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Emapalumab-lzsg

Class: Immunosuppressive Agents
Chemical Name: Immunoglobulin G1, anti-(human interferon γ) (human monoclonal NI-0501 heavy chain), disulfide with human monoclonal NI-0501 light chain, dimer
Molecular Formula: C6430H9898N1718O2038S46
CAS Number: 1709815-23-5
Brands: Gamifant

Medically reviewed by Drugs.com on Nov 30, 2020. Written by ASHP.

Introduction

Emapalumab-lzsg, an interferon gamma (IFNγ) blocking antibody, is an immunosuppressive agent.

Uses for Emapalumab-lzsg

Emapalumab-lzsg has the following uses:

Emapalumab-lzsg is indicated for the treatment of adult and pediatric (newborn and older) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy.

Emapalumab-lzsg Dosage and Administration

General

Emapalumab-lzsg is available in the following dosage form(s) and strength(s):

Injection:

  • 10 mg/2 mL (5 mg/mL) solution in a single-use vial.

  • 50 mg/10 mL (5 mg/mL) solution in a single-use vial.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Conduct testing for latent tuberculosis infections using the purified protein derivative (PPD) or IFNγ release assay and evaluate patients for tuberculosis risk factors prior to initiating emapalumab-lzsg. Administer tuberculosis prophylaxis to patients at risk for tuberculosis, or known to have a positive PPD test result, or positive IFNγ release assay.

Monitor for tuberculosis, adenovirus, Epstein-Barr virus, and cytomegalovirus every 2 weeks and as clinically indicated.

Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and for fungal infections prior to emapalumab-lzsg administration.

Pediatric Patients

Dosage and Administration

The recommended starting dose of emapalumab-lzsg in pediatric patients (newborn and older) is 1 mg/kg given as an intravenous infusion over 1 hour twice per week (every three to four days). Doses subsequent to the initial dose may be increased based on clinical and laboratory criteria.

Administer emapalumab-lzsg until hematopoietic stem cell transplantation (HSCT) is performed or unacceptable toxicity. Discontinue emapalumab-lzsg when a patient no longer requires therapy for the treatment of HLH.

For patients who are not receiving baseline dexamethasone treatment, begin dexamethasone at a daily dose of at least 5 to 10 mg/m2 the day before emapalumab-lzsg treatment begins. For patients who were receiving baseline dexamethasone, they may continue their regular dose provided the dose is at least 5 mg/m2. Dexamethasone can be tapered according to the judgment of the treating physician.

The emapalumab-lzsg dose may be titrated up if disease response is unsatisfactory. After the patient’s clinical condition is stabilized, decrease the dose to the previous level to maintain clinical response.

Adults

Dosage and Administration

The recommended starting dose of emapalumab-lzsg in adults is 1 mg/kg given as an intravenous infusion over 1 hour twice per week (every three to four days). Doses subsequent to the initial dose may be increased based on clinical and laboratory criteria.

Administer emapalumab-lzsg until HSCT is performed or unacceptable toxicity. Discontinue emapalumab-lzsg when a patient no longer requires therapy for the treatment of HLH.

For patients who are not receiving baseline dexamethasone treatment, begin dexamethasone at a daily dose of at least 5 to 10 mg/m2 the day before emapalumab-lzsg treatment begins. For patients who were receiving baseline dexamethasone, they may continue their regular dose provided the dose is at least 5 mg/m2. Dexamethasone can be tapered according to the judgment of the treating physician.

The emapalumab-lzsg dose may be titrated up if disease response is unsatisfactory. After the patient’s clinical condition is stabilized, decrease the dose to the previous level to maintain clinical response.

Cautions for Emapalumab-lzsg

Contraindications

  • None.

Warnings/Precautions

Infections

Emapalumab-lzsg may increase the risk of fatal and serious infections to include specific pathogens favored by IFNγ neutralization, including mycobacteria, Herpes Zoster virus, and Histoplasma Capsulatum.

Do not administer emapalumab-lzsg in patients with infections caused by these pathogens until appropriate treatment has been initiated.

