Bamlanivimab (Page 6 of 12)

3 DOSAGE FORMS AND STRENGTHS

Bamlanivimab is a sterile, preservative-free, clear to opalescent and colorless to slightly yellow to slightly brown solution available as:

  • Injection: 700 mg/20 mL (35 mg/mL) in a single-dose* vial.

Etesevimab is a sterile, preservative-free, clear to opalescent and colorless to slightly yellow to slightly brown solution available as:

  • Injection: 700 mg/20 mL (35 mg/mL) in a single-dose* vial.

* Under this EUA, single-dose vials may be used to prepare more than one pediatric dose.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

There are limited clinical data available for bamlanivimab and etesevimab. Serious and unexpected adverse events may occur that have not been previously reported with use of bamlanivimab and etesevimab together.

5.1 Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions

Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab and etesevimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.

Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of bamlanivimab and etesevimab together. These reactions may be severe or life threatening.

Signs and symptoms of infusion related reactions may include [see Overall Safety Summary (6.1)]:

  • fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g., 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, vasovagal reactions (e.g., pre-syncope, syncope), dizziness and diaphoresis.

Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs.

Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of bamlanivimab and etesevimab under Emergency Use Authorization.

5.2 Clinical Worsening After Bamlanivimab and Etesevimab Administration

Clinical worsening of COVID-19 after administration of bamlanivimab and etesevimab together has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to bamlanivimab and etesevimab use or were due to progression of COVID-19.

5.3 Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19

Treatment with bamlanivimab and etesevimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such bamlanivimab and etesevimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Therefore,

  • Bamlanivimab and etesevimab are not authorized for use in patients 2 years and older who are hospitalized due to COVID-192,
  • Bamlanivimab and etesevimab are not authorized for use in patients, regardless of age, who:
    • require oxygen therapy and/or respiratory support due to COVID-19, OR
    • require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19 and are on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity [see Limitations of Authorized Use (1.1)].

6 OVERALL SAFETY SUMMARY

6.1 Clinical Trials Experience

Adults (≥18 Years) and Pediatric Patients (<18 Years and weighing at least 40 kg)

The safety of bamlanivimab administered with etesevimab is primarily based on exposure of approximately 1,400 ambulatory (non-hospitalized) subjects who received doses of bamlanivimab and etesevimab together, at the recommended dose or higher, in BLAZE-1 and BLAZE-4. BLAZE-1 is a Phase 2/3, randomized, double-blind, placebo-controlled clinical trial studying bamlanivimab and etesevimab administered together for the treatment of subjects with mild to moderate COVID-19. Thirty-four pediatric patients (ages 12 to <18 years and weighing at least 40 kg) were included in the Phase 3 portion of BLAZE-1 (14 received placebo, 14 received the authorized dose or a higher dose for their age, and 6 received a lower dose than authorized for their age). In the Phase 3 portion of the trial, enrolled participants had at least one risk factor for the development of severe COVID-19 illness. BLAZE-4 is a Phase 2, randomized, double-blind, placebo-controlled clinical trial studying bamlanivimab and etesevimab for the treatment of subjects with mild to moderate COVID-19. Subjects ≥65 years old or with BMI ≥35 were excluded from enrollment. In clinical trials, approximately 4,000 subjects have received bamlanivimab (either alone or with etesevimab) at doses ranging from 700 to 7,000 mg. Bamlanivimab and etesevimab at the authorized doses of 700 mg and 1,400 mg have been administered together to approximately 800 subjects in clinical trials [see Clinical Pharmacology (14.2)].

The following adverse reactions (i.e., adverse events assessed as causally related) have been observed in those who have received bamlanivimab and etesevimab together at the authorized dose or higher [see Warnings and Precautions (5.1)]:

  • anaphylaxis (n=1, 0.07%)
  • infusion-related reactions (n=16, 1.1%)

In the case of anaphylaxis and serious infusion-related reactions, all infusions were stopped, and treatment was administered. One case required epinephrine. All events resolved.

The most common treatment-emergent adverse events in the bamlanivimab and etesevimab treatment group in BLAZE-1 and BLAZE-4 included nausea, dizziness, and pruritus. No treatment-emergent adverse events occurred in more than 1% of participants and the rates were comparable in the treatment and placebo groups.

Pediatric Patients (Birth to <18 Years)

In addition to the 34 pediatric patients (ages 12 to <18 and weighing at least 40 kg) enrolled in the Phase 3 portion of BLAZE-1, an open-label pediatric addendum to BLAZE-1 enrolled 40 patients aged 12 to <18, 36 aged 6 to <12, 10 aged 2 to <6, and 5 birth to <2 for a total of 125 pediatric patients. All pediatric patients had at least one risk factor for the development of severe COVID-19 illness. Pediatric patients weighing 8.6 kg to <40 kg received doses of bamlanivimab and etesevimab that were adjusted for their body weight, to achieve comparable exposures as adults and adolescents receiving the authorized dosage of bamlanivimab 700 mg and etesevimab 1,400 mg, respectively. The adverse drug reaction profile in pediatric patients is consistent with the established profile.

7 PATIENT MONITORING RECOMMENDATIONS

Clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete [see Warnings and Precautions (5.1) and Overall Safety Summary (6.1)].

8 ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING REQUIREMENTS AND INSTRUCTIONS

Clinical trials evaluating the safety of bamlanivimab and etesevimab are ongoing [see Overall Safety Summary (6)].

Completion of FDA MedWatch Form to report all medication errors and serious adverse events* occurring during bamlanivimab and etesevimab use and considered to be potentially related to bamlanivimab and etesevimab is mandatory and must be done by the prescribing healthcare provider and/or the provider’s designee. These adverse events must be reported within 7 calendar days from the onset of the event:

*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;
  • a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly.

If a serious and unexpected adverse event occurs and appears to be associated with the use of bamlanivimab and etesevimab under this EUA, the prescribing healthcare provider and/or the provider’s designee must complete and submit a MedWatch form to FDA using one of the following methods:

  • Complete and submit the report online: 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:
    • Mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787, or
    • Fax (1-800-FDA- 0178), or
  • Call 1-800-FDA-1088 to request a reporting form

IMPORTANT: When reporting adverse events or medication errors to MedWatch, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information that must be included:

  • Patient demographics (e.g., patient initials, date of birth)
  • Pertinent medical history
  • Pertinent details regarding adverse events and course of illness
  • Concomitant medications
  • Timing of adverse event(s) in relationship to administration of bamlanivimab and etesevimab
  • Pertinent laboratory and virology information
  • Outcome of the event and any additional follow-up information if it is available at the time of the MedWatch report. Subsequent reporting of follow-up information should be completed if additional details become available.

The following steps are highlighted to provide the necessary information for safety tracking:

  1. In section A, box 1, provide the patient’s initials in the Patient Identifier
  2. In section A, box 2, provide the patient’s date of birth
  3. In section B, box 5, description of the event:
    1. Write “bamlanivimab and etesevimab use for COVID-19 under Emergency Use Authorization (EUA)” as the first line
    2. Provide a detailed report of medication error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. Please see information to include listed above.
  4. In section G, box 1, name and address:
    1. Provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
    2. Provide the address of the treating institution (NOT the healthcare provider’s office address).

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