Emapalumab, sold under the brand name Gamifant, is a medication used for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) in pediatric and adult patients with refractory, recurrent, or progressive disease or intolerance to conventional HLH therapy. HLH is a life-threatening syndrome characterized by severe inflammation and tissue damage due to an overactive immune response. Emapalumab is a monoclonal antibody that works by blocking interferon gamma, a protein involved in the immune response, thereby reducing inflammation and preventing further tissue damage.

Emapalumab (Gamifant) is a fully human monoclonal immunoglobulin of the IgG-1 subtype that non-competitively inhibits Interferon Gamma. It is used in the treatment of primary hemophagocytic lymphohistiocytosis syndrome that is characterized by immune dysregulation and multiple organ dysfunction.

Emapalumab (Gamifant) Uses:

• Primary hemophagocytic lymphohistiocytosis:
  • Treatment of primary hemophagocytic lymphohistiocytosis (HLH) in adult and pediatric (newborn and older) patients with refractory, recurrent or progressive disease or intolerance to conventional HLH therapy.

Emapalumab Adult dose:

 Note:

• Emapalumab, also known as Gamifant, is a medication used to treat a severe and life-threatening condition called primary hemophagocytic lymphohistiocytosis (HLH), which involves harmful inflammation caused by an overactive immune system.
• Before starting emapalumab treatment, doctors should test for latent tuberculosis and assess the risk factors for tuberculosis.
• Throughout the treatment with emapalumab, patients should be monitored every two weeks for tuberculosis, adenovirus, Epstein-Barr virus, and cytomegalovirus, as well as for any clinical signs of concern.
• It's also important for patients to receive premedication before taking emapalumab, and the dosage should be determined based on their actual body weight.

Emapalumab (Gamifant) dose in Primary hemophagocytic lymphohistiocytosis:

• Initial Dose: Administered Intravenously (IV) at 1 mg/kg twice a week (every 3 or 4 days).
• Subsequent Doses: May be increased based on clinical and laboratory criteria. Once the clinical condition stabilizes, decrease the dose to the previous level to maintain the clinical response. Continue until hematopoietic stem cell transplantation (HSCT) or if there's unacceptable toxicity, discontinue when therapy is no longer required for HLH.

Dosage Modification:

• Treatment Day and Dose:
  • Day 1 (Initial Dose): 1 mg/kg
  • Day 3: May increase to 3 mg/kg if criteria for dose increase are met.
  • Day 6 and Beyond: Increase to 6 mg/kg if criteria for dose increase are met.
  • Day 9 and Beyond: Increase to 10 mg/kg if assessment by the healthcare provider indicates further increase may be beneficial based on initial signs of response.
• Criteria for Dose Increase: Unsatisfactory improvement in clinical condition (assessed by healthcare provider) AND meeting specific criteria related to fever, platelets, neutrophils, ferritin, splenomegaly, and coagulopathy.

Premedication and Concomitant Therapy:

• Administer prophylaxis for herpes zoster, pneumocystis jirovecii, and fungal infections before emapalumab administration.
• Administer tuberculosis prophylaxis to patients at risk for tuberculosis or those with a positive PPD test result or a positive IFNγ release assay.
• For patients not receiving baseline dexamethasone treatment, start dexamethasone at a dose of at least 5 to 10 mg/m²/day one day before initiating emapalumab.
• For patients receiving baseline dexamethasone, continue regular dexamethasone dose, at least 5 mg/m²/day. Dexamethasone may be tapered according to clinical judgment.

Emapalumab Dose in children:

 Note:

• Tuberculosis screening should be completed before emapalumab therapy.
• The dose has to be based on actual body weight.

Emapalumab (Gamifant) Dose in the treatment of Primary Hemophagocytic Lymphohistiocytosis (HLH):

For Infants, Children, and Adolescents:

• Initial Dose: Intravenous (IV) administration at 1 mg/kg/dose twice weekly (every 3 to 4 days).
• Subsequent Doses: May increase based on clinical and laboratory criteria. Upon stabilization of the clinical condition, decrease the dose to the previous level to maintain the clinical response. Continue until hematopoietic stem cell transplantation (HSCT) or if there's unacceptable toxicity, discontinue when therapy is no longer required for HLH.

