ContenidosdeElseviersobremedicamentos

TRANSFORME LA FORMA DE USAR LA INFORMACIÓN SOBRE MEDICAMENTOS

¡Conozca más acerca de la información sobre medicamentos de Elsevier hoy mismo! Obtenga los datos sobre medicamentos y el apoyo para la toma de decisiones que necesita, incluidas TRUE Daily Updates™, información actualizada todos los días, incluidos fines de semana y festivos.

Sep.29.2023

Sotrovimab

Indications/Dosage

Labeled

    NOTE: As of April 5, 2022, sotrovimab is NO LONGER AUTHORIZED for use in any U.S. state or territory. Healthcare providers are encouraged to consider use of other approved/authorized products when selecting appropriate treatment options for coronavirus disease (COVID-19). The FDA removed the Emergency Use Authorization (EUA) for sotrovimab after data from the Centers for Disease Control and Prevention found more than 50% of cases in all U.S. regions are due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants with reduced susceptibility to sotrovimab. The FDA will continue to monitor conditions to determine whether use in a geographic region is consistent with this scope of authorization, referring to available information, including information on variant susceptibility, and CDC regional variant frequency data available at: covid.cdc.gov/covid-data-tracker/#variant-proportions.[66695][67488][65314]

    NOTE: Due to Omicron being the dominant variant in the United States, the National Institutes of Health (NIH) NO LONGER recommends use of sotrovimab for treatment of mild to moderate COVID-19. The NIH recommends using 1 of the following therapeutics:

    • Preferred therapies (Adult and pediatric patients, listed in order of preference)
      • nirmatrelvir; ritonavir
      • remdesivir
    • Alternative therapies (Adults only)
      • molnupiravir

    NOTE: Logistical or supply constraints may make it impossible to offer the available therapy to all eligible patients, making patient triage necessary. Prioritize the use of these therapies for patients at highest risk of clinical progression. Information on which individuals might receive the greatest benefit from anti-SARS-CoV-2 therapeutics for treatment or prevention can be obtained from www.covid19treatmentguidelines.nih.gov/therapies/statement-on-patient-prioritization-for-outpatient-therapies.[65314]

    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: Medical conditions and factors associated with an increased risk for progression to severe COVID-19 can be obtained on the Centers for Disease Control and Prevention (CDC) website at www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions. Healthcare providers are advised to consider the benefit-to-risk of an individual patient.[66695]

    NOTE: Sotrovimab was NOT authorized for use in patients who were hospitalized due to COVID-19, who required oxygen therapy or respiratory support for COVID-19, or who required an increase in baseline oxygen flow rate or respiratory support 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]

    Intravenous dosage

    Adults weighing 40 kg or more

    500 mg as a single intravenous infusion. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 7 days of symptom onset.[65314] [66695]

    Children and Adolescents 12 to 17 years weighing 40 kg or more

    500 mg as a single intravenous infusion. Administer the infusion as soon as possible after the positive test for SARS-CoV-2 and within 7 days of symptom onset.[65314] [66695] Guidelines in pediatric patients suggest the use of monoclonal antibodies for the treatment of mild to moderate COVID-19 in adolescents at the highest risk of severe disease. Highest risk patients include those with obesity, patients who are severely immunocompromised, and those with medical complexity with respiratory technology dependence. The use of monoclonal antibodies for the treatment of mild to moderate COVID-19 could be considered in adolescents with moderate risk of severe disease based on individualized risk assessment and shared decision-making. Moderate-risk conditions include mild-to-moderately immunocompromised, chronic respiratory conditions, congenital heart disease, and sickle cell disease. Guidelines do not suggest routine use of monoclonal antibodies for treatment in adolescents at lower risk of severe disease (i.e., diabetes, chronic kidney disease).[67381]

    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: 09/29/2023, 01:50:00 AM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Accessed March 1, 2024. Available at https://www.covid19treatmentguidelines.nih.gov/66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) for sotrovimab. Retrieved April 24, 2023. Available on the World Wide Web at https://www.fda.gov/media/149534/download?utm_medium=email&utm_source=govdelivery67381 - Wolf J, Abzug MJ, Anosike BI, et al. Updated guidance on use and prioritization of monoclonal antibody therapy for treatment of COVID-19 in adolescents. J Pediatric Infect Dis Soc 2022 Feb 2; epub ahead of print.67488 - US Food and Drug Administration (FDA). FDA updates sotrovimab emergency use authorization. Accessed April 5, 2022. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization?utm_medium=email&utm_source=govdelivery

    How Supplied

    Sotrovimab Solution for injection

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

    Description/Classification

    Description

    NOTE: As of April 5, 2022, sotrovimab is NO LONGER AUTHORIZED for use in any U.S. state or territory. Health care providers are encouraged to consider use of other approved/authorized products when selecting appropriate treatment options for coronavirus diseases 2019 (COVID-19). The FDA removed the Emergency Use Authorization (EUA) for sotrovimab after data from the Centers for Disease Control and Prevention found more than 50% of cases in all U.S. regions are due to an Omicron SARS-CoV-2 subvariant with reduced susceptibility to sotrovimab. The FDA will continue to monitor conditions to determine whether use in a geographic region is consistent with this scope of authorization, referring to available information, including information on variant susceptibility, and CDC regional variant frequency data available at: covid.cdc.gov/covid-data-tracker/#variant-proportions.[66695][67488]

     

    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 or respiratory support for COVID-19, or who require an increase in baseline oxygen flow rate or respiratory support 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]

     

    NOTE: Omicron variants have become the dominant variants in the United States. Sotrovimab is active against Omicron BA.1 and BA.1.1 subvariants, but has substantially decreased in vitro neutralization activity against Omicron BA.2, BA.4, and BA.5 subvariants; thus, the National Institutes of Health (NIH) COVID-19 guidelines NO LONGER recommends use of sotrovimab for treatment of mild to moderate COVID-19. Health care providers are encouraged to consider use of other approved/authorized products when selecting appropriate treatment options for COVID-19.[65314]

    Classifications

    • General Anti-infectives Systemic
      • Antivirals For Systemic Use
        • SARS-CoV-2 Antivirals
          • Antiviral Monoclonal Antibodies for SARS-CoV-2
    Revision Date: 09/29/2023, 01:50:00 AM

    References

    65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Accessed March 1, 2024. Available at https://www.covid19treatmentguidelines.nih.gov/66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) for sotrovimab. Retrieved April 24, 2023. Available on the World Wide Web at https://www.fda.gov/media/149534/download?utm_medium=email&utm_source=govdelivery67488 - US Food and Drug Administration (FDA). FDA updates sotrovimab emergency use authorization. Accessed April 5, 2022. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization?utm_medium=email&utm_source=govdelivery

    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 health care provider's awareness 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 1 of the following diluents: Polyvinyl chloride (PVC) or polyolefin (PO), sterile, prefilled 50 mL or 100 mL infusion bag containing either 0.9% Sodium Chloride Injection or 5% Dextrose injection.
    • 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 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 up to 25 degrees C (up to 77 degrees F) for no more than 6 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.
    • Administer the entire infusion solution in the bag over 15 minutes (if using a 50 mL infusion bag) or 30 minutes (if using a 100 mL infusion bag); 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 and 5% Dextrose Injection is not known.
    • Once the infusion is complete, flush the IV line with 0.9% Sodium Chloride or 5% Dextrose 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: 09/29/2023, 01:50:00 AMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

      References

      66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) for sotrovimab. Retrieved April 24, 2023. Available on the World Wide Web at https://www.fda.gov/media/149534/download?utm_medium=email&utm_source=govdelivery

      Adverse Reactions

      Mild

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

      Moderate

      • dyspnea
      • infusion-related reactions

      Severe

      • anaphylactoid reactions
      • bronchospasm

      Adverse reactions that developed within 24 hours of sotrovimab treatment during clinical trials involving non-hospitalized patients included fever, chills, dizziness, dyspnea, pruritus, rash (1%), and infusion-related reactions (up to 1%). Additionally, up to 2% of sotrovimab recipients and 1% of patients who received the placebo developed hypersensitivity reactions; none of which required pausing or discontinuation of the infusions. 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 2% 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: 09/29/2023, 01:50:00 AM

      References

      66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) for sotrovimab. Retrieved April 24, 2023. Available on the World Wide Web at https://www.fda.gov/media/149534/download?utm_medium=email&utm_source=govdelivery

      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 or respiratory support for COVID-19, or who require an increase in baseline oxygen flow rate or respiratory support 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]

      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] When evaluating the risk and benefits of sotrovimab, consider that COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death. 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. There is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to sotrovimab during pregnancy. Pregnant and recently pregnant patients can enroll at covid-pr.pregistry.com or call 1-800-616-3791 to obtain more information.[66695]

      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: 09/29/2023, 01:50:00 AM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Accessed March 1, 2024. Available at https://www.covid19treatmentguidelines.nih.gov/66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) for sotrovimab. Retrieved April 24, 2023. Available on the World Wide Web at https://www.fda.gov/media/149534/download?utm_medium=email&utm_source=govdelivery

      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.[66130][66695]

       

      Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies. Health care providers should refer to the CDC website as well as information from state and local health authorities regarding reports of viral variants of importance in their region to guide treatment decisions. In cell cultures, epitope amino acid substitutions P337H/K/L/R/T, E340A/I/K/G/Q/V, T345P, K356T, and L441N resulted in reduced susceptibility to sotrovimab: P337H (5.13-fold), P337K (more than 304-fold), P337L (more than 192-fold), P337R (more than 192-fold), P337T (10.62-fold), E340A (more than 100-fold), E340G (18.21-fold), E340I (more than 190-fold), E340K (more than 297-fold), E340Q (more than 50-fold), E340V (more than 200-fold), T345P (225-fold), K356T (5.9-fold), and L441N (72-fold). Neutralization data of sotrovimab against SARS-CoV-2 variant substitutions identified through global surveillance are as follows:

      • United Kingdom B.1.1.7 variant (Alpha):
        • Key substitution: N501Y
        • less than 5-fold reduced susceptibility
      • South Africa B.1.351 variant (Beta):
        • Key substitutions: K417N + E484K + N501Y
        • less than 5-fold reduced susceptibility
      • Brazil P.1 variant (Gamma):
        • Key substitutions: K417T + E484K + N501Y
        • less than 5-fold reduced susceptibility
      • California B.1.427/B.1.429 variant (Epsilon):
        • Key substitution: L452R
        • less than 5-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)
        • less than 5-fold reduced susceptibility
      • India B.1.617.1 variant (Kappa):
        • Key substitution: L452R + E484Q
        • less than 5-fold reduced susceptibility
      • India B.1.617.2/AY.4.2 variant (Delta):
        • Key substitutions: L452R + T478K
        • less than 5-fold susceptibility
      • India AY.1/AY.2 variant (Delta Plus):
        • Key substitutions: L452R + T478K + K417N
        • less than 5-fold reduced susceptibility
      • Peru C.37 variant (Lambda):
        • Key substitutions: L452Q + F490S
        • less than 5-fold reduced susceptibility
      • Columbia B.1.621 variant (Mu):
        • Key substitutions: R346K + E484K + N501Y
        • less than 5-fold reduced susceptibility
      • South Africa B.1.1.529/BA.1 variant (Omicron):
        • Key substitutions: G339D + S371L + S373P + S375F + K417N + N440K + G446S + S477N + T478K + E484A + Q493R + G496S + Q498R + N501Y + Y505H
        • less than 5-fold reduced susceptibility
      • South Africa B.1.1.529/BA.1.1 variant (Omicron):
        • Key substitutions: G339D + R346K + S371L + S373P + S375F + K417N + N440K + G446S + S477N + T478K + E484A + Q493R + G496S + Q498R + N501Y + Y505H
        • less than 5-fold reduced susceptibility
      • South Africa B.1.1.529/BA.2 variant (Omicron):
        • Key substitutions: G339D + S371F + S373P + S375F + T376A + D405N + R408S + K417N + N440K + S477N + T478K + E484A + Q493R + Q498R + N501Y + Y505H
        • 16-fold reduced susceptibility
      • South Africa B.1.1.529/BA.3 (Omicron):
        • Key substitutions: G339D + S371F + S373P + S375F + D405N + K417N + N440K + G446S + S477N + T478K + E484A + Q493R + Q498R + N501Y + Y505H
        • 7.3-fold reduced susceptibility[66695]
      Revision Date: 09/29/2023, 01:50:00 AM

      References

      66130 - 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) for sotrovimab. Retrieved April 24, 2023. Available on the World Wide Web at https://www.fda.gov/media/149534/download?utm_medium=email&utm_source=govdelivery

      Pharmacokinetics

      Sotrovimab is administered via intravenous infusion. The monoclonal antibody has a mean steady-state volume of distribution of 8.1 L, and is degraded by proteolytic enzymes that are distributed throughout the body. The mean systemic clearance is 125 mL/day and the median terminal half-life is approximately 49 days.[66695]

       

      Affected cytochrome P450 isoenzymes: none

      Route-Specific Pharmacokinetics

      Intravenous Route

      The geometric mean maximum plasma concentration (Cmax) at the end of a sotrovimab intravenous infusion is 143 mcg/mL (n = 102, CV% 34.5) and the geometric mean Day 29 concentration is 40.7 mcg/mL (n = 135, CV% 40.3). Systemic drug exposure (AUC) from Study Day 1 to Day 29 is 1,410 mcg/mL x day (n = 20, CV% 25.6).[66695]

      Special Populations

      Renal Impairment

      Monoclonal antibodies with molecular weights greater than 69 kDa do not undergo renal elimination. Therefore, neither renal impairment nor the presence of dialysis are expected to impact the pharmacokinetics of sotrovimab (149 kDa).[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: 09/29/2023, 01:50:00 AM

      References

      66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) for sotrovimab. Retrieved April 24, 2023. Available on the World Wide Web at https://www.fda.gov/media/149534/download?utm_medium=email&utm_source=govdelivery

      Pregnancy/Breast-feeding

      pregnancy

      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] When evaluating the risk and benefits of sotrovimab, consider that COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death. 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. There is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to sotrovimab during pregnancy. Pregnant and recently pregnant patients can enroll at covid-pr.pregistry.com or call 1-800-616-3791 to obtain more information.[66695]

      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: 09/29/2023, 01:50:00 AM

      References

      65314 - COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. Accessed March 1, 2024. Available at https://www.covid19treatmentguidelines.nih.gov/66695 - Food and Drug Administration (FDA). Fact sheet for healthcare providers: emergency use authorization (EUA) for sotrovimab. Retrieved April 24, 2023. Available on the World Wide Web at https://www.fda.gov/media/149534/download?utm_medium=email&utm_source=govdelivery

      Interactions

      There are no drug interactions associated with Sotrovimab products.
      Revision Date: 09/29/2023, 01:50:00 AM

      References

      Monitoring Parameters

      • laboratory monitoring not necessary
      ;