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Aug.05.2021

Sotrovimab

Indications/Dosage

Labeled

    Off-Label

    • coronavirus disease 2019 (COVID-19)
    • severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
    † Off-label indication

    INVESTIGATIONAL USE: For the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection† resulting in mild to moderate coronavirus disease 2019 (COVID-19)† in patients who are at high risk for progressing to severe COVID-19, including hospitalization or death

    NOTE: Patients may be at high risk for progressing to severe COVID-19 if they meet at least 1 of the following criteria:

    • Elderly (65 years or older)
    • Obesity or overweight
      • Body mass index (BMI) greater than 25 kg/m2
      • If age 12 to 17 years, BMI greater than or equal to 85th percentile for age and gender based on CDC growth charts
    • Pregnancy
    • Chronic kidney disease
    • Diabetes
    • Immunosuppressive disease or receiving immunosuppressive therapy
    • Cardiovascular disease (including congential heart disease) or hypertension
    • Chronic lung disease (e.g., chronic obstructive pulmonary disease, moderate-to-severe asthma, interstitial lung disease, cystic fibrosis, pulmonary hypertension)
    • Sickle cell disease
    • Neurodevelopmental disorder (e.g., cerebral palsy) or other conditions that confer medical complexity (e.g., genetic or metabolic syndromes, severe congential anomalies)
    • Medical-related technological dependency (e.g., tracheostomy, gastrostomy, positive pressure ventilation not related to COVID-19)

    In addition, other medical conditions or factors (e.g., race, ethnicity) may also place individual patients at high risk, and authorization of sotrovimab under the EUA is not limited to only those medical conditions or factors listed above. Health care providers are advised to consider the benefit-to-risk of an individual patient.[66695]

    NOTE: Sotrovimab is not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of the drug in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[66695]

    NOTE: The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend anti-SARS-CoV-2 antibodies be considered for use in high risk persons with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19. Additionally, although these antibodies are not authorized for use in patients hospitalized due to severe COVID-19, the NIH states that they may be available through expanded access programs for patients who have not developed an antibody response or who are not expected to mount an effective immune response to SARS-CoV-2 infection.[65314]

    Intravenous dosage

    Adults weighing 40 kg or more

    500 mg as a single intravenous infusion over 30 minutes. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66695]

    Children and Adolescents 12 years and older weighing 40 kg or more

    500 mg as a single intravenous infusion over 30 minutes. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 10 days of symptom onset.[66695] According to the National Institutes of Health (NIH) COVID-19 treatment guidelines, there are insufficient pediatric data to recommend either for or against the routine use of anti-SARS-CoV-2 antibodies in high risk pediatric patients with mild to moderate COVID-19. The NIH recommends the use of these antibodies be considered on a case-by-case basis in consultation with a pediatric infectious diseases specialist.[65314]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      40 kg or more: 500 mg IV.

      less than 40 kg: Use not authorized.

    • Geriatric

      40 kg or more: 500 mg IV.

      less than 40 kg: Use not authorized.

    • Adolescents

      40 kg or more: 500 mg IV.

      less than 40 kg: Use not authorized.

    • Children

      12 years and weighing 40 kg or more: 500 mg IV.

      12 years and weighing less than 40 kg: Use not authorized.

      1 to 11 years: Use not authorized.

    • Infants

      Use not authorized.

    • Neonates

      Use not authorized.

    Patients with Hepatic Impairment Dosing

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Patients with Renal Impairment Dosing

    No dosage adjustments are needed.

