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Atoltivimab, maftivimab, and odesivimab (United States: Available via manufacturer expanded access or public health distribution): Drug information

Atoltivimab, maftivimab, and odesivimab (United States: Available via manufacturer expanded access or public health distribution): Drug information
(For additional information see "Atoltivimab, maftivimab, and odesivimab (United States: Available via manufacturer expanded access or public health distribution): Pediatric drug information" and see "Atoltivimab, maftivimab, and odesivimab (United States: Available via manufacturer expanded access or public health distribution): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Antiviral Agent;
  • Monoclonal Antibody
Dosing: Adult
Zaire ebolavirus infection

Zaire ebolavirus infection: IV: 50 mg/kg each of atoltivimab, maftivimab, and odesivimab as a single dose (Ref).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Atoltivimab, maftivimab, and odesivimab (United States: Available via manufacturer expanded access or public health distribution): Pediatric drug information")

Zaire ebolavirus infection

Zaire ebolavirus infection: Infants, Children, and Adolescents: IV: 50 mg/kg each of atoltivimab, maftivimab, and odesivimab as a single dose.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Hypotension (15%), tachycardia (20%)

Endocrine & metabolic: Increased serum potassium (13%)

Gastrointestinal: Diarrhea (11%), vomiting (19%)

Hepatic: Increased serum aspartate aminotransferase (21%)

Nervous system: Chills (39%)

Renal: Increased serum creatinine (15%)

Respiratory: Tachypnea (19%)

Miscellaneous: Fever (54%)

1% to 10%:

Endocrine & metabolic: Decreased serum potassium (9%), decreased serum sodium (7%), increased serum sodium (9%)

Hepatic: Increased serum alanine aminotransferase (10%)

Respiratory: Hypoxia (10%)

Postmarketing:

Hypersensitivity: Hypersensitivity reaction

Miscellaneous: Infusion related reaction

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions, including life-threatening infusion-related reactions, have been reported during and after receipt of atoltivimab, maftivimab, and odesivimab. Monitor for signs and symptoms such as fever, chills, and hypotension. May slow or interrupt infusion for any signs of infusion-related reaction or other adverse effects; immediately discontinue for severe or life-threatening hypersensitivity reaction.

Other warnings/precautions:

• Immunizations: Avoid concurrent administration of a live vaccine during treatment with atoltivimab, maftivimab, and odesivimab.

Product Availability

Inmazeb: FDA approved October 2020. Product will not be commercially available; will only be distributed for a public health emergency in the US.

Prescribing and Access Restrictions

Regeneron will provide atoltivimab, maftivimab, and odesivimab in response to outbreaks in the Democratic Republic of the Congo through the Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) protocol for compassionate use and is actively working with non-governmental agencies to ensure continued access to atoltivimab, maftivimab, and odesivimab in low- and middle-income countries. See inmazeb.com for more information.

Administration: Adult

IV: Allow diluted infusion solution to come to room temperature prior to administration; preparations diluted with D5W may be infused at temperatures up to 35°C (95°F); if temperature is >25°C (>77°F) administer immediately after preparation. Administer IV with 0.2-micron filter. Infusion rate is based on total volume: for 250 mL to 1 L, infuse over 2 hours; for 2 L, infuse over 4 hours. May slow or interrupt infusion for signs of infusion-associated events or other adverse events.

Administration: Pediatric

IV: Must be diluted prior to administration. Allow diluted infusion to reach room temperature prior to administration; preparations diluted with D5W may be infused at temperatures up to 35°C (95°F), if temperature is >25°C (77°F) administer immediately after preparation. Administer through an IV line containing a 0.2-micron filter. Infusion time is based on patient weight. Slow or interrupt infusion if the patient develops any signs of infusion-associated events (eg, hypotension, chills, fever elevation) or other adverse events; if severe or life-threatening hypersensitivity reactions occur, immediately discontinue infusion and provide emergency care.

Infusion duration based on patient weight:

0.5 to <2 kg: Infuse over 4 hours.

2 to <16 kg: Infuse over 3 hours.

16 to <150 kg: Infuse over 2 hours.

≥150 kg: Infuse over 4 hours.

Use: Labeled Indications

Zaire ebolavirus infection: Treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection.

