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TRANSFORMAR COMO VOCÊ USA INFORMAÇÕES SOBRE DROGAS
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NOTE: As of November 30, 2022, bebtelovimab is NO LONGER AUTHORIZED for use in any U.S. region. Healthcare providers are encouraged to consider use of other approved/authorized products when selecting appropriate treatment options for coronavirus disease (COVID-19). Revocation of the Emergency Use Authorization (EUA) was due to the increased circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants that are likely to be resistant to bebtelovimab (i.e., BQ.1, BQ.1.1, XBB). The Centers for Disease Control and Prevention Nowcast data estimate that the combined prevalence of these subvariants is over 68% nationally. The FDA will continue to monitor variant susceptibility and frequency data and provide additional updates as new information becomes available.[65314][68236]
NOTE: Due to the increased prevalence of resistant Omicron subvariants, the National Institutes of Health (NIH) NO LONGER recommends use of bebtelovimab 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-risk for each individual patient.[67385]
NOTE: Bebtelovimab 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 monoclonal antibodies in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[67385]
NOTE: Administer bebtelovimab only in a setting with immediate access to medications used for the treatment of severe infusion or hypersensitivity reactions (e.g., anaphylaxis) and with the ability to activate the emergency medical system (EMS), if necessary. Patients should be monitored during administration and observed for at least 1 hour after the injection is complete.[67385]
175 mg as a single intravenous injection. Administer as soon as possible after the positive test for SARS-CoV-2 and within 7 days of symptom onset.[65314] [67385]
175 mg as a single intravenous injection. Administer as soon as possible after the positive test for SARS-CoV-2 and within 7 days of symptom onset.[67385] The NIH states that there is insufficient evidence to recommend either for or against the use of bebtelovimab in pediatric patients.[65314]
175 mg IV.
175 mg IV.
weight 40 kg or more: 175 mg IV.
weight less than 40 kg: Safety and efficacy have not been established.
12 years and weight 40 kg or more: 175 mg IV.
12 years and weight less than 40 kg: Safety and efficacy have not been established.
1 to 11 years: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
No dosage adjustment is recommended in patients with mild hepatic impairment. Bebtelovimab has not been studied in patients with moderate or severe hepatic impairment.[67385]
No dosage adjustment is recommended in patients with renal impairment.[67385]
† Off-label indicationNOTE: As of November 30, 2022, bebtelovimab is NO LONGER AUTHORIZED for use in any U.S. region. The National Institutes of Health (NIH) NO LONGER recommends use of bebtelovimab for treatment of coronavirus diseases 2019 (COVID-19). Health care providers are encouraged to consider use of other approved/authorized products when selecting appropriate treatment options for COVID-19. The Emergency Use Authorization (EUA) for bebtelovimab was revoked because of the increased circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants that are likely to be resistant to bebtelovimab (i.e., BQ.1, BQ.1.1, XBB). The Centers for Disease Control and Prevention Nowcast data estimate that the combined prevalence of these subvariants is now over 68% nationally. The FDA will continue to monitor variant susceptibility and frequency data and provide additional updates as new information becomes available.[65314][68236]
Bebtelovimab is an investigational monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is not FDA-approved for any indication; however, it has been authorized for emergency use for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients 12 years of age and older weighing at least 40 kg with a positive SARS-CoV-2 test, and who are at high risk for progression to severe disease, including hospitalization or death, and for whom approved or authorized alternative COVID-19 treatment options are not accessible or clinically appropriate. Bebtelovimab 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 monoclonal antibodies in hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation may be associated with worsening clinical outcomes.[67385]
For storage information, see the specific product information within the How Supplied section.
