Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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)
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
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
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.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
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
Images
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
