IV, or sub-Q vaccines or therapies): ACIP considers this a precaution, but not a contraindication, to COVID-19 vaccination. ACIP states that history of allergic reaction to sub-Q immunotherapy for allergies (i.e., allergy shots) is not a contraindication or precaution to COVID-19 vaccination.

History of immediate allergic reaction to a vaccine or injectable therapy that contains multiple components (one or more of which is a component of a COVID-19 vaccine), but it is not known which component elicited the reaction: ACIP considers this a precaution, but not a contraindication, to the COVID-19 vaccine.

History of allergic reactions (including severe allergic reactions) not related to COVID-19 vaccines, other vaccines, or injectable therapies: ACIP states that food, pet, insect, venom, or environmental allergies and allergic reactions to oral medications (including the oral equivalents of injectable medications) are not a contraindication or precaution to COVID-19 vaccination. Latex allergy is not a contraindication or precaution since vial stoppers of COVID-19 vaccines are not made with natural rubber latex. Allergies to eggs or gelatin are not a contraindication or precaution since COVID-19 vaccines do not contain eggs or gelatin. In addition, a family history of allergies is not a contraindication or precaution to COVID-19 vaccination.

History of delayed-onset local reactions (e.g., erythema, induration, pruritus) around the injection site area after first dose of an mRNA COVID-19 vaccine: ACIP states that these local reactions are not a contraindication or precaution for administration of second dose of mRNA COVID-19 vaccine. Such individuals should receive the second dose using the same mRNA COVID-19 vaccine used for first dose at the recommended interval, preferably in the opposite arm.

If a precaution for COVID-19 vaccination is identified, ACIP recommends performing a risk assessment to help decide whether the individual should be vaccinated.

ACIP states to observe the following individuals for 30 minutes after vaccination: those with a history of an immediate allergic reaction of any severity to any other vaccine or injectable therapy, those with a contraindication to a different type of COVID-19 vaccine (i.e., viral vector), those with a history of a non-severe, immediate allergic reaction to a previous dose of COVID-19 vaccine, and those with a history of anaphylaxis due to any cause not considered a contraindication; observe all other individuals for 15 minutes. Instruct vaccine recipients to seek immediate medical care if they develop signs or symptoms of an allergic reaction after their observation period ends and they have left the vaccination site.

Appropriate medications and supplies to manage immediate allergic reactions (e.g., epinephrine) must be immediately available in the event that an acute anaphylactic reaction occurs following administration of a COVID-19 vaccine. Early recognition of clinical signs and symptoms of anaphylaxis is important. Immediately treat individuals with suspected anaphylaxis with IM epinephrine.

ACIP interim guidance regarding preparation for and management of anaphylaxis at COVID-19 vaccination sites are available at the CDC website at [Web] and [Web].

When confronted with a complex COVID-19 vaccine safety question concerning an individual patients that is not readily addressed by ACIP guidance, US healthcare personnel or health departments can request a clinical consultation from the Clinical Immunization Safety Assessment COVIDvax project ([Web]).

Lymphadenopathy

Lymphadenopathy reported in clinical trials evaluating COVID-19 vaccine (Pfizer-BioNTech).

Unilateral axillary adenopathy, including palpable axillary mass, identified through self-detection or incidentally on breast imaging in individuals who received an mRNA COVID-19 vaccine outside of clinical trials. Consider vaccine-induced hyperplastic axillary adenopathy in differential diagnosis if unilateral axillary adenopathy identified on breast imaging in individuals who recently received an mRNA COVID-19 vaccine. Some experts suggest scheduling routine screening mammography or ultrasound prior to first dose of an mRNA COVID-19 vaccine or 4–6 weeks following second dose of the vaccine, if possible, and if this would not unduly delay appropriate care.

Consider that increased axillary lymph node or deltoid uptake has been detected on positron emission tomography (PET) or other imaging performed in individuals who recently received an mRNA vaccine.

Myocarditis and Pericarditis

Rare reports of acute myocarditis or pericarditis following receipt of mRNA COVID-19 vaccines. Symptom onset typically within 0–7 days (range: 0–40 days) after receipt of a vaccine dose; reported more frequently after the second vaccine dose than the first dose. Observational data have suggested an increased risk with the Moderna COVID-19 vaccine compared with other authorized or approved COVID-19 vaccines.

Data to date indicate that myocarditis and pericarditis following vaccination with an mRNA COVID-19 vaccine have predominantly occurred in male adolescents and young adults (range: 12–29 years of age). Observed risk of myocarditis and pericarditis is higher among males <40 years of age. Although most patients were hospitalized and some required intensive care support, the majority of cases responded to conservative treatment. Additional data needed regarding potential for long-term sequelae.

Consider the possibility of myocarditis and pericarditis in the differential diagnosis for adolescents or young adults with acute chest pain, shortness of breath, or palpitations. During initial evaluation of suspected cases, query the patient about prior COVID-19 vaccination and pertinent medical, travel, and social history; in addition, consider assessing ECG, troponin levels, and inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate. Consider expert consultation regarding diagnosis, management, and follow-up.

