COVID-19 prevention:
Janssen COVID-19 Vaccine:
Note: mRNA COVID-19 vaccines are preferred for primary series and booster doses; however, the Janssen COVID-19 Vaccine may be considered in limited situations (eg, patients who had anaphylactic reaction after mRNA COVID-19 vaccine) and is preferable to no COVID-19 vaccine (CDC 2022a).
Primary dose: IM: 0.5 mL as a single dose (FDA 2022).
For patients who are moderately to severely immunocompromised (CDC 2022a):
• If received a single dose of Janssen for the primary series, administer a second primary dose using an mRNA COVID-19 vaccine (eg, Pfizer or Moderna) ≥4 weeks after the first primary dose.
• If received 2 doses of Janssen (ie, for the primary series and first booster dose), administer an mRNA primary series dose ≥2 months after the second Janssen dose.
Booster dose:
First booster dose (NOT for second booster dose): Note: Recommended for all persons ≥18 years of age (mRNA vaccines preferred) (CDC 2022a).
Following Janssen primary dose: IM: 0.5 mL administered ≥2 months after the primary dose (or after the additional primary dose for moderately to severely immunocompromised individuals).
Following mRNA vaccine (Moderna, Pfizer-BioNTech) primary series: IM: 0.5 mL administered ≥5 months following completion of the mRNA vaccine primary series. Note: For persons who are moderately or severely immunocompromised, administer ≥3 months following last primary series dose.
Note: The Janssen COVID-19 vaccine cannot be used as a second booster dose. See the COVID-19 Vaccine (mRNA) monograph.
Revaccination: Note: In patients who were vaccinated prior to or while receiving a hematopoietic cell transplant (HCT) or chimeric antigen receptor (CAR)-T-cell therapy, revaccination with a primary series (preferably with an mRNA vaccine) is recommended for patients who are ≥3 months post HCT or CAR-T-cell therapy. (CDC 2022a).
Interchangeability:
Following the first primary series dose with an mRNA COVID-19 vaccine: In limited, exceptional situations where a patient's first dose was an mRNA vaccine and they are unable to complete the series with the same or different mRNA vaccine (eg, due to a contraindication), then a single dose of the Janssen vaccine may be considered at a minimum interval of 28 days from the mRNA vaccine dose (CDC 2022a).
Following a non–FDA-approved/authorized COVID-19 vaccine: If a non–FDA-approved/authorized COVID-19 vaccine (or WHO-listed vaccine) has been administered, allow a minimum interval of 28 days between the non–FDA-approved/authorized vaccine (or WHO-listed vaccine) and an FDA-approved/authorized vaccine (CDC 2022a).
Booster dose: Following completion of the primary vaccination with an FDA-approved/authorized COVID-19 vaccine, a different COVID-19 vaccine may be used for the booster dose; mRNA vaccines are preferred even if the Janssen vaccine was received for the primary series (CDC 2022a).
AstraZeneca COVID-19 Vaccine [Canadian product]:
Note: mRNA and subunit COVID-19 vaccines are preferred; adenovirus vector vaccines may be offered only when all other COVID-19 vaccines are contraindicated (NACI 2022).
Primary series: IM: 0.5 mL per dose for 2 doses administered 28 to 84 days (4 to 12 weeks) apart. Note: The Canadian National Advisory Committee on Immunization (NACI) recommends an mRNA COVID-19 vaccine as the preferred second dose (≥28 days after the first dose) of a series initiated with AstraZeneca COVID-19 Vaccine (NACI 2022). For primary series consisting of 2 doses of AstraZeneca COVID-19 Vaccine, the WHO recommends an interval of 56 to 84 days (8 to 12 weeks) between doses due to increased efficacy and immunogenicity observed with a longer dose interval (WHO 2022).
Additional primary series dose: An additional (third) primary series dose may be offered to moderately to severely immunocompromised individuals ≥28 days after the second dose ONLY when other authorized COVID-19 vaccines (ie, mRNA vaccines) are contraindicated or inaccessible (NACI 2022).
Booster dose: mRNA vaccines are recommended for booster doses; see NACI guidelines for more information (NACI 2022).
Premedication: The CDC does not recommend routine prophylactic administration of antipyretic/analgesic medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) for the purpose of preventing postvaccination symptoms. These agents may be taken after vaccination for the treatment of postvaccination local/systemic symptoms (if medically appropriate) (CDC 2022a).
Dosing recommendations for deviation in administration, preparation, or storage (CDC 2022a):
• If dose volume was too low, repeat dose immediately (no minimum interval).
• If dose volume was too high, do not repeat dose; administer subsequent dose at the appropriate interval.
• If a Janssen COVID-19 Vaccine booster dose is administered too early (ie, <3 months after the mRNA vaccine primary series or <2 months after a Janssen primary dose).
- First booster: Repeat dose after the minimum recommended interval from the dose given too early.
• If vaccine was stored or handled inappropriately (eg, temperature excursion, dose administered past expiration date) and the manufacturer does not have supportive stability data, repeat dose immediately (no minimum interval).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Intramuscular [preservative free]:
Janssen COVID-19 Vaccine: 50 billion viral particles per 0.5 mL (2.5 mL) [contains alcohol, usp, polysorbate 80]
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intramuscular:
Vaxzevria: 50 billion viral particles per 0.5 mL (5 mL) [contains alcohol, usp, edetate (edta) disodium, polysorbate 80]
Generic: 50 billion viral particles per 0.5 mL ([DSC])
Suspension, Intramuscular:
Jcovden: 50 billion viral particles per 0.5 mL (2.5 mL) [contains alcohol, usp, polysorbate 80]
The Janssen COVID-19 Vaccine is not commercially available; it is available under emergency use authorization (EUA) from the FDA. The US federal government, in conjunction with state health departments, allocates supply to individual sites of care across the United States.
As part of the EUA, information consistent with fact sheets pertaining to emergency use of the COVID-19 vaccines must be provided to health care providers and recipients/caregivers, and certain mandatory requirements for administration under the EUA must be met as outlined in the FDA EUA letter.
Janssen COVID-19 Vaccine: The health care provider fact sheet is located at: https://www.fda.gov/media/146304/download. The recipient/caregiver fact sheet is located at: https://www.fda.gov/media/146305/download.
The vaccine provider should include vaccination information in the state/local jurisdiction Immunization Information System (IIS) or other designated system and provide a paper record card as a backup.
Additionally, the vaccination provider is responsible for mandatory reporting of the following to the Vaccine Adverse Event Reporting System (VAERS) (https://vaers.hhs.gov/reportevent.html or 1-800-822-7967):
vaccine administration errors whether or not associated with an adverse event
serious adverse events (irrespective of attribution to vaccination)
cases of multisystem inflammatory syndrome (MIS) in adults
cases of COVID-19 that result in hospitalization or death
The vaccination provider is also responsible for responding to FDA requests for more information. Additional adverse events may be reported to VAERS and the manufacturer. Adverse events related to the Janssen vaccine may be reported to Janssen Biotech, Inc via email: JNJvaccineAE@its.jnj.com; phone: 1-800-565-4008; or fax: 1-215-293-9955.