Dose Modification:

• Titration Protocol: If there's an inadequate response (see Criteria for Dose Increase), titrate the dose as follows:
  • Day 3: May increase dose to 3 mg/kg/dose if criteria for dose increase are met.
  • Day 6 and Beyond: May increase dose to 6 mg/kg/dose if criteria for dose increase are met.
  • Day 9 and Beyond: May increase dose to 10 mg/kg/dose if assessment by the healthcare provider indicates further increase may be beneficial based on initial signs of response.
• Criteria for Dose Increase: Inadequate response as determined by healthcare provider assessment and meeting specific criteria related to fever, platelets, neutrophils, ferritin, splenomegaly, and coagulopathy.

Premedication and Concomitant Therapy:

• Administer prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infections before emapalumab administration.
• Administer tuberculosis prophylaxis to patients at risk for tuberculosis or those with a positive purified protein derivative (PPD) test result or a positive interferon gamma (IFNγ) release assay.
• If the patient is not receiving baseline dexamethasone treatment (≥5 mg/m²/day), begin dexamethasone at a dose of at least 5 to 10 mg/m²/day one day before initiating emapalumab.
• For patients receiving baseline dexamethasone, continue the regular dexamethasone dose, as long as the dose is at least 5 mg/m²/day. Dexamethasone may be tapered according to clinical judgment.

Pregnancy Risk Category: N (Not assigned)

• No harmful effects were seen in studies where animals were given the medicine during pregnancy or breeding, suggesting that the medication didn't cause any problems for the animals or their offspring.

Emapalumab use during breastfeeding:

• It's uncertain whether emapalumab is found in breast milk.
• The manufacturer suggests that if a mother is considering breastfeeding while undergoing emapalumab therapy, she should weigh the potential risk of exposing her infant to the medication against the benefits of breastfeeding for the baby, as well as the benefits of the treatment for herself.

Emapalumab (Gamifant) Dose in Kidney disease:

• The manufacturer's labeling does not include any specific adjustments to the dosage of emapalumab.
• However, studies have shown that even in individuals with renal impairment, including those undergoing dialysis, emapalumab's pharmacokinetics - how the body processes the medication - were not significantly affected in a clinically meaningful way.
• This suggests that no dosage adjustments are necessary for individuals with renal impairment.

Emapalumab (Gamifant) Dose in Liver disease:

• The manufacturer's labeling does not recommend any dosage adjustments for emapalumab based on hepatic impairment.
• Studies have shown that emapalumab's pharmacokinetics, or how the body processes the medication, were not significantly affected by mild, moderate, or severe hepatic impairment in a way that would require dosage adjustments.
• Therefore, individuals with hepatic impairment do not need their emapalumab dosage adjusted based on their liver function.

Common Side Effects of Emapalumab (Gamifant):

• Cardiovascular:
  • Hypertension
  • tachycardia
• Central nervous system:
  • Irritability
• Dermatologic:
  • Skin rash
• Endocrine & metabolic:
  • Hypokalemia
• Gastrointestinal:
  • Appendicitis
  • constipation
  • abdominal pain
  • diarrhea
• Hematologic & oncologic:
  • Lymphocytosis
• Infection:
  • Infection
  • viral infection
  • bacterial infection
  • bacteremia
  • histoplasmosis
  • necrotizing fasciitis
  • sepsis
  • cytomegalovirus disease
• Respiratory:
  • Pneumonia
  • cough
  • tachypnea
• Miscellaneous:
  • Infusion related reaction
  • fever

Less Common Side Effects of Emapalumab (Gamifant):

• Cardiovascular:
  • Bradycardia
  • peripheral edema
• Gastrointestinal:
  • Gastrointestinal hemorrhage
  • vomiting
• Immunologic:
  • Antibody development
• Infection:
  • Fungal infection
• Neuromuscular & skeletal:
  • Asthenia
• Renal:
  • Acute renal failure
• Respiratory:
  • Dyspnea
  • epistaxis
• Miscellaneous:
  • Multi-organ failure

Contraindications to Emapalumab (Gamifant):

• The manufacturer's labeling does not list any specific contraindications for emapalumab.
• This means there are no absolute reasons why someone should not use this medication based on specific medical conditions or circumstances.

