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TRANSFORMAR COMO VOCÊ USA INFORMAÇÕES SOBRE DROGAS
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NOTE: Pemivibart is authorized for use in persons who:
NOTE: Pemivibart is NOT authorized for:
4,500 mg IV once. For people requiring ongoing protection, may repeat doses of 4,500 mg IV once every 3 months. Repeat dosing should be timed from the date of the most recent dose.[70471]
4,500 mg IV once. For people requiring ongoing protection, may repeat doses of 4,500 mg IV once every 3 months. Repeat dosing should be timed from the date of the most recent dose.[70471]
40 kg or more: 4,500 mg IV.
less than 40 kg: Use not authorized.
40 kg or more: 4,500 mg IV.
less than 40 kg: Use not authorized.
40 kg or more: 4,500 mg IV.
less than 40 kg: Use not authorized.
12 years and weighing 40 kg or more: 4,500 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.
No dosage adjustments are needed.
No dosage adjustments are needed.
† Off-label indicationPemivibart is a recombinant human immunoglobulin G1 (IgG1) 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 issued an Emergency use Authorization (EUA) by the FDA for pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in certain adult and pediatric individuals (12 years of age and older weighing at least 40 kg). Specifically, pemivibart is authorized for use in persons who:
Circumstances in which the drug is NOT authorized for use include:
Cases of anaphylaxis have been observed following the use of pemivibart. Therefore, the drug must be administered in a setting in which the health care provider has immediate access to medications used to treat anaphylaxis and the ability to activate the emergency medical system (EMS), as necessary. Prior to administering pemivibart, consider the potential benefits of COVID-19 prevention along with the risk of anaphylaxis.[70471]
For storage information, see the specific product information within the How Supplied section.
NOTE: Pemivibart is not an FDA-approved medication; however, it has been authorized for emergency use as pre-exposure prophylaxis of COVID-19 in certain persons who may not mount an adequate immune response to COVID-19 vaccination. 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.
NOTE: Inform patients that certain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may have substantially reduced susceptibility to pemivibart, and thus, pemivibart may not be effective at preventing COVID-19 caused by these variants. Instruct patients to undergo viral testing and seek medical attention if they develop signs or symptoms of COVID-19 after receiving pemivibart. Symptoms of COVID-19 may include fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea. Pemivibart will remain authorized for use so long as the combined national frequency of SARS-CoV-2 variants with substantially reduced susceptibility to pemivibart does not exceed 90%. The FDA will continue to monitor variant susceptibility and frequency data.
NOTE: Under the EUA, health care providers are required to report all medication errors and serious adverse events potentially related to pemivibart therapy within 7 calendar days from the health care provider's awareness of the event.[70471]
Preparation:
Intravenous infusion:
The most common treatment-emergent adverse events reported by moderate-to-severely immunocompromised recipients of pemivibart during clinical trials (n = 306) included upper respiratory tract infection (6%), viral infection (4%), influenza-like illness (3%), fatigue (3%), headache (2%), and nausea (2%).[70471]
During clinical trials, 2% (n = 6 of 306) of moderate-to-severely immunocompromised patients experienced a local injection site reaction during either the first or second pemivibart dose; no local injection site reactions were noted in immunocompetent drug recipients. Local reactions were reported as bruising or hematoma, erythema, rash, and injection site reaction. All local reactions were mild, and none resulted in treatment discontinuation. Additionally, 5% (n = 14 of 306) of the moderate-to-severely immunocompromised patients experienced an infusion site infiltration, extravasation, or vein rupture during either the first or second pemivibart dose.[70471]