IM: Do not shake. For the Janssen product, gently swirl the vial in an upright position for 10 seconds before withdrawing each dose of vaccine (FDA 2022). Administer IM in the deltoid muscle or anterolateral thigh (CDC 2022a). Use proper injection technique in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013). To prevent syncope-related injuries, adolescents and adults should be vaccinated while seated or lying down (ACIP [Kroger 2022]).
If administering simultaneously with other vaccines, administer each vaccine at a different injection site, at least 1 inch apart if possible; if administering simultaneously with vaccines that are likely to cause a local reaction, administer COVID-19 vaccine in a different limb if possible (CDC 2022a).
Inappropriate administration technique: If administered SUBQ or into a muscle other than the deltoid or anterolateral thigh (alternate administration site), do not repeat dose. If an additional dose (ie, booster) is needed, administer at the recommended interval (CDC 2022a).
Patients at risk for hemorrhage: For patients at risk of hemorrhage following IM injection, the vaccine should be administered IM if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, IM vaccination can be scheduled shortly after such therapy is administered. A fine needle (≤23 gauge) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2022]).
COVID-19 prevention (AstraZeneca [Vaxzevria] and Janssen COVID-19 Vaccines [Canadian products]): Health Canada approved the AstraZeneca and Janssen COVID-19 Vaccines for active immunization to prevent COVID-19 in persons ≥18 years of age.
Canadian Guidance: The National Advisory Committee on Immunization (NACI) has made recommendations on the use of COVID-19 vaccines; see recommendations for details (NACI 2022).
For US product, see "Use: Off-Label: Adult."
COVID-19 prevention
Similarity of COVID-19 vaccine names may lead to confusion among products with subtle differences (eg, dosage volumes, dosing schedules, storage requirements, preparation for administration).
COVID-19 vaccine may be confused with influenza virus vaccine. Medication errors have occurred when COVID-19 vaccine was inadvertently administered instead of influenza virus vaccine (and vice versa). These products may be stored in close proximity to each other. Confirm the correct vaccine has been selected prior to administration (ISMP/NAN 2021).
COVID-19 vaccine may be confused with epinephrine injection. Medication errors have occurred when epinephrine injection was inadvertently administered instead of COVID-19 vaccine. Most mix-ups were due to look-alike, predrawn syringes of epinephrine and the vaccine, which were stored in close proximity (ISMP [Smetzer 2022]).
Janssen :
Guillain-Barre syndrome (GBS) has been reported with the Janssen COVID-19 Vaccine (Ref).
Onset: Varied; most cases occurred within 42 days of vaccination (Ref).
Risk factors:
• Males 50 to 64 years of age (Ref)
Precautions (but not contraindications) include:
• General history of GBS (Ref)
• History of GBS with a previous dose of the Janssen COVID-19 Vaccine (Ref)
Hypersensitivity reactions, including anaphylaxis, have been reported with the Janssen COVID-19 Vaccine during clinical trials. Angioedema (not associated with respiratory distress) and urticaria (nonserious) have also been reported (Ref). Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (Ref). Of importance, polysorbate 80 is an ingredient in the COVID-19 adenovirus vector vaccines (Janssen COVID-19 Vaccine and the AstraZeneca (Vaxzevria) COVID-19 Vaccine (adenovirus vector [Canadian product]) and is a contraindication in patients with a known hypersensitivity. Polyethylene glycol (PEG) is an ingredient in another type of COVID-19 vaccine (eg, mRNA). Polysorbate and PEG are structurally related; therefore, cross-sensitivity may occur (Ref).
Onset: Anaphylaxis: Onset of the single case reported with Janssen COVID-19 Vaccine is unknown; however, drug-induced anaphylaxis, in general, is IgE-mediated with rapid onset (ie, within 1 hour of administration, but may occur up to 6 hours after exposure) (Ref). Angioedema: Rapid; in the single reported case, onset was 4 days after vaccination (Ref) and was associated with urticaria. Urticaria: Varied; in reported cases, onset was 2 to 7 days after vaccination (Ref).
Risk factors:
Precautions (but not contraindications) include:
• History of any non-severe, immediate (onset <4 hours) allergic reaction to a previous dose (Ref)
• History of any immediate allergic reaction (eg, anaphylaxis) to any other vaccine or injectable therapy (eg, IM, IV, or SubQ vaccines or therapies [excluding SubQ immunotherapy for allergies]) (Ref)
• Patients with a contraindication to another type of COVID-19 vaccine (eg, mRNA) (certain measures must be taken before a different type of COVID-19 [eg, adenovirus vector] is administered to these patients) (Ref)
Local reactions include erythema at injection site, pain at injection site, and swelling at injection site. Local reactions were reported more frequently in younger patients (18 to 59 years of age) compared to patients ≥60 years of age with the Janssen COVID-19 Vaccine primary series. Local reactions were similar to the primary series and were reported more frequently in younger patients (18 to 55 years of age) compared to patients ≥65 years of age with the Janssen COVID-19 Vaccine (mRNA) booster dose. In general, local reactions were mild to moderate in severity and resolved after a median duration of 1 to 2 days. One case of severe pain at injection site, persistent (74 days following vaccination) and nonresponsive to analgesics was reported (Ref).
Onset: Varied; within 7 days after vaccination (Ref).
Systemic reactions include asthenia, fatigue, fever, headache, myalgia, and nausea. Systemic reactions were reported more frequently in younger patients (18 to 59 years of age) compared to patients ≥60 years of age with the Janssen COVID-19 Vaccine primary series. Systemic reactions were similar to the primary series and were reported more frequently in younger patients (18 to 55 years of age) compared to patients ≥65 years of age with the Janssen COVID-19 Vaccine (mRNA) booster dose. In general, local reactions were mild to moderate in severity and resolved after a median duration of 1 to 2 days (Ref).
Onset: Varied; within 7 days after vaccination (Ref).
Thrombosis with new onset thrombocytopenia syndrome (TTS), which clinically mimics autoimmune heparin-induced thrombocytopenia, has been reported rarely with the Janssen COVID-19 Vaccine. Thrombotic events (including fatal cases) primarily included cerebral sinus thrombosis (in some cases accompanied by cerebral hemorrhage). Other reported thrombotic events included portal vein thrombosis, thrombosis of the splanchnic-vein, and arterial thrombosis (Ref). Cases have occurred in both females and males; however, the majority of cases have occurred in females between the ages of 30 to 49 years (Ref). Reported cases of TTS with the Janssen COVID-19 Vaccine are similar to reported cases with the AstraZeneca (Vaxzevria) COVID-19 Vaccine. Patients with neurological symptoms (including severe or persistent headaches or blurred vision), persistent abdominal pain, chest pain, leg swelling, shortness of breath, or petechiae beyond the site of vaccination should seek immediate medical care. Health care professionals should be aware that the use of heparin may be harmful and alternative treatments may be needed; hematology consultation is strongly recommended (Ref). Administration of the Janssen COVID-19 Vaccine is contraindicated in patients with a history of TTS following the Janssen COVID-19 Vaccine or any other adenovirus vector-based COVID-19 Vaccine (Ref).