    † Off-label indication
    Revision Date: 08/05/2021, 02:12:06 PM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) of sotrovimab. Retrieved May 27, 2021. Available on the World Wide Web at https://www.fda.gov/media/149534/download

    How Supplied

    Sotrovimab Solution for injection

    Sotrovimab 500mg/8mL Solution for Injection (00173-0901) (GlaxoSmithKline Group of Companies) null

    Description/Classification

    Description

    Sotrovimab is an investigational human immunoglobulin G-1 (IgG1-kappa) monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is not an FDA-approved drug; however, it has been authorized by the FDA for emergency treatment of mild to moderate coronavirus diseases 2019 (COVID-19) in patients (12 years and older weighing at least 40 kg) with positive SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19. Sotrovimab is NOT authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen for an underlying condition. Use of the drug in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[66695] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend using anti-SARS-CoV-2 monoclonal antibodies (including sotrovimab) to treat nonhospitalized patients with mild to moderate COVID-19 who are at high risk of clinical progression as defined by the Emergency Use Authorization (EUA) criteria. Anti-SARS-CoV-2 antibodies should also be considered for use in high risk persons with mild to moderate COVID-19 who are hospitalized for a reason other than COVID-19. While these antibodies are not authorized for use in patients hospitalized due to severe COVID-19, they may be available through expanded access programs for patients who have not developed an antibody response or who are not expected to mount an effective immune response to SARS-CoV-2 infection. Anti-SARS-CoV-2 antibodies should be started as soon as possible after positive test results for SARS-CoV-2 and within 10 days of symptom onset. In situations where it is necessary to triage eligible patients (i.e., antibody shortages, logistical constraints), the NIH suggests prioritizing treatment to unvaccinated/incompletely vaccinated high risk individuals or vaccinated individuals not expected to mount an adequate immune response over vaccinated individuals who are expected to have developed an adequate immune response. These considerations should NOT limit the use of anti-SARS-CoV-2 antibodies when there are no logistical constraints. For patients who receive anti-SARS-CoV-2 antibodies, defer administration of the COVID-19 vaccination for at least 90 days as a precaution to avoid interference with vaccine-induced immune responses. Conversely, the use and timing of treatment with anti-SARS-CoV-2 antibodies should not be affected by prior vaccinations in patients who develop COVID-19 after receiving the vaccine.[65314]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • Antiviral Monoclonal Antibodies for SARS-CoV-2
    Revision Date: 09/03/2021, 03:08:49 PM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) of sotrovimab. Retrieved May 27, 2021. Available on the World Wide Web at https://www.fda.gov/media/149534/download

    Administration Information

    General Administration Information

    For storage information, see the specific product information within the How Supplied section.

     

    NOTE: Sotrovimab is not an FDA-approved medication; however, it has been authorized for use under an Emergency Use Authorization (EUA) to treat mild to moderate COVID-19 in patients with positive SARS-CoV-2 viral testing who are at high risk for progressing to severe COVID-19, including hospitalization or death. Under the EUA, health care providers are required to communicate to the patient, parent, or caregiver information consistent with the "Fact Sheet for Patients, Parents, and Caregivers" prior to the patient receiving treatment; such information includes the following:

    • The option to accept or refuse sotrovimab
    • The significant known and potential risks and benefits of treatment, and the extent to which such potential risks and benefits are unknown
    • Available alternative treatments and the risk and benefits of those alternatives
    • The need to continue to self-isolate and use infection control measures (e.g., wear mask, isolate, social distance, avoid sharing personal items, clean and disinfect, frequent handwashing) according to CDC guidelines

    NOTE: Under the EUA, health care providers are required to report all medication errors and serious adverse events potentially related to sotrovimab therapy within 7 calendar days from the onset of the event.[66695]

    Route-Specific Administration

    Injectable Administration

    • Must be administered in a setting in which health care providers have immediate access to medications used to treat a severe infusion reaction and the ability to activate the emergency medical system, as necessary.
    • Visually inspect parenteral products for particulate matter and discoloration prior to drug administration. Sotrovimab is a clear, colorless or yellow to brown solution. Discard the vial if particulate matter or discoloration is observed.[66695]

    Intravenous Administration

    Preparation and Dilution:

    • The infusion should be prepared and administered by a qualified health care professional using aseptic technique. The product does not contain a preservative.
    • Remove 1 sotrovimab vial (500 mg/8 mL) from the refrigerator and allow it to equilibrate to room temperature (approximately 15 minutes) while protecting from light.
    • Select a polyvinyl chloride (PVC) or polyolefin (PO) 50 mL or 100 mL 0.9% Sodium Chloride Injection prefilled infusion bag. Choose 1 size.
    • Gently swirl the sotrovimab vial several times without creating bubbles; DO NOT shake.
    • Withdraw 8 mL of sotrovimab from the vial and inject into the 0.9% Sodium Chloride Injection prefilled infusion bag. Discard any product remaining in the vial.
    • Gently rock the infusion bag by hand 3 to 5 times to mix. DO NOT invert or shake the bag. Avoid forming air bubbles.
    • Storage: Use immediately after dilution. If immediate administration is not possible, the diluted solution may be stored at room temperature 20 to 25 degrees C (68 to 77 degrees F) for no more than 4 hours or under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours (including transportation and infusion time). If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 15 minutes before administration.[66695]

     

    Intravenous Infusion:

    • Obtain a polyvinyl chloride (PVC) or polyolefin (PO) infusion set and a 0.2 micron polyethersulfone (PES) filter (use of the filter is strongly recommended).
    • Attach the infusion set to the IV infusion bag.
    • Prime the infusion set with 0.9% Sodium Chloride Injection.
    • Administer the entire infusion solution in the bag over 30 minutes; DO NOT bolus. Due to potential overfill of prefilled bags, the entire infusion solution in the bag should be administered to avoid underdosage.
    • The prepared infusion solution should not be administered simultaneously with other medications. The compatibility of sotrovimab with solutions or medications other than 0.9% Sodium Chloride Injection is not known.
    • Once the infusion is complete, flush the IV line with 0.9% Sodium Chloride Injection to ensure delivery of the required dose.
    • Clinically monitor patients during the infusion and for at least 1 hour after the infusion is complete.[66695]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

    Sotrovimab

      Revision Date: 05/28/2021, 04:50:51 PMCopyright 2004-2021 by Lawrence A. Trissel. All Rights Reserved.

      References

      66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) of sotrovimab. Retrieved May 27, 2021. Available on the World Wide Web at https://www.fda.gov/media/149534/download

      Adverse Reactions

      Mild

      • chills
      • diarrhea
      • dizziness
      • fever
      • pruritus
      • rash

      Moderate

      • dyspnea
      • infusion-related reactions

      Severe

      • anaphylactoid reactions
      • bronchospasm

      Adverse events that developed within 24 hours of sotrovimab treatment during the COMET-ICE trial (i.e., non-hospitalized patients) included fever, chills, dizziness, dyspnea, pruritus, rash (2%), and infusion-related reactions (1%). All the reported events in this trial were mild to moderate in severity (Grade 1 or 2). In a different trial involving hospitalized patients, 1 patient experienced anaphylactic or anaphylactoid reactions during the infusion. In this case, the infusion was immediately stopped and the patient recovered following treatment with 2 doses of epinephrine. Other serious infusion-related reactions observed in hospitalized recipients of sotrovimab included Grade 3 or 4 bronchospasm and dyspneas; however, these events were also reported following infusion of the placebo.[66695]

      Diarrhea was reported by 1% of patients treated with sotrovimab during the COMET-ICE trial. In all patients, the severity of the diarrhea was mild to moderate (Grade 1 or 2).[66695]

      Revision Date: 06/01/2021, 09:15:01 AM

      References

      66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) of sotrovimab. Retrieved May 27, 2021. Available on the World Wide Web at https://www.fda.gov/media/149534/download

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • breast-feeding
      • infusion-related reactions
      • pregnancy

      Sotrovimab is not authorized for use in patients who are hospitalized due to COVID-19, who require oxygen therapy for COVID-19, or who require an increase in baseline oxygen flow rate due to COVID-19 if already on chronic oxygen therapy for an underlying condition. Use of the drug in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes. Recipients of anti-SARS-CoV-2 monoclonal antibodies, such as sotrovimab, have experienced fever, hypoxia, increased respiratory difficulty, arrythmia exacerbation, fatigue, and altered mental status; some of these events required hospitalization. It is not known if these events were related to administration of the antibody or progression of the COVID-19.[66695]