Individuals who developed myocarditis or pericarditis after a dose of an mRNA COVID-19 vaccine: Because it is unclear whether such individuals are at increased risk of further adverse cardiac effects following a subsequent dose of the vaccine, experts recommend deferring subsequent doses until additional safety data are available.

Individuals with a history of myocarditis or pericarditis unrelated to mRNA COVID-19 vaccination (e.g., prior to COVID-19 vaccination): Data are limited regarding the safety and efficacy of COVID-19 vaccines in such individuals. ACIP states that any COVID-19 vaccine approved or authorized by FDA can be administered after the episode of myocarditis or pericarditis unrelated to COVID-19 vaccination has completely resolved.

Inform individuals receiving an mRNA COVID-19 vaccine, about the possibility of myocarditis or pericarditis after receiving the vaccine and advise them to seek medical care if symptoms occur after vaccination.

If myocarditis or pericarditis occurs after receipt of a COVID-19 vaccine, report the case to VAERS.

Thrombocytopenia

Very rare reports of thrombocytopenia, including immune thrombocytopenia (ITP), in recipients of mRNA COVID-19 vaccines (Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine) during post-authorization surveillance.

As of April 24, 2021, 11 cases of cerebral venous sinus thrombosis (CVST) have been reported in recipients of mRNA COVID-19 vaccines (3 in recipients of the Pfizer-BioNTech vaccine and 8 in recipients of the Moderna vaccine). However, only 6 were considered to be potential incident cases of CVST; thrombocytopenia was not reported in any of these patients. At the time of this analysis, 6.3 million doses of mRNA COVID-19 vaccines had been administered, and there were no confirmed cases of CVST with thrombocytopenia in recipients of the Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine.

Concomitant Illness

Base decision to administer or delay vaccination in an individual with a current or recent febrile illness on the severity of symptoms and etiology of the illness.

ACIP states that a moderate or severe acute illness is a precaution for administration of vaccines and recommends that a risk assessment be performed with potential deferral of vaccination. Deferring vaccination until an individual has recovered avoids superimposing vaccine adverse effects on the underlying illness or mistakenly concluding that a manifestation of the underlying illness resulted from vaccine administration.

Individuals with a History of Multisystem Inflammatory Syndrome

Data not available to date regarding safety and efficacy of COVID-19 vaccines in adults or children with a history of multisystem inflammatory syndrome (MIS-A or MIS-C, respectively). ACIP recommends weighing theoretical concerns of dysregulated immune response to SARS-CoV-2 against the known risks of COVID-19 following reinfection and the benefits of protection following COVID-19 vaccination.

ACIP states that individuals with a history of MIS-A or MIS-C may choose to be vaccinated.

If MIS-A or MIS-C associated with a confirmed SARS-CoV-2 infection develops after receipt of a COVID-19 vaccine, consider referral to a specialist in infectious diseases, rheumatology, or cardiology. US healthcare providers and health departments can also request a clinical consultation from the Clinical Immunization Safety Assessment COVIDvax project ([Web]).

If MIS-A or MIS-C occurs following COVID-19 vaccination, report the case to VAERS.

Individuals with Underlying Medical Conditions

ACIP states that individuals with altered immunocompetence or certain underlying medical conditions may receive any COVID-19 vaccine approved or authorized by FDA, unless they have a contraindication to the vaccine. Current FDA-approved or FDA-authorized COVID-19 vaccines are not live vaccines, so they may be safely administered to immunocompromised individuals.

US healthcare providers and health departments can request a clinical consultation from the Clinical Immunization Safety Assessment COVIDvax project ([Web]) if they have concerns about vaccinating individuals with certain underlying medical conditions.

Individuals with Altered Immunocompetence

Individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have diminished immune responses to vaccines, including the Pfizer-BioNTech COVID-19 vaccine.

Immunocompromised individuals (e.g., solid organ transplant recipients, those with lymphoid malignancies) may have reduced immune responses following a 2-dose vaccination series of an mRNA COVID-19 vaccine compared with those who are not immunocompromised.

Administration of an additional dose of mRNA COVID-19 vaccine after the initial 2-dose vaccination series may enhance immune responses to the vaccine.

ACIP recommends that individuals who are moderately or severely immunocompromised follow booster recommendations for the general population.

Counsel immunocompromised individuals about the unknown safety profile and effectiveness of COVID-19 vaccines in immunocompromised populations and the potential for reduced immune responses. Advise them of the need to continue following all current CDC guidelines for fully vaccinated individuals to protect themselves from COVID-19.

Individuals with Autoimmune Conditions

ACIP states that individuals with autoimmune conditions may receive any COVID-19 vaccine approved or authorized by FDA, unless they have a contraindication to the vaccine.

Individuals with a History of Guillain-Barré Syndrome (GBS)

To date, GBS not reported in clinical trials evaluating mRNA COVID-19 vaccines.

