Local injection site reaction was the most commonly reported adverse reaction after COVID-19 vaccine administration during clinical trials. In general, the rates and severity of the reactions were higher after the second dose compared to after the first. After Novavax COVID-19 vaccine administration in patients 12 to 17 years, injection site pain and tenderness (79.8%), erythema or redness (7.7%), and swelling (8.5%) at the injection site were reported. In patients 18 to 64 years, injection site pain and tenderness (82.2%), erythema or redness (7%), and swelling (6.3%) at the injection site were reported. In patients 65 years and older, the incidence of injection site pain and tenderness (63.4%), erythema or redness (4.8%), and swelling (5.3%) was lower compared to younger patients. Injection site pruritus was also reported in 0.1% to 0.2% of patients. After the booster dose, injection site pain and tenderness (81.1%), erythema or redness (6.3%), and swelling (8.4%) at the injection site were reported.[67669]

During clinical trials, fatigue, malaise, and headache occurred after administration of the COVID-19 vaccine. The rates and severity of the reactions were generally higher after the second dose compared to the first dose. After Novavax COVID-19 vaccine administration in patients 12 to 17 years, fatigue and malaise (61.6%) and headache (63.3%) were reported. In patients 18 to 64 years, fatigue and malaise (62%) and headache (52.9%) were reported. In patients 65 years and older, the incidence of fatigue and malaise (39.2%) and headache (29.2%) was lower than that in younger patients. After the booster dose, fatigue and malaise (63.4%) and headache (52.9%) were reported.[67669]

Musculoskeletal adverse reactions were reported during COVID-19 vaccine clinical trials. The rates and severity of the reactions were generally higher after the second dose compared to the first dose. After Novavax COVID-19 vaccine administration in patients 12 to 17 years, arthralgia (19.5%) and myalgia (56.9%) were reported. In patients 18 to 64 years, arthralgia (25.4%) and myalgia (54.1%) were reported. In patients 65 years and older, the incidence of arthralgia (15.4%) and myalgia (30.2%) was lower than that in younger patients. After the booster dose, arthralgia (30.3%) and myalgia (63%) were reported.[67669]

Fever was reported after Novavax COVID-19 vaccine administration in patients 12 to 17 years (16.7%) and in patients 18 to 64 years (6%). In patients 65 years and older, the incidence of fever (2%) was lower than that in younger patients. Chills were also reported in 0.4% of patients. After the booster dose, fever (6.3%) was reported.[67669]

Nausea and vomiting was reported after Novavax COVID-19 vaccine administration in patients 12 to 17 years (23.1%) and in patients 18 to 64 years (15.6%). In patients 65 years and older, the incidence of nausea and vomiting (7.3%) was lower than that in younger patients. Anorexia or decreased appetite was reported in 0.3% of patients receiving the Novavax COVID-19 vaccine during clinical trials. After the booster dose, nausea and vomiting (14.7%) was reported.[67669]

Within 7 days of any dose, hypersensitivity reactions (including urticaria, hypersensitivity, angioedema, and swelling of the face, lips, ear and/or eyelids) were reported by 0.1% of patients receiving the Novavax COVID-19 vaccine and 0.03% of patients receiving placebo. Of these events, 1 reaction (generalized urticaria and facial angioedema lasting for 2 days) was serious and occurred 2 days after Dose 1 of the vaccine. Anaphylactoid reactions were reported during postmarketing experience.[67669]

Lymphadenopathy-related adverse reactions, including lymphadenopathy, lymphadenitis, lymph node pain, and axillary pain, were reported in 0.3% (18 to 64 years) and 0.9% (12 to 17 years) of patients receiving the Novavax COVID-19 vaccine during clinical trials.[67669]

