Vaccine Information: EVUSHELD (Page 2 of 7)


1
For additional information please see https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html.Healthcare providers should consider the benefit-risk for an individual patient.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage for Emergency Use of EVUSHELD

The dosage of EVUSHELD in adults and pediatric individuals (12 years of age and older weighing at least 40 kg) is 150 mg of tixagevimab and 150 mg of cilgavimab administered as two separate consecutive intramuscular (IM) injections.

Repeat Dosing

Longer term data from the study PROVENT indicate that EVUSHELD may be effective for pre-exposure prophylaxis for 6 months post-administration [see Clinical Studies (14)]. While SARS-CoV-2 remains in circulation, individuals who qualify for EVUSHELD, per the conditions of the EUA, can be redosed every 6 months.

EVUSHELD has only been studied in single-dose studies. There are no safety and efficacy data available with repeat dosing. The recommendation for repeat dosing is based on the totality of the scientific evidence including clinical pharmacology data and clinical trial data [see Clinical Pharmacology (12.3) and Clinical Studies (14)].

2.2 Dosage Adjustment in Specific Populations

No dosage adjustment is recommended in pregnant or lactating individuals, in geriatrics, and in individuals with renal impairment [see Use in Specific Populations (8)].

2.3 Dose Preparation and Administration

Each EVUSHELD carton contains two vials; one of each antibody. Each vial contains an overfill to allow the withdrawal of 150 mg (1.5 mL).

Table 1 Dosage of Tixagevimab and Cilgavimab
*
150 mg of tixagevimab and 150 mg of cilgavimab are to be administered as separate, consecutive intramuscular injections

EVUSHELD *

(tixagevimab co-packaged with cilgavimab)

Antibody dose

Number of vials needed

Volume to withdraw from vial(s)

tixagevimab

150 mg

1 vial

(dark grey vial cap)

1.5 mL

cilgavimab

150 mg

1 vial

(white vial cap)

1.5 mL

Preparation

Tixagevimab and cilgavimab must be prepared by a qualified healthcare provider.
Tixagevimab and cilgavimab are each supplied in individual single-dose vials. Do not shake the vials.
Visually inspect the vials for particulate matter and discoloration. Tixagevimab and cilgavimab are clear to opalescent, colorless to slightly yellow solutions. Discard the vials if the solution is cloudy, discolored or visible particles are observed.
Withdraw 1.5 mL of tixagevimab solution and 1.5 mL of cilgavimab solution into TWO separate syringes (see Table 1). Discard unused portion in vials.
This product is preservative-free and therefore, the prepared syringes should be administered immediately. If immediate administration is not possible, and the prepared tixagevimab and cilgavimab syringes need to be stored, the total time from vial puncture to administration must not exceed 4 hours:
in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF), or
at room temperature up to 25ºC (77ºF).

Administration

Tixagevimab and cilgavimab must be administered by a qualified healthcare provider.
Administer the two components of EVUSHELD consecutively.
Administer the IM injections at different injection sites, preferably one in each of the gluteal muscles, one after the other.
Clinically monitor individuals after injections and observe for at least 1 hour [see Warnings and Precautions (5.1)].

3 DOSAGE FORMS AND STRENGTHS

EVUSHELD is available as an individual single-dose vial of tixagevimab as a clear to opalescent, colorless to slightly yellow solution co-packaged with an individual single-dose vial of cilgavimab as a clear to opalescent, colorless to slightly yellow solution as:

Injection: 150 mg/1.5 mL (100 mg/mL) of tixagevimab
Injection: 150 mg/1.5 mL (100 mg/mL) of cilgavimab

4 CONTRAINDICATIONS

EVUSHELD is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to any component of EVUSHELD [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS

There are limited clinical data available for EVUSHELD. Serious and unexpected adverse events may occur that have not been previously reported with EVUSHELD use.