NOTE: Bebtelovimab is not an FDA-approved medication; however, it has been authorized for emergency use 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 Emergency Use Authorization (EUA), health care providers are required to communicate to the patient, parent, or caregiver information consistent with the "Fact Sheet for Patients, Parents or Caregivers" and provide them with a copy of this Fact Sheet prior to the patient receiving treatment.[67385]
NOTE: Under the EUA, health care providers are required to report all medication errors and serious adverse events potentially related to bebtelovimab therapy within 7 calendar days from the onset of the event.[67385]
Preparation
IV Push
Serious hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, have been observed with human immunoglobulin G1 (IgG1) monoclonal antibodies, and may occur with bebtelovimab. Infusion-related reactions (0.3%), including rash (0.8%) and pruritus (0.3%), were reported in patients who received bebtelovimab, alone or in combination with bamlanivimab and etesevimab, in the phase 1 and 2 portions of a randomized, single-dose clinical trial (n = 602). Monitor patients for possible infusion-related reactions during administration and for at least 1 hour after the injection is complete.[67385]
The most common adverse reactions that were reported in patients who received bebtelovimab, alone or in combination with bamlanivimab and etesevimab, in the phase 1 and 2 portions of a randomized, single-dose clinical trial (n = 602) were nausea (0.8%) and vomiting (0.7%).[67385]
Clinical worsening of COVID-19 has been reported after administration of SARS-CoV-2 monoclonal antibodies. Signs and symptoms included fever, hypoxia or increased respiratory difficulty, arrythmia exacerbation (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. Some of these events have required hospitalization. It is not known if these events were related to monoclonal antibody treatment or were due to the progression of COVID-19. Additionally, monoclonal antibodies may be associated with worsening clinical outcomes when administered to hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation. Therefore, these drugs are 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.[67385]
Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of other SARS-CoV-2 monoclonal antibodies and could occur with administration of bebtelovimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration of the drug and initiate appropriate medications and supportive care. Infusion-related reactions, which may occur up to 24 hours after the injection, have been observed in clinical trials of bebtelovimab when administered with other monoclonal antibodies and may occur with use of bebtelovimab alone; these reactions may be severe or life-threatening. Signs and symptoms of these reactions include fever, chills, nausea, headache, bronchospasm, 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, vasovagal reactions (e.g., pre-syncope, syncope), dizziness, and diaphoresis. Monitor patients for possible infusion-related reactions during administration and for at least 1 hour after the injection is complete. If an infusion-related reaction develops, administer appropriate medications and supportive care. Hypersensitivity reactions have also been reported to occur more than 24 hours after the injection with the use of SARS-CoV-2 monoclonal antibodies under Emergency Use Authorization.[67385]
Bebtelovimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus. There are insufficient data regarding the use of bebtelovimab 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, bebtelovimab 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. There are risks to the mother and fetus associated with untreated COVID-19 in pregnancy. There are also risks of severe hypersensitivity and infusion-related reactions following administration of bebtelovimab, including in pregnant patients. Pregnant patients who develop severe hypersensitivity or infusion-related reactions should be managed appropriately, including obstetrical care.[67385]
There are no data regarding the presence of bebtelovimab 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 developmental and health benefits of breast-feeding along with the mother's clinical need for bebtelovimab and any potential adverse effects on the breast-fed infant from bebtelovimab or the underlying maternal condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.[67385]
Bebtelovimab is a recombinant neutralizing human IgG1 monoclonal antibody (mAb) to the spike protein of SARS-CoV-2 and is unmodified in the Fc region. Bebtelovimab binds the spike protein with a dissociation constant KD of 0.046 to 0.075 nM and blocks spike protein attachment to the human ACE2 receptor with an IC50 value of 0.39 nM (0.056 mcg/mL). The cell culture neutralization activity of bebtelovimab against SARS-CoV-2 was measured in a dose-response model quantifying plaque reduction using cultured Vero E6 cells. Bebtelovimab neutralized the USA/WA/1/2020 isolate of SARS-CoV-2 with estimated EC50 value = 0.044 nM (6.4 ng/mL). Bebtelovimab demonstrated antibody-dependent cell-mediated cytotoxicity on Jurkat reporter cells expressing Fc gamma RIIIa following engagement with target cells expressing spike protein. Bebtelovimab did not elicit complement-dependent cytotoxicity activity in cell-based assays.