Warnings and precautions

Infection

• Infections are quite common when taking emapalumab.
• This medication can increase the risk of serious and even life-threatening infections caused by specific germs like mycobacteria, herpes zoster virus, and Histoplasma capsulatum.
• It's important not to give emapalumab to patients who already have infections caused by these germs until they've started the right treatment.
• In clinical trials, about one-third of patients who received emapalumab experienced serious infections like pneumonia, blood infections, and others.
• These infections were mostly viral or bacterial, but some were fungal or caused by germs that weren't identified.
• Before starting emapalumab, doctors should check for tuberculosis risk factors and test for hidden infections using methods like PPD testing or PCR.
• Patients at risk for tuberculosis or those with a positive PPD test should get preventive treatment.
• To lower the risk of infections, patients should also get preventive treatment for herpes zoster, pneumocystis jirovecii, and fungal infections while taking emapalumab.
• Doctors should keep a close watch for any signs or symptoms of infection and start the right tests and treatments promptly if needed.

Infusion reactions

• Infusion reactions, like drug eruption, fever, rash, redness, and sweating, have been reported in more than a quarter of patients who received emapalumab.
• About one-third of these reactions happened during the first infusion.
• These reactions were usually mild to moderate.
• It's important to keep an eye out for any infusion-related reactions during treatment.
• If a reaction happens, the infusion should be stopped temporarily and managed properly.
• After that, the infusion can continue at a slower rate.

Emapalumab: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Monitoring for Clinical Improvement:

• Keep track of platelet counts, neutrophil counts, ferritin levels, D-dimer, and fibrinogen levels.
• Monitor for fever and signs/symptoms of splenomegaly.

Evaluation and Testing Before Emapalumab:

• Evaluate for tuberculosis risk factors before starting emapalumab.
• Test for latent infection using purified protein derivative (PPD) testing, PCR, or IFNγ release assay.
• Regularly monitor for tuberculosis, adenovirus, Epstein-Barr virus, and cytomegalovirus during emapalumab treatment, typically every 2 weeks or as clinically indicated.
• Conduct surveillance testing for herpes zoster, pneumocystis jirovecii, and fungal infections throughout the treatment period.

Monitoring for Signs of Infection:

• Watch closely for any signs or symptoms of infection.
• If an infection is suspected, promptly start a complete diagnostic workup suitable for someone with a weakened immune system.

Monitoring for Infusion-Related Reactions:

• Keep an eye out for any signs of infusion-related reactions, such as drug eruption, fever, rash, redness, or sweating.
• If a reaction occurs, temporarily stop the infusion and manage it appropriately before continuing at a slower rate.

How to administer Emapalumab (Gamifant)?

Administration via Intravenous (IV) Infusion:

• Administer emapalumab intravenously over a period of 1 hour.
• Use an IV line with a sterile, non-pyrogenic, low-protein binding 0.2 micron inline filter.
• Do not shake the solution.
• Allow the solution to reach room temperature before infusion.
• Do not mix emapalumab with other medications during infusion.

Managing Infusion Reactions:

• If an infusion reaction happens, pause the infusion immediately.
• Manage the reaction appropriately based on its severity and symptoms.
• After managing the reaction, the infusion can continue, but at a reduced rate.

Mechanism of action of Emapalumab (Gamifant):

• Emapalumab is a type of medicine called a monoclonal antibody that works by blocking a protein in the body called interferon gamma (IFNγ).
• In conditions like hemophagocytic lymphohistiocytosis (HLH), there's too much IFNγ being produced.
• Emapalumab attaches to IFNγ and stops it from working properly, which helps to reduce the harmful effects associated with its overproduction in HLH.

Distribution:

• In a 70 kg patient, the distribution volume (V) is approximately 4.2 L for the central compartment and 5.6 L for the peripheral compartment.

Metabolism:

• Emapalumab is broken down into smaller peptides and amino acids through catabolic pathways.

Half-life elimination:

• In healthy individuals, the half-life of emapalumab is around 22 days.
• However, in patients with hemophagocytic lymphohistiocytosis (HLH), the half-life can range from 2.5 to 18.9 days, indicating variability in elimination rates among individuals with this condition.

International Brand Names of Emapalumab:

• Gamifant

Emapalumab Brand Names in Pakistan:

• No Brands are Available in Pakistan.