ACIP states that individuals with a history of GBS may receive any COVID-19 vaccine approved or authorized by FDA, unless they have a contraindication to the vaccine.

If GBS occurs following COVID-19 vaccination, report the case to VAERS.

Individuals with a History of Bell's Palsy

Although a causal relationship not established, several cases of Bell's palsy reported in individuals who received the Pfizer-BioNTech or the Moderna COVID-19 vaccines.

ACIP states, in the absence of a causal relationship between COVID-19 vaccines and Bell's palsy, individuals with a history of Bell’s palsy may receive COVID-19 vaccination, unless they have a contraindication to the vaccine.

If Bell’s palsy occurs following COVID-19 vaccination, report the case to VAERS.

Individuals with Increased Bleeding Risk

Advise individuals who have bleeding disorders or are receiving anticoagulant therapy about the risk of hematoma from IM injections.

ACIP states that IM vaccines may be given to individuals who have bleeding disorders if a clinician familiar with the patient’s bleeding risk determines that the preparation can be administered with reasonable safety. In these cases, use a fine needle (23 gauge or smaller) to administer the vaccine and apply firm pressure to the injection site (without rubbing) for ≥2 minutes. In individuals receiving therapy for hemophilia, schedule IM vaccines for administration shortly after a dose of such therapy.

Individuals receiving anticoagulation therapy presumably have the same bleeding risk as those with clotting factor disorders and should follow the same guidelines for IM administration. If possible, schedule IM vaccines prior to use of an anticoagulant so that patient's risk of bleeding is not increased by the drug's therapeutic action.

History of Dermal Filler Use

Administration of an mRNA COVID-19 vaccine to individuals who have received injectable dermal fillers (e.g., hyaluronic acid dermal fillers) has infrequently resulted in swelling at or near site of dermal filler injection (usually face or lips) starting 1–2 days after vaccination. This effect reported when the vaccine was given 2 weeks to 6 months or longer after last dermal filler injection; appears to be temporary and resolves with medical treatment, including corticosteroid therapy.

ACIP states that individuals who have received injectable dermal fillers may receive COVID-19 vaccination, unless they have a contraindication. Advise such individuals to contact their healthcare provider for evaluation if they develop swelling at or near site of dermal filler injection following vaccination.

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against COVID-19.

Use of COVID-19 vaccines for outbreak management or for postexposure prophylaxis to prevent SARS-CoV-2 infection in individuals with a specific known exposure to the virus is unlikely to be effective, and not currently recommended.

Duration of Immunity

Duration of protection against SARS-CoV-2 infection following vaccination with a primary regimen of the Pfizer-BioNTech COVID-19 vaccine not fully evaluated.

The immunogenicity of COVID-19 vaccines has been demonstrated through 6 to 8 months after completion of the primary vaccine series. However, waning antibody levels and reduced neutralization of variants have been documented.

Improper Storage and Handling

Improper storage or handling of vaccines may reduce or destroy vaccine potency resulting in inadequate or no immune response in vaccine recipients. Inspect all vaccines on delivery and monitor during storage to ensure that recommended storage temperatures are maintained.

The Pfizer-BioNTech COVID-19 vaccine must be shipped, stored, and handled under specific conditions at all times, including maintaining cold chain conditions and chain of custody, according to specifications in the EUA fact sheet for healthcare providers and guidance from the manufacturer and CDC.

EUA Requirements for Postvaccination Monitoring and Mandatory Vaccine Adverse Event Reporting

Monitor all vaccine recipients for immediate adverse reactions according to CDC (ACIP) guidelines.

Provide vaccine recipients or their caregivers with information on, and encourage participation in, CDC's voluntary smartphone-based tool (v-safe) that uses text messaging and web surveys to check in with individuals who have received a COVID-19 vaccine to identify potential adverse effects. Information on v-safe is available at [Web].

It is mandatory that vaccination providers administering the Pfizer-BioNTech COVID-19 vaccine report all vaccine administration errors (even if not associated with an adverse event) and serious adverse events (irrespective of attribution to vaccination) that occur following vaccination and also report all cases of multisystem inflammatory syndrome (MIS) and COVID-19 that result in hospitalization or death in vaccine recipients to VAERS. Can complete and submit VAERS reports online at [Web] or by faxing to 877-721-0366; include the words “Pfizer-BioNTech COVID-19 Vaccine EUA” in description section of the report. Obtain additional information on submitting a VAERS report by calling 800-822-7967 or emailing [email protected]. To the extent feasible, also provide a copy of the VAERS form to the manufacturer (Pfizer) at [Web], 866-635-8337 (fax), or 800-438-1985 (phone).

Consult FDA fact sheet for healthcare providers administering the Pfizer-BioNTech COVID-19 vaccine under the EUA that is available at FDA website ([Web]) and manufacturer's website ([Web]) for requirements and instructions regarding reporting of adverse reactions and vaccination errors.

Interpretation of SARS-CoV-2 Testing in Vaccinated Individuals

Results of SARS-CoV-2 viral tests (nucleic acid amplification or antigen tests) are not affected by prior COVID-19 vaccination.