During clinical trials, systemic infusion-related reactions and hypersensitivity reactions were observed during the first pemivibart dose in 4% (n = 24 of 623) of all drug recipients. These reactions started within 24 hours of the first dose and were reported as infusion-related reactions, infusion-related hypersensitivity, hypersensitivity, fatigue, headache, sinus tachycardia, brain fog, dermatitis, diarrhea, myalgia, nausea, paresthesias, pre-syncope, and tremor. All reactions were mild or moderate in severity, but 2 reactions were classified as anaphylaxis. Infusion-related or hypersensitivity reactions resulted in discontinuation of the first dose in 1% (n = 6 of 623) of all drug recipients. In the cohort of patients who were moderate-to-severely immunocompromised, 9% (n = 27 of 306) developed an infusion-related or hypersensitivity reactions during either the first or second pemivibart dose. The severity of these reactions was generally mild or moderate; however, 2 of the reactions that occurred during the second pemivibart dose were classified as life-threatening. Infusion-related or hypersensitivity reactions resulted in discontinuation of the first or second dose in 2% (n = 7 of 306) of the moderate-to-severely immunocompromised patients.[70471]
Serious hypersensitivity reactions or anaphylaxis were observed in 4 of 623 (0.6%) patients who received pemivibart during clinical trials, all 4 occurring in the cohort of patients who were moderate-to-severely immunocompromised (n = 306). Two of the patients developed anaphylaxis during the first infusion, and 2 had anaphylaxis during the second infusion. Symptoms of anaphylaxis that occurred during the first pemivibart dose included dyspnea, diaphoresis, facial erythema, chest pain (unspecified), and sinus tachycardia in 1 patient, and flushing, dizziness, tinnitus, and wheezing in the other. Both of these patients received treatment with diphenhydramine. The cases of anaphylaxis that occurred during the second pemivibart dose were both reported as life-threatening. In both of these patients, the symptoms included pruritus, urticaria, angioedema, dyspnea, erythema, and flushing. One of the patients also experienced headache, dizziness, and chest pain during the infusion, with additional symptoms of pruritus, erythema, and urticaria reoccurring within 24 hours of the initial anaphylaxis onset. Both patients were treated with diphenhydramine and epinephrine, and 1 patient also received oral prednisone and metoprolol for an associated flare of an underlying condition. In all 4 patients, pemivibart was permanently discontinued.[70471]
Inform patients that certain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may have substantially reduced susceptibility to pemivibart, and pemivibart may not be effective at preventing COVID-19 caused by these variants. Instruct patients to undergo viral testing and seek medical attention if they develop signs or symptoms of COVID-19 after receiving pemivibart. Symptoms of COVID-19 may include fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, or diarrhea. Pemivibart will remain authorized for use so long as the combined national frequency of SARS-CoV-2 variants with substantially reduced susceptibility to pemivibart does not exceed 90%. The FDA will continue to monitor variant susceptibility and frequency data.[70471]
Administration of pemivibart requires an experienced clinician with appropriate medical support, as serious hypersensitivity reactions or anaphylaxis have been observed during treatment. Use of the pemivibart is contraindicated in patients with previous severe hypersensitivity reactions to any component of the drug. Additionally, the drug contains polysorbate 80, which is in some COVID-19 vaccines and is structurally similar to polyethylene glycol (PEG), an ingredient in other COVID-19 vaccines. For individuals who have previously experienced a severe hypersensitivity reaction to a COVID-19 vaccine, consider consultation with an allergist-immunologist prior to administering pemivibart. Clinically monitor patients during the infusion and for at least 2 hours after completion of the infusion. If a mild infusion-related reaction occurs, consider slowing or stopping the infusion and administering appropriate supportive care. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur during the infusion, immediately discontinue administration and initiate appropriate medications and supportive care. Signs and symptoms of hypersensitivity or infusion-related reactions may include fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vaso-vagal reactions (e.g., pre-syncope, syncope), dizziness, and diaphoresis.[70471]
Administer pemivibart during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus. There are insufficient data regarding the use of pemivibart 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, pemivibart 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.[70471]