Mechanism: Not clearly established; may be immune-mediated, involving platelet-activating antibodies against platelet factor 4 (PF4) (CDC 2021d).
Onset: Varied; median 8 days (range 6 to 15) after vaccination (CDC 2021d).
Risk factors:
• Females between the ages of 30 and 49 years (Ref)
AstraZeneca (Vaxzevria) (Canadian product):
Cases (including fatal cases) of capillary leak syndrome (CLS) have been reported rarely. Some cases have occurred in patients with a history of CLS; patients with a known history of CLS should not receive the vaccine. CLS symptoms include acute episodes of limb edema, hypotension, hemoconcentration, and hypoalbuminemia and require prompt medical attention and treatment.
Onset: Rapid; within the first days after vaccination.
Local reactions include erythema at injection site, induration at injection site, injection site pruritus, pain at injection site, swelling at injection site, tenderness at injection site, and warm sensation at injection site. Local reactions were reported more frequently in younger patients (18 to 64 years of age) compared to patients ≥65 years of age with the AstraZeneca (Vaxzevria) COVID-19 Vaccine (adenovirus vector) [Canadian product]; frequency of local reactions was also higher after the first dose compared to the second dose (Ref).
Onset: Varied; within 7 days after either injection (Ref).
Systemic reactions include arthralgia, asthenia, chills, decreased appetite, fatigue, fever, headache, malaise, myalgia, nausea, and vomiting. Systemic reactions were reported more frequently in younger patients (18 to 64 years of age) compared to patients ≥65 years of age with the AstraZeneca (Vaxzevria) COVID-19 Vaccine (adenovirus vector) [Canadian product]; frequency of systemic reactions was also higher after the first dose compared to the second dose. One case of severe fever (40.5°C) (possibly related to vaccine) was reported (Ref).
Onset: Varied; within 7 days after either injection. Severe fever: In the single case reported, onset was 2 days after the first dose (Ref).
Thrombosis with new onset thrombocytopenia syndrome (TTS), which clinically mimics autoimmune heparin-induced thrombocytopenia, has been reported rarely with the AstraZeneca (Vaxzevria) COVID-19 Vaccine (adenovirus vector) (Ref). Thrombotic events (including fatal cases) included cerebral sinus thrombosis (in some cases accompanied by cerebral hemorrhage), portal vein thrombosis, pulmonary embolism, thrombosis of the splanchnic-vein, and arterial thrombosis (Ref). Disseminated intravascular coagulation has also been reported (Ref). In one review, the median age was 36 (range: 22 to 49 years) and most reported cases occurred in females (Ref). In another study, the median age was 48 (range: 18 to 79 years) with no sex predominance or medical risk factors identified (Ref). More cases of TTS were reported after the first dose compared to the second dose. Patients with neurological symptoms (including severe or persistent headaches, blurred vision, confusion, or seizures), persistent abdominal pain, chest pain, leg swelling, shortness of breath, or petechiae or unusual bruising beyond the site of vaccination should seek immediate medical care. Patients who experience major arterial or venous thrombosis with thrombocytopenia with the AstraZeneca (Vaxzevria) COVID-19 Vaccine should not receive a second dose of the AstraZeneca (Vaxzevria) COVID-19 Vaccine. Treatment may differ from management of other thromboses; consult current guidance and hematology specialists (Ref).
Mechanism: Immune-mediated; vaccine-induced platelet-activating antibodies against platelet factor 4 (PF4). This proposed mechanism is based on the observation that affected patients tested positive for antibodies against PF4-heparin; however, none of the patients received heparin prior to onset (Ref).
Onset: Varied; most cases occurred within the first 3 weeks after vaccination (Ref). In one review describing 11 patients, cases occurred 5 to 16 days after vaccination (Ref). In another study describing 170 definite and 50 probable cases of VITT, onset occurred 5 to 48 days (median 14) after vaccination (Ref).
The following adverse reactions and incidences are derived from the FDA-issued emergency use authorization (EUA) for the Janssen COVID-19 Vaccine primary series and booster dose and the product information for the AstraZeneca (Vaxzevria) COVID-19 Vaccine (adenovirus vector) [Canadian product], unless otherwise specified. Refer to EUA and Canadian product information for respective products for information regarding reporting adverse reactions (Vaxzevria Canadian product monograph; FDA 2021).
Janssen:
>10%:
Gastrointestinal: Nausea (2% to 16%) (table 1)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Placebo |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
16% |
9% |
18 to 59 years of age |
2,036 |
2,049 |
Primary series |
|
12% |
11% |
≥60 years of age |
1,320 |
1,331 |
Primary series |
|
10% |
N/A |
18 to 55 years of age |
89 |
N/A |
Booster dose |
|
2% |
N/A |
≥65 years of age |
48 |
N/A |
Booster dose |
Local: Pain at injection site (21% to 60%) (table 2)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Placebo |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
59% |
17% |
18 to 59 years of age |
2,036 |
2,049 |
Primary series |
|
33% |
16% |
≥60 years of age |
1,320 |
1,331 |
Primary series |
|
60% |
N/A |
18 to 55 years of age |
89 |
N/A |
Booster dose |
|
21% |
N/A |
≥65 years of age |
48 |
N/A |
Booster dose |
Nervous system: Fatigue (30% to 52%) (table 3), headache (27% to 44%) (table 4)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Placebo |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
44% |
22% |
18 to 59 years of age |
2,036 |
2,049 |
Primary series |
|
30% |
21% |
≥60 years of age |
1,320 |
1,331 |
Primary series |
|
52% |
N/A |
18 to 55 years of age |
89 |
N/A |
Booster dose |
|
33% |
N/A |
≥65 years of age |
48 |
N/A |
Booster dose |
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Placebo |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
44% |
25% |
18 to 59 years of age |
2,036 |
2,049 |
Primary series |
|
30% |
22% |
≥60 years of age |
1,320 |
1,331 |
Primary series |
|
42% |
N/A |
18 to 55 years of age |
89 |
N/A |
Booster dose |
|
27% |
N/A |
≥65 years of age |
48 |
N/A |
Booster dose |
Neuromuscular & skeletal: Myalgia (10% to 39%) (table 5)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Placebo |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
39% |
12% |
18 to 59 years of age |
2,036 |
2,049 |
Primary series |
|
24% |
14% |
≥60 years of age |
1,320 |
1,331 |
Primary series |
|
36% |
N/A |
18 to 55 years of age |
89 |
N/A |
Booster dose |
|
10% |
N/A |
≥65 years of age |
48 |
N/A |
Booster dose |
Miscellaneous: Fever (0% to 13%) (table 6)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Placebo |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
13% |
0.7% |
18 to 59 years of age |
2,036 |
2,049 |
Primary series |
|
3% |
0.5% |
≥60 years of age |
1,320 |
1,331 |
Primary series |
|
6% |
N/A |
18 to 55 years of age |
89 |
N/A |
Booster dose |
|
0% |
N/A |
≥65 years of age |
48 |
N/A |
Booster dose |