Use a test that specifically evaluates IgM/IgG to the nucleocapsid protein to assess for evidence of prior infection in an individual with a history of COVID-19 vaccination (e.g., for public health surveillance or diagnosis of MIS-C or MIS-A).

Interpretation of Tuberculosis Tests in Vaccinated Individuals

ACIP states do not delay COVID-19 vaccination in situations when an immune-based method of tuberculosis testing (i.e., intradermal tuberculin skin test [TST] or serum interferon gamma release assay [IGRA]) is required or indicated.

If TST or IGRA is required, ACIP states that such testing can be administered without regard to timing of COVID-19 vaccination.

Specific Populations

Pregnancy

Data insufficient to date regarding use of the Pfizer-BioNTech COVID-19 vaccine to inform vaccine-associated risks during pregnancy.

A reproductive and developmental toxicity study in female rats using a vaccine formulation containing same quantity of mRNA and other ingredients as the Pfizer-BioNTech COVID-19 vaccine did not reveal evidence of vaccine-related adverse effects on female fertility, fetal development, or postnatal development.

Available data suggest that, while the absolute risk is low, pregnant and recently pregnant women with COVID-19 are at increased risk of severe illness, including illness resulting in hospitalization, admission to an intensive care unit (ICU), mechanical ventilation, extracorporeal membrane oxygenation (ECMO), or death compared with women who are not pregnant. Pregnant and recently pregnant women with comorbidities such as obesity and diabetes mellitus may be at even higher risk of severe COVID-19. Additionally, pregnant women with COVID-19 are at increased risk of preterm birth and may be at an increased risk of adverse pregnancy complications or outcomes, such as preeclampsia, coagulopathy, and stillbirth.

Post-authorization surveillance safety data are accumulating regarding COVID-19 vaccination during pregnancy and clinical trials evaluating safety and efficacy of COVID-19 vaccines in pregnant women are underway or planned. Early data from VAERS, v-safe active surveillance, and v-safe pregnancy registry have not identified any safety concerns in pregnant women who were vaccinated late in their pregnancy or their infants; additional evidence has not found an increased risk for miscarriage with receipt of a mRNA vaccine before 20 weeks gestation. There is some evidence that pregnant women who receive an mRNA vaccine (Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine) during pregnancy have immune responses comparable to those observed in nonpregnant individuals and may develop anti-SARS-CoV-2 antibody titers greater than those observed in women diagnosed with SARS-CoV-2 infection during pregnancy. The Pfizer-BioNTech COVID-19 vaccine cannot cause SARS-CoV-2 infection in the pregnant woman or her fetus.

FDA states pregnancy is not a contraindication to use of the Pfizer-BioNTech COVID-19 vaccine; pregnant women should discuss potential benefits and risks of vaccination with their healthcare providers.

ACIP states vaccination against COVID-19 is recommended for pregnant women. These experts state that evidence regarding safety and efficacy of COVID-19 vaccines available from both animal and human studies indicates that benefits of vaccination against COVID-19 during pregnancy outweigh any known or potential risks. For purposes of decisions regarding administration of both the primary vaccination series and a booster dose, ACIP states consider pregnant and recently pregnant women (up until at least 42 days following the end of pregnancy) in the same group as individuals with underlying medical conditions.

ACOG recommends that pregnant women be vaccinated against COVID-19. When recommending the COVID-19 vaccine to pregnant women, ACOG suggests that clinicians review available data on risks and benefits of vaccination, including risks of not getting vaccinated, in the context of the individual patient’s current health status and risk of exposure (e.g., possibility for exposure at work or home) and possibility for exposing high-risk household members. In addition, take into account the individual patient’s values and perceived risk of various outcomes; autonomous decision-making should be respected and supported.

ACIP and ACOG state that a conversation between the pregnant woman and her clinical team may assist with decisions regarding use of COVID-19 vaccines; however, such a conversation is not required and written permission is not needed prior to vaccination.

ACIP and ACOG recommend that women who become pregnant after receiving the first dose of an mRNA COVID-19 vaccination series should receive the second dose according to the usual schedule, unless contraindicated.

ACOG states do not withhold Rh_o(D) immune globulin when indicated in an individual who is planning to receive or recently received a COVID-19 vaccine.

Adverse effects similar to those reported in non-pregnant individuals can occur following COVID-19 vaccination in pregnant women. Advise pregnant women who experience fever following vaccination to take acetaminophen; may also offer acetaminophen as an option for pregnant women experiencing other postvaccination symptoms.

Encourage women who receive the Pfizer-BioNTech COVID-19 vaccine during pregnancy to enroll in a pregnancy exposure registry at [Web] Also encourage women who receive a COVID-19 vaccine during pregnancy and those who become pregnant within 30 days after receiving a COVID-19 vaccine to participate in CDC's v-safe program.

Females and Males of Reproductive Capacity

Routine pregnancy testing not recommended before receiving a COVID-19 vaccine.

