Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 500mg/8 mL (62.5mg/mL)
COVID-19 (EUA)
May 27, 2021: Emergency use authorization (EUA) issued by the FDA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients aged ≥12 years who weigh ≥40 kg with positive results of direct acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death
500 mg as a single IV infusion
Administer as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization
Limited distribution regions
- April 5, 2022: Distribution paused to all U.S. regions owing to high frequency of omicron BA.2 subvariant and data showing sotrovimab is unlikely to be effective
- March 25, 2022: Distribution paused to Health and Human Service (HHS) regions 1 and 2 owing to high frequency of omicron BA.2 subvariant and data showing sotrovimab is unlikely to be effective
- March 30, 2022: Distribution to additional HHS regions (ie, 5, 9, and 10) paused
- February 23, 2022: The FDA revised this EUA to further limit use when treating COVID-19 to exclude geographic regions where, based on available information (eg, variant drug susceptibility, regional variant frequency), infection is likely due to a variant that is nonsusceptible to sotrovimab
Dosage Modifications
Renal impairment
- Mild, moderate, or severe: No dose adjustment required
Hepatic impairment
- Not studied; pharmacokinetics unknown
Dosing Considerations
Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies; not authorized in geographic regions where infection is likely to have been caused by a nonsusceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency
Benefit of treatment with sotrovimab has not been observed in patients hospitalized for COVID-19; SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation
Limitations of use
- Benefit of treatment not observed in patients hospitalized due to COVID-19
- Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
-
Not authorized for use in patients
- Who are hospitalized with COVID-19, OR
- Who require oxygen therapy for COVID-19, OR
- Who require an increase in baseline oxygen flow rate because of COVID-19 (in those on long-term oxygen therapy for underlying non-COVID-19–related comorbidity)
Patient selection
- Obesity/overweight (body mass index [BMI] ≥25 kg/m2 [adults]; BMI ≥85th percentile for age/sex based on CDC growth charts [if aged 12-17 years])
- Pregnancy
- Chronic kidney disease
- Diabetes
- Immunosuppressive disease or immunosuppressive treatment
- Cardiovascular disease (including congenital heart disease) or hypertension
- Chronic lung diseases (eg, chronic obstructive pulmonary disease [COPD], moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
- Sickle cell disease
- Neurodevelopmental disorders (eg, cerebral palsy) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes, severe congenital anomalies)
- Having a medical-related technological dependence (eg, tracheostomy, gastrostomy, positive-pressure ventilation [not related to COVID 19])
- EUA is not limited to the medical conditions or factors listed above; for additional information on medical conditions and factors associated with increased risk for progression to severe COVID, see the CDC website
Dosage Forms & Strengths
injectable solution
- 500mg/8 mL (62.5mg/mL)
COVID-19 (EUA)
May 27, 2021: Emergency use authorization (EUA) issued by the FDA for treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients aged ≥12 years who weigh ≥40 kg with positive results of direct acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death
≥12 years and weight ≥40 kg
- 500 mg as a single IV infusion
- Administer as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization
Limited distribution regions
- April 5, 2022: Distribution paused to all U.S. regions owing to high frequency of omicron BA.2 subvariant and data showing sotrovimab is unlikely to be effective
- March 25, 2022: Distribution paused to Health and Human Service (HHS) regions 1 and 2 owing to high frequency of omicron BA.2 subvariant and data showing sotrovimab is unlikely to be effective
- March 30, 2022: Distribution to additional HHS regions (ie, 5, 9, and 10) paused
- February 23, 2022: The FDA revised this EUA to further limit use when treating COVID-19 to exclude geographic regions where, based on available information (eg, variant drug susceptibility, regional variant frequency), infection is likely due to a variant that is nonsusceptible to sotrovimab
Dosage Modifications
Renal impairment
- Mild, moderate, or severe: No dose adjustment required
Hepatic impairment
- Not studied; pharmacokinetics unknown
Dosing Considerations
Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies; not authorized in geographic regions where infection is likely to have been caused by a nonsusceptible SARS-CoV-2 variant based on available information including variant susceptibility to these drugs and regional variant frequency