There are no data regarding the presence of pemivibart 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, and the mother's clinical need for pemivibart. 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.[70471]
Pemivibart is a recombinant human immunoglobulin G1 (IgG1) monoclonal antibody used as a preventative antiviral medication against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antibody binds to the spike protein receptor binding domain (RBD) of SARS-CoV-2, thereby preventing the virus from interacting with the human ACE2 receptor and blocking viral attachment. For the ancestral SARS-CoV-2 and Omicron BA.2.86 variant, pemivibart blocks attachment of the RBD proteins to the human ACE2 receptor with half-maximal inhibitory concentrations (IC50) of 10 ng/mL and 3,370 ng/mL, respectively. For the Omicron variants, the 50% effective concentrations (EC50) are 14.2 ng/mL against BA.1, 5.8 ng/mL against BA.2, 25.8 ng/mL against BA.4.1, 118 to 661.2 ng/mL against XBB.1.16, 290 to 479.9 ng/mL against XBB.1.5, 1,445 ng/mL against EG.5.1, and 529.4 ng/mL against HV.1. The Fc-mediated effector functions and the antibody dependent enhancement (ADE) of infection has not been directly evaluated for pemivibart; however, the parent antibody of pemivibart, which contains an identical Fc region and targets an overlapping epitope, exhibits antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent complement deposition (ADCD), but does not exhibit detectable ADE in cell culture.
There is a potential for prophylaxis failure due to the development of viral variants that are resistant to pemivibart. Health care providers are advised to consider the prevalence of SARS-CoV-2 variants in their area when considering prophylactic treatment options. Data are limited regarding spike substitutions in Omicron-lineage variants that may confer significantly reduced susceptibility to pemivibart. However, escape variants were identified following serial passage of Omicron XBB.1.5.6 in cell culture in the presence of pemivibart that contained a T500N spike substitution or a combination of R498Q, Y501N, and H505Y spike substitutions. Evaluations of pemivibart neutralization susceptibility of variants that have been identified through global surveillance are ongoing.[70471]
Revision Date: 09/27/2024, 12:35:52 PMPemivibart is administered via intravenous infusion. Once in systemic circulation, the steady state volume of distribution is 5.54 L. Pemivibart is metabolized in the same manner as endogenous IgG via catabolic pathways. It is unlikely to undergo renal elimination and has clearance of 0.0909 L/day. The half-live is 44.8 days (range: 28.1 to 64.6 days).[70471]
Affected cytochrome P450 isoenzymes: none
Following a single 4,500 mg intravenous infusion of pemivibart in adults, the maximum plasma concentration (Cmax) is 1,750 mcg/mL and the systemic exposure (AUC0-3 months) is 36,600 days x mcg/mL. At post-dose Days 28 and 90, drug concentrations fall to 460 mcg/mL and 175 mcg/mL, respectively.[70471]
Hepatic impairment is not expected to impact the pharmacokinetics of pemivibart.[70471]
Monoclonal antibodies with molecular weights greater than 69 kDa are known not to undergo renal elimination; therefore, neither renal impairment nor dialysis are expected to impact the pharmacokinetics of pemivibart (molecular weight: 147.51 kDa).[70471]
The pharmacokinetics of pemivibart have not been evaluated in pediatric patients; however, the recommended dosing regimen is expected to result in pemivibart plasma exposures in pediatric patients (12 years and older weighing at least 40 kg) that are comparable to those observed in adult drug recipients.[70471]
The pharmacokinetics of pemivibart are not substantially affected by age.[70471]
The pharmacokinetics of pemivibart are not substantially affected by gender.[70471]
The pharmacokinetics of pemivibart are not substantially affected by ethnicity.[70471]
Body weight is not expected to have a clinically relevant effect on the pharmacokinetics of pemivibart in patients weighing between 43 and 190 kg.[70471]
Administer pemivibart during pregnancy only if the potential benefit outweighs the potential risk for the mother and fetus. There are insufficient data regarding the use of pemivibart 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, pemivibart 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.[70471]
There are no data regarding the presence of pemivibart 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, and the mother's clinical need for pemivibart. 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.[70471]
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