      Infusion-related reactions have been observed during and up to 24 hours after treatment with sotrovimab; these reactions may be severe or life-threatening. Signs and symptoms of these reactions include fever, chills, nausea, headache, bronchospasms, dyspnea, reduced oxygen saturation, fatigue, arrhythmia exacerbation (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, hypotension, hypertension, angioedema, throat irritation, rash, urticaria, pruritus, myalgia, dizziness, syncope, and diaphoresis. If an infusion-related reaction develops, consider slowing or stopping the infusion and administer appropriate medications and supportive care. Similarly, serious hypersensitivity reactions, including anaphylaxis, have been observed with sotrovimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue treatment and initiate appropriate medications and supportive care.[66695]

      There are insufficient data regarding the use of sotrovimab during pregnancy to determine a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, sotrovimab has the potential to be transferred from the mother to the developing fetus. It is unknown if this potential in utero transfer provides any therapeutic benefit or risk to the fetus. According to the manufacturer, sotrovimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66695] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend anti-SARS-CoV-2 monoclonal antibodies not be withheld from a pregnant woman at high risk of progressing to severe COVID-19 if the clinician thinks that the potential benefit outweighs potential risk.[65314]

      There are no data regarding the presence of sotrovimab in human milk, the effects on the breast-fed infant, or the effects on milk production; however, maternal immunoglobulin G (IgG) is known to be present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the potential for viral transmission to SARS-CoV-2-negative infants, and the risk of an untreated or inadequately treated condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.[66695]

      Revision Date: 05/28/2021, 05:38:48 PM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) of sotrovimab. Retrieved May 27, 2021. Available on the World Wide Web at https://www.fda.gov/media/149534/download

      Mechanism of Action

      Sotrovimab is a recombinant human immunoglobulin G-1 (IgG1-kappa) monoclonal antibody used as an antiviral medication to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This antibody binds to an epitope on the spike protein receptor binding domain (RBD) of SARS-CoV-2, where it inhibits an undefined step that occurs after viral attachment but before fusion of the viral and host cell membranes. In cell cultures, sotrovimab elicited antibody-dependent cell-mediated cytotoxicity (ADCC) using human natural killer (NK) cells and antibody-dependent cellular phagocytosis (ADCP) using CD14 monocytes. The average 50% effective concentration (EC50) of sotrovimab in neutralizing SARS-CoV-2 in Vero cells is 100.1 ng/mL and the average EC90 is 186.3 ng/mL.[66127][66130]

       

      There is a potential for treatment failure due to the development of viral variants that are resistant to sotrovimab. Health care providers are advised to consider the prevalence of SARS-CoV-2 variants in their area when considering treatment options. In cell cultures, epitope amino acid sequence polymorphisms P337H/L/R/T and E340A/K/G resulted in reduced susceptibility to sotrovimab: E340K (more than 297-fold), P337R (more than 276-fold), P337L (180-fold), E340A (more than 100-fold), E340G (27-fold), P337H (7.5-fold), and P337T (5.4-fold). However, neutralization data for SARS-CoV-2 variant substitutions identified through global surveillance have found no change in susceptibility (i.e., less than 5-fold reduction) to sotrovimab. The variants and key substitutions are as follows:

      • United Kingdom B.1.1.7 variant (Alpha):
        • Key substitution: N501Y
        • 2.3-fold reduced susceptibility
      • South Africa B.1.351 variant (Beta):
        • Key substitutions: K417N + E484K + N501Y
        • 0.6-fold reduced susceptibility
      • Brazil P.1 variant (Gamma):
        • Key substitutions: K417T + E484K + N501Y
        • 0.35-reduced susceptibility
      • California B.1.427/B.1.429 variant (Epsilon):
        • Key substitution: L452R
        • 0.7-fold reduced susceptibility
      • New York B.1.526 variant (Iota):
        • Key substitution: E484K (not all New York B.1.526 isolates harbored the E484K substitution)
        • 0.6-fold reduced susceptibility
      • India B.1.617 variant (Delta):
        • Key substitution: L452R + E484Q
        • 0.7-fold reduced susceptibility[66695]
      Revision Date: 08/02/2021, 06:04:46 PM

      References

      66127 - Food and Drug Administration (FDA). Fact sheet for health care providers: emergency use authorization (EUA) of REGEN-COV (casirivimab with imdevimab). Retrieved July 30, 2021. Available on the World Wide Web at https://www.fda.gov/media/145611/download66130 - Hansen J, Baum A, Pascal KE, et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 2020;369:1010-1014.66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) of sotrovimab. Retrieved May 27, 2021. Available on the World Wide Web at https://www.fda.gov/media/149534/download

      Pharmacokinetics

      Sotrovimab is administered via intravenous infusion. Data regarding the pharmacokinetics of sotrovimab are limited; however, because sotrovimab includes 2 amino acid substitutions on the Fc domain (i.e., M428L and N434S), the half-life of sotrovimab is expected to be longer than Fc-unmodified IgG monoclonal antibodies. Sotrovimab is not metabolized by cytochrome P450 enzymes, nor is it renally excreted.[66695]

       

      Affected cytochrome P450 isoenzymes: none

      Route-Specific Pharmacokinetics

      Intravenous Route

      Data from a non-compartmental analysis found the mean maximum plasma concentration (Cmax) after a 1 hour sotrovimab intravenous infusion to be 137 mcg/mL (n = 129) and the mean Day 29 concentration to be 34 mcg/mL (n = 78).[66695]

      Special Populations

      Renal Impairment

      Sotrovimab is not eliminated via the kidneys; therefore, neither renal impairment nor the presence of dialysis are expected to impact the pharmacokinetics of sotrovimab.[66695]

      Pediatrics

      Administration of the recommended dose to pediatric patients ages 12 years and older who weigh at least 40 kg is expected to result in serum sotrovimab exposures that are comparable to those observed in adults.[66695]

      Revision Date: 05/28/2021, 04:44:50 PM

      References

      66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) of sotrovimab. Retrieved May 27, 2021. Available on the World Wide Web at https://www.fda.gov/media/149534/download

      Pregnancy/Breast-feeding

      pregnancy

      There are insufficient data regarding the use of sotrovimab during pregnancy to determine a drug-associated risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, sotrovimab has the potential to be transferred from the mother to the developing fetus. It is unknown if this potential in utero transfer provides any therapeutic benefit or risk to the fetus. According to the manufacturer, sotrovimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus.[66695] The National Institutes of Health (NIH) COVID-19 treatment guidelines recommend anti-SARS-CoV-2 monoclonal antibodies not be withheld from a pregnant woman at high risk of progressing to severe COVID-19 if the clinician thinks that the potential benefit outweighs potential risk.[65314]

      breast-feeding

      There are no data regarding the presence of sotrovimab in human milk, the effects on the breast-fed infant, or the effects on milk production; however, maternal immunoglobulin G (IgG) is known to be present in human milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, the potential for viral transmission to SARS-CoV-2-negative infants, and the risk of an untreated or inadequately treated condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.[66695]

      Revision Date: 05/28/2021, 05:38:48 PM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Diseases 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Accessed September 15, 2021. Available at on the World Wide Web at: https://covid19treatmentguidelines.nih.gov/.66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) of sotrovimab. Retrieved May 27, 2021. Available on the World Wide Web at https://www.fda.gov/media/149534/download

      Interactions

      There are no drug interactions associated with Sotrovimab products.
      Revision Date: 05/28/2021, 02:33:00 AM

      References

      Monitoring Parameters

      • laboratory monitoring not necessary
      ;