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TRANSFORMAR COMO VOCÊ USA INFORMAÇÕES SOBRE DROGAS
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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:
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]
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]
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]
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]
40 kg or more: 500 mg IV.
less than 40 kg: Use not authorized.
40 kg or more: 500 mg IV.
less than 40 kg: Use not authorized.
40 kg or more: 500 mg IV.
less than 40 kg: Use not authorized.
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.
Use not authorized.
Use not authorized.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
No dosage adjustments are needed.
† Off-label indicationNOTE: 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]
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:
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]
Preparation and Dilution:
Intravenous Infusion:
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]
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]
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:
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
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]
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]
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]
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]
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