ACIP states vaccination against COVID-19 recommended for women currently trying to become pregnant and those who might become pregnant in the future. Women trying to become pregnant do not need to avoid pregnancy after COVID-19 vaccination.

ACOG recommends vaccination for all eligible individuals, including those who may consider future pregnancy.

There is no evidence that any FDA-approved or FDA-authorized COVID-19 vaccines affect current or future fertility. FDA states there is no scientific evidence to suggest that Pfizer-BioNTech COVID-19 vaccine could cause infertility in women. In addition, infertility not known to occur as a result of natural COVID-19 disease, further demonstrating that immune responses to the virus, whether induced by infection or a vaccine, are not a cause of infertility.

Lactation

Not known whether Pfizer-BioNTech COVID-19 vaccine is distributed into milk. Data not available to assess whether the vaccine administered to a woman who is breast-feeding has any effects on breast-fed infant or milk production.

Consider benefits of breast-feeding and the importance of the Pfizer-BioNTech COVID-19 vaccine to the woman along with any potential adverse effects on the breast-fed child from the vaccine or from the underlying maternal condition (i.e., susceptibility to SARS-CoV-2 infection).

FDA states that breast-feeding is not a contraindication to use of the Pfizer-BioNTech COVID-19 vaccine; breast-feeding women should discuss benefits and risks of vaccination with their healthcare providers.

ACIP states that vaccination against COVID-19 recommended for lactating women. FDA-authorized COVID-19 vaccines administered to breast-feeding women cannot cause SARS-CoV-2 infection in women or their infants; therefore, breast-feeding women can receive COVID-19 vaccination.

ACOG recommends that lactating women be vaccinated against COVID-19. ACOG also states that theoretical concerns regarding safety of vaccinating lactating women do not outweigh potential benefits of the vaccine; there is no need for individuals who receive a COVID-19 vaccine to avoid initiating breast-feeding or to discontinue breast-feeding.

Although there is some evidence that antibodies that develop following vaccination with mRNA COVID-19 vaccines are present in breast milk, additional data needed to determine if these antibodies convey protection against SARS-CoV-2 infection in breast-fed infants.

Pediatric Use

Pfizer-BioNTech COVID-19 vaccine, bivalent is authorized for use in individuals 6 months through 17 years of age. The bivalent vaccine is not authorized for use in individuals <6 months of age.

Geriatric Use

Data from the ongoing clinical trial evaluating the Pfizer-BioNTech COVID-19 vaccine indicate that, as of March 13, 2021, 20.7% of individuals who received a 2-dose primary series of the monovalent vaccine were ≥65 years of age and 4.2% were ≥75 years of age. No overall differences in safety or effectiveness observed between those ≥65 years of age and younger recipients of the vaccine.

A clinical study with the bivalent Pfizer-BioNTech COVID-19 vaccine (Original and Omicron BA.1) included 197 individuals ≥65 years of age and data from these patients contribute to the overall assessment of safety and effectiveness of the vaccine.

Common Adverse Effects

Local adverse effects (≥10%) in adults and adolescents ≥16 years of age following any dose in clinical trials: Injection site pain (88.6%) and swelling (10.6%) in those 16 through 55 years of age and injection site pain (78.2%), erythema (10.4%), and swelling (11.8%) in those ≥56 years of age. Generally mild to moderate in severity; severe pain reported in up to 1.5% of vaccine recipients. Mean duration of adverse local effects following the second dose of the 2-dose vaccination series was 2.1–3 days (range: 1–70 days for injection site pain, 1–34 days for erythema, and 1–34 days for swelling).

Systemic adverse effects (≥10%) in adults and adolescents ≥16 years of age following any dose in clinical trials: Fatigue (70.1%), headache (64.9%), muscle pain (45.5%), chills (41.5%), joint pain (27.5%), and fever (17.8%) in those 16 through 55 years of age and fatigue (56.9%), headache (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), and fever (11.5%) in those ≥56 years of age. Systemic adverse effects reported more frequently after second dose of the 2-dose primary vaccination series and reported more frequently in those 16–55 years of age than in those ≥56 years of age. Generally observed within first 1–2 days after vaccination and resolved within a few days. Use of antipyretic or pain medication within 7 days after receiving the first or second vaccine dose reported in 27.8 or 45.2%, respectively, of those 18–55 years of age and in 19 or 37%, respectively, of those ≥56 years of age. In study participants 16–55 years of age, serious adverse events reported in 0.8% of vaccine recipients and 0.9% of placebo recipients; in those ≥56 years of age, serious adverse events reported in 1.8 or 1.7% of vaccine or placebo recipients, respectively.

Adolescents 12 through 15 years of age^{† [off-label]} who received a 2-dose primary series: Local adverse effects reported in a clinical trial were injection site pain (90.5%), swelling (9.2%), and erythema (8.6%); mean duration of pain at injection site was 2.4 days (range: 1–10 days) after first dose of the 2-dose vaccination series. Systemic adverse effects were fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), lymphadenopathy (0.8%), and nausea (0.4%). Use of antipyretic or pain medication within 7 days after receiving the first or second vaccine dose reported in 36.6 or 50.8%, respectively. Serious adverse events reported in 0.4% of vaccine recipients and 0.1% of placebo recipients.

