Tagraxofusp, sold under the brand name Elzonris, is a medication used in the treatment of certain rare blood disorders. It is specifically approved for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adult and pediatric patients aged 2 years and older. BPDCN is a rare and aggressive blood cancer that primarily affects the bone marrow, blood, and skin.

Tagraxofusp is classified as a CD123-directed cytotoxin. CD123 is a cell surface protein that is overexpressed in BPDCN cells. Tagraxofusp binds to CD123 and delivers a cytotoxic agent directly to the cancer cells, which helps to kill them.

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:

• Before starting Tagraxofusp treatment, your serum albumin level in the blood should be at least 3.2 grams per deciliter (g/dL).
• Your healthcare provider will regularly check your serum albumin levels before each Tagraxofusp dose and as needed during treatment.
• Before each infusion of Tagraxofusp, you will receive premedication to help reduce the risk of side effects. This premedication includes:
  • An H1-antagonist, such as diphenhydramine.
  • An H2-antagonist, like ranitidine.
  • A corticosteroid, typically 50 milligrams of IV methylprednisolone or an equivalent medication.
  • Acetaminophen, which should be taken approximately 60 minutes before the Tagraxofusp infusion.

These precautions are important to ensure the safety and effectiveness of your Tagraxofusp treatment.

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

• Tagraxofusp is given through an intravenous (IV) infusion.
• The recommended dose is 12 micrograms (mcg) per kilogram of your body weight.
• It is administered once daily for 5 consecutive days as part of a 21-day treatment cycle.
• You continue this treatment until your disease progresses or you experience unacceptable side effects.
• If there are any delays in your treatment, you can extend the dosing period up to day 10 of the 21-day cycle.
• The first cycle of Tagraxofusp should be given in a hospital or inpatient setting.
• Patients should be observed for at least 24 hours after the last infusion in the first cycle.
• Subsequent cycles can be administered either inpatient or outpatient (if suitable), but close monitoring should be available.
• After each Tagraxofusp infusion in subsequent cycles, patients should be observed for a minimum of 4 hours to monitor for any immediate reactions or side effects.

Elzonris (Tagraxofusp) dose in Childrens

Elzonris (Tagraxofusp) dosage:

Note:

• Before starting treatment with Tagraxofusp, make sure that the patient's serum albumin level in the blood is at least 3.2 grams per deciliter (g/dL) and that their heart is working properly.
• The first cycle of Tagraxofusp doses should be given while the patient is in the hospital (inpatient setting).
• In the following treatment cycles, you can give Tagraxofusp either in the hospital (inpatient) or in an outpatient setting, but the outpatient facility must have the equipment to monitor patients with blood-related cancers.
• About 60 minutes before each Tagraxofusp infusion, the patient should receive premedication. This includes:
  • An H1-histamine antagonist like diphenhydramine.
  • An H2-histamine antagonist such as ranitidine.
  • A corticosteroid, usually administered intravenously (IV) like methylprednisolone.
  • Acetaminophen should also be given at this time.

These precautions help ensure the safety and effectiveness of Tagraxofusp treatment.

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

In pediatric patients, including children aged 2 years and older and adolescents:

• The medication is given through an intravenous (IV) infusion.
• The recommended dose is 12 micrograms (mcg) per kilogram of the child's body weight.
• It is administered once a day for 5 consecutive days as part of a 21-day treatment cycle.
• If there are any delays in treatment, you can extend the dosing period up to day 10 of the 21-day cycle.
• The treatment should continue until the disease gets worse (progression) or if the patient experiences severe side effects.

It's important to note that the approval for using Tagraxofusp in pediatric patients is based on limited experience, with the minimum reported age being 10 years as of the information available.

Dosing adjustment for toxicity:

• When treating children aged 2 years and older and adolescents with Tagraxofusp, it's important to monitor for certain side effects and adjust the treatment as needed, keeping in mind the limited data available for pediatric patients (minimum reported age: 10 years).
• Regularly monitor vital signs, including blood pressure (BP), heart rate (HR), body temperature, serum albumin levels, transaminases, and creatinine before preparing each Tagraxofusp dose.
• If the patient experiences significantly low or high systolic blood pressure (SBP), such as SBP ≤80 mm Hg or ≥160 mm Hg, therapy should be withheld until SBP returns to a more normal range (e.g., >80 mm Hg or <160 mm Hg).
• If the patient has a significantly low or high heart rate (HR), like HR ≤40 bpm or ≥130 bpm, withhold therapy until HR returns to a more normal range (e.g., >40 bpm or <130 bpm).
• If the patient's body temperature is ≥38°C, hold off on therapy until the body temperature falls below 38°C.
• In cases of hypersensitivity reactions:
  • For mild to moderate reactions, withhold therapy until the symptoms resolve, and then resume therapy at the same infusion rate.
  • For severe or life-threatening reactions, discontinue therapy permanently.
• In cases of Capillary Leak Syndrome (CLS):
  • If the patient's serum albumin drops below 3.5 g/dL, interrupt therapy. Administer intravenous (IV) albumin until serum albumin is raised to ≥3.5 g/dL and not more than 0.5 g/dL lower than the baseline albumin of the current cycle. Resume therapy upon resolution.
  • If there is a predose body weight increase (e.g., ≥1.5 kg in adult patients) over the previous day's predose weight, interrupt therapy. Administer IV albumin and manage fluid status until the body weight increases have resolved. Resume therapy upon resolution.
  • In cases of edema, fluid overload, and/or hypotension, interrupt therapy. Administer IV albumin until serum albumin is ≥3.5 g/dL, provide IV methylprednisolone (or equivalent), and aggressively manage fluid status and blood pressure as necessary. Resume therapy upon resolution.
• When resuming therapy, consider the following:
  • If hemodynamic instability did not require interventions to treat, you may resume with the same cycle.
  • If signs/symptoms of CLS are unresolved or interventions were required to treat hemodynamic instability (even if resolved), withhold therapy for the remainder of a cycle.
  • Therapy may resume with the next cycle if all CLS signs/symptoms have resolved, and the patient is hemodynamically stable.

Pergnancy Risk Category: C

• Animal studies on the effects of Tagraxofusp on reproduction have not been conducted.
• However, based on how Tagraxofusp works, it is possible that it could have adverse effects on the development of a fetus if a pregnant woman is exposed to it.
• Therefore, if a female of reproductive potential is considering Tagraxofusp treatment, her pregnancy status should be evaluated within 7 days before starting the therapy.
• Effective contraception methods should be used during the treatment with Tagraxofusp and for at least 1 week after the last dose of Tagraxofusp to prevent pregnancy. This is important to minimize the risk of harm to a developing fetus.

Use Tagraxofusp during breastfeeding  

• It is not known whether Tagraxofusp is present in breast milk.
• Because there is a potential for serious adverse reactions in a breastfed infant, the manufacturer does not recommend breastfeeding during the course of Tagraxofusp treatment and for at least 1 week after the last dose of Tagraxofusp.
• The safety of breastfeeding while using Tagraxofusp has not been established, and it's essential to prioritize the well-being of both the mother and the infant.
• Therefore, alternative feeding options should be considered during this period to ensure the infant's safety.

Elzonris (Tagraxofusp) dose in Renal Disease:

Assessing Kidney Function Before Starting Treatment

• Before beginning Tagraxofusp treatment, the doctor will check how well your kidneys are working. They do this by using a formula called the MDRD formula to estimate your kidney function.
• Your kidney function will be measured in something called eGFR, which stands for "estimated glomerular filtration rate."
• If your eGFR is between 30 and 89 mL/minute/1.73 m (a measure of kidney function), there's usually no need to adjust the Tagraxofusp dose. People with mild or moderate kidney problems didn't show big differences in how Tagraxofusp behaves in their bodies.
• If your eGFR is between 15 and 29 mL/minute/1.73 m, no specific dose adjustments are recommended, but this situation hasn't been studied thoroughly.

Dealing with Kidney Problems During Treatment

• While you're receiving Tagraxofusp, your doctor will keep an eye on your kidney health.
• If your blood test shows that your serum creatinine is higher than 1.8 mg/dL or your CrCl (another measure of kidney function) drops below 60 mL/minute, the doctor will stop the Tagraxofusp treatment for a while.
• The treatment will be put on hold until your serum creatinine goes back down to 1.8 mg/dL or your CrCl comes back up to 60 mL/minute. This is to make sure your kidneys are working well before continuing the treatment.

Elzonris (Tagraxofusp) Dose in Liver Disease:

Assessing Liver Function Before Starting Treatment

• Before beginning Tagraxofusp treatment, the doctor will check how well your liver is functioning.
• They will look at your total bilirubin levels and your AST levels. Total bilirubin is a substance your liver produces, and AST is an enzyme produced by the liver.
• If you have mild or moderate liver impairment, which means your total bilirubin levels are slightly elevated but not severely so, or if your total bilirubin is within the normal range but your AST is high, there's typically no need to adjust the Tagraxofusp dose. Studies have shown that people with mild or moderate liver problems didn't experience significant differences in how Tagraxofusp works in their bodies.
• If you have severe liver impairment, which means your total bilirubin levels are very high along with any level of AST elevation, there are no specific dosage adjustments recommended, but this situation hasn't been studied thoroughly.

Dealing with Liver Problems During Treatment

• While you're receiving Tagraxofusp, your doctor will also keep an eye on your liver health.
• If your blood tests show that your AST or ALT levels become more than five times higher than the upper limit of normal (ULN), the doctor will temporarily stop the Tagraxofusp treatment.
• They will only resume the treatment once your AST and/or ALT levels return to a level that is no more than 2.5 times the upper limit of normal. This is done to ensure your liver is functioning properly before continuing with the treatment.
• For reductions in serum albumin (another marker of liver function), refer to the dosage adjustment recommendations for dealing with toxicity.

