Atoltivimab, maftivimab, and odesivimab-ebgn
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
Atoltivimab, maftivimab, and odesivimab-ebgn is a fixed-dose combination of three monoclonal antibodies that is FDA approved for the treatment of of infection caused by Orthoebolavirus zairense in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Orthoebolavirus zairense infection. Common adverse reactions include Hypersensitivity Reactions Including Infusion-Associated Events.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
INMAZEB is indicated for the treatment of infection caused by Orthoebolavirus zairense in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Orthoebolavirus zairense infection
DOSAGE INMAZEB is a combination of three human monoclonal antibodies co-formulated in a 1:1:1 ratio of atoltivimab, maftivimab, and odesivimab. INMAZEB is available as two different strength presentations, containing either 16.67 mg of each antibody per mL or 33.33 mg of each antibody per mL
The recommended dosage of INMAZEB is 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg diluted and administered as a single intravenous infusion
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Atoltivimab, maftivimab, and odesivimab-ebgn in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Atoltivimab, maftivimab, and odesivimab-ebgn in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Same as adult version.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Atoltivimab, maftivimab, and odesivimab-ebgn in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Atoltivimab, maftivimab, and odesivimab-ebgn in pediatric patients.
Contraindications
None
Warnings
Hypersensitivity Reactions Including Infusion-Associated Events Hypersensitivity reactions including infusion-associated events have been reported during and post-infusion with INMAZEB. 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 INMAZEB infusion. In the case of severe or life-threatening hypersensitivity reactions, discontinue the administration of INMAZEB immediately and administer appropriate emergency care
Infusion could not be completed in 1% of subjects who received INMAZEB due to infusion-associated adverse events. The rate of infusion of INMAZEB 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 may not reflect the rates observed in practice.
Overall, 382 adult and pediatric subjects with Orthoebolavirus zairense infection received INMAZEB in one clinical trial (the PALM trial) and as part of an expanded access program conducted in the Democratic Republic of Congo during a Orthoebolavirus zairense outbreak in 2018-2019. In the PALM trial, the safety of INMAZEB was evaluated in a multi-center, open-label, randomized controlled trial, in which 154 subjects (115 adult subjects and 39 pediatric subjects) received INMAZEB [50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg (3 mL/kg)] intravenously as a single infusion and 168 subjects received an investigational control. All subjects received optimized standard of care treatment. During the same outbreak, INMAZEB [50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg (3 mL/kg)] was given to 228 subjects (190 adult subjects and 38 pediatric subjects) in the expanded access program.
The safety data described below is derived from the PALM trial.
Postmarketing Experience
There is limited information regarding Atoltivimab, maftivimab, and odesivimab-ebgn Postmarketing Experience in the drug label.
Drug Interactions
No vaccine-therapeutic interaction studies have been performed in human subjects using INMAZEB. However, because of the potential for INMAZEB 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 INMAZEB. The interval between live vaccination following initiation of INMAZEB therapy should be in accordance with current vaccination guidelines. The efficacy of INMAZEB among subjects who reported receipt of a recombinant live vaccine prior to their enrollment in the PALM clinical trial was similar to subjects who did not receive a vaccine.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Atoltivimab, maftivimab, and odesivimab-ebgn in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Atoltivimab, maftivimab, and odesivimab-ebgn 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 and an expanded access program in which pregnant women with Orthoebolavirus zairense infection were treated with INMAZEB 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 INMAZEB have not been conducted. Human monoclonal antibodies, such as INMAZEB, are transported across the placenta; therefore, INMAZEB has the potential to be transferred from the mother to the developing fetus.
Nursing Mothers
The Centers for Disease Control and Prevention recommend that patients 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 atoltivimab, maftivimab, and odesivimab-ebgn 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 atoltivimab, maftivimab, or odesivimab-ebgn are unknown.
Pediatric Use
The safety and effectiveness of INMAZEB 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 INMAZEB for this indication is supported by evidence from a multi-center, open label, randomized controlled trial of INMAZEB in adults and pediatric subjects that included 39 pediatric subjects birth to less than 18 years of age, including neonates born to a mother who is RT-PCR positive for Orthoebolavirus zairense infection. The 28-day mortality and safety in adult and pediatric subjects treated with INMAZEB were similar. An additional 38 pediatric subjects from birth to less than 18 years of age received INMAZEB in an expanded access program.
Geriatic Use
Clinical studies of INMAZEB did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Of the 154 subjects with Orthoebolavirus zairense infection who received INMAZEB in the randomized controlled trial, 5 (3.2%) were 65 years or older. The limited clinical experience has not identified differences in responses between the elderly and younger subjects.
Gender
There is no FDA guidance on the use of Atoltivimab, maftivimab, and odesivimab-ebgn with respect to specific gender populations.
Race
There is no FDA guidance on the use of Atoltivimab, maftivimab, and odesivimab-ebgn with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Atoltivimab, maftivimab, and odesivimab-ebgn in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Atoltivimab, maftivimab, and odesivimab-ebgn in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Atoltivimab, maftivimab, and odesivimab-ebgn in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Atoltivimab, maftivimab, and odesivimab-ebgn in patients who are immunocompromised.
