Ansuvimab-zykl (Monograph)

Brand name: Ebanga
Drug class: Monoclonal Antibodies

Medically reviewed by Drugs.com on Dec 14, 2023. Written by ASHP.

Introduction

Recombinant human immunoglobulin G (IgG)1κ monoclonal antibody with activity against Zaire ebolavirus.

Uses for Ansuvimab-zykl

Zaire ebolavirus Infection

Treatment of infection caused by Zaire ebolavirusin adults and pediatric patients, including neonates born to a mother who is reverse transcription polymerase chain reaction (RT-PCR) positive for Zaire ebolavirusinfection (designated an orphan drug by FDA for this use).

Efficacy not established for other species of the Ebolavirus and Marburgvirus genera.

Zaire ebolavirus can change over time, and factors such as emergence of resistance or changes in viral virulence could diminish clinical benefit. Consider available information on drug susceptibility patterns for circulating Zaire ebolavirus strains when deciding whether to use ansuvimab-zykl.

International experts recommend either ansuvimab-zykl or atoltivimab, maftivimab, and odesivimab-ebgn for patients with RT-PCR confirmed Zaire ebolavirus disease and for neonates ≤7 days of age with unconfirmed Zaire ebolavirus disease status born to mothers with confirmed Zaire ebolavirus disease.

Ansuvimab-zykl Dosage and Administration

General

Patient Monitoring

• Monitor for signs and symptoms of hypersensitivity and infusion-related reactions (e.g., hypotension, chills, elevation of fever) during and after ansuvimab-zykl administration.

Other General Considerations

• Consider drug susceptibility patterns for Zaire ebolavirus strains when evaluating the appropriateness of ansuvimab-zykl therapy.

Administration

IV Administration

Administer as an IV infusion over 60 minutes through a central line or peripheral catheter; do not administer as an IV push or bolus.

Adminster using an IV line containing a 1.2 micron in-line filter.

If a syringe pump is used, flush infusion line with 2–5 mL of diluent, not to exceed the total infusion volume, after administration to ensure full dose delivery. If an infusion bag is used, flush infusion line with 25 mL of diluent following administration to ensure full dose delivery.

Available as a lyophilized powder that must be reconstituted and further diluted before IV administration.

Do not mix with or administer as an infusion with other medicinal products.

Reconstitution

Calculate dose and number of vials required using the patient's actual weight.

Before reconstitution, allow vials to reach ambient temperature (15–27°C) for approximately 20 minutes. If vials are not immediately reconstituted, may be kept at ambient temperature, protected from light, for ≤ 24 hours.

Reconstitute each vial with 7.7 mL of sterile water for injection using an 18-gauge needle and a sterile 10 mL syringe. While holding the vial horizontally, angle the needle downward at a 45º angle above the lyophilized powder; slowly inject diluent along the wall of the vial without adding any air to avoid foaming and bubbles. Gently swirl the vial for approximately 10 seconds, and set the vial down to rest for at least 10 seconds; repeat until fully dissolved (may take up to 20 minutes). Do not shake.

Once reconstituted, each vial delivers 8 mL of solution containing 50 mg/mL of ansuvimab-zykl. Immediately dilute the reconstituted solution.

Dilution

Use an 18–20 gauge, 1–1.5" needle with an appropriately sized syringe up to 60 mL to perform further dilution steps. Further dilute with either 0.9% sodium chloride injection or 5% dextrose injection. Select infusion bag or syringe of appropriate size based on patient weight (see Table 1).

For patients weighing ≥2 kg, further dilute ansuvimab-zykl in a latex-free, di-ethylhexylphthalate (DEHP)-free infusion bag. 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 (see Table 1). Then, add the calculated volume of ansuvimab-zykl to the bag. Gently invert bag 5–10 times to mix; do not shake.

For patients weighing 0.5 to < 2 kg, further dilute ansuvimab-zykl in a 10 mL syringe compatible with an infusion pump. Fill the 10 mL syringe with the appropriate amount of diluent (see Table 1), then add the calculated volume of ansuvimab-zykl to the syringe. Gently invert syringe 3–5 times to mix; do not shake.

Based on the recommended total infusion volume in Table 1, final dilution will yield ansuvimab-zykl concentrations of approximately 8–30 mg/mL. Administer diluted solution immediately after preparation.

For IV bag administration, the diluent volume column includes the volume of diluent that must remain in the infusion bag.

Rate of Administration

Administer as an IV infusion over 60 minutes. Infusion may be slowed or stopped if necessary to alleviate adverse reactions.

Dosage

Pediatric Patients

Zaire ebolavirus infection

IV

Birth to <18 years of age: 50 mg/kg as a single IV infusion.

Adults

Zaire ebolavirus infection

IV

50 mg/kg as a single IV infusion.

Special Populations

Hepatic Impairment

No dosage recommendations.

Renal Impairment

No dosage recommendations.

Geriatric Patients

No dosage recommendations.

Cautions for Ansuvimab-zykl

Contraindications

• None.

Warnings/Precautions

Hypersensitivity Reactions Including Infusion-Associated Events

Hypersensitivity reactions, including acute, life-threatening reactions, and infusion-associated events reported.