5.1 Hypersensitivity Including Anaphylaxis

Serious hypersensitivity reactions, including anaphylaxis, have been observed with Human immunoglobulin G1 (IgG1) monoclonal antibodies like EVUSHELD [see Adverse Reactions (6.1)]. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur while taking EVUSHELD, immediately discontinue administration and initiate appropriate medications and/or supportive care. Clinically monitor individuals after injections and observe for at least 1 hour.

5.2 Clinically Significant Bleeding Disorders

As with any other intramuscular injection, EVUSHELD should be given with caution to individuals with thrombocytopenia or any coagulation disorder.

5.3 Cardiovascular Events

In PROVENT there was a higher rate of cardiovascular serious adverse events (SAEs), including myocardial infarction (one fatal SAE) and cardiac failure, in subjects who received EVUSHELD compared to placebo [see Adverse Reactions (6.1)]. All subjects who experienced cardiac SAEs had cardiac risk factors and/or a prior history of cardiovascular disease, and there was no clear temporal pattern. A causal relationship between EVUSHELD and these events has not been established. There was no signal for cardiac toxicity or thrombotic events identified in the nonclinical studies.

Consider the risks and benefits prior to initiating EVUSHELD in individuals at high risk for cardiovascular events, and advise individuals to seek immediate medical attention if they experience any signs or symptoms suggestive of a cardiovascular event.

6 ADVERSE REACTIONS

6.1 Adverse Reactions from Clinical Studies

The following adverse events have been observed in the clinical studies of EVUSHELD that supported the EUA. The adverse event rates observed in these clinical studies cannot be directly compared to rates in the clinical studies of other products and may not reflect the rates observed in clinical practice. Additional adverse events associated with EVUSHELD may become apparent with more widespread use.

Approximately 4,220 subjects have been exposed to EVUSHELD (tixagevimab 150 mg and cilgavimab 150 mg) in clinical trials.

The safety of EVUSHELD is based on analyses from two ongoing Phase III trials, PROVENT and STORM CHASER. In both studies, adults received EVUSHELD (150 mg of tixagevimab and 150 mg of cilgavimab) administered as two separate consecutive IM injections or placebo [see Clinical Studies (14)].

The primary safety analysis was based on data through to an event driven efficacy data cut-off, such that individual subjects had variable follow-up times [see Clinical Studies (14)] , with a median (range) of follow-up of 83 days (3-166 days) for PROVENT and 49 days (5-115 days) for STORM CHASER. An additional data cut-off was conducted to provide updated analyses with a median (range) of follow-up of 6.5 months (3-282 days) for PROVENT and approximately 6 months (5-249 days) for STORM CHASER. The median and range of follow-up times were similar between EVUSHELD and placebo recipients in each trial.

PROVENT

PROVENT enrolled adults ≥18 years of age who were either ≥60 years of age, had pre-specified co-morbidities [see Clinical Studies (14)] , or were at increased risk of SARS-CoV-2 infection due to their living situation or occupation. Subjects could not have previously received a COVID-19 vaccine or have known prior or current SARS-CoV-2 infection. Subjects received a single dose of EVUSHELD (N= 3,461) or placebo (N= 1,736).

Adverse events were reported in 1,221 (35%) subjects receiving EVUSHELD and 593 (34%) receiving placebo. SAEs were reported in 50 (1%) subjects receiving EVUSHELD and 23 (1%) receiving placebo. There was 1 adverse event reported as anaphylaxis among subjects who received EVUSHELD. The event began within minutes of EVUSHELD administration and was treated with epinephrine. The event resolved.

Of the reported adverse events (N= 4,507), the majority were mild (73%) or moderate (24%) in severity. All adverse events, occurring in at least 1% of subjects, were reported at similar incidence rates among subjects receiving EVUSHELD compared to those receiving placebo (difference <1%). The most common treatment-emergent adverse events, occurring in at least 3% of subjects receiving EVUSHELD or placebo are shown in Table 2.

