emapalumab (Rx)

Brand and Other Names:Gamifant, emapalumab-lzsg

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

solution for injection

  • Single-dose vial
  • 10mg/2mL (5mg/mL)
  • 50mg/10mL (5mg/mL)

Hemophagocytic Lymphohistiocytosis

Indicated for adults with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy

Initial: 1 mg/kg IV twice weekly (q3-4 days)

Subsequent doses after initiation

  • Dose may be increased based on clinical laboratory criteria (see following specific values)
  • Day 3: Increase to 3 mg/kg
  • From Day 6 onwards: Increase to 6 mg/kg
  • From Day 9 onwards: Increase to 10 mg/kg; increase only if assessment by physician determines a further increased dose is beneficial as based on initial signs of response
  • Platelet count
    • If baseline <50,000/mm³ and no improvement to >50,000/mm³
    • If baseline >50,000/mm³ and <30% improvement
    • If baseline >100,000/mm³ any decrease to <100,000/mm³
  • Neutrophil count
    • If baseline <500/mm³ and no improvement to >500/mm³
    • If baseline >500-1000/mm³ and decrease to <500/mm³
    • If baseline 1,000-1,500/mm³ and decrease to <1,000/mm³
  • Ferritin
    • If baseline ≥3,000 ng/mL and <20% decrease
    • If baseline <3,000 ng/mL and any increase to >3,000 ng/mL
  • Fibrinogen
    • If baseline levels ≤100 mg/dL and no improvement
    • If baseline levels >100 mg/dL and any decrease to <100 mg/dL
  • Other criteria
    • Fever: Persistence or recurrence
    • Splenomegaly: Any worsening
    • Coagulopathy (both D-dimer and fibrinogen must apply): D-dimer abnormal at baseline and no improvement

Dosage Modifications

Renal or hepatic impairment

  • No dosage adjustment required
  • No clinically significant differences in pharmacokinetics observed with renal impairment, including dialysis or any degree of hepatic impairment

Dosing Considerations

Before initiating treatment

  • Conduct testing for latent TB infections using purified protein derivative (PPD) or IFN-gamma release assay and evaluate patients for TB risk factors
  • Administer TB prophylaxis to patients at risk or who have tested positive

During treatment

  • Monitor for TB, adenovirus infection, EBV infection, and CMV infection q2wk and as clinically indicated

Dosage Forms & Strengths

solution for injection

  • Single-dose vial
  • 10mg/2mL (5mg/mL)
  • 50mg/10mL (5mg/mL)

Hemophagocytic Lymphohistiocytosis

Indicated for pediatric patients (newborn and older) with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent, or progressive disease or intolerance with conventional HLH therapy

Initial: 1 mg/kg IV twice weekly (q3-4 days)

Subsequent doses after initiation

  • Dose may be increased based on clinical laboratory criteria (see following specific values)
  • Day 3: Increase to 3 mg/kg
  • From Day 6 onwards: Increase to 6 mg/kg
  • From Day 9 onwards: Increase to 10 mg/kg; increase only if assessment by physician determines a further increased dose is beneficial as based on initial signs of response
  • Platelet count
    • If baseline <50,000/mm³ and no improvement to >50,000/mm³
    • If baseline >50,000/mm³ and <30% improvement
    • If baseline >100,000/mm³ any decrease to <100,000/mm³
  • Neutrophil count
    • If baseline <500/mm³ and no improvement to >500/mm³
    • If baseline >500-1,000/mm³ and decrease to <500/mm³
    • If baseline 1,000-1,500/mm³ and decrease to <1,000/mm³
  • Ferritin
    • If baseline ≥3,000 ng/mL and <20% decrease
    • If baseline <3,000 ng/mL and any increase to >3,000 ng/mL
  • Fibrinogen
    • If baseline levels ≤100 mg/dL and no improvement
    • If baseline levels >100 mg/dL and any decrease to <100 mg/dL
  • Other criteria
    • Fever: Persistence or recurrence
    • Splenomegaly: Any worsening
    • Coagulopathy (both D-dimer and fibrinogen must apply): D-dimer abnormal at baseline and no improvement

Dosage Modifications

Renal or hepatic impairment

  • No dosage adjustment required
  • No clinically significant differences in pharmacokinetics observed with renal impairment, including dialysis or any degree of hepatic impairment

Dosing Considerations

Before initiating treatment

  • Conduct testing for latent TB infections using purified protein derivative (PPD) or IFN-gamma release assay and evaluate patients for TB risk factors
  • Administer TB prophylaxis to patients at risk or who have tested positive

During treatment

  • Monitor for TB, adenovirus infection, EBV infection, and CMV infection q2wk and as clinically indicated
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Interactions

Interaction Checker

and emapalumab

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (1)

            • upadacitinib

              emapalumab, upadacitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Contraindicated.

            Serious - Use Alternative (6)

            • axicabtagene ciloleucel

              emapalumab, axicabtagene ciloleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

            • brexucabtagene autoleucel

              emapalumab, brexucabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

            • ciltacabtagene autoleucel

              emapalumab, ciltacabtagene autoleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

            • idecabtagene vicleucel

              emapalumab, idecabtagene vicleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

            • lisocabtagene maraleucel

              emapalumab, lisocabtagene maraleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

            • tisagenlecleucel

              emapalumab, tisagenlecleucel. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug.

            Monitor Closely (7)

            • isavuconazonium sulfate

              emapalumab and isavuconazonium sulfate both decrease immunosuppressive effects; risk of infection. Use Caution/Monitor.

            • ozanimod

              ozanimod, emapalumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Coadministration with immunosuppressive therapies may increase the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs in order to avoid unintended additive immunosuppressive effects.