Benefit of treatment with sotrovimab has not been observed in patients hospitalized for COVID-19; SARS-CoV-2 monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation
Limitations of use
- Benefit of treatment not observed in patients hospitalized due to COVID-19
- Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
-
Not authorized for use in patients
- Who are hospitalized with COVID-19, OR
- Who require oxygen therapy for COVID-19, OR
- Who require an increase in baseline oxygen flow rate because of COVID-19 (in those on long-term oxygen therapy for underlying non-COVID-19–related comorbidity)
Patient selection
- Obesity/overweight (body mass index [BMI] ≥25 kg/m2 [adults]; BMI ≥85th percentile for age/sex based on CDC growth charts [if aged 12-17 years])
- Pregnancy
- Chronic kidney disease
- Diabetes
- Immunosuppressive disease or immunosuppressive treatment
- Cardiovascular disease (including congenital heart disease) or hypertension
- Chronic lung diseases (eg, chronic obstructive pulmonary disease [COPD], moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
- Sickle cell disease
- Neurodevelopmental disorders (eg, cerebral palsy) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes, severe congenital anomalies)
- Having a medical-related technological dependence (eg, tracheostomy, gastrostomy, positive-pressure ventilation [not related to COVID 19])
- EUA is not limited to the medical conditions or factors listed above; for additional information on medical conditions and factors associated with increased risk for progression to severe COVID, see the CDC website
Adverse Effects
EUA requirement: Completion of FDA MedWatch Form to report all medication errors and serious adverse events is mandatory
Warnings
Contraindications
None
Cautions
Hypersensitivity
- Serious hypersensitivity reaction, including anaphylaxis, may occur
- Hypersensitivity reactions occurring more >24 hr after the infusion have also been reported with SARS-CoV-2 monoclonal antibodies under EUA
- If signs and symptoms occur, immediately discontinue IV infusion, and initiate appropriate medications and/or supportive care
- Infusion-related reactions reported, including fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness, and diaphoresis
Clinical worsening after administration
- Clinical worsening of COVID-19 after administration reported; signs or symptoms may include fever, hypoxia or increased respiratory difficulty, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status
- Some of these events required hospitalization
- Unknown if these events were related to the monoclonal antibodies or were due to progression of COVID-19
Severe COVID-19
- Treatment benefit not observed in patients hospitalized with COVID-19
- Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation
-
Therefore, use is not authorized for use in patients
- Who are hospitalized with COVID-19, OR
- Who require oxygen therapy for COVID-19, OR
- Who require an increase in baseline oxygen flow rate because of COVID-19 (in those on long-term oxygen therapy for underlying non-COVID-19–related comorbidity)
Viral variants
- Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies
- Prescribing clinicians should consider prevalence of etesevimab resistant variants in their area
- Healthcare providers should review antiviral resistance information provided by state and local health departments
- Variant proportions circulating in the United States can be monitored at the CDC website
-
Pseudotyped viruslike particle neutralization data of sotrovimab (March, 2022)
- B.1.1.7 (Alpha; UK origin): No change: <5-fold reduction in susceptibility
- B.1.351 (Beta; South Africa origin): No change: <5-fold reduction in susceptibility
- P.1 (Gamma; Brazil origin): No change: <5-fold reduction in susceptibility
- B.1.427/B.1.429 (Epsilon; California origin): No change: <5-fold reduction in susceptibility
- B.1.526 (Iota; New York origin): No change: <5-fold reduction in susceptibility
- B.1.617.1 (Kappa; India origin): No change: <5-fold reduction in susceptibility
- B.1.617.2/AY.4.2 (Delta; India origin): No change: <5-fold reduction in susceptibility
- AY.1/AY.2 (Delta [+K417N]; India origin): No change: <5-fold reduction in susceptibility
- C.37 (Lambda; Peru origin): No change: <5-fold reduction in susceptibility
- B.1.621 (Mu; Colombia origin): No change: <5-fold reduction in susceptibility
- B.1.1.529/BA.1 (Omicron; South Africa origin): No change: <5-fold reduction in susceptibility
- B.1.1.529/BA.1.1 subvariant (Omicron; South Africa origin): No change: <5-fold reduction in susceptibility