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

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Ebola Zaire Vaccine (Live): Ebola-Directed Monoclonal Antibodies may diminish the therapeutic effect of Ebola Zaire Vaccine (Live). Management: Wait several months (3 to 6 months, and up to 11 months) after use of Ebola-directed antibodies before administering the live Ebola Zaire vaccine. Repeat vaccination may be required if antibody therapy and vaccination cannot be adequately separated. Risk D: Consider therapy modification

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Pregnancy Considerations

Atoltivimab, maftivimab, and odesivimab are humanized IgG1κ monoclonal antibodies and would be expected to cross the placenta. Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

A limited number of pregnant patients were included in a study that included treatment with atoltivimab, maftivimab, and odesivimab (Mulangu 2019).

Following maternal infection, the Ebola virus can be detected in maternal body fluids and transmitted to the fetus. Maternal Ebola infection carries a high rate of mortality for both the fetus and the mother. Maternal Ebola virus infection typically results in miscarriage, stillbirth, and maternal and/or neonatal death (Olgun 2018). Treatment with atoltivimab/maftivimab/odesivimab should not be withheld due to pregnancy.

Pregnant health care providers should not care for patients with Ebola virus disease (CDC 2018).

Breastfeeding Considerations

It is not known if atoltivimab, maftivimab, or odesivimab are present in breast milk; however, atoltivimab, maftivimab, and odesivimab are humanized IgG1κ monoclonal antibodies and IgG is known to be present in breast milk.

Following maternal infection, the Ebola virus can be detected in body fluids, including breast milk. Infected mothers can transmit the Ebola virus to their infant via breast milk (Olgun 2018; WHO 2020).

The Centers for Disease Control and Prevention recommends mothers with Ebola virus infection completely avoid breastfeeding to decrease the potential transmission to their infants (CDC 2018). The World Health Organization recommends lactating patients with acute Ebola virus infection be separated from their breastfeeding child and milk substitutes be provided. Patients who have recovered from Ebola virus disease should have 2 consecutive negative Ebola virus breast milk tests by RT-PCR separated by 24 hours before feeding with breast milk is resumed (WHO 2020).

Monitoring Parameters

Monitor for infusion-related reactions.

Mechanism of Action

Atoltivimab, maftivimab, and odesivimab is an antiviral drug combination of 3 recombinant human IgG1κ monoclonal antibodies, each targeting the Zaire ebolavirus glycoprotein, which mediates viral attachment and host membrane fusion. Atoltivimab, maftivimab, and odesivimab can bind to the glycoprotein simultaneously. Maftivimab is a neutralizing antibody that blocks viral entry into host cells. Odesivimab is a non-neutralizing antibody that induces antibody-dependent effector function through FcyRIIIa signaling when bound to target; odesivimab also binds to soluble Zaire ebolavirus glycoprotein. Atoltivimab combines both neutralization and FcyRIIIa signaling activities.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Mean Vd, steady state: Atoltivimab: 58.2 mL/kg; Maftivimab: 57.6 mL/kg; Odesivimab: 56 mL/kg.

Half-life elimination: Atoltivimab: 21.2 days; Maftivimab: 22.3 days; Odesivimab: 25.3 days.

  1. Centers for Disease Control (CDC). Centers for Disease Control and Prevention guidance for screening and caring for pregnant women with Ebola virus disease for healthcare providers in U.S. hospitals. https://www.cdc.gov/vhf/ebola/clinicians/evd/pregnant-women.html. Updated May 30, 2018. Accessed January 7, 2021.
  2. Inmazeb (atoltivimab, maftivimab, and odesivimab) [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; May 2022.
  3. Mulangu S, Dodd LE, Davey RT Jr, et al; PALM Consortium Study Team. A randomized, controlled trial of ebola virus disease therapeutics. N Engl J Med. 2019;381(24):2293-2303. doi:10.1056/NEJMoa1910993 [PubMed 31774950]
  4. Olgun NS. Viral infections in pregnancy: a focus on Ebola virus. Curr Pharm Des. 2018;24(9):993-998. doi:10.2174/1381612824666180130121946 [PubMed 29384053]
  5. Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. doi:10.1155/2012/985646 [PubMed 22235228]
  6. Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]
  7. World Health Organization (WHO). Guidelines for the management of pregnant and breastfeeding women in the context of Ebola virus disease. https://apps.who.int/iris/bitstream/handle/10665/330851/9789240001381-eng.pdf?ua=1. Published February 2020. Accessed January 28, 2021. [PubMed 32091684]
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