Emapalumab

Emapalumab is a prescription medication indicated for the treatment of:

• adult and pediatric (including newborn) patients with primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy
• adult and pediatric (including newborn) patients with HLH/macrophage activation syndrome (MAS) in known or suspected Still’s disease, including systemic Juvenile Idiopathic Arthritis (sJIA), with an inadequate response or intolerance to glucocorticoids, or with recurrent MAS
• Emapalumab is available under the following different brand names: Gamifant, emapalumab-lzsg

Common side effects of Emapalumab include:

• infections
• high blood pressure (hypertension)
• infusion-related reactions (rash, redness, and increased sweating)
• fever
• low blood potassium (hypokalemia)
• constipation
• abdominal pain
• cytomegalovirus infection
• diarrhea
• increased white blood cells
• cough
• irritability
• fast heart rate
• rapid/shallow breathing

Serious side effects of Emapalumab include:

• increased risk of infections, including tuberculosis, histoplasmosis, herpes zoster (shingles), and other infections caused by viruses, fungi, or bacteria
• symptoms of infusion reactions may include skin redness, itching, fever, rash, excessive sweating, headache, bone pain, chills, chest pain, shortness of breath, nausea or vomiting, lightheadedness or dizziness, tingling, burning, or numbness and cold hands, arms, legs or feet

Rare side effects of Emapalumab include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Solution for injection

• Single-dose vial
  • 5 mg/mL (10 mg/2 mL, 50 mg/10 mL, 100 mg/20 mL)
  • 25 mg/mL (50 mg/2 mL, 100 mg/4 mL, 250 mg/10 mL, 500 mg/20 mL)

Hemophagocytic lymphohistiocytosis

Adult dosage and pediatric dosage

• Initial: 1 mg/kg IV twice weekly (every 3-4 days)
  • Administer until hematopoietic stem cell transplantation (HSCT) performed or unacceptable toxicity; discontinue when patient no longer requires therapy for HLH
  • Subsequent doses may be increased based on clinical and laboratory criteria
• From Day 4 onward: Increase to 3 mg/kg IV
• From Day 7 onwards: Increase to 6 mg/kg IV
• From Day 10 onwards: Increase to 10 mg/kg IV, based on initial signs of response by clinician assessment that a further dose increase can be beneficial

See the following criteria for dose increases

Dose titration criteria for unsatisfactory improvement after initiation

• Platelet count
  • If baseline is less than 50,000/mm3 and no improvement to more than 50,000/mm3
  • If the baseline is more than 50,000/mm3 and less than 30% improvement
  • If baseline is more than 100,000/mm3 and decrease to less than 100,000/mm3
• Neutrophil count
  • If the baseline is less than 500/mm3 and no improvement to more than 500/mm3
  • If baseline is more than 500-1000/mm3 and decrease to less than 500/mm3
  • If baseline is 1000-1500/mm3 and decrease to less than 1000/mm3
• Ferritin
  • If baseline is 3000 ng/mL and more and less than 20% decrease
  • If the baseline is less than 3000 ng/mL and any increase to more than 3000 ng/mL
• Fibrinogen
  • If baseline levels are 100 mg/dL and less, and no improvement
  • If baseline levels are more than 100 mg/dL and any decrease to less than 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

HLH/Macrophage Activation Syndrome

Adult dosage

• Day 1: 6 mg/kg IV
• Days 4-16: 3 mg/kg IV every 3 days for 5 doses
• Day 19 onward: 3 mg/kg IV twice/week (i.e., every 3-4 days)
• Discontinue when the patient no longer requires therapy for HLH/MAS
• Dose titration criteria for unsatisfactory improvement after initiation
• May increase dose to a maximum cumulative dose of 10 mg/kg over 3 days, and
• May increase frequency to every 2 days or once daily
• After the clinical condition improves, consider decreasing dose to the previous level and assess whether clinical response is maintained
• If clinical condition is not stabilized while receiving the maximum dosage, consider discontinuing emapalumab

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• 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 weeks after the last dose
  • Safety of immunization with live vaccines during or following emapalumab therapy has not been studied

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Emapalumab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Emapalumab?"

Cautions

• Infections
  • May increase the risk for fatal and serious infections to include specific pathogens favored by interferon-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 tuberculosis (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 the dosage of CYP450 substrates as needed
  • Live vaccines
    • Do not administer live or live-attenuated vaccines while receiving emapalumab and for at least 4 weeks after the last dose
    • Safety of immunization with live vaccines during or following emapalumab therapy has not been studied

Pregnancy and Lactation

• Data are not available regarding human use during pregnancy
• Lactation
  • Data are not available regarding the presence of emapalumab in human milk, its effects on breastfed children, or 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