            • ponesimod

              ponesimod and emapalumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • siponimod

              siponimod and emapalumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

            • trastuzumab

              trastuzumab, emapalumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

            • trastuzumab deruxtecan

              trastuzumab deruxtecan, emapalumab. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy. .

            • ublituximab

              ublituximab and emapalumab both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered

            Minor (0)

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              Adverse Effects

              >10%

              Infection (56%)

              Hypertension (41%)

              Infusion-related reactions (27%)

              Pyrexia (24%)

              Hypokalemia (15%)

              Constipation (15%)

              Rash (12%)

              Abdominal pain (12%)

              CMV infection (12%)

              Diarrhea (12%)

              Lymphocytosis (12%)

              Cough (12%)

              Irritability (12%)

              Tachycardia (12%)

              Tachypnea (12%)

              1-10%

              Vomiting

              Acute kidney injury

              Asthenia

              Bradycardia

              Dyspnea

              GI hemorrhage

              Epistaxis

              Peripheral edema

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              Warnings

              Contraindications

              None

              Cautions

              Infections

              • May increase risk of fatal and serious infections to include specific pathogens favored by IFN-gamma neutralization, including mycobacteria, herpes zoster virus, and Histoplasma capsulatum; do not administer in patients with infections caused by these pathogens until appropriate treatment initiated
              • Evaluate patients for TB risk factors and test for latent infection; administer TB prophylaxis to those testing positive
              • Administer prophylaxis for herpes zoster, Pneumocystis jirovecii infection, and fungal infection to mitigate the risk to patients while receiving emapalumab

              Infusion-related reactions

              • Mild-to-moderate infusion-related reactions reported, including drug eruption, pyrexia, rash, erythema, and hyperhidrosis
              • One third of infusion-related reactions occurred during the first infusion
              • Interrupt infusion if reaction occurs and institute appropriate medical management before continuing infusion at slower rate

              Drug interaction overview

              • Normalization of CYP450 activity
                • Formation of CYP450 enzymes may be suppressed by increased levels of cytokines (eg, INF-gamma) during chronic inflammation
                • By neutralizing IFN-gamma, emapalumab may normalize CYP450 activities and reduce the efficacy of drugs that are CYP450 substrates, owing to increased metabolism
                • Upon initiation or discontinuation of concomitant emapalumab, monitor for reduced efficacy and adjust dosage of CYP450 substrates as needed
              • Live vaccines
                • Do not administer live or live-attenuated vaccines while receiving emapalumab and for at least 4 wk after the last dose
                • Safety of immunization with live vaccines during or following emapalumab therapy has not been studied
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              Pregnancy

              Pregnancy

              Data are not available regarding human use during pregnancy

              Animal data

              • In an animal reproduction study, a murine surrogate antimouse IFN-gamma antibody administered to pregnant mice throughout gestation crossed the placental barrier, and no fetal harm was observed

              Lactation

              Data are not available regarding presence of emapalumab in human milk, effects on breastfed children, or 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

              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.

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              Pharmacology

              Mechanism of Action

              Human monoclonal antibody that binds to and neutralizes IFN-gamma

              Nonclinical data suggest that IFN-gamma plays a pivotal role in the pathogenesis of HLH by being hypersecreted

              Absorption

              Peak plasma concentration: 44 mcg/mL

              Trough concentration: 25 mcg/mL

              Steady-state: Achieved by 7th infusion

              Distribution

              Vd (wt 70 kg): 4.2 L (central); 5.6 L (peripheral)

              Metabolism

              Not characterized; like other protein therapeutics, expected to degrade into small peptides and amino acids via catabolic pathways

              Elimination

              Half-life: ~22 days (healthy volunteers); 2.5-18.9 days (HLH)

              Clearance: ~0.007 L/hr (healthy volunteers); significantly influenced by IFN-gamma production in patients

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              Administration

              IV Compatibilities

              0.9% NaCl

              IV Preparation

              Calculate dose (mg/kg) and total volume (mL) required and the number of vials needed based on patient actual body weight

              Inspect vials visually for particulate matter and discoloration prior to dilution; should appear as a clear to slightly opalescent, colorless to slightly yellow liquid; do not administer if discolored or foreign particulate matter present

              Withdraw calculated volume and dilute with 0.9% NaCl to a final concentration range of 0.25-2.5 mg/mL

              Discard any unused portion left in the vial(s)

              Diluted solution can be placed in either a syringe or an infusion bag, depending on the volume needed

              Use a gamma-irradiated, latex-free, PVC-free syringe; do not use with ethylene oxide-sterilized syringes

              Use non-PVC polyolefin infusion bag

              IV Administration

              For IV infusion only

              If refrigerated, allow diluted solution to come to room temperature before administration

              Administer diluted solution IV over 1 hr through an IV line containing a sterile, nonpyrogenic, low-protein-binding 0.2-micron in-line filter

              Do not infuse concomitantly with other agents and do not add any other product to the infusion bag or syringe

              Do not store any unused portion of the infusion solution for reuse

              Concomitant drugs and premedication

              • Dexamethasone: If not already taking dexamethasone, begin daily dose of at least 5-10 mg/m² the day before initiating emapalumab; patients already receiving baseline dexamethasone, continue regular dose provided if at least 5 mg/m²
              • Administer prophylaxis for herpes zoster, Pneumocystis jirovecii infection, and fungal infections before initiating emapalumab

              Storage

              Preservative-free product

              Unopened vials

              • Refrigerate at 2-8°C (36-46°F) in original carton to protect from light
              • Do not freeze
              • Do not shake

              Diluted solution

              • Refrigerate at 2-8°C (36-46°F) for up to 4 hr from time of dilution
              • Do not freeze
              • Do not shake
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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.