(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):

According to the manufacturer's labeling, there are no specific contraindications (conditions or situations in which the use of a medication is not recommended) listed for Tagraxofusp.

Warnings and precautions

Capillary leak syndrome: [US-Boxed Warning]

• Capillary leak syndrome (CLS) is a serious and potentially life-threatening condition that can happen to people taking Tagraxofusp.
• In clinical trials, more than half of the patients experienced CLS, with some cases being less severe (grades 1 and 2) and others more severe (grades 3 and 4).
• CLS can cause symptoms like low levels of albumin in the blood, swelling, sudden weight gain, and low blood pressure.
• It's essential to make sure the heart is working well before starting Tagraxofusp, with serum albumin levels at or above 3.2 grams per deciliter.
• Doctors should keep a close eye on patients for signs of CLS, like weight gain, swelling, and low blood pressure, and provide appropriate medical care if needed to manage this condition.

Hepatotoxicity

• Hepatotoxicity, which means problems with the liver, is common when using Tagraxofusp.
• Nearly 90% of patients experience elevated liver enzymes called ALT and AST.
• About half of these cases are not very severe (grade 1 or 2), but around one-third of patients have more severe liver enzyme elevations (grade 3), and some have the most severe form (grade 4).
• To keep an eye on this, doctors will regularly check ALT and AST levels before each dose of Tagraxofusp.
• If needed, they may temporarily stop the treatment to manage these liver issues.

Hypersensitivity

• Hypersensitivity reactions, which are severe allergic responses, can happen when using Tagraxofusp.
• In clinical trials, almost half of the patients experienced these reactions, with 10% of them being quite severe (grade 3 or higher).
• These reactions can lead to symptoms like rash, itching, mouth sores, and wheezing.
• It's crucial for healthcare providers to watch for signs of hypersensitivity during Tagraxofusp treatment and be ready to temporarily pause the infusion or even stop it permanently if necessary.
• Supportive care will be given as needed to manage these reactions.

Tagraxofusp: Drug Interaction

Monitor:

Monitoring Before and During Tagraxofusp Treatment

• Lab Tests: Before each dose of Tagraxofusp, your healthcare provider will check your blood for levels of serum albumin, transaminases (like ALT and AST), and creatinine. These tests help them keep an eye on your kidney and liver function.
• Pregnancy Check: If you're a woman of reproductive age, your pregnancy status will be evaluated within 7 days before starting Tagraxofusp therapy. This is to make sure you're not pregnant before beginning treatment.
• Vital Signs: Before each dose, your healthcare provider will also check your vital signs, including your heart rate, blood pressure, and weight. These measurements help them monitor your overall health.

Watching for Specific Reactions: During Tagraxofusp treatment, you'll be monitored for signs and symptoms of three important potential side effects:

• Capillary Leak Syndrome: Look out for signs like swelling, sudden weight gain, low blood pressure, and breathing problems.
• Hepatotoxicity: Be alert to any symptoms related to liver problems, such as jaundice (yellowing of the skin or eyes) or stomach pain.
• Hypersensitivity Reactions: Pay attention to any allergic reactions like rash, itching, mouth sores, or difficulty breathing.

How to administer Elzonris (Tagraxofusp)?

• Equipment Setup: Use an infusion syringe pump for the Tagraxofusp dose and saline flush. Maintain IV access with sodium chloride 0.9%. Use a prepared/primed mini-bifuse Y-connector, infusion set, and 0.2 micron polyethersulfone inline filter.
• Tagraxofusp Dose: Insert the Tagraxofusp syringe into the syringe pump. Open the clamp on the Tagraxofusp side of the Y-connector and deliver the dose. Infuse it over a total time of 15 minutes.
• Saline Flush: After completing the Tagraxofusp infusion, remove it from the pump and replace it with the saline flush syringe. Open the clamp on the saline flush side of the Y-connector. Resume the infusion at the pre-specified flow rate to push any remaining Tagraxofusp out of the infusion line.
• Timing: Administer the infusion within 4 hours of preparation.

Premedication

• About 60 minutes before each Tagraxofusp infusion, premedicate the patient with the following medications:
  • An H1-antagonist.
  • An H2-antagonist.
  • A corticosteroid.
  • Acetaminophen.

Observation and Setting

• The first cycle of Tagraxofusp should be given in a hospital or inpatient setting.
• After the first cycle, subsequent cycles can be administered either inpatient or outpatient, but make sure that appropriate monitoring is available.
• Regardless of the setting, patients should be observed for a minimum of 4 hours following each Tagraxofusp infusion.
• For the first cycle, patients should be observed