Monitor for signs and symptoms of hypersensitivity and infusion-associated reactions (e.g., hypotension, chills, fever) during and after infusion. Infusion rate may be slowed or interrupted if signs of infusion-related reactions or other adverse events occur. If severe or life-threatening hypersensitivity reactions develop, immediately discontinue the infusion and initiate appropriate medical care.

Specific Populations

Pregnancy

Zaire ebolavirus infection is life threatening to both the mother and fetus; do not withhold treatment during pregnancy. Available data not adequate to evaluate for drug-associated risk of major birth defects, miscarriage, or maternal/fetal harm. No animal reproductive data available. Other monoclonal antibodies are transported across the placenta; potential for fetal exposure to ansuvimab-zykl.

Fetal, neonatal, and maternal outcomes are poor in women infected with Zaire ebolavirus during pregnancy. Most cases result in maternal death with miscarriage, stillbirth, or death of the neonate.

Lactation

To reduce risk of postnatal transmission, the Centers for Disease Control and Prevention (CDC) recommends that women with confirmed Zaire ebolavirus infection avoid breastfeeding.

No data available on the presence of ansuvimab-zykl in milk. Effects on the breast-fed infant or on milk production not known. Maternal IgG is present in the milk of lactating women.

Pediatric Use

Safety and efficacy established in pediatric patients from birth to <18 years of age.

Geriatric Use.

Insufficient experience in patients ≥65 years of age to determine whether safety profile differs from younger adults. Based on limited clinical experience, no overall differences in response between geriatric patients and younger adults.

Hepatic Impairment.

Effect on pharmacokinetics not known.

Renal Impairment.

Effect on pharmacokinetics not known.

Common Adverse Effects

Most common adverse reactions (≥5%): pyrexia, tachycardia, diarrhea, vomiting, hypotension, tachypnea, chills.

Drug Interactions

No formal drug interaction studies conducted.

Specific Drugs

Ansuvimab-zykl Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetic profile similar to other IgG1 monoclonal antibodies.

No pharmacokinetic data in patients with active Zaire ebolavirus infection.

Special Populations

Effects of renal impairment, hepatic impairment, or age on pharmacokinetics not known.

Distribution

Extent

Not known if excreted in milk. Maternal IgG present in milk.

Stability

Storage

Parenteral

For Injection, for IV Infusion

Store vials at 2–8ºC in the original carton to protect from light. May be kept at 15–27°C, protected from light, for ≤24 hours prior to reconstitution.

If not immediately diluted, reconstituted solution may be stored at 2–8ºC, protected from light, for ≤4 hours (4-hour time window includes time required for further dilution).

If not immediately administered, diluted solution may be stored at 2–8ºC for ≤4 hours (4-hour time window includes reconstitution time). Allow approximately 20 minutes for diluted solution to come to ambient temperature before administration.

Actions and Spectrum

• Recombinant human IgG1κ monoclonal antibody with activity against Zaire ebolavirus.

• Inhibits viral host cell entry by binding to glycan cap and inner chalice of the Zaire ebolavirus glycoprotein-1 (GP-1) subunit; this blocks GP-1 binding to the Neiman Pick cell receptor 1 in host cells.

• Demonstrated fragment crystallizable (Fc)-mediated antibody-dependent cellular cytotoxicity (ADCC) against cells that express Zaire ebolavirus GP after the addition of effector cells.

• Neutralized Zaire ebolavirus Mayinga with a half-maximal effective concentration (EC₅₀) of 0.06 µg/mL in a live virus plaque-reduction neutralization assay in Vero E6 cells.

• In a Zaire ebolavirus GP lentivirus infectivity assay using HEK293 cells, the EC₅₀ inhibitory values of ansuvimab-zykl were 0.09 μg/mL against Zaire ebolavirus Mayinga and and 0.15 μg/mL against Zaire ebolavirus Makona.

• Treatment of rhesus macaques infected with Zaire ebolavirus with a single 50 mg/kg IV dose of ansuvimab-zykl generally protected against death due to Zaire ebolavirus when administered 5 days post-infection.

• No clinical or nonclinical data available to evaluate ansuvimab-zykl resistance; in patients who fail to respond, or experience disease relapse after treatment, consider possible ansuvimab-zykl resistance.

Advice to Patients

• Inform patients that hypersensitivity reactions, including infusion-associated events, have occurred during and after completion of ansuvimab-zykl infusion. Advise patients to immediately report any signs or symptoms of a systemic hypersensitivity reaction.

• Instruct patients infected with Zaire ebolavirus to avoid breastfeeding to avoid transmission of infection to the infant.

• Advise patient to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Ansuvimab-zykl is stored in the US Strategic National Stockpile (SNS) and is not commerically available in the US. The SNS ensures that certain drugs and medical supplies are readily available to prevent or treat specific diseases, including during public health emergencies, and is managed by the US Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR). To request a drug from the SNS, state health departments can contact the US Centers for Disease Control and Prevention (CDC) Emergency Operations Center at 770-488-7100 or the HHS Secretary's Operations Center at 202-619-7800.

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