Administration and Monitoring
Administration
INMAZEB must be prepared and administered under the supervision of a healthcare provider. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. INMAZEB should be clear to slightly opalescent, colorless to pale yellow solution that is free from visible particulates. Discard the vial if the solution is cloudy, discolored or contains particulate matter.
Monitoring
Monitor all patients for signs and symptoms including, but not limited to, hypotension, chills and elevation of fever, during and following INMAZEB infusion. In the case of severe or life-threatening hypersensitivity reactions, discontinue the administration of INMAZEB immediately and administer appropriate emergency care
IV Compatibility
Preparation for Intravenous Infusion:
- The recommended dosage is based on 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg. For example, a patient weighing 50 kg the recommended dosage is 2,500 mg of atoltivimab, 2,500 mg of maftivimab, and 2,500 mg of odesivimab.
- Determine the number of vials needed based on the calculated dose in volume (mL).
–The number of vials needed depends on the INMAZEB strength used. Refer to Table 1 for the corresponding volume per kg needed to withdraw from each available strength presentation to prepare dose. –Multiple INMAZEB vials may be needed. Each vial contains 14.5 mL of INMAZEB solution, regardless of the strength presentation. For example, for a 50 kg patient, the volume of INMAZEB needed is 150 mL (11 vials) if using the 16.67 mg/16.67 mg/16.67 mg per mL solution or 75 mL (6 vials) if using the 33.33 mg/33.33 mg/33.33 mg per mL solution.
Overdosage
There is limited information regarding Atoltivimab, maftivimab, and odesivimab-ebgn 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 Atoltivimab, maftivimab, and odesivimab-ebgn Pharmacology in the drug label.
Mechanism of Action
INMAZEB is an antiviral drug combination of three recombinant human IgG1κ monoclonal antibodies (atoltivimab, maftivimab, and odesivimab) that inhibit Orthoebolavirus zairense
Structure
There is limited information regarding Atoltivimab, maftivimab, and odesivimab-ebgn Structure in the drug label.
Pharmacodynamics
Atoltivimab, maftivimab, and odesivimab exposure-response relationships and the time course of pharmacodynamic response are unknown.
Pharmacokinetics
No pharmacokinetic data are available in patients with Orthoebolavirus zairense infection. The pharmacokinetics of atoltivimab, maftivimab, and odesivimab in 18 healthy subjects 21 to 60 years of age are linear and dose-proportional over the range of 1 mg of atoltivimab, 1 mg of maftivimab, and 1 mg of odesivimab per kg to 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg (0.02 to 1 times the approved recommended dosage) of INMAZEB following a single intravenous (IV) infusion. Pharmacokinetic parameters for the individual antibodies of INMAZEB
Nonclinical Toxicology
Carcinogenicity, genotoxicity, and fertility studies have not been conducted with INMAZEB.
Clinical Studies
The efficacy of INMAZEB was evaluated in PALM, a multi-center, open-label, randomized controlled trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID; NCT03719586). The trial was conducted in the Democratic Republic of Congo, where an outbreak began in August 2018, and enrolled 681 subjects of all ages, including pregnant women, with documented Orthoebolavirus zairense infection and symptoms of any duration who were receiving optimized standard of care (oSOC). Subjects were randomized to receive INMAZEB (50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg) intravenously as a single infusion, an investigational control 50 mg/kg intravenously every third day, for a total of 3 doses, or other investigational drugs. Eligible subjects 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. 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 subjects received oSOC consisting of a minimum of intravenous fluids, daily clinical laboratory testing, correction of hypoglycemia and electrolyte imbalances, and broad-spectrum antibiotics and antimalarials, as indicated.
The primary efficacy endpoint was 28-day mortality. The primary analysis population includes all subjects who were randomized and concurrently eligible to receive either INMAZEB or the investigational control during the same time period of the trial.
How Supplied
INMAZEB (atoltivimab, maftivimab, and odesivimab-ebgn) injection is a clear to slightly opalescent and colorless to pale yellow solution. It is supplied in a carton containing one single dose vial of:
- 241.7 mg of atoltivimab, 241.7 mg of maftivimab, and 241.7 mg of odesivimab per 14.5 mL (16.67 mg/16.67 mg/16.67 mg per mL) (NDC 61755-018-01)
- 483.3 mg of atoltivimab, 483.3 mg of maftivimab, and 483.3 mg of odesivimab per 14.5 mL (33.33 mg/33.33 mg/33.33 mg per mL) (NDC 61755-019-01)
Storage
Store INMAZEB vial refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake.
Images
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Patient Counseling Information
Hypersensitivity Reactions Including Infusion-Associated Events Inform patients that hypersensitivity reactions including infusion-associated events have been reported during and post-infusion with INMAZEB and to immediately report if they experience any symptoms of systemic hypersensitivity reactions
Lactation Instruct patients with Orthoebolavirus zairense infection not to breastfeed because of the risk of passing Orthoebolavirus zairense to the baby
Precautions with Alcohol
Alcohol-Atoltivimab, maftivimab, and odesivimab-ebgn interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
INMAZEB
Look-Alike Drug Names
There is limited information regarding Atoltivimab, maftivimab, and odesivimab-ebgn 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.