Additional (third) primary dose^{† [off-label]} in solid organ transplant recipients: Adverse event profile following a third dose in transplant (heart, kidney, liver, lung pancreas) recipients was similar to that following the second dose; no grade 3 or 4 adverse events reported during 1 month of follow-up after third dose.

Bivalent booster dose (Original and Omicron BA.1)^{† [off-label]} in adults 55 years of age and older who competed a primary series and a first booster dose: pain at the injection site (58.1%), fatigue (49.2%), headache (33.6%), muscle pain (22.3%), chills (13.0%), joint pain (11.3%), injection site redness (7.0%), injection site swelling (6.6%), fever (5.0%), lymphadenopathy (0.3%), nausea (0.3%), and malaise (0.3%).

Children 5–11 years of age ^{† [off-label]} who received a 2-dose primary series: Local adverse effects reported in a clinical trial were pain at the injection site (84.3%), injection site redness (26.4%), injection site swelling (20.4%); mean duration of pain at the injection site after second dose was 2.3 days in children. Systemic adverse effects were fatigue (51.7%), headache (38.2%), muscle pain (17.5%), chills (12.4%), fever (8.3%), joint pain (7.6%), lymphadenopathy (0.9%), nausea (0.4%), rash (0.3%), malaise (0.1%), and decreased appetite (0.1%). Use of antipyretic or pain medication within 7 days after receiving the first or second vaccine dose was reported in 14.4 or 19.7%, respectively, of these children. No serious adverse events were reported that were considered related to vaccination.

Children 6–23 months of age^{† [off-label]} who received a 3-dose primary series: irritability, decreased appetite, tenderness at the injection site, injection site redness and swelling, fever, and lymphadenopathy.

Children 24 months through 4 years of age^† who received a 3-dose primary series: pain at the injection site, fatigue, injection site redness and swelling, fever, headache, chills, muscle pain, joint pain, and lymphadenopathy.

Other adverse effects reported during post-authorization and post-marketing surveillance include cardiac effects (myocarditis, pericarditis), GI effects (diarrhea, vomiting), hypersensitivity reactions (anaphylaxis, rash, pruritus, urticaria, angioedema), extremity pain (arm), and syncope.

General

Pretreatment Screening

• Screen all individuals for contraindications and precautions to vaccination.

Patient Monitoring

• Monitor all individuals who receive a COVID-19 vaccine for immediate adverse reactions according to CDC (ACIP) guidelines. ACIP states that vaccination providers should consider observing the following individuals for 30 minutes after receiving the vaccine: those with a history of anaphylaxis to a non-COVID-19 vaccine or injectable therapy; those with an allergy-related contraindication to a different type of COVID-19 vaccine; those with a history of a non-severe, immediate (onset within 4 hours) allergic reaction to a previous dose of COVID-19 vaccine. Vaccination providers should consider observing all other individuals for 15 minutes because of the risk of syncope.

Premedication and Prophylaxis

• Antipyretics or analgesics (e.g., acetaminophen, nonsteroidal anti-inflammatory agents) may be taken for the treatment of postvaccination local or systemic symptoms, if medically appropriate. However, these medications should not be used prophylactically for the purposes of prevention of post-vaccination symptoms.

• Premedication with antihistamines prior to vaccination to prevent allergic reactions is generally not recommended; however, while antihistamines will not prevent anaphylaxis, some experts advise antihistamine use as a means of preventing milder allergic reactions in patients who might be at higher risk for allergic reactions.

Dispensing and Administration Precautions

• Appropriate medications and supplies for managing immediate allergic reactions must be immediately available in the event that an acute anaphylactic reaction occurs following administration of COVID-19 vaccines.

• Syncope may occur following administration of parenteral vaccines, especially in adolescents. Patients should be seated or lying down during vaccination. Vaccination providers should consider observing vaccine recipients (especially adolescents) for 15 minutes after vaccination. If syncope develops, patients should be observed until symptoms resolve.

Administration

IM Administration

Administer only by IM injection into the deltoid muscle in the upper arm for individuals 3 years of age and older. Administer by IM injection in the vastus muscle in the anterolateral thigh for children 6 months through 2 years of age. Confirm dosing volume prior to administration based on age of the recipient, product used, and whether a primary series dose or a booster dose.

The Pfizer-BioNTech COVID-19 vaccine is supplied in various formulations and vial presentations. There are important differences between these formulations such as method of preparation, requirement for dilution, dose volume, and storage requirements; consult the manufacturer's labeling (for the Comirnaty product) or the FDA EUA Fact Sheets for the Pfizer-BioNTech COVID-19 vaccine authorized for use under an EUA for specific instructions on each formulation. The various formulations and vial presentations are distinguished by different color vial caps and labels. As of April 18, 2023, the monovalent Pfizer-BioNTech COVID-19 vaccine is no longer authorized for use in US.