There is a potential risk of treatment failure due to the development of viral variants that are resistant to bebtelovimab. 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. Data from non-clinical studies have shown a 5-fold or greater reduction in susceptibility to bebtelovimab of viral variants with the following substitutions: K444E (more than 862-fold), K444N (more than 1,901-fold), K444Q (208-fold), K444T (more than 1,814-fold), V445A (111-fold), V445F (369-fold), V445G (more than 730-fold), G446D (69-fold), G446R (7-fold), G446V (8-fold), P499H (more than 1,606-fold), P499R (more than 1,870-fold), and P499S (25-fold). In the context of Delta spike protein, G446V substitution had reduced susceptibility of 16.4-fold.
Bebtelovimab pseudotyped virus-like particle (VLP) neutralization data for SARS-CoV-2 spike protein variants are as follows:
In authentic SARS-CoV-2 assays, bebtelovimab retained activity (less than 5-fold reduction) against variant virus isolates from the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2/AY.3), Omicron (B.1.1.529/BA.1), Omicron [+R346K] (BA.1.1), Omicron BA.2, Omicron BA.2 [+L452Q] (BA.2.12.1), Omicron BA.2 [+D339H, G446S, N460K, R493Q] (BA.2.75), Omicron BA.4, Omicron BA.4 [+R346T] (BA.4.6), and Omicron BA.5 lineages; as well as SARS-CoV-2 (USA/WA/1/2020 isolate) engineered to express the L452R substitution present in the Epsilon (B.1.427/B.1.429) lineage or the E484K substitution present in the Iota (B.1.526) lineage.[67385]
Revision Date: 09/29/2023, 01:50:00 AMBebtelovimab is administered by intravenous injection. Once in systemic circulation, the mean steady state volume of distribution is 4.61 L. Bebtelovimab is expected to be degraded into small peptides and component amino acids via catabolic pathways similarly to endogenous IgG antibodies. The mean clearance and elimination half-life for bebtelovimab are 0.014 L/hour and 11.5 days, respectively.[67385]
Affected cytochrome P450 isoenzymes: none
Following administration of a single dose of 175 mg bebtelovimab, the mean Cmax and AUC were 59.9 mcg/mL and 539 mcg x day/mL, respectively. The mean drug concentration on day 29 was 4.55 mcg/mL.[67385]
Based on population pharmacokinetic analysis, there is no significant difference in pharmacokinetics of bebtelovimab in patients with mild hepatic impairment compared to patients with normal hepatic function. Bebtelovimab has not been studied in patients with moderate or severe hepatic impairment.[67385]
Renal impairment is not expected to impact the pharmacokinetics of bebtelovimab, since monoclonal antibodies with molecular weight more than 69 kDa are known not to undergo renal elimination. Similarly, dialysis is not expected to impact the pharmacokinetics of bebtelovimab.[67385]
Based on population pharmacokinetic analysis, there is no difference in the pharmacokinetics of bebtelovimab in geriatric patients as compared to younger patients.[67385]
Based on population pharmacokinetic analysis, gender does not affect the pharmacokinetics of bebtelovimab.[67385]
Based on population pharmacokinetic analysis, ethnicity does not affect the pharmacokinetics of bebtelovimab.[67385]
Body weight has no clinically relevant effect on the pharmacokinetics of bebtelovimab in adults with COVID-19 who weigh between 45 kg to 194 kg.[67385]
Disease Severity
Based on population pharmacokinetic analysis, baseline viral load does not affect the pharmacokinetics of bebtelovimab.[67385]
Bebtelovimab should be administered during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus. There are insufficient data regarding the use of bebtelovimab 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, bebtelovimab 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. There are risks to the mother and fetus associated with untreated COVID-19 in pregnancy. There are also risks of severe hypersensitivity and infusion-related reactions following administration of bebtelovimab, including in pregnant patients. Pregnant patients who develop severe hypersensitivity or infusion-related reactions should be managed appropriately, including obstetrical care.[67385]
There are no data regarding the presence of bebtelovimab 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 developmental and health benefits of breast-feeding along with the mother's clinical need for bebtelovimab and any potential adverse effects on the breast-fed infant from bebtelovimab or the underlying maternal condition. Lactating mothers are advised to follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.[67385]
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