ETESEVIMAB Solution for injection Ref.[10777] Active ingredients: Bamlanivimab and Etesevimab

2.1 Patient Selection

The optimal dosing regimen for treatment of COVID-19 has not yet been established.

The recommended dosing regimen may be updated as data from clinical trials become available.

Bamlanivimab and etesevimab should be administered together as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset in adults and pediatric patients (12 years of age and older weighing at least 40 kg) who are at high risk for progressing to severe COVID-19 and/or hospitalization.

High risk is defined as patients who meet at least one of the following criteria:

• Have a body mass index (BMI) ≥35
• Have chronic kidney disease
• Have diabetes
• Have immunosuppressive disease
• Are currently receiving immunosuppressive treatment
• Are ≥65 years of age
• Are ≥55 years of age AND have
  • cardiovascular disease, OR
  • hypertension, OR
  • chronic obstructive pulmonary disease/other chronic respiratory disease.
• Are 12-17 years of age AND have
  • BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm, OR
  • sickle cell disease, OR
  • congenital or acquired heart disease, OR
  • neurodevelopmental disorders, for example, cerebral palsy, OR
  • a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
  • asthma, reactive airway or other chronic respiratory disease that requires daily medication for control.

2.2 Dosage

The dosage of bamlanivimab and etesevimab for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) is:

• bamlanivimab 700 mg
• etesevimab 1,400 mg.

Administer bamlanivimab and etesevimab together as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset.

Under this EUA, bamlanivimab and etesevimab must be diluted and administered together as a single intravenous infusion.

Rationale for Authorized Dosage

The dosage of 700 mg bamlanivimab and 1,400 mg etesevimab administered together was selected based on analyses of available data incorporating the following factors:

• Available data demonstrate that a dosage of 700 mg bamlanivimab and 1,400 mg etesevimab administered together has similar antiviral activity to a dosage of 2,800 mg bamlanivimab and 2,800 mg etesevimab administered together, which is also supported by in vitro data and pharmacokinetics/pharmacodynamics (PK/PD) modeling [see Pharmacodynamics (14.2)].
• A dosage of 2,800 mg bamlanivimab and 2,800 mg etesevimab administered together reduced COVID-19 related hospitalizations and deaths in addition to significantly reducing viral load relative to placebo [see Clinical Trial Results and Supporting Data for EUA (18.1)].
• Bamlanivimab and etesevimab administered together resulted in fewer treatment-emergent variants relative to bamlanivimab administered alone [see Microbiology/Resistance Information (15)].

Based on analyses of the available nonclinical, clinical, and virologic data, as well as supportive data from pharmacokinetic/pharmacodynamic modeling, the authorized dosage of 700 mg bamlanivimab and 1,400 mg etesevimab is expected to have similar clinical effect to a dosage of 2,800 mg bamlanivimab and 2,800 mg etesevimab.

2.3 Dosage Adjustment in Specific Populations

Pregnancy or Lactation

No dosage adjustment is recommended in pregnant or lactating women [see Use in Specific Populations (11.1, 11.2)].

Pediatric Use

No dosage adjustment is recommended in pediatric patients who weigh at least 40 kg and are 12 years of age and older. Bamlanivimab and etesevimab are not authorized for patients weighing less than 40 kg or those less than 12 years of age [see Use in Specific Populations (11.3)].

Geriatric Use

No dosage adjustment is recommended in geriatric patients [see Use in Specific Populations (11.4)].

Renal Impairment

No dosage adjustment is recommended in patients with renal impairment [see Use in Specific Populations (11.5)].

Hepatic Impairment

No dosage adjustment is recommended in patients with mild hepatic impairment. Bamlanivimab and etesevimab has not been studied in patients with moderate or severe hepatic impairment [see Use in Specific Populations (11.6)].

