ansuvimab (Rx)

>10%

During admission for treatment

• Diarrhea (≥40%)
• Pyrexia (≥40%)
• Abdominal pain (≥40%)
• Vomiting (≥40%)

During infusion

• Creatinine >1.8x ULN or ≥1.5x baseline (27%)
• Pyrexia (17%)
• Potassium, high ≥6.5 mmol/L (15%)
• AST ≥5x ULN (13%)
• ALT ≥5x ULN (12%)

1-10%

During infusion

• Tachycardia (9%)
• Diarrhea (9%)
• Vomiting (8%)
• Hypotension (8%)
• Sodium, low <125 mmol/L (7%)
• Tachypnea (6%)
• Potassium, low <2.5 mmol/L (6%)
• Sodium, high ≥154 mmol/L (5%)
• Chills (5%)
• Hypoxia (3%)

Contraindications

None

Cautions

Hypersensitivity reactions

• Hypersensitivity reactions, including infusion-associated events, have been reported
• These may include acute, life-threatening reactions during and after infusion
• Monitor for signs and symptoms (eg, hypotension, chills, elevation of fever) during and following infusion
• Infusion rate may be slowed or interrupted if any signs of infusion-associated events or other adverse events develop
• Discontinue infusion immediately if severe or life-threatening reaction occurs and administer appropriate emergency care

Drug interaction overview

• Avoid coadministration of live vaccine during treatment
• Potential for monoclonal antibodies to inhibit replication of live vaccine virus indicated for prevention of Zaire ebolavirus infection and possibly reduce vaccine efficacy
• Follow current immunization guidelines for interval needed between monoclonal antibodies and administering live vaccine

Pregnancy

Zaire ebolavirus infection is life-threatening for both the mother and fetus and treatment should not be withheld because of pregnancy; majority of such pregnancies result in maternal death with miscarriage, stillbirth, or neonatal death

Data from clinical trial demonstrate a high rate maternal and fetal/neonatal morbidity in treated pregnant females with Zaire ebolavirus infection consistent with published literature regarding the risk associated with underlying maternal Zaire ebolavirus infection

Data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal/fetal outcome

Animal reproduction studies have not been conducted

Human monoclonal antibodies cross the placenta; therefore, monoclonal antibodies are potentially transferred from mother to fetus

Lactation H3

CDC recommends patients with confirmed Zaire ebolavirus not breastfeed their infants to reduce the risk of postnatal transmission

No data are available on presence in human or animal milk, effects on breastfed infants, or effects on milk production

Maternal IgG is known to be present in human milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant human IgG1 monoclonal antibody binds to glycoprotein on the Ebola virus surface and blocks attachment and entry of the virus on the host cell membranes

Ansuvimab exhibited Fc-mediated antibody-dependent cellular cytotoxicity activity against cells expressing Zaire ebolavirus glycoprotein 1 when effector cells were added

Pharmacokinetics

Limited data from 18 healthy subjects (aged 22-56 years) suggest that the pharmacokinetic profile is consistent with the profile of other IgG1 monoclonal antibodies

Pharmacokinetic data are not available for Zaire ebolavirus-infected patients

IV Incompatibilities

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

IV Compatibilities

0.9% NaCl

Lactated Ringers (LR)

IV Preparation

Reconstitution

• Calculate dose and number of vials required
• Remove vials from refrigerator and allow vials to reach room temperature (15-27ºC [59-81ºF]) for ~20 min
• Vials that cannot immediately be reconstituted can be kept at room temperature, protected from light, for no more than 24 hr
• Reconstitute each vial with 7.7 mL of sterile water for injection diluent
• Slowly inject diluent along vial wall by angling needle down at a ~45º angle above powder cake and without any air to avoid foaming and bubbles
• Gently swirl (do NOT shake) for ~10 seconds; then set vial down to rest for at least 10 seconds; repeat until cake is dissolved; may take up to 20 minutes
• Upon reconstitution, 1 vial yields 8 mL (final concentration: 50 mg/mL); solution appears clear to slightly opalescent and colorless to slightly yellow; discard if reconstituted solution is discolored or contains visible particles

Dilution

Refer to prescribing information for exact diluent and drug volumes

Following reconstitution, ansuvimab must be further diluted with 0.9% NaCl or LR before administering

Weight 0.5 to <2 kg

• Use a 10-mL syringe compatible with IV infusion pump
• Fill 10-mL syringe with appropriate amount of diluent
• Add calculated drug volume to 10-mL syringe
• Gently invert diluted solution 3-5x until admixed; do NOT shake
• Final concentration of diluted solution is ~8-30 mg/mL

Weight >2 kg

• Use either a PVC 0.9% NaCl infusion bag or a non-PVC or non-DEHP LR IV infusion bag
• Based on body weight, select an infusion bag with the appropriate volume
• Withdraw and discard from bag a volume that accounts for drug and final infusion volume according to patient’s weight
• Add calculated drug volume to bag based on patient’s weight
• For example, for a 55-kg patient, withdraw and discard 150 mL of diluent from a 250-mL infusion bag, then add 55 mL of drug to obtain a final volume of 155 mL
• Gently invert IV bag 5-10x until diluted solution is mixed; do NOT shake
• Final concentration of diluted solution is ~8-30 mg/mL
• Discard vial(s) and all unused contents

IV Administration

Administer as IV infusion; do NOT administer as IV push or bolus

Do not coadminister other drugs simultaneously through same infusion line

Prepare IV infusion line with 1.2-micron in-line filter extension set

Infuse over 60 minutes; can be infused via a central line or peripheral catheter

Infusions may be slowed or stopped if necessary, to alleviate any effects

At end of infusion

• Syringe pump:Remove syringe and flush line with 2-5 mL of diluent, but not to exceed the total infusion volume
• Infusion bag: Replace empty bag and flush line by infusing at least 25 mL of diluent, to ensure complete product administration

Storage

Unopened vials

• Refrigerate at 2-8ºC (36-46ºF) in the original carton to protect from light
• Do not freeze
• Do not shake
• Vials that cannot immediately be reconstituted upon reaching room temperature may be kept at room temperature, protected from light, for no more than 24 hr

Reconstituted vials

• Store at room temperature (15-27ºC [59-81ºF]) or refrigerate at 2-8ºC (36-46ºF) for up to 4 hr; includes time required for further dilution and infusion
• Protect from light

Diluted solutions

• If not used immediately, store at room temperature (15-27ºC [59-81ºF]) or refrigerate at 2-8ºC (36-46ºF) for up to 4 hr; time limits include reconstitution time
• Do not freeze
• If refrigerated, allow diluted solution to come to room temperature before use