1% to 10%: Local: Erythema at injection site (0% to 9%) (table 7), swelling at injection site (0% to 7%) (table 8)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Placebo |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
9% |
4% |
18 to 59 years of age |
2,036 |
2,049 |
Primary series |
|
5% |
3% |
≥60 years of age |
1,320 |
1,331 |
Primary series |
|
1% |
N/A |
18 to 55 years of age |
89 |
N/A |
Booster dose |
|
0% |
N/A |
≥65 years of age |
48 |
N/A |
Booster dose |
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Placebo |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|
|
7% |
2% |
18 to 59 years of age |
2,036 |
2,049 |
Primary series |
|
3% |
2% |
≥60 years of age |
1,320 |
1,331 |
Primary series |
|
0% |
N/A |
18 to 55 years of age |
89 |
N/A |
Booster dose |
|
0% |
N/A |
≥65 years of age |
48 |
N/A |
Booster dose |
Frequency not defined:
Cardiovascular: Thromboembolism (including deep vein thrombosis, pulmonary embolism, and transverse sinus thrombosis; unsolicited; data insufficient to determine causal relationship)
Dermatologic: Urticaria
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Asthenia, seizure (unsolicited; data insufficient to determine causal relationship)
Otic: Tinnitus (unsolicited; data insufficient to determine causal relationship)
Post-authorization:
Cardiovascular: Arterial thrombosis, capillary leak syndrome, myocarditis, pericarditis, portal vein thrombosis, syncope, thrombosis (splanchnic-vein), venous thromboembolism
Gastrointestinal: Diarrhea, vomiting
Hematologic & oncologic: Immune thrombocytopenia (risk may be increased in the 42 days after vaccination and in patients with a history of immune thrombocytopenia), lymphadenopathy, thrombocytopenia (syndrome in combination with thrombosis [TTS]) (CDC 2021d)
Nervous system: Cerebral hemorrhage, cerebral sinus thrombosis, Guillain-Barre syndrome, hypoesthesia, paresthesia
AstraZeneca (Vaxzevria) (Canadian product):
>10%:
Gastrointestinal: Nausea (8% to 22%) (table 9)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
22% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
11% |
8% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
8% |
7% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
Local: Injection-site pruritus (13%), pain at injection site (35% to 54%) (table 10), tenderness at injection site (49% to 64%) (table 11), warm sensation at injection site (18%)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
54% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
52% |
10% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
35% |
9% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
64% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
62% |
15% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
49% |
10% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
Nervous system: Chills (9% to 32%) (table 12), fatigue (27% to 53%) (table 13), headache (29% to 53%) (table 14), malaise (16% to 44%) (table 15)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
32% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
25% |
6% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
9% |
6% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
53% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
44% |
24% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
27% |
18% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
53% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
42% |
29% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
29% |
19% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
44% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
30% |
12% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
16% |
9% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
Neuromuscular & skeletal: Arthralgia (27%), myalgia (19% to 44%) (table 16)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
44% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
37% |
14% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
19% |
11% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
1% to 10%:
Gastrointestinal: Vomiting (≤2%) (table 17)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
2% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
1% |
1% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
0.8% |
0.8% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
Local: Erythema at injection site (1% to 3%) (table 18), induration at injection site (1% to 3%) (table 19), swelling at injection site (3%)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
3% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
2% |
0.5% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
1% |
0.1% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
3% |
0.1% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
1% |
0% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
Nervous system: Asthenia (≥2%)
Neuromuscular & skeletal: Limb pain (1%)
Respiratory: Flu-like symptoms (≤1%), oropharyngeal pain (≥2%), rhinorrhea (≥2%)
Miscellaneous: Fever (≤8%; feverishness: 34%) (table 20)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
Comments |
|---|---|---|---|---|---|
|
8% |
N/A |
≥18 years of age |
12,282 |
N/A |
N/A |
|
7% |
0.7% |
≥18 years of age |
2,037 |
1,013 |
Dose 1 |
|
0.7% |
0.1% |
≥18 years of age |
1,962 |
968 |
Dose 2 |
<1%:
Dermatologic: Hyperhidrosis, pruritus, skin rash, urticaria
Gastrointestinal: Abdominal pain, decreased appetite (table 21)
|
Drug (COVID-19 Vaccine [Adenovirus Vector]) |
Comparator (MenACWY Vaccine, Placebo, or a Combination) |
Population |
Number of Patients (COVID-19 Vaccine [Adenovirus Vector]) |
Number of Patients (Comparator [MenACWY Vaccine, Placebo, or a Combination]) |
|---|---|---|---|---|
|
0.2% |
0.1% |
≥18 years of age |
12,282 |
11,962 |
Hematologic & oncologic: Lymphadenopathy
Nervous system: Dizziness, drowsiness, facial nerve paralysis (unsolicited)
Otic: Tinnitus
Post-authorization:
Cardiovascular: Arterial thrombosis, capillary leak syndrome, portal vein thrombosis (Greinacher 2021), pulmonary embolism (Greinacher 2021), thrombosis (splanchnic-vein and other) (Greinacher 2021)
Hematologic & oncologic: Disseminated intravascular coagulation (Greinacher 2021), immune thrombocytopenia (risk may be increased in the first 4 weeks after vaccination and in patients with a history of immune thrombocytopenia), thrombocytopenia (with thrombosis, also referred to as vaccine-induced [VITT]; or without thrombosis [risk may be increased in the first 4 weeks after vaccination])
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Cerebral hemorrhage (Greinacher 2021; Schultz 2021), cerebral sinus thrombosis (with thrombocytopenia; or without thrombocytopenia [risk may be increased in the first 4 weeks after vaccination]), chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, hypoesthesia, paresthesia, transverse myelitis
History of a severe allergic reaction (eg, anaphylaxis) after a previous dose or to a component of the formulation (eg, polysorbate 80); history of thrombosis with thrombocytopenia syndrome (TTS) following previous dose of Janssen COVID-19 Vaccine or any other adenovirus vector COVID-19 vaccine (eg, AstraZeneca COVID-19 Vaccine) (CDC 2022a).
Canadian labeling: Additional contraindications (not in US labeling): History of capillary leak syndrome.
Concerns related to adverse effects:
• Shoulder injury related to vaccine administration: Vaccine administration that is too high on the upper arm may cause shoulder injury (eg, shoulder bursitis or tendinopathy) resulting in shoulder pain and reduced range of motion following injection. Use proper injection technique for vaccines administered in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).
• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Kroger 2022]).
Disease-related concerns:
• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. In general, it is recommended to defer vaccine administration in patients with moderate or severe acute illness (with or without fever) and to provide vaccination in patients with mild acute illness (with or without fever) (ACIP [Kroger 2022]). The Canadian product information for the AstraZeneca vaccine states to postpone vaccination in patients with acute severe febrile illness or acute infection.
• Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia); bleeding or hematoma may occur from IM administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2022]). For more information on administering the COVID-19 vaccine in patients with bleeding disorders, see society recommendations (eg, US National Hemophilia Foundation, World Federation of Hemophilia).
• Guillain-Barré syndrome: The Janssen COVID-19 Vaccine has been associated with an increased risk of Guillain-Barré Syndrome (GBS). Not recommended in patients who developed GBS within 6 weeks after a dose of Janssen COVID-19 Vaccine; an mRNA COVID-19 vaccine should be used for subsequent doses. In patients who develop GBS ≥6 weeks following a dose of the Janssen vaccine, an mRNA vaccine should be strongly considered for any subsequent doses (CDC 2022a).
• Immune-mediated syndrome/thrombosis with thrombocytopenia syndrome: For primary immunization, persons with a history of immune-mediated syndrome characterized by thrombosis and thrombocytopenia (eg, heparin-induced thrombocytopenia) should receive an mRNA COVID-19 vaccine. For patients who developed thrombosis with thrombocytopenia syndrome (TTS) following the Janssen COVID-19 Vaccine (or another adenovirus vector COVID-19 vaccine), do not administer the Janssen vaccine; an mRNA vaccine booster dose is recommended in these patients ≥2 months after the initial Janssen vaccine dose and after stabilization of the clinical condition (CDC 2022a).
• Multisystem inflammatory syndrome: In patients with a history of multisystem inflammatory syndrome (MIS), it is typically recommended to delay COVID-19 vaccination until clinical recovery from MIS. For pediatric patients with MIS in children (MIS-C), deferral until ≥90 days after diagnosis is typically recommended. Data on the safety of COVID-19 vaccination following MIS-C or MIS in adults (MIS-A) are limited; risks and benefits should be weighed with consideration given to patient-specific factors (eg, recovery from illness [including normal cardiac function], risk of COVID-19). In pediatric patients who developed MIS-C within 90 days following a dose of COVID-19 mRNA vaccine, subsequent doses should be deferred, but may be offered on a case-by-case basis per provider discretion. In pediatric patients who developed MIS-C ≥90 days after a previous dose of COVID-19 mRNA vaccine, subsequent doses should be considered ≥90 days after MIS-C diagnosis for patients who have clinically recovered (including return to normal cardiac function) and who are at increased risk of COVID-19 exposure. For adults with MIS-A, decisions to administer further doses should be made in collaboration with expert healthcare providers; see CDC recommendations for details (CDC 2022a).
• SARS-CoV-2 infection or exposure (CDC 2022a):
- Persons with current or prior history of COVID-19 or asymptomatic SARS-CoV-2 infection: Vaccination should be offered to persons regardless of history of symptomatic or asymptomatic SARS-CoV-2 infection, including those with prolonged symptoms. Based on data from clinical trials, vaccination in persons with evidence of prior SARS-CoV-2 infection is safe.
Defer vaccination in persons with known current SARS-CoV-2 infection until the person has recovered from acute illness (if symptomatic) and no longer requires isolation. This applies to those persons who develop SARS-CoV-2 infection before receiving any vaccine doses (primary or booster dose) and also those who develop infection after the first dose but before the second dose of the primary series. For booster doses, persons who recently had SARS-CoV-2 infection may consider delaying booster dose (either first or second) by 3 months from symptom onset or positive test (if asymptomatic); increased time between infection and vaccination may improve vaccination immune response.
- Persons who received passive antibody COVID-19 therapy: Vaccination does not need to be delayed for persons who previously received COVID-19 monoclonal antibody therapy or convalescent plasma (postexposure prophylaxis or treatment). For persons who are to receive tixagevimab/cilgavimab for pre-exposure prophylaxis, delay administration until ≥2 weeks after COVID-19 vaccination.
- Persons with known SARS-CoV-2 exposure: Vaccination for postexposure prophylaxis is not currently recommended. Persons with known exposure should typically wait to seek vaccination until after their quarantine period has ended. However, may consider vaccination during quarantine either at the time of postexposure testing or during outreach and contact tracing activities if the person does not present with symptoms consistent with COVID-19 and appropriate infection prevention and control procedures are in place during vaccination.
Concurrent drug therapy issues:
• Anticoagulant or aspirin therapy: Clinicians administering vaccine should be aware of potential bleeding or hematoma that could occur due to IM administration (ACIP [Kroger 2022]).
• Medications for postvaccination adverse reactions: Antipyretic or analgesic medications (eg, acetaminophen, nonsteroidal anti-inflammatory drugs) may be taken for the treatment of postvaccination local/systemic symptoms (if medically appropriate) but should not be used prophylactically to prevent postvaccination symptoms (CDC 2022a).
• Vaccines: The CDC and AAP recommend simultaneous administration of the COVID-19 vaccine with other vaccines or administration in the days before and after receipt of other vaccines (AAP 2021; CDC 2022a). When administering multiple vaccines, consider risks and benefits of each vaccine; administer each vaccine at a different injection site (at least 1 inch apart), and administer COVID-19 vaccine in a different limb than other vaccines that are more likely to cause a local reaction (CDC 2022a).
Special populations:
• Altered immunocompetence: COVID-19 vaccines can be safely administered to immunocompromised persons (including those with HIV or receiving immunosuppressant therapy) if no contraindications exist; as with the general population, mRNA vaccines are preferred. Immunocompromised persons may have a diminished immune response to the vaccine, but the potential benefit of the vaccine outweighs the uncertainties. Booster doses should be administered as appropriate for age and medical conditions. If possible, complete COVID-19 vaccination ≥2 weeks prior to initiation of immunosuppressive therapy (CDC 2022a; NACI 2022). For more information on administering COVID-19 vaccine in specific disease states, see society recommendations (eg, American Cancer Society, National Multiple Sclerosis Society).
• Autoimmune conditions: The safety and efficacy of COVID-19 vaccines in persons with autoimmune conditions were similar to the general population. The CDC and the Canadian National Advisory Committee on Immunization recommend vaccination of patients with autoimmune conditions if there are no contraindications; as with the general population, mRNA vaccines are preferred (CDC 2022a; NACI 2022).