2.4 Dose Preparation and Administration

Preparation

Bamlanivimab and etesevimab solution for infusion should be prepared by a qualified healthcare professional using aseptic technique:

• Gather the materials for preparation:
  • Polyvinyl chloride (PVC) or polyethylene (PE)-line PVC, sterile infusion bag. Choose one of the following sizes:
    • Prefilled 50 mL, 100 mL, 150 mL, or 250 mL infusion bag containing 0.9% Sodium Chloride Injection (see Table 1 and Table 2).
  • One vial of bamlanivimab (700 mg/20 mL) and two vials of etesevimab (700 mg/20 mL).
• Bamlanivimab and etesevimab are supplied in individual single-dose vials but are administered together using a single infusion bag.
• Remove 1 bamlanivimab vial and 2 etesevimab vials from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation. Do not expose to direct heat. Do not shake the vials.
• Inspect both bamlanivimab and etesevimab vials visually for particulate matter and discoloration.
  • Bamlanivimab and etesevimab are clear to opalescent and colorless to slightly yellow to slightly brown solutions.
• Withdraw 20 mL from one bamlanivimab vial and 40 mL from two etesevimab vials and inject all 60 mL into a prefilled infusion bag containing 0.9% Sodium Chloride (see Table 1 or Table 2).
• Discard any product remaining in the vials.
• Gently invert the bag by hand approximately 10 times to mix. Do not shake.
• These products are preservative-free and therefore, the diluted infusion solution should be administered immediately.
  • If immediate administration is not possible, store the diluted infusion solution for up to 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]) and up to 7 hours at room temperature (20°C to 25°C [68°F to 77°F]) including infusion time. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 20 minutes prior to administration.

Administration

Bamlanivimab and etesevimab infusion solution should be administered by a qualified healthcare professional.

• Gather the materials for infusion:
  • Polyvinyl chloride (PVC) or polyethylene (PE)-lined PVC infusion set
  • Use of an in-line or add-on 0.2/0.22 micron polyethersulfone (PES) filter is strongly recommended.
• Attach the infusion set to the IV bag.
• Prime the infusion set.
• Administer the entire infusion solution in the bag via pump or gravity according to the size of infusion bag used (see Table 1 for patients weighing ≥50 kg or Table 2 for patients weighing <50 kg). Due to potential overfill of prefilled saline bags, the entire infusion solution in the bag should be administered to avoid underdosage.
• The prepared infusion solution should not be administered simultaneously with any other medication. The compatibility of bamlanivimab and etesevimab injection with IV solutions and medications other than 0.9% Sodium Chloride Injection is not known.
• Once infusion is complete, flush the tubing with 0.9% Sodium Chloride to ensure delivery of the required dose.
• Clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete.
• If the infusion must be discontinued due to an infusion reaction, discard any unused product.
• The use of closed system transfer devices (CSTDs), elastomeric pumps, and pneumatic transport with bamlanivimab has not been studied.

Table 1. Recommended Dilution and Administration Instructions for Bamlanivimab and Etesevimab for IV Infusion^a in Patients Weighing 50 kg or More:

^a 700 mg of bamlanivimab and 1,400 mg of etesevimab are added to the same infusion bag and administered together as a single intravenous infusion.

Table 2. Recommended Dilution and Administration Instructions for Bamlanivimab and Etesevimab for IV Infusion^a in Patients Weighing Less Than 50 kg:

^a 700 mg of bamlanivimab and 1,400 mg of etesevimab are added to the same infusion bag and administered together as a single intravenous infusion.
^b The minimum infusion time for patients weighing less than 50 kg who are administered bamlanivimab and etesevimab together using the 250 mL prefilled 0.9% Sodium Chloride infusion bag must be extended to at least 70 minutes to ensure safe use (endotoxin load).

Storage

This product is preservative-free and therefore, the diluted infusion solution should be administered immediately. If immediate administration is not possible, store the diluted infusion solution for up to 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]) and up to 7 hours at room temperature (20°C to 25°C [68°F to 77°F]) including transportation and infusion time. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 20 minutes prior to administration.

Doses up to 7,000 mg of bamlanivimab (10 times the authorized dose of bamlanivimab) or 7,000 mg of etesevimab (5 times the authorized dose of etesevimab) have been administered in clinical trials without dose-limiting toxicity. Treatment of overdose with bamlanivimab and etesevimab should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with either bamlanivimab or etesevimab.

Bamlanivimab is preservative-free. Discard unused portion.

Etesevimab is preservative-free. Discard unused portion.

Store unopened vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

DO NOT FREEZE, SHAKE, OR EXPOSE TO DIRECT LIGHT.

Solution in vial requires dilution prior to administration. The prepared infusion solution is intended to be used immediately. If immediate administration is not possible, store diluted infusion solution in the refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours and at room temperature (20°C to 25°C [68°F to 77°F]) and for up to 7 hours, including infusion time. If refrigerated, allow the infusion solution to equilibrate to room temperature prior to administration.