In 32% of patients receiving emapalumab-lzsg in clinical trials, serious infections such as sepsis, pneumonia, bacteremia, disseminated histoplasmosis, necrotizing fasciitis, viral infections, and perforated appendicitis were observed. The reported infections were viral (41%), bacterial (35%), fungal (9%), and the pathogen was not identified in 15% of cases.

Evaluate patients for tuberculosis risk factors and test for latent infection (PPD testing, PCR, or IFNγ release assay) prior to initiating emapalumab-lzsg. Administer tuberculosis prophylaxis to patients at risk for tuberculosis or known to have a positive PPD test result.

Administer prophylaxis for Herpes Zoster, Pneumocystis jirovecii, and fungal infection to mitigate the risk to patients while receiving emapalumab-lzsg. Employ surveillance testing during treatment with emapalumab-lzsg.

Closely monitor patients receiving emapalumab-lzsg for signs or symptoms of infection, promptly initiate a complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.

Increased Risk of Infection with Use of Live Vaccine

Do not administer live or live attenuated vaccines to patients receiving emapalumab-lzsg and for at least 4 weeks after the last dose of emapalumab-lzsg. The safety of immunization with live vaccines during or following emapalumab-lzsg therapy has not been studied.

Infusion-related Reactions

Infusion-related reactions including drug eruption, pyrexia, rash, erythema, and hyperhidrosis were reported with emapalumab-lzsg treatment in 27% of patients. In one-third of these patients, the infusion-related reaction occurred during the first infusion.

All infusion related reactions were reported as mild to moderate. Monitor patients for infusion-related reactions. Interrupt infusion for infusion reactions and institute appropriate medical management prior to continuing infusion at a slower rate.

Specific Populations

Pregnancy

Risk Summary: There are no available data on emapalumab-lzsg use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In an animal reproduction study, a murine surrogate anti-mouse IFNγ antibody administered to pregnant mice throughout gestation crossed the placental barrier, and no fetal harm was observed. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Animal Data: In a mouse embryo-fetal development study, a murine surrogate anti-mouse IFNγ antibody was administered every 3-4 days throughout organogenesis and late gestation at doses of 0, 30, 75, or 150 mg/kg/occasion. The surrogate antibody was detected in the plasma of all treated pregnant mice and their corresponding fetuses. No maternal toxicity occurred and there was no evidence of teratogenicity or effects on embryo-fetal survival or growth.

Lactation

Risk Summary: There is no information regarding the presence of emapalumab-lzsg in human milk, the effects on the breastfed child, or the effects on milk production. Published data suggest that only limited amounts of therapeutic antibodies are found in breast milk and they do not enter the neonatal and infant circulations in substantial amounts. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for emapalumab-lzsg and any potential adverse effects on the breastfed child from emapalumab-lzsg or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness of emapalumab-lzsg have been established in pediatric patients, newborn and older, with primary HLH that is reactivated or refractory to conventional therapies. Use of emapalumab-lzsg is supported by a single-arm trial in 27 pediatric patients with reactivated or refractory primary HLH. This study included pediatric patients in the following age groups: 5 patients newborn to 6 months, 10 patients 6 months to 2 years, and 12 patients from 2 years to 13 years.

Geriatric Use

Clinical studies of emapalumab-lzsg did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Common Adverse Effects

The most common adverse reactions (≥ 20%) were: infections, hypertension, infusion-related reactions, and pyrexia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Emapalumab-lzsg is a monoclonal antibody that binds to and neutralizes IFNγ. Nonclinical data suggest that IFNγ plays a pivotal role in the pathogenesis of HLH by being hypersecreted.

Advice to Patients

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Inform patients and their caregivers of the risk of developing infections during treatment with emapalumab-lzsg, and to report any symptoms of infection.

Advise patients and their caregivers that the patient should not receive live or live attenuated vaccines during emapalumab-lzsg treatment.

Advise patients and their caregivers of the potential for developing infusion-related reactions during treatment with emapalumab-lzsg.

Additional Information

AHFSfirstRelease. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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.

Emapalumab-lzsg

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

10 mg/2 mL

Gamifant

Sobi

50 mg/10 mL

Gamifant

Sobi

AHFS Drug Information. © Copyright 2021, Selected Revisions December 10, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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