There are 4 presentations of Pfizer-BioNTech COVID-19 vaccine, bivalent. The bivalent vaccine supplied in single dose and multiple dose vials with a gray cap and label with a gray border is authorized for use in individuals ≥12 years of age; this formulation must not be diluted prior to use. The bivalent vaccine supplied in a multiple dose vial with an orange cap and label with an orange border is authorized for use in individuals 5 through 11 years of age; this formulation must be diluted prior to use. The bivalent vaccine supplied in a multiple dose vial with a maroon cap and label with a maroon border is authorized for use in individuals 6 months through 4 years of age; this formulation must be diluted prior to use.

Comirnaty Vials with Purple Caps

The Pfizer-BioNTech COVID-19 vaccine labeled as Comirnaty with a purple cap must be diluted with 0.9% sodium chloride injection prior to use; the vaccine is supplied as a frozen suspension in multiple-dose vials that must be thawed prior to dilution. See manufacturer's prescribing information for specific instructions for thawing.

Prior to dilution, gently invert vial 10 times; do not shake. Using aseptic technique, withdraw 1.8 mL of 0.9% sodium chloride injection into a 3- or 5-mL transfer syringe (21-gauge or narrower needle) and inject into vial of thawed vaccine suspension.

To equalize vial pressure, withdraw 1.8 mL of air into empty diluent syringe before removing the needle from the vial. Gently invert vial 10 times to mix; do not shake.

Following dilution, the Pfizer-BioNTech COVID-19 vaccine should appear as an off-white suspension; do not use if it is discolored or contains particulates.

May store vials containing diluted Pfizer-BioNTech COVID-19 vaccine between 2–25°C, but must use within 6 hours after dilution (regardless of storage temperature). Discard any unused diluted vaccine remaining in vials if not used within 6 hours after dilution.

To administer a dose, withdraw 0.3 mL of the diluted vaccine from the vial using aseptic technique and an appropriate syringe and needle, and administer immediately.

A low dead-volume syringe and needle is preferred for administration of the vaccine.

Each multiple-dose vial of thawed and diluted vaccine provides six 0.3-mL doses when low dead-volume syringes and needles are used. If standard syringes and needles are used, remaining volume of vaccine may be insufficient to extract a sixth dose from the vial. Irrespective of the type of syringe and needle used, each dose must contain 0.3 mL of vaccine.

Discard any vaccine remaining in the vial that does not constitute a full 0.3-mL dose; do not pool with vaccine from other vials to obtain a dose.

Comirnaty Vials with Gray Cap

The COVID-19 vaccine (Pfizer-BioNTech) labeled as Comirnaty with a gray cap must NOT be diluted prior to use; the vaccine is supplied as a frozen suspension in multiple-dose vials that must be thawed prior to administration. See manufacturer's prescribing information for specific instructions for thawing.

Prior to use, gently invert the vial 10 times; do not shake. After gently inverting the vial, the vaccine should appear as a white to off-white suspension with no visible particulates. Do not use if the liquid is discolored or if particles are observed.

To administer a dose, withdraw 0.3 mL of the vaccine from the vial using aseptic technique and an appropriate syringe and needle, and administer immediately. A low dead-volume syringe and needle is preferred for administration of the vaccine; however, a standard 1-mL syringe can be used if a low dead-volume syringe is not available.

Each thawed multiple dose Comirnaty vial with a gray cap provides six 0.3-mL doses when low dead-volume syringes and needles are used to extract doses from the vial. If standard syringes and needles are used, the volume of remaining vaccine may be insufficient to extract a sixth dose from the vial.

Irrespective of the type of syringe and needle used, each dose must contain 0.3 mL of vaccine. Discard any vaccine remaining in the vial that does not constitute a full 0.3-mL dose and do not pool with vaccine from other vials to obtain a dose.

Pfizer BioNTech COVID-19 Vaccine, Bivalent (Omicron BA.4/BA.5) Vials with Gray Cap and Gray Label Border

The Pfizer-BioNTech COVID-19 vaccine, bivalent authorized for use under an FDA EUA for individuals ≥12 years of age is supplied in single and multiple dose vials with a gray cap and label.

Each 0.3-mL dose of the vaccine contains 15 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 15 mcg of modRNA encoding the S glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5).

The vaccine formulation is supplied as a frozen suspension that must be thawed prior to use; do not dilute. See manufacturer's prescribing information for specific instructions for thawing.

To administer a dose, withdraw 0.3 mL of the vaccine from the vial using aseptic technique and an appropriate syringe and needle; administer immediately.

A low dead-volume syringe and needle is preferred for administration of the vaccine.

Each multiple dose vial provides six 0.3-mL doses when low dead-volume syringes and needles are used to extract doses from the vial. If standard syringes and needles are used, the volume of remaining vaccine may be insufficient to extract a sixth dose from the vial. Irrespective of the type of syringe and needle used, each dose must contain 0.3 mL of vaccine.