Dosage form specific issues:
• Polysorbate 80: Some COVID-19 vaccines may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). See manufacturer's labeling. Polysorbate and polyethylene glycol are structurally related; cross-reactive hypersensitivity may occur (CDC 2022a).
Other warnings/precautions:
• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval (ACIP [Kroger 2022]). Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Kroger 2022]; CDC 2022a).
• Mammograms: Temporary contralateral or ipsilateral lymphadenopathy after a COVID-19 vaccination has been reported. To avoid possible misinterpretation of mammogram screening, mammograms are recommended prior to vaccination or 4 to 6 weeks after the second dose. When this is not possible, the mammogram technologist or radiologist should be informed when and which vaccine was administered and what arm the injection was given (ACOG 2022). Imaging needed for acute symptoms, or urgent treatment planning or complications, should not be delayed (Becker 2021).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abatacept: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding SQ abatacept for 1 to 2 weeks after each vaccine dose and timing vaccine dose so that it is given 1 week prior to the next IV abatacept dose. Risk D: Consider therapy modification
Acetaminophen: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification
Anti-CD20 B-Cell Depleting Therapies: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Administer COVID-19 vaccine 2 to 4 weeks prior to the next scheduled dose of anti-CD20 therapy, if used chronically for the treatment of autoimmune disease. Revaccinate 6 months after completion of anti-CD20 therapy if used over a limited period. Risk D: Consider therapy modification
Apremilast: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding apremilast for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. These guidelines consider apremilast to be an immunomodulatory or immunosuppressive medication. Risk D: Consider therapy modification
AzaTHIOprine: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding azathioprine for 1 to 2 weeks after each vaccine dose as permitted by the underlying disease. This recommendation is specific to patients using azathioprine for rheumatic and musculoskeletal disease. Risk D: Consider therapy modification
Baricitinib: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding baricitinib, tofactinib, or upadacitinib for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification
Belimumab: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding subcutaneous belimumab doses for 1 to 2 weeks after each COVID-19 vaccine dose as disease activity permits. The recommendation specifies subcutaneous belimumab and does not mention intravenous belimumab. Risk D: Consider therapy modification
Calcineurin Inhibitors (Systemic): May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding calcineurin inhibitors for 1 to 2 weeks after each vaccine dose as permitted by the underlying disease. This is specific to the use of calcineurin inhibitors for rheumatologic or musculoskeletal disease. Risk D: Consider therapy modification
CAR-T Cell Immunotherapy: May diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: The CDC recommends that CAR-T-cell recipients who received COVID-19 vaccine prior to or during treatment with CAR-T-cell therapy should be revaccinated with a primary mRNA vaccine series at least 3 months (12 weeks) after CAR-T-cell therapy. Risk D: Consider therapy modification
Corticosteroids (Systemic): May diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters) Risk D: Consider therapy modification
Cyclophosphamide: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Adjust timing of intravenous cyclophosphamide so that administration occurs 1 week after each vaccine dose, if feasible; hold oral cyclophosphamide for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification
Elivaldogene Autotemcel: May enhance the adverse/toxic effect of Vaccines. Specifically, there may be a greater risk for contracting an infection from any live vaccine. Elivaldogene Autotemcel may diminish the therapeutic effect of Vaccines. Management: Administration of vaccines is not recommended in the 6 weeks before myeloablative conditioning, and until hematologic recovery after elivaldogene autotemcel treatment. Risk X: Avoid combination
Immunosuppressants (Cytotoxic Chemotherapy): May diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
Immunosuppressants (Miscellaneous Oncologic Agents): May diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
Immunosuppressants (Therapeutic Immunosuppressant Agents): May diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
Leflunomide: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding leflunomide for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification
Methotrexate: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding methotrexate for 1 to 2 weeks after vaccine administration as permitted by underlying disease. This is specific to patients using methotrexate for rheumatic and musculoskeletal disease. Risk D: Consider therapy modification
Mycophenolate: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding mycophenolate for 1 to 2 weeks after each vaccine dose as permitted by the underlying disease. This recommendation is specific to patients using mycophenolate for rheumatic and musculoskeletal diseases. Risk D: Consider therapy modification
Propacetamol: May diminish the therapeutic effect of Vaccines. Management: Consider avoiding routine prophylactic use of propacetamol before or during vaccine administration when possible. Propacetamol is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider therapy modification
SulfaSALAzine: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding sulfasalazine for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. These guidelines consider sulfasalazine to be an immunomodulatory or immunosuppressive medication. Risk D: Consider therapy modification
Teplizumab: May diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administration of inactivated vaccines is not recommended during the 2 weeks prior to teplizumab treatment, during therapy, or for 6 weeks following completion of therapy. Risk D: Consider therapy modification
Tixagevimab and Cilgavimab: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Wait at least 2 weeks after receipt of a COVID-19 vaccine before administering tixagevimab and cilgavimab for pre-exposure prophylaxis. Risk D: Consider therapy modification
Tofacitinib: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding baricitinib, tofactinib, or upadacitinib for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification
Upadacitinib: May diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding baricitinib, tofactinib, or upadacitinib for 1 to 2 weeks after vaccine administration as permitted by the underlying disease. Risk D: Consider therapy modification
The Janssen COVID-19 (adenovirus vector) Vaccine is an investigational vaccine permitted for use under FDA emergency use authorization (EUA). Pregnancy testing is not required prior to vaccination. Pregnancy does not need to be delayed following vaccination (ACOG 2022).
There is no evidence that COVID-19 vaccines affect the fertility of either partner among couples trying to conceive (ACOG 2022; CDC 2022b).
• COVID-19 vaccines did not affect the ability to conceive in 2,123 couples planning a pregnancy. Couples were not using fertility treatments and prospectively provided information via an online questionnaire related to vaccine status, COVID-19 infections, menstrual cycles, and pregnancy status for 12 months. Outcome data were available for the female partner administered the Pfizer-BioNTech COVID-19 Vaccine (n = 713), Moderna COVID-19 Vaccine (n = 446), Janssen COVID-19 (adenovirus vector) Vaccine (n = 67), or unvaccinated (n = 897); vaccine status was known for 1,369 male partners. Female patients vaccinated with 1 dose of a vaccine prior to their last menstrual period had a similar probability (fecundability ratio [FR]) of conceiving during that cycle compared to the unvaccinated females (FR: vaccinated 1.08; unvaccinated 1). The FR was also similar in fully vaccinated females (FR: 1.07; two doses of an mRNA vaccine or one dose of the adenovirus vector). The FR in couples with vaccinated males was 0.95 (1 dose) and 1 (fully vaccinated). The FR did not vary by brand of vaccine (Wesselink 2022).
• COVID-19 infection has been shown to decrease sperm quality and may temporarily impair fertility (Donders 2022; Enikeev 2022; Wesselink 2022).
There have been anecdotal reports of temporary menstrual changes following vaccination. Vaccines have not previously been associated with menstrual disturbances. Environmental stresses can impact menses. COVID-19 vaccines may be given to patients who are menstruating, and vaccination does not need to be scheduled based on menstrual cycle. Based on available data, any effect of the COVID-19 vaccine on menstruation is minimal and temporary; not a reason to avoid vaccination (ACOG 2022).
• Menstrual cycle length was evaluated in a retrospective analysis of prospectively collected data from vaccinated (n=2,403) and unvaccinated individuals (n=1,556) who were tracking menstrual cycles for nonhormonal pregnancy prevention or planning. Included were persons 18 to 45 who had normal menstrual cycle lengths (24 to 38 days), provided 6 consecutive cycles of data, and had not been pregnant or used hormonal contraception for ≥3 cycles. Data was collected from persons residing in the United States between December 2020 and July 2021. Vaccinated patients received the Pfizer-BioNTech COVID-19 Vaccine (55%), Moderna COVID-19 Vaccine (35%) or the Janssen COVID-19 (adenovirus vector) Vaccine (7%). When adjusting for age, race, BMI, education, parity, and relationship status, the length of a menstrual cycle differed by less than 1 day following vaccination. This was not considered clinically significant. A small subgroup of patients (n=358) received 2 vaccine doses within the same cycle; these patients had an increase in cycle length by 2 days (Edelman 2022a). A second prospective study included data from an international cohort between October 2020 and November 2021, following vaccination between January and October 2021. Included were 14,936 vaccinated and 4,686 unvaccinated persons. Vaccinated patients received the Pfizer-BioNTech COVID-19 Vaccine (66.48%), Moderna COVID-19 Vaccine (17.46%), or the Janssen COVID-19 (adenovirus vector) Vaccine (1.89%). As in the previous study, the length of a menstrual cycle differed by less than 1 day following vaccination. In addition, a subgroup of persons had an increase in cycle length of 3.7 days when 2 doses of the vaccine were received within a single cycle, compared to persons who were not vaccinated. Any changes in cycle length were temporary (Edelman 2022b).
• Menstrual cycle length, menstrual bleeding, and other parameters were evaluated in a prospective study including 76 women tracking their menstrual cycles for natural family planning (fertility monitoring). All women in the study had regular menstrual cycles (21 to 42 days) prior to vaccination and recorded data for at least 3 months after receiving the vaccine. Women primarily received an mRNA vaccine (n=73); however, a single dose of the Janssen COVID-19 (adenovirus vector) Vaccine was received by 2 women. Outcome data were obtained using reports generated by the tracking program used by the participant and available for 227 cycles prior to vaccination, 145 cycles between the first and second doses, and 216 postvaccine cycles. Based on the recorded data, cycle length did not change as a result of vaccination, although a subset of women (22%) perceived a change. Depending on the tracking method, the study was also able to evaluate bleeding volume, signs of ovulation, and hormonal changes; no differences in these parameters were observed (Bouchard 2022).
• A meta-analysis of 14 observational studies evaluated menstrual irregularities following vaccination with various COVID-19 vaccines (AstraZeneca, CoronaVax, CoVac, Janssen, Moderna, Novavax, Pfizer, Sinopharm, Sinovac). Changes to menstrual flow were among the outcomes reported; changes were considered intermittent and self-limiting. Until data are available from prospective cohort studies, individualized counseling is suggested, particularly for patients who already have menstrual irregularities or fertility issues (Nazir 2022).
Thrombosis with thrombocytopenia syndrome (TTS) has been reported with use of the Janssen COVID-19 (adenovirus vector) Vaccine; although rare, the highest rate reported is in females 30 to 49 years of age. The risk of TTS is not increased with the use of hormonal contraceptives (CDC 2022a).
Due to the risk of severe illness, pregnancy complications, and death from COVID-19 infection during pregnancy, vaccination with an appropriate vaccine is strongly recommended for all patients planning a pregnancy, patients trying to become pregnant now, and patients who might become pregnant in the future, including those patients previously diagnosed with COVID-19 infection (ACOG 2022; CDC 2022b).
The Janssen COVID-19 Vaccine should only be used in limited situations (eg, contraindications to preferred vaccines, limited access to a preferred vaccine). Patients who are to be vaccinated with the Janssen COVID-19 Vaccine should be counseled about the risk of TTS, which usually occurs within 2 weeks of vaccination, and to seek medical care if symptoms develop (CDC 2022a).
Refer to country-specific recommendations for AstraZeneca COVID-19 (adenovirus vector) Vaccine (not available in the United States.)
The Janssen COVID-19 (adenovirus vector) Vaccine is an investigational vaccine permitted for use under FDA emergency use authorization (EUA). Adverse events were not observed in animal reproduction studies. The vaccine is an Ad26-vectored vaccine; other Ad26-vectored vaccines have acceptable safety profiles when used during pregnancy (AGOG 2022).
Antibodies generated following vaccination of pregnant patients can be detected in cord blood. Placental transfer of IgG antibodies to the neonate increases from time of vaccination to delivery following administration of a COVID-19 vaccine during pregnancy. Antibodies generated in response to the vaccine are higher than those in infants born to infected mothers (Rawal 2022).
There was not an increased risk of congenital fetal anomalies (identified via ultrasonography) based on data collected from 1,149 pregnant patients vaccinated within 30 days prior to conception until 14 weeks' gestation when compared to nonvaccinated pregnant patients (n=534) or pregnant patients vaccinated outside of this time period (n=1,473) (ACOG 2022; Ruderman 2022). Meta-analyses, one that included data from the V-safe Surveillance System and pregnancy registry and the Vaccine Adverse Event Reporting System (VAERS), found the rates of small-for-gestational age, stillbirth, preterm birth, miscarriage, and congenital anomalies to be similar following COVID-19 vaccination when compared to the general population (Ma 2022; Rawal 2022). The rates of gestational diabetes, gestational hypertension, preeclampsia, or eclampsia following COVID-19 vaccination are also within the known background rate (ACOG 2022; Ma 2022; Rawal 2022).
The rates of injection-site pain, injection-site soreness, and fatigue following COVID-19 vaccination occurred at rates similar to nonpregnant patients (Rawal 2022). Using data from the VAERS, reports of acute adverse events requiring medical attention following vaccination during pregnancy are uncommon (DeSilva 2022). COVID-19 vaccination effectively prevents COVID-19 infection and hospitalization in pregnant patients (Ma 2022; Rawal 2022). If severe infection and hospitalization occur, pregnant patients who are vaccinated are significantly less likely to require ICU admission, intubation, or die (de Freitas Paganoti 2022).
The risk of severe illness from COVID-19 infection is increased in symptomatic pregnant patients compared to nonpregnant patients. Pregnant and recently pregnant patients with moderate or severe infection are at increased risk of complications such as hypertensive disorders of pregnancy, postpartum hemorrhage, or other infections compared to pregnant patients without COVID. Pregnant patients with symptoms may require ICU admission, mechanical ventilation, or ventilatory support (ECMO) compared to symptomatic nonpregnant patients. Other adverse pregnancy outcomes include preterm birth and stillbirth. The risk of coagulopathy, cesarean delivery, and maternal death may be increased; neonates have an increased risk for NICU admission. Maternal age and comorbidities such as diabetes, hypertension, lung disease, and obesity may also increase the risk of severe illness in pregnant and recently pregnant patients (ACOG FAQ 2022; NIH 2022). The Janssen COVID-19 (adenovirus vector) Vaccine cannot cause infection in the pregnant patient or fetus (ACOG 2022).
Due to the risk of severe illness, pregnancy complications, and death from COVID-19 infection during pregnancy, vaccination with an appropriate vaccine is strongly recommended. A COVID-19 vaccine is recommended for all pregnant patients who otherwise meet the criteria for vaccination, including those previously diagnosed with COVID-19 infection (ACOG 2022; CDC 2022b). The Janssen COVID-19 (adenovirus vector) Vaccine should only be used in limited situations (eg, contraindications to preferred vaccines, limited access to a preferred vaccine). Patients who are to be vaccinated with the Janssen COVID-19 (adenovirus vector) Vaccine should be counseled about the risk of thrombosis with thrombocytopenia syndrome, which usually occurs within 2 weeks of vaccination, and to seek medical care if symptoms develop (CDC 2022a). Infants of mothers who were vaccinated during pregnancy or had COVID-19 infection during pregnancy should be vaccinated according to recommended schedules (CDC 2022b).
Vaccination of pregnant patients may be done in any setting authorized to administer the vaccine. COVID-19 vaccines may be administered simultaneously with other vaccines routinely administered during pregnancy. The COVID-19 vaccine may be administered in any trimester and should be given as soon as possible to maximize maternal health. Vaccination status should be documented for all pregnant patients; for patients who do not receive the COVID-19 vaccine, the discussion should be documented in the medical record and vaccination offered again at subsequent visits (ACOG 2022).
Rho(D) immune globulin is not expected to interfere with an immune response to the COVID-19 vaccine. Treatment should not be withheld in patients planning to be vaccinated or who recently received the COVID-19 vaccine (ACOG 2022).
Information related to COVID-19 vaccines continues to emerge; refer to current guidelines for vaccinating pregnant patients.
Refer to country-specific recommendations for AstraZeneca COVID-19 (adenovirus vector) Vaccine (not available in the United States).
Data collection to monitor maternal and infant outcomes following exposure to COVID-19 vaccines during pregnancy is ongoing:
Pregnant patients who are vaccinated with the Janssen COVID-19 Vaccine (adenovirus vector) vaccine are encouraged to enroll in the International Registry of Coronavirus Exposure in Pregnancy (IRCEP) (https://c-viper.pregistry.com/).
All patients who receive a COVID-19 vaccine are encouraged to enroll in the CDC V-SAFE monitoring program (https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/vsafe.html) (ACOG 2022).
Health care providers are encouraged to enroll pregnant patients exposed to COVID-19 vaccines in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (1-877-311-8972; https://mothertobaby.org/join-study/).
It is not known if components of the Janssen COVID-19 (adenovirus vector) Vaccine are present in breast milk.
The Janssen COVID-19 (adenovirus vector) Vaccine is an investigational vaccine permitted for use under FDA emergency use authorization (EUA). Patients who were breastfeeding were excluded from the original clinical trials (Sadoff 2021).
SARS-CoV-2-specific IgG and IgA antibodies are present in breast milk following administration of the Janssen COVID-19 (adenovirus vector) Vaccine (Cabanillas-Bernal 2022; Yang 2022). It is not yet known if anti–SARS-CoV-2 antibodies present in breast milk provide protection to a breastfed infant (additional data needed) (ACOG 2022; CDC 2022b).
The risk of severe illness from COVID-19 infection is increased in recently pregnant patients compared to nonpregnant patients (ACOG FAQ 2022). Vaccination with an appropriate vaccine is strongly recommended for lactating patients (ACOG 2022; CDC 2022b). A COVID-19 vaccine is recommended for all lactating patients who otherwise meet the criteria for vaccination, including those previously diagnosed with COVID-19 infection. The initiation of breastfeeding does not need to be avoided, and breastfeeding does not need to be discontinued in patients who are vaccinated (ACOG 2022).
The Janssen COVID-19 (adenovirus vector) Vaccine should only be used in limited situations (eg, contraindications to preferred vaccines, limited access to a preferred vaccine) (ACOG 2022; CDC 2022a). Patients who are to be vaccinated with the Janssen COVID-19 (adenovirus vector) Vaccine should be counseled about the risk of thrombosis with thrombocytopenia syndrome, which usually occurs within 2 weeks of vaccination, and to seek medical care if symptoms develop (CDC 2022a).
Refer to country-specific recommendations for AstraZeneca COVID-19 (adenovirus vector) Vaccine (not available in the United States).
Health care providers are encouraged to enroll breastfeeding patients exposed to COVID-19 vaccines in the Organization of Teratology Information Specialists (OTIS) pregnancy registry (1-877-311-8972; https://mothertobaby.org/join-study/).
Monitor for hypersensitivity and syncope for 15 minutes following administration (ACIP [Kroger 2022]). Observe patients for 30 minutes after vaccination in patients with the following: a history of anaphylaxis (due to any cause); a history of any allergic reaction of any severity within 4 hours of receipt to other non-COVID-19 vaccines or injectable therapies; a history of nonsevere, immediate (within 4 hours) allergic reaction after receipt of a previous dose of COVID-19 vaccine; or a person with a contraindication to a different type of COVID-19 vaccine (CDC 2022a). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.
Antibody testing to assess for SARS-CoV-2 immunity before or following vaccination is not currently recommended (CDC 2022a).
Promotes active immunity against COVID-19 caused by SARS-CoV-2 virus. The adenovirus vector in the vaccine is a recombinant, replication-incompetent adenovirus vector that expresses the SARS-CoV-2 spike (S) antigen without virus propagation. The vaccine then elicits an immune response to the S antigen, which contributes to protection against COVID-19 disease. The Janssen vaccine contains a human adenovirus type 26 (Ad26) vector (FDA 2022). The AstraZeneca vaccine [Canadian product] contains a chimpanzee adenovirus (ChAdOx1) vector.
Onset of action:
Janssen COVID-19 Vaccine: Vaccine efficacy assessment for moderate to severe/critical laboratory-confirmed COVID-19 and severe/critical COVID-19 was based on disease cases occurring from day 14 onward after the single dose. Vaccine efficacy assessment for severe/critical COVID-19 was based on cases occurring from day 28 onward after the single dose (FDA 2022).
AstraZeneca COVID-19 Vaccine [Canadian product]: Protection was shown to begin ~3 weeks after the first dose.
