emapalumab (Rx)

Brand and Other Names:Gamifant, emapalumab-lzsg
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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

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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

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            Formulary

            FormularyPatient Discounts

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            • Compare formulary status to other drugs in the same class.
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            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.