Table 2 Adverse Events (All Grades) Regardless of Causality Occurring in at Least 3% of Subjects Receiving EVUSHELD or Placebo in Primary Safety Analysis

EVUSHELD

N= 3,461

Placebo

N= 1,736

Headache

6%

5%

Fatigue

4%

3%

Cough

3%

3%

At the additional data cut-off (median follow-up 6.5 months), the overall adverse event profile for subjects who received EVUSHELD remained similar to events displayed in Table 2.

Cardiac Serious Adverse Events

Through the additional data cut-off in PROVENT, a higher proportion of subjects who received EVUSHELD versus placebo in PROVENT reported myocardial infarction SAEs, one of which resulted in death, and cardiac failure SAEs (see Table 3 below). All subjects who experienced cardiac SAEs had cardiac risk factors and/or a prior history of cardiovascular disease at baseline. There was no clear temporal pattern, with events reported from several hours after EVUSHELD receipt through the end of the follow-up period.

Table 3 Cardiac SAEs Regardless of Causality in PROVENT with Onset Prior to Day 183 Using the Median 6-Month Data Cut-off Date
EVUSHELD
N= 3,461
Placebo
N= 1,736
*
One EVUSHELD recipient and one placebo recipient had two cardiac SAEs each.
Includes the preferred terms angina pectoris, coronary artery disease, arteriosclerosis, troponin increased, acute myocardial infarction, and myocardial infarction.
Includes the preferred terms acute myocardial infarction, myocardial infarction, and troponin increased (with a discharge diagnosis of myocardial infarction).
§
Includes the preferred terms cardiac failure congestive, acute left ventricular failure, cardiac failure, and cardiac failure acute.
Includes the preferred terms atrial fibrillation, arrhythmia, paroxysmal atrioventricular block, and heart rate irregular.

Subjects with any cardiac SAE *

22 (0.6%)

3 (0.2%)

SAEs related to coronary artery disease or myocardial ischemia

10 (0.3%)

2 (0.1%)

Myocardial infarctions

8 (0.2%)

1 (0.1%)

SAEs related to cardiac failure §α

6 (0.2%)

1 (0.1%)

SAEs related to an arrhythmia

4 (0.1%)

1 (0.1%)

Other (cardiomegaly, cardiomyopathy, and cardio-respiratory arrest)

3 (0.1%)

0

STORM CHASER

STORM CHASER enrolled adults ≥18 years of age following potential exposure (within 8 days) to an identified individual with a laboratory-confirmed SARS-CoV-2 infection (symptomatic or asymptomatic). Subjects could not have previously received a COVID-19 vaccine, have symptoms consistent with COVID-19, or have a known prior SARS-CoV-2 infection. Subjects received a single dose of EVUSHELD (N= 749) or placebo (N= 372).

Adverse events were reported in 162 (22%) subjects receiving EVUSHELD and 111 (30%) receiving placebo. SAEs were reported in 5 (<1%) subjects receiving EVUSHELD and 3 (<1%) receiving placebo. Of the reported adverse events (N= 777), the majority were mild (75%) or moderate (23%) in severity.

At the additional data cut-off (median follow-up approximately 6 months), the overall adverse event profile for subjects who received EVUSHELD remained similar to earlier results. EVUSHELD is not authorized for post-exposure prophylaxis of COVID-19 in individuals who have been exposed to someone infected with SARS-CoV-2 [see Emergency Use Authorization (1)].

Cardiac Serious Adverse Events

In STORM CHASER (N= 1,121) no cardiac SAEs were reported (median follow-up approximately 6 months). Compared to PROVENT, the subjects in STORM CHASER were younger (median age 48 versus 57 years) and had fewer baseline cardiac risk factors (24% versus 36% with hypertension, 11% versus 14% with diabetes, and 3% versus 8% with cardiovascular disease in STORM CHASER versus PROVENT, respectively).

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