adverse reactions
6 ADVERSE REACTIONS The following serious adverse reaction is described in more detail in the Warnings and Precautions section of the labeling: • Hypersensitivity including anaphylaxis and infusion related reactions [see Warnings and Precautions ( 5.1 )] . 6.1 Adverse Reactions from Clinical Studies The following adverse reactions have been observed in the clinical studies of sotrovimab that supported EUA. The adverse reaction rates observed in these clinical studies cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Additional adverse events associated with sotrovimab may become apparent with more widespread use. The safety of sotrovimab in subjects with mild-to-moderate COVID-19 (subjects with COVID-19 symptoms who are not hospitalized) is based on analyses from COMET-ICE and COMET-TAIL [see Clinical Studies ( 14 )] . In COMET-ICE, subjects received a single 500-mg IV infusion of sotrovimab (n = 523) or placebo (n = 526). In COMET-TAIL, subjects received a single 500-mg IV infusion of sotrovimab (n = 393). Infusion-Related Reactions Including Hypersensitivity Infusion-related reactions, including immediate hypersensitivity reactions, were observed in 1% of subjects treated with sotrovimab and 1% of subjects treated with placebo in COMET-ICE and in <1% of subjects treated with IV sotrovimab in COMET-TAIL. Reported events that started within 24 hours of study treatment were pyrexia, chills, dizziness, dyspnea, pruritus, rash, and infusion-related reactions; all events were Grade 1 (mild) or Grade 2 (moderate). One case of anaphylaxis was reported following sotrovimab infusion in a separate study evaluating sotrovimab in hospitalized subjects; the infusion was immediately discontinued, and the subject received epinephrine. The event resolved but recurred within 2 hours; the subject received another dose of epinephrine and improved with no additional symptoms. Other serious infusion-related reactions (including immediate hypersensitivity reactions) reported following sotrovimab infusion in the hospitalized study included Grade 3 (serious) or Grade 4 (life-threatening) bronchospasm and shortness of breath. These events were also reported following infusion of placebo. Sotrovimab is not authorized for use in subjects hospitalized due to COVID-19 [see Warnings and Precautions ( 5.3 )] . Hypersensitivity adverse reactions (i.e., adverse events assessed as causally related) were observed in 2% of subjects treated with sotrovimab and 1% of subjects treated with placebo in COMET-ICE and in <1% of subjects treated with sotrovimab in COMET-TAIL. All were Grade 1 (mild) or Grade 2 (moderate), and none of the reactions in either trial led to permanent discontinuation of the infusions. One reaction led to pausing of the infusion [see Warnings and Precautions ( 5.1 )] . Common Adverse Events The most common treatment-emergent adverse events observed in the sotrovimab treatment group in COMET-ICE were rash (1%) and diarrhea (2%), all of which were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse events were reported at a higher rate with sotrovimab compared to placebo. 6.2 Adverse Reactions from Spontaneous Reports The following adverse reactions have been identified during post-authorization use of sotrovimab. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders Anaphylaxis [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 )] . 6.4 Required Reporting for Serious Adverse Events and Medication Errors The prescribing healthcare provider and/or the provider’s designee is/are responsible for mandatory reporting of all serious adverse events* and medication errors potentially related to sotrovimab within 7 calendar days from the healthcare provider’s awareness of the event, using FDA Form 3500 (for information on how to access this form, see below). The FDA requires that such reports, using FDA Form 3500, include the following: • Patient demographics and baseline characteristics (e.g., patient identifier, age or date of birth, gender, weight, ethnicity, and race) • A statement "Sotrovimab use for COVID-19 under Emergency Use Authorization (EUA)” under the “Describe Event, Problem, or Product Use/Medication Error” heading • Information about the serious adverse event or medication error (e.g., signs and symptoms, test/laboratory data, complications, timing of drug initiation in relation to the occurrence of the event, duration of the event, treatments required to mitigate the event, evidence of event improvement/disappearance after stopping or reducing the dosage, evidence of event reappearance after reintroduction, clinical outcomes) • Patient’s preexisting medical conditions and use of concomitant products • Information about the product (e.g., dosage, route of administration, NDC #) Submit adverse event and medication error reports, using Form 3500, to FDA MedWatch using one of the following methods: • Complete and submit the report online at www.fda.gov/medwatch/report.htm , or • Complete and submit a postage-paid FDA Form 3500 ( https://www.fda.gov/media/76299/download ) and return by: o Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or o Fax to 1-800-FDA-0178, or • Call 1-800-FDA-1088 to request a reporting form. • In addition, please provide a copy of all FDA MedWatch forms to: GlaxoSmithKline, Global Safety Fax: 919-287-2902 Email: WW.GSKAEReportingUS@gsk.com Or call GSK at 1-866-475-2684 to report adverse events. The prescribing health care provider and/or the provider’s designee is/are responsible for mandatory responses to requests from FDA for information about adverse events and medication errors following receipt of sotrovimab. *Serious adverse events are defined as: • Death; • A life-threatening adverse event; • Inpatient hospitalization or prolongation of existing hospitalization; • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; • A congenital anomaly/birth defect; • Other important medical event, which may require a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly.