Elzonris (Tagraxofusp) is a CD - 123 directed fusion protein that inhibits protein synthesis in the target cells. It is used to treat blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and children more than 2 years of age.

Elzonris (Tagraxofusp) dose in Adults

Elzonris (Tagraxofusp) dosage:

Note:

• Premedicate the patient one hour prior to each infusion with diphenhydramine, ranitidine, 50 mg intravenous methylprednisolone or equivalent, and acetaminophen.
• Monitor serum albumin prior to the infusion. It should be kept above 3.2 gms/dl to avoid the risks of capillary leak syndrome.

Elzonris (Tagraxofusp) dose in the treatment of Blastic plasmacytoid dendritic cell neoplasm:

• 12 mcg/kg intravenous once a day on days 1 - 5 of a 21-day cycle.
• Treatment should be continued until toxicity develops or the disease progresses despite treatment.
• The first cycle should be administered within the hospital and the patient should be monitored for at least 24 hours following the infusion.
• The subsequent doses may be administered as inpatient or outpatient but in settings where appropriate monitoring can be done for at least 4 hours after each infusion.

Elzonris (Tagraxofusp) dose in Childrens

Elzonris (Tagraxofusp) dosage:

Note:

• Premedicate the patient one hour prior to each infusion with diphenhydramine, ranitidine, intravenous methylprednisolone or equivalent, and acetaminophen.
• Monitor serum albumin prior to the infusion. It should be kept above 3.2 gms/dl to avoid the risks of capillary leak syndrome.

Dose in the treatment of Blastic plasmacytoid dendritic cell neoplasm (BPDCN):

• Children older than 2 years and Adolescents:
  • 12 mcg/kg/dose intravenously once a day on days 1 - 5 of a 21-day cycle.
  • The dosing period may be extended to delays up to day 10 of the 21-day cycle.
  • Treatment must be continued until unacceptable toxicity or disease progression.

Dosing adjustment for toxicity:

• Children older than 2 years and Adolescents:
  • Data is scant regarding its use in the pediatric population.
  • The patient should be properly monitored prior to each dose. Vital signs, serum albumin, transaminases, and creatinine should be checked prior to each dose.
  • Treatment must be withheld in patients with very high or low blood pressures (systolic blood pressure of more than 160 mmHg or diastolic blood pressure of less than 80 mmHg).
  • Likewise, treatment must also be withheld in patients with a heart rate of less than 40 bpm or more than 130 bpm or when the body temperature is greater than 38°C

• Hypersensitivity reactions:

  • For Mild to moderate hypersensitivity reactions, treatment must be withheld until the resolution of the symptoms.
  • Treatment must be permanently discontinued in patients with severe or life-threatening hypersensitivity reactions.

• Capillary leak syndrome (CLS):

  • Serum albumin of less than 3.5 g/dL:

    • Interrupt the treatment.
    • The serum albumin may need to be corrected with albumin infusions until the levels are above 3.5 gms/dl.

  • An increase in body weight of 1.5 Kgs or more over the previous days' predose weight:

    • Treatment must not be resumed until the fluid overload status is managed with albumin infusion and diuretics.

  • Edema, fluid overload and/or hypotension:

    • Treatment must be interrupted and the patient should be treated with albumin infusions until the levels reach 3.5 gms/dl or more.
    • The fluid status should be aggressively managed and methylprednisolone should be administered intravenously to patients with hypotension.

Pergnancy Risk Category: C

• Although no studies have been done, it is possible that in utero exposure could lead to adverse outcomes for fetal health.
• Studies on animal reproduction have not been done. In utero tagraxofusp exposure can have adverse effects on fetal development, according to the mechanism of action.
• Before therapy initiation for females with reproductive potential, it is important to evaluate your pregnancy status. 
• Effective contraception must be used throughout treatment and at least one week following the last dose of tagraxofusp.

Use Tagraxofusp during breastfeeding  

• It is unknown if the drug will be excreted into breastmilk.
• The manufacturer recommends that breastfeeding be stopped for at least one week after the last dose of tagraxofusp.

Elzonris (Tagraxofusp) dose in Renal Disease:

Renal impairment before treatment initiation: 

• eGFR 30 - 89 mL/minute/1.73 m² :

  • The manufacturer has not recommended any adjustment in the dose, however, dose adjustment is not necessary for patients with mild to moderate renal impairment.

• eGFR 15 - 29 mL/minute/1.73 m :

  • The manufacturer has not recommended any adjustment in the dose as it has not been studied in these patients.

Renal toxicity during treatment:

• Serum creatinine more than 1.8 mg/dL or CrCl less than 60 mL/minute:

  • The treatment should be withheld until the serum creatinine is 1.8 mg/dl or less or the CrCl is 60 ml/min or more.

Elzonris (Tagraxofusp) dose in Liver Disease:

Hepatic impairment prior to therapy initiation:

• Mild (total bilirubin ≤ ULN and AST >ULN or total bilirubin 1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment:

  • The manufacturer has not recommended any adjustment in the dose, however, dose adjustment is not necessary for patients with mild to moderate hepatic impairment.

• Severe hepatic impairment (total bilirubin more than 3 times the ULN and any AST):

  • The manufacturer has not recommended any adjustments in the dose.

Hepatotoxicity during treatment:

• AST or ALT greater than 5 times the ULN:

  • Withhold tagraxofusp until AST and ALT are 2.5 times the ULN or less.

(Tagraxofusp) Elzonris side Effects (common):

• Cardiovascular:

  • Capillary Leak Syndrome
  • Peripheral Edema
  • Hypotension
  • Tachycardia
  • Hypertension

• Central Nervous System:

  • Fatigue
  • Chills
  • Headache
  • Dizziness
  • Insomnia
  • Anxiety
  • Confusion

• Endocrine & Metabolic:

  • Increased Serum Glucose
  • Decreased Serum Albumin
  • Decreased Serum Calcium
  • Decreased Serum Sodium
  • Decreased Serum Potassium
  • Weight Gain
  • Decreased Serum Phosphate
  • Increased Serum Potassium
  • Decreased Serum Magnesium
  • Hypermagnesemia
  • Decreased Serum Glucose

• Gastrointestinal:

  • Nausea
  • Decreased Appetite
  • Constipation
  • Vomiting
  • Diarrhea

• Hematologic & Oncologic:

  • Decreased Platelet Count
  • Decreased Hemoglobin
  • Decreased Neutrophils
  • Febrile Neutropenia

• Hepatic:

  • Increased Liver Enzymes
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Alkaline Phosphatase
  • Increased Serum Bilirubin

• Hypersensitivity:

  • Hypersensitivity Reaction

• Immunologic:

  • Antibody Development

• Neuromuscular & Skeletal:

  • Back Pain

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Dyspnea
  • Cough
  • Epistaxis
  • Oropharyngeal Pain

• Miscellaneous:

  • Fever

(Tagraxofusp) Elzonris side Effects (less common):

• Dermatologic:

  • Pruritus
  • Skin Rash

• Endocrine & Metabolic:

  • Increased Serum Sodium

• Gastrointestinal:

  • Stomatitis

• Genitourinary:

  • Hematuria

• Hematologic & Oncologic:

  • Petechia

• Neuromuscular & Skeletal:

  • Limb Pain

• Respiratory:

  • Wheezing

Contraindication to Tagraxofusp (Elzonris contraindications):

The manufacturer has not provided any information about contraindications to the drug.

Warnings and precautions

• Capillary leak syndrome: [US-Boxed Warning]
  • Capillary leak syndrome can be fatal or life-threatening and patients should be closely monitored.
  • Capillary leak syndrome monitoring parameters include weight gain, hypotension, edema and hypoalbuminemia.
  • Before the infusion, patients should have adequate cardiac function.
  • In particular, before the first dose Elzonris (tagraxofusp), albumin levels should not exceed 3.2 gm/dl. Patients should also be regularly monitored for any changes.
  • Capillary leak syndrome can be diagnosed in patients who experience weight gain, pulmonary or worsening swelling, hemodynamic instability, and edema.
• Hepatotoxicity
  • Up to 90% of patients experience an increase in liver enzymes.
  • Up to half of patients experience mild liver enzyme elevations, while up to one third may suffer from severe hepatotoxicity.
  • Before each infusion, patients should have their liver enzymes checked. The treatment may need to be stopped.
• Hypersensitivity
  • It is possible to have severe allergic reactions.
  • As many as half of patients experience an allergic reaction. This can be serious in 10%.
  • Itching, rash and stomatitis are all possible allergic reactions.
  • For patients who have severe allergic reactions, it may be necessary to interrupt treatment.
  • If severe reactions occur, patients should be treated with support.

Tagraxofusp: Drug Interaction

Monitor:

• Prior to each dose:
  • Heart rate, Blood pressure, and weight
  • Serum albumin
  • Transaminases, and
  • creatinine
• Pregnancy status should be evaluated in females of reproductive potential within 7 days prior to initiating tagraxofusp therapy.
• monitor for clinical features of hepatotoxicity,  hypersensitivity reaction, and capillary leak syndrome.

How to administer Elzonris (Tagraxofusp)?

• The infusion should take place via an infusion pump for 15 minutes, followed by a 0.9% sodium flush.
• To infuse the drug, you should use the primed mini-bifuse connector, infusion set and 0.2-micron Polyethersulfone Inline Filter.
• Place the tagraxofusp Syringe in the syringe Pump, and then open the clamp on either side of the Y connector.
• After the infusion of tagraxofusp has been completed, take it out of the pump and insert the saline flush needle in the pump.
• To push the remaining dose of tagraxofusp out of the infusion line, open the clamp on the saline flush end of the Y connector.
• Within 4 hours of preparation, administer. One hour before the infusion, prepare the patient with an H1 or H2 antagonist, acetaminophen and a corticosteroid.
• The patient should be admitted to a hospital for the first infusion. They should also be closely monitored for 24 hours following the end of the infusion.
• The patient must be monitored for at least 4 hours after the infusion.

(Elzonris) Tagraxofusp mechanism of action:

• Tagraxofusp, also known as Elzonris, is a CD123-directed CD123-directed protein fusion. 
• It is made up of human interleukin-3 and truncated diphtheria xin.
• After binding to CD123, Elzonris (Tagraxofusp) is internalized. 
• It blocks protein synthesis in target cells, ultimately leading to cell death.

Eliminating half-life The average time of taking the drug is 0.7 hours.

International Brands of Tagraxofusp:

• Elzonris

Elzonris (Tagraxofusp) Brands in Pakistan:

No Brands Available in Pakistan.