- B.1.1.529/BA.2 subvariant (Omicron; South Africa origin): 16-fold reduction (unlikely effective)
- B.1.1.529/BA.3 subvariant (Omicron; South Africa origin): 7.3-fold reduction (clinical relevance of 7.3-fold reduction unknown)
-
Authentic SARS-CoV-2 neutralization data of sotrovimab (March, 2022)
- B.1.1.7 (Alpha; UK origin): No change: <5-fold reduction in susceptibility
- B.1.351 (Beta; South Africa origin): No change: <5-fold reduction in susceptibility
- P.1 (Gamma; Brazil origin): No change: <5-fold reduction in susceptibility
- B.1.617.1 (Kappa; India origin): No change: <5-fold reduction in susceptibility
- B.1.617.2 (Delta; India origin): No change: <5-fold reduction in susceptibility
- B.1.1529/BA.1 (Omicron; South Africa origin): No change: <5-fold reduction in susceptibility
- B.1.1529/BA.1.1 (Omicron; South Africa origin): No change: <5-fold reduction in susceptibility
- B.1.1529/BA.2 (Omicron; South Africa origin): 15.7-fold (EC50) and 25.3-48.1–fold (EC90) reduction in susceptibility
Drug interaction overview
- Not renally excreted or metabolized by CYP450 enzymes
- Interactions with concomitant renally excreted drugs or drugs that are CYP450 substrates, inducers, or inhibitors are unlikely
Pregnancy & Lactation
Pregnancy
Insufficient data to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Use during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus
No dosage adjustment recommended by the manufacturer
Nonclinical reproductive toxicity studies have not been conducted
Sotrovimab is an Fc-enhanced human IgG and may have the potential for placental transfer from mother to developing fetus
Lactation
Data are unknown regarding presence in human or animal milk, effects on breastfed infants, or effects on milk production
Maternal IgG is known to be present in human milk
No dosage adjustment recommended by the manufacturer
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Recombinant human IgG1-kappa monoclonal antibody
Binds to a conserved epitope on the spike protein receptor binding domain of SARS-CoV-2 with a dissociation constant KD = 0.21 nM) but does not compete with human ACE2 receptor binding (IC50 value >33.6 nM [5 mcg/mL])
Inhibits an undefined step that occurs after virus attachment and before fusion of the viral and cell membranes
Absorption
AUC; Days 1-29: 1410 day⋅mcg/mL
Peak plasma concentration
- Following 1-hr infusion: 137 mcg/mL
- Day 29: 34 mcg/mL
Pharmacogenomics
Genotypic and phenotypic testing are ongoing to monitor for development of resistance-associated spike variations in clinical trials
Administration
IV Incompatibilities
Do not administer simultaneously with any other medications; compatibility with IV solutions and medications other than 0.9% NaCl is unknown
IV Compatibilities
0.9% NaCl
IV Preparation
Remove 1 vial of sotrovimab from refrigerated storage and allow to equilibrate to room temperature, protected from light, for ~15 minutes.
Inspect for particulate matter and discoloration; solution should appear clear, colorless, or yellow to brown
Gently swirl vial several times before use without creating air bubbles; do not shake vial
Dilution
- Withdraw 8 mL of sotrovimab from one vial and inject into the prefilled 50-mL or 100-mL infusion bag containing 0.9% NaCl
- Discard any product remaining in vials
- Before infusion, gently rock infusion bag back and forth by hand 3-5 times; do not invert infusion bag; avoid forming air bubbles
- Administer immediately after preparation; if unable to administer immediately, store according to directions
IV Administration
If solution refrigerated, allow to equilibrate to room temperature for ~20 minutes
Administer IV via pump or gravity according to size of infusion bag used
Infuse by polyvinyl chloride (PVC) or polyolefin (PO) infusion set, and use of a 0.2-micron polyethersulfone (PES) filter is strongly recommended
Attach infusion set to IV bag and prime infusion set
Infuse over 15 minutes for 50-mL bag or 30 minutes for 100-mL bag
Do not administer IV push or bolus
Owing to potential overfill of prefilled saline bags, administer entire infusion solution in bag to avoid underdosage
Flush line with 0.9% NaCl after infusion completed to ensure entire dose delivered
Discard unused product
Monitor during infusion and observe patients for at least 1 hr after infusion completed
Clinically monitor patients during infusion and observe patients for at least 1 hr after infusion is complete
Storage
Preservative-free product
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
- Do not freeze, shake, or expose to direct light
Diluted solution
- Refrigerate at 2-8ºC (36-46ºF) for up to 24 hr OR
- Store at room temperature 20-25ºC (68-77ºF) for up to 4 hr
- These storage times include the infusion time
