Ansuvimab-zykl
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alara Ece Dagsali, M.D.
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Overview
Ansuvimab-zykl is a ebolavirus (EBOV) glycoprotein 1 (GP1)-directed recombinant, human Immunoglobulin G1 (IgG1) monoclonal antibody. that is FDA approved for the treatment of of infection caused by Orthoebolavirus zairense(formerly Zaire ebolavirus) in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Orthoebolavirus zairense infection. Common adverse reactions include {{{adverseReactions}}}.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Recommended Dosage for Adult and Pediatric Patients: The recommended dosage of EBANGA is 50 mg/kg administered as a single intravenous (IV) infusion over 60 minutes. EBANGA must be reconstituted with Sterile Water for Injection, USP then further diluted in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP prior to IV infusion
Preparation, Administration, and Storage Instructions: EBANGA must be prepared and administered under the supervision of a health care professional.
EBANGA must be prepared and administered under the supervision of a health care professional.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Ansuvimab-zykl in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ansuvimab-zykl in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
The recommended dosage of EBANGA is 50 mg/kg administered as a single intravenous (IV) infusion over 60 minutes. EBANGA must be reconstituted with Sterile Water for Injection, USP then further diluted in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP prior to IV infusion.
Preparation, Administration, and Storage Instructions: EBANGA must be prepared and administered under the supervision of a health care professional.
EBANGA must be prepared and administered under the supervision of a health care professional.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Ansuvimab-zykl in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Ansuvimab-zykl in pediatric patients.
Contraindications
None.
Warnings
Hypersensitivity Reactions Including Infusion-Associated Events: Hypersensitivity reactions including infusion-associated events have been reported with EBANGA. These may include acute, life-threatening reactions during and after the infusion. Monitor all patients for signs and symptoms including, but not limited to, hypotension, chills and elevation of fever, during and following EBANGA infusion. In the case of severe or life-threatening hypersensitivity reactions, discontinue the administration of EBANGA immediately and administer appropriate emergency care.
Infusion could not be completed in 1% of participants who received EBANGA due to infusion-associated adverse events. The rate of infusion of EBANGA may be slowed or interrupted if the patient develops any signs of infusion-associated events or other adverse events
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice.
Overall, 424 adult and pediatric participants with Orthoebolavirus zairense infection received EBANGA in one clinical trial and as part of an expanded access program during the 2018 Orthoebolavirus zairense outbreak in the Democratic Republic of Congo (DRC).
In the PALM trial, the safety of EBANGA was evaluated in a multi-center, open-label, randomized controlled trial, in which 173 participants (119 adults and 54 pediatric participants) with confirmed Orthoebolavirus zairense infection received EBANGA as a single 50 mg/kg IV infusion and 168 participants received an investigational control.
All participants received optimized standard of care treatment (oSOC). The median age of the study population that received EBANGA was 26 years (range: 1 day to 85 years) and 55% were female.
During the same outbreak, 251 participants (173 adults and 78 pediatric participants) with laboratory- confirmed Orthoebolavirus zairense infection received EBANGA under an expanded access program, 57% of whom were female. Ages ranged from 6 days to 80 years, with a median age of 25 years.
Postmarketing Experience
There is limited information regarding Ansuvimab-zykl Postmarketing Experience in the drug label.
Drug Interactions
Vaccine Interactions: No vaccine-therapeutic interaction studies have been performed in human participants using EBANGA. However, because of the potential for EBANGA to inhibit replication of a live vaccine virus indicated for prevention of Orthoebolavirus zairense infection and possibly reduce the efficacy of the vaccine, avoid the concurrent administration of a live vaccine during treatment with EBANGA. The interval between administration of EBANGA therapy and live vaccination should be in accordance with current vaccination guidelines. The efficacy of EBANGA among participants who reported receipt of a recombinant live vaccine prior to their enrollment in the PALM trial was similar to participants who did not report receiving a vaccine prior to enrollment.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Ansuvimab-zykl in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ansuvimab-zykl in women who are pregnant.
Labor and Delivery
Orthoebolavirus zairense infection is life-threatening for both the mother and fetus and treatment should not be withheld due to pregnancy. Available data from the PALM trial in which pregnant women with Orthoebolavirus zairense infection were treated with EBANGA demonstrate the high rate of maternal and fetal/neonatal morbidity consistent with published literature regarding the risk associated with underlying maternal Orthoebolavirus zairense infection. These data are insufficient to evaluate for a drug associated risk of major birth defects, miscarriage, or adverse maternal/fetal outcome.
Animal reproduction studies with ansuvimab-zykl have not been conducted. Monoclonal antibodies, such as EBANGA, are transported across the placenta; therefore, EBANGA has the potential to be transferred from the mother to the developing fetus.
Disease-associated maternal and/or embryo/fetal risk
Maternal, fetal and neonatal outcomes are poor among pregnant women infected with Orthoebolavirus zairense. The majority of such pregnancies result in maternal death with miscarriage, stillbirth, or neonatal death. Treatment should not be withheld due to pregnancy.
Nursing Mothers
The Centers for Disease Control and Prevention recommend that mothers with confirmed Orthoebolavirus zairense not breastfeed their infants to reduce the risk of postnatal transmission of Orthoebolavirus zairense infection.
There are no data on the presence of ansuvimab-zykl in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to ansuvimab-zykl are unknown.
Pediatric Use
The safety and effectiveness of EBANGA for the treatment of infection caused by Orthoebolavirus zairense have been established in pediatric patients from birth to less than 18 years of age. Use of EBANGA for this indication is supported by evidence from a multi-center, open label, randomized controlled trial of EBANGA in adults and pediatric participants that included 54 pediatric participants birth to less than 18 years of age, including neonates born to a mother who is RT-PCR positive for Orthoebolavirus zairense infection. Of the total number of participants administered EBANGA in the PALM trial, pediatric participants (1 day to 17 years) accounted for 31% (n=54) of the study population in the PALM trial. The 28-day mortality and safety in adult and pediatric participants treated with EBANGA were similar.
An additional 78 (31%) pediatric participants from birth to less than 18 years of age received EBANGA in an expanded access program.
Geriatic Use
Clinical trials of EBANGA did not include sufficient numbers of participants aged 65 and over to determine whether the safety profile of EBANGA is different in this population compared to younger participants. Of the total number of participants administered EBANGA in the PALM trial, 6 participants (3%) were 65 years or older. The limited clinical experience has not identified differences in responses between the elderly and younger participants.
Gender
There is no FDA guidance on the use of Ansuvimab-zykl with respect to specific gender populations.
Race
There is no FDA guidance on the use of Ansuvimab-zykl with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Ansuvimab-zykl in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Ansuvimab-zykl in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Ansuvimab-zykl in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Ansuvimab-zykl in patients who are immunocompromised.
Administration and Monitoring
Administration
- Aseptically reconstitute and further dilute EBANGA prior to IV infusion. Do not administer as an IV push or bolus.
- More than one vial may be needed for a full dose. Calculate the dose (mg) based on the patient’s actual weight in kg and the number of EBANGA vials required
- Prior to reconstitution, allow EBANGA vial(s) to reach ambient temperature (15°C to 27°C [59°F to 81°F]) for approximately 20 minutes. If for any reason reconstitution cannot proceed immediately upon reaching ambient temperature, vials that have NOT been reconstituted may be kept at ambient temperature, protected from light, for no more than 24 hours.
- Immediately upon reaching ambient temperature, use a sterile 10 mL syringe and an 18-gauge needle to withdraw 7.7 mL of Sterile Water for Injection, USP. Insert the needle tip into the EBANGA vial. Holding horizontally, angle the needle down at an approximate 45° angle, above the lyophilized powder, which has a cake-like appearance. Slowly inject the diluent along the wall of the vial and without any air to avoid foaming and bubbles.
- Gently swirl (do NOT shake) for approximately 10 seconds; then set the vial down to rest for at least 10 seconds. Repeat until the cake is dissolved. This may take up to 20 minutes.
- Upon reconstitution, one vial delivers 8 mL of solution that is clear to slightly opalescent and colorless to slightly yellow containing 50 mg/mL of ansuvimab-zykl. Do NOT administer and discard the vial if the reconstituted solution is discolored or contains visible particles.
- Dilute the EBANGA solution immediately upon reconstitution. If needed, the reconstituted solution may be stored refrigerated at 2°C to 8°C (36°F to 46°F), protected from light, for up to 4 hours. This 4-hour window includes time required for further dilution and EBANGA solution should be infused immediately upon further dilution.
Dilution Instructions:
Following reconstitution, EBANGA must be further diluted prior to IV infusion. Use an 18-20 gauge, 1-1.5" needle with an appropriately sized syringe up to 60 mL to perform the dilution steps.
Prepare the EBANGA IV dosing solution using an appropriately sized syringe up to 60 mL.
- For patients weighing ≥ 2 kg, prepare the diluent using either a latex-free, di-ethylhexylphthalate (DEHP)-free 0.9% Sodium Chloride Injection USP infusion bag, or latex-free, DEHP-free 5% Dextrose Injection USP infusion bag. For patients weighing 0.5 to < 2 kg use a pump-compatible syringe
- For adult and pediatric patients, either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP can be used as the diluent.
- The total volume of the infusion solution to be administered is based on the patient’s body weight
- For patients weighing 0.5 to < 2 kg:
- Use a 10 mL syringe compatible with the IV infusion pump. - Fill the 10 mL syringe with the appropriate amount of diluent - Add the calculated volume of EBANGA to the 10 mL syringe - Mix the diluted solution by gentle inversion (3 to 5 times) until admixed. Do not shake.
- For patients weighing ≥ 2 kg:
- Select a diluent solution infusion bag size of appropriate fill volume based on the patient's body weight - Withdraw and discard from the bag a volume of diluent solution that will leave remaining in the bag the appropriate volume based on the patient's weight - Gently invert the IV bag 5 to 10 times until the diluted solution is admixed. Do NOT shake.
- Infuse the EBANGA solution immediately upon dilution. If needed, the diluted infusion solution may be stored refrigerated at 2°C to 8°C (36°F to 46°F), for up to 4 hours. Do not freeze the diluted solution. If refrigerated, allow approximately 20 minutes for the diluted solution to come to ambient temperature prior to use. These time limits include reconstitution time.
- Prepare a medical label including patient weight in kg, date, and time of reconstitution.
Monitoring
Monitor all patients for signs and symptoms including, but not limited to, hypotension, chills and elevation of fever, during and following EBANGA infusion. In the case of severe or life-threatening hypersensitivity reactions, discontinue the administration of EBANGA immediately and administer appropriate emergency care
IV Compatibility
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not administer if discolored or if the vial contains visible particles.
- Do not mix with or administer as an infusion with other medicinal products.
- Prepare the IV infusion line with 1.2 micron in-line filter extension set.
- Administer the IV infusion solution over 60 minutes.
- At the end of the infusion, if a syringe pump was used, then remove the syringe and flush the line with 2 to 5 mL of diluent, but not to exceed the total infusion volume. If an infusion bag was used, replace the empty bag and flush the line by infusing at least 25 mL of the diluent, to ensure complete product administration.
Overdosage
There is limited information regarding Ansuvimab-zykl overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Ansuvimab-zykl Pharmacology in the drug label.
Mechanism of Action
Ansuvimab-zykl is a recombinant human monoclonal antibody with antiviral activity against Orthoebolavirus zairense
Structure
There is limited information regarding Ansuvimab-zykl Structure in the drug label.
Pharmacodynamics
Ansuvimab-zykl exposure-response relationship and the time course of pharmacodynamic response is unknown.
Pharmacokinetics
Limited data from 18 healthy participants 22 to 56 years of age suggests that the pharmacokinetic profile of ansuvimab-zykl is consistent with the profile of other IgG1 monoclonal antibodies. Pharmacokinetic data are not available for Orthoebolavirus zairense infected patients.
Nonclinical Toxicology
Carcinogenicity, genotoxicity and fertility studies have not been conducted with ansuvimab-zykl.
Clinical Studies
The efficacy of EBANGA has been evaluated in 174 participants with confirmed Orthoebolavirus zairense infection in the PALM trial, a multi-center, open-label, randomized, controlled trial (NCT03719586). The trial was conducted in the North Kivu and Ituri provinces in the Democratic Republic of Congo, where an outbreak began in August 2018, and enrolled 681 participants of all ages, including pregnant women, with documented Orthoebolavirus zairense infection and symptoms of any duration who were receiving oSOC. Eligible participants had a positive reverse transcriptase-polymerase chain reaction (RT-PCR) for the nucleoprotein (NP) gene of Orthoebolavirus zairense and had not received other investigational treatments (with the exception of experimental vaccines) within the previous 30 days. Neonates ≤7 days of age were eligible if the mother had documented infection. Neonates born to a mother who had cleared Orthoebolavirus zairense following a course of her assigned investigational medication were also eligible to be enrolled at investigator discretion regarding the likelihood that the neonate was infected. Participants were randomized to receive EBANGA 50 mg/kg IV as a single infusion, an investigational control 50 mg/kg IV every third day, for a total of 3 doses, or other investigational drugs. Randomization was stratified by reverse transcription-PCR cycle threshold calculated using NP targets (CtNP ≤22.0 vs ˃22.0; corresponding to high and low viral load, respectively) and Ebola Treatment Unit (ETU) site. All participants received oSOC consisting, at a minimum, of IV fluids, daily clinical laboratory testing, correction of hypoglycemia and electrolyte imbalances, and broad-spectrum antibiotics and antimalarials, as indicated.
How Supplied
EBANGA (ansuvimab-zykl) for injection is supplied as a sterile, preservative-free, off-white to white lyophilized powder in a single-dose vial (NDC 71655-578-01) for reconstitution and further dilution.
One primary carton (NDC 71655-578-02) contains thirty-six 400 mg vials packaged in a box containing either one primary carton (NDC 71655-578-03), four primary cartons (NDC 71655-578-04), or eight primary cartons (NDC 71655-578-08).
Storage
Prior to reconstitution, allow EBANGA vial(s) to reach ambient temperature (15°C to 27°C [59°F to 81°F]) for approximately 20 minutes. If for any reason reconstitution cannot proceed immediately upon reaching ambient temperature, vials that have NOT been reconstituted may be kept at ambient temperature, protected from light, for no more than 24 hours.
Store refrigerated at 2ºC to 8ºC (36ºF to 46ºF) in the original carton to protect from light. Do not freeze. Do not shake.
Prior to reconstitution, allow EBANGA vial(s) to reach ambient temperature (15°C to 27°C [59°F to 81°F]) for approximately 20 minutes. If for any reason reconstitution cannot proceed immediately upon reaching ambient temperature, vials that have NOT been reconstituted may be kept at ambient temperature, protected from light, for no more than 24 hours.
After reconstitution, if storage is needed, the entire storage time for the reconstituted solution in the vial and the diluted solution in the IV bag should be protected from light and limited to 4 hours refrigerated at 2°C to 8°C (36°F to 46°F)
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Inform patients that hypersensitivity reactions including infusion-associated events have been reported during and post-infusion with EBANGA and to immediately report if they experience any symptoms of systemic hypersensitivity reactions.
Instruct patients with Orthoebolavirus zairense not to breastfeed because of the risk of passing Orthoebolavirus zairense to the baby
Precautions with Alcohol
Alcohol-Ansuvimab-zykl interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
Ebanga
Look-Alike Drug Names
There is limited information regarding Ansuvimab-zykl Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.