Cases of myocarditis and/or pericarditis were identified in clinical trials of Novavax COVID-19 vaccine and through passive surveillance during postauthorization use outside the United States. The risk of myocarditis may be reduced by extending the interval to 8-weeks between the first and second dose in patients 12 years and older, especially males 12 to 39 years.[66175] Myocarditis and/or pericarditis were reported by 2 patients after the Novavax COVID-19 vaccine. The first patient was a 67-year-old male reporting the reaction 28 days after Dose 1 and the second patient was a 20-year-old male reporting the reaction 10 days after Dose 1. Additionally, myocarditis was reported in 2 patients, a 16-year-old patient 2 days after Dose 2 and a 28-year-old male 3 days after a booster dose. The adverse reaction after the booster dose was adjudicated as a non-ST elevation myocardial infarction; however, clinical features were also consistent with myocarditis (chest pain and elevated troponin). No cardiac catheterization or cardiac MRI was performed during the acute presentation. Among the 4 reported events, 3 were reported as resolved and the fourth did not have follow-up available. In a study with a recombinant spike protein COVID-19 vaccine manufactured by a different process than the Novavax COVID-19 vaccine, myocarditis was reported in a 19-year-old male and pericarditis in a 60-year-old female within 10 days of administration of Dose 2 and Dose 1, respectively. Both events were reported as resolved.[67669]

Cardiomyopathy or cardiac failure was reported by 8 patients (0.03%) after the Novavax COVID-19 vaccine compared to 1 patient (less than 0.01%) after placebo. All events were serious. Additionally, an event of congestive heart failure was reported after Novavax COVID-19 vaccination by a patient who was excluded from the safety analysis. Current available information on cardiomyopathy or cardiac failure is insufficient to determine a causal relationship with the vaccine.[67669]

Acute cholecystitis was reported by 6 patients (0.02%) after the Novavax COVID-19 vaccine compared to 2 patients (0.01%) after placebo. All events were serious. Current available information on acute cholecystitis is insufficient to determine a causal relationship with the vaccine.[67669]

A total of 12 non-cardiac, non-neurovascular thrombotic and embolic events were reported by 11 patients (0.04%) after the Novavax COVID-19 vaccine and a total of 7 events were reported by 9 patients (0.03%) after placebo. Events included pulmonary embolism (n = 5), deep vein thrombosis (n = 2), thrombosis (n = 2), and portal vein thrombosis, mesenteric artery thrombosis, and peripheral arterial occlusive disease (n = 1 each). Of the events, 6 were serious including pulmonary embolism (n = 5) and deep vein thrombosis (n = 1). Events after placebo included pulmonary embolism (n = 3), deep vein thrombosis, and peripheral arterial occlusive disease (n = 2 each). Current available information on non-cardiac, non-neurovascular thrombotic and embolic events is insufficient to determine a causal relationship with the vaccine.[67669]

Uveitis, including iritis, uveitis, iridocyclitis, was reported by 3 patients (0.01%) after the Novavax COVID-19 vaccine and 2 patients (0.01%) after placebo. All events were non-serious. One patient had onset of uveitis after Dose 1 of the vaccine which resolved and then recurred after Dose 2. The 2 placebo patients appeared to have a previous history of uveitis and 1 of the Novavax COVID-19 vaccine patients had a history of iritis. Current available information on uveitis is insufficient to determine a causal relationship with the vaccine.[67669]

In a study with a recombinant spike protein COVID-19 vaccine manufactured by a different process than the Novavax COVID-19 vaccine, Guillain-Barre syndrome was reported 9 days after administration of Dose 1 of the vaccine.[67669]

Paresthesias and hypoesthesia were reported during postmarketing use of the Novavax COVID-19 vaccine.[67669]

Immunocompromised patients, including patients with immunosuppression or receiving immunosuppressive therapy, may not have an adequate immune response to the COVID-19 vaccine.[67669] Immunosuppressed persons may include patients with severe combined immunodeficiency (SCID), hypogammaglobulinemia, agammaglobulinemia, or an immune system compromised by drug therapy (i.e., corticosteroid therapy with greater than physiologic doses). Short-term (less than 2 weeks) corticosteroid therapy or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive. COVID-19 vaccines may be administered without regard to timing of corticosteroid treatment, including topical or intra-articular treatment, bursal, or tendon injection.[65107] [66175] Ideally, complete COVID-19 vaccination at least 2 weeks before initiation or resumption of immunosuppressive therapies, but timing of COVID-19 vaccination should take into consideration current or planned immunosuppressive therapies and optimization of both the patient's medical condition and response to vaccine. Serologic testing or cellular immune testing to assess for immunity after COVID-19 vaccination, outside the context of research studies, is not recommended.[66175]

