sotrovimab (Investigational)

Brand and Other Names:
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Dosing & Uses

AdultPediatric

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 10 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization

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

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 10 days of symptom onset in patients at high risk for progressing to severe COVID-19 and/or hospitalization

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

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
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Adverse Effects

EUA requirement: Completion of FDA MedWatch Form to report all medication errors and serious adverse events is mandatory

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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 (May, 2021)
    • B.1.1.7 (UK origin): No change: <5-fold reduction in susceptibility
    • B.1.351 (South Africa origin): No change: <5-fold reduction in susceptibility
    • P.1 (Brazil origin): No change: <5-fold reduction in susceptibility
    • B.1.427/B.1.429 (California origin): No change: <5-fold reduction in susceptibility
    • B.1.526 (New York origin): No change: <5-fold reduction in susceptibility
  • Authentic SARS-CoV-2 neutralization data of sotrovimab (May, 2021)
    • B.1.1.7 (UK origin): No change: <5-fold reduction in susceptibility
    • B.1.351 (South Africa origin): No change: <5-fold reduction in susceptibility
    • P.1 (Brazil origin): No change: <5-fold 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
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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.

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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

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

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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 30 min; 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
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Images

No images available for this drug.
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Patient Handout

A Patient Handout is not currently available for this monograph.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.