Discard any vaccine remaining in the vial that does not constitute a full 0.3-mL dose; excess vaccine remaining in the vial must not be pooled from multiple vials to obtain a dose.

Pfizer BioNTech COVID-19 vaccine, Bivalent (Omicron BA.4/BA.5) Vials with Orange Cap and Orange Label Border

The Pfizer-BioNTech COVID-19 vaccine, bivalent authorized for use under an FDA EUA for individuals 5–11 years of age is supplied in multiple dose vials with a orange cap and label.

Each 0.2 mL dose of the vaccine is formulated to contain 5 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 5 mcg of modRNA encoding the S-glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5).

The vaccine formulation is supplied as a frozen suspension that must be thawed and diluted prior to use. See manufacturer's prescribing information for specific instructions for thawing.

Prior to dilution, gently invert the vial 10 times; do not shake. Using aseptic technique, withdraw 1.3 mL of 0.9% sodium chloride diluent into a transfer syringe (21-gauge or narrower needle) and add diluent to the vaccine vial. Gently invert the vial 10 times to mix; do not shake. The vaccine should appear as a white to off-white suspension with no visible particulates. Do not use the vaccine if the liquid is discolored or if particles are observed.

To administer a dose, withdraw 0.2 mL of the vaccine from the vial using aseptic technique and an appropriate syringe and needle, and administer immediately. A low dead-volume syringe and needle is preferred for administration of the vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume.

Pfizer BioNTech COVID-19 vaccine, Bivalent (Omicron BA.4/BA.5) Vials with Maroon Cap and Maroon Label Border

The Pfizer-BioNTech COVID-19 vaccine, bivalent authorized for use under an FDA EUA for individuals 6 months through 4 years of age is supplied in multiple dose vials with a maroon cap and label.

Each 0.2 mL dose is formulated to contain 1.5 mcg of modRNA encoding the S-glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original) and 1.5 mcg of modRNA encoding the S-glycoprotein of SARS-CoV-2 Omicron variant lineages BA.4 and BA.5 (Omicron BA.4/BA.5). Each dose contains 3 mcg modRNA.

The vaccine formulation is supplied as a frozen suspension that must be thawed and diluted prior to use. See manufacturer's prescribing information for specific instructions for thawing.

Prior to dilution, gently invert the vial 10 times; do not shake. Using aseptic technique, dilute the vaccine with 2.2 mL of 0.9% sodium chloride injection. Gently invert the vial 10 times to mix; do not shake. The vaccine should appear as a white to off-white suspension with no visible particulates. Do not use the vaccine if the liquid is discolored or if particles are observed.

To administer a dose, withdraw 0.2 mL of the vaccine from the vial using aseptic technique and an appropriate syringe and needle, and administer immediately. A low dead-volume syringe and needle is preferred for administration of the vaccine. If the amount of vaccine remaining in the vial cannot provide a full dose of 0.2 mL, discard the vial and any excess volume.

Dosage

Pfizer-BioNTech COVID-19 vaccine is available in various formulations and vial presentations. Ensure the correct age-appropriate formulation is selected for administration. The monovalent Pfizer-BioNTech COVID-19 vaccine is no longer authorized for use in US; therefore, dosing recommendations are provided only for the bivalent vaccine below.

See the following tables for recommended doses and dosing intervals for the Pfizer-BioNTech COVID-19 vaccine, bivalent.

In certain immunocompromised individuals ≥5 years of age, a single additional age-appropriate dose of Pfizer-BioNTech COVID-19 vaccine, bivalent may be administered at least 2 months following the initial bivalent vaccine dose; additional doses may be administered at clinician discretion.

Vaccines

Data not available to date to assess safety and immunogenicity of concomitant administration of COVID-19 vaccine (Pfizer-BioNTech) with other vaccines.

Extensive experience with non-COVID-19 vaccines demonstrated that immunogenicity and adverse event profiles are generally similar whether vaccines are administered concomitantly or alone. However, it is not known whether reactogenicity of COVID-19 vaccines is increased when administered concomitantly with other vaccines, including those known to be more reactogenic (e.g., adjuvanted vaccines). Base decisions to administer a COVID-19 vaccine concomitantly with other vaccine(s) on whether routine immunizations with the other vaccines have been delayed or missed, the individual's risk of vaccine-preventable disease (e.g., during an outbreak or occupational exposures), and reactogenicity profiles of the vaccines.

ACIP states that COVID-19 vaccines may be administered without regard to timing of other vaccines, including simultaneous administration on the same day. If a COVID-19 vaccine is administered concomitantly with other vaccines, give each parenteral vaccine at a different injection site and, if possible, separate injection sites by ≥1 inch. ACIP states that, although >1 vaccine can be given IM into the deltoid muscle in adolescents and adults, give COVID-19 vaccines and vaccines likely to cause a local reaction in different limbs, if possible.

Specific Drugs