Patients with altered immune states due to generalized neoplastic disease or an immune system compromised by radiation therapy or chemotherapy may not have an adequate immune response to the COVID-19 vaccine. Patients at increased risk include, but are not limited to, those receiving active treatment for solid tumor and hematologic malignancies, receipt of chimeric antigen receptor (CAR) T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppresive therapy), and active treatment with alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor-necrosis (TNF) blockers, and other biologic agents that are immunosuppressive or immunomodulatory. Administration of an additional Novavax COVID-19 vaccine dose at least 2 months after the last dose of COVID-19 vaccine has been authorized for individuals who have undergone solid organ transplantation, or are diagnosed with a condition that is considered to have an equivalent level of immunocompromise.[66175] [67669] Ideally, complete COVID-19 vaccination at least 2 weeks before initiation or resumption of immunosuppressive therapies, but timing of COVID-19 vaccination should take into consideration current or planned immunosuppressive therapies and optimization of both the patient's medical condition and response to vaccine. Serologic testing or cellular immune testing to assess for immunity after COVID-19 vaccination, outside the context of research studies, is not recommended.[66175] Delay vaccination for at least 3 months after hematopoietic cell transplantation (HCT) or engineered cellular therapy (e.g. CAR-T cells) to maximize vaccine efficacy.[66335] Revaccinate patients who received 1 or more doses of COVID-19 vaccine prior to or during HCT or CAR-T-cell therapy for any doses administered before or during treatment starting at least 3 months after transplant or CAR-T-cell therapy. Consider revaccination 6 months after therapy completion for patients who received 1 or more doses of COVID-19 vaccine during treatment with B-cell-depleting therapies (e.g., rituximab, ocrelizumab) that were administered over a limited period (e.g., as part of a treatment regimen for certain malignancies). For patients receiving B-cell-depleting therapies on a continuing basis, COVID-19 vaccines should be administered approximately 4 weeks before the next scheduled therapy.[66175] For patients with hematologic malignancies receiving intensive cytotoxic chemotherapy (e.g., cytarabine/anthracycline-based induction regimens for AML), delay vaccination until absolute neutrophil count (ANC) recovery. For patients with solid tumor malignancies undergoing major surgery, separate date of surgery from vaccination by at least a few days to allow symptoms (e.g. fever) to be correctly attributed to surgery vs. vaccination. For more complex surgeries (e.g. splenectomy or surgery that may lead to an immunosuppressive state) surgeons may recommend a wider window (+/- 2 weeks) from the time of surgery.[66335]

Although patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) could have a diminished response, the COVID-19 vaccine should be offered to patients with chronic, stable HIV. Administration of an additional Novavax COVID-19 dose at least 2 months after last dose of COVID-19 vaccine has been authorized for individuals who have undergone solid organ transplantation, or are diagnosed with a condition that is considered to have an equivalent level of immunocompromise. Patients at increased risk include, but are not limited to, those with advanced or untreated HIV infection (people with HIV and CD4 counts less than 200/mm³, history of AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV infection).[66175] [67669]

The COVID-19 vaccine is administered by intramuscular (IM) injection only. Carefully consider the risks and benefits in patients at increased risk for bleeding after an intramuscular injection, such as thrombocytopenia, bleeding disorders (e.g., hemophilia), coagulopathy, vitamin K deficiency, and those receiving anticoagulant therapy. Caution and appropriate precautions to minimize the risk of bleeding or hematoma formation are advised.[65107] [67669]

The available data regarding use of the Novavax COVID-19 vaccine during pregnancy is insufficient to inform a vaccine-associated risk. Animal data did not reveal evidence of impaired fertility or harm to the fetus when administered at doses containing the same quantity of SARS-CoV-2 recombinant spike protein (5 mcg), one-fifth the quantity of adjuvant (10 mcg), and inactive ingredients contained in a single dose of the Novavax COVID-19 vaccine. A pregnancy exposure registry is available that monitors pregnancy outcomes in women vaccinated with the Novavax COVID-19 vaccine during pregnancy. Encourage women vaccinated during pregnancy to enroll in the registry by going to https://c-viper.pregistry.com.[67669]

There are insufficient data to assess the effects of the Novavax COVID-19 vaccine during breast-feeding, on milk production, and excretion in human breast milk.[67669]

Injectable vaccines, including the Novavax COVID-19 vaccine, have been associated with episodes of syncope and fainting. Prior to administration, ensure procedures are in place to prevent falls and manage syncopal reactions. Patients should remain seated or lying down during the observation period to decrease the risk for injury. If syncope develops, observe patients until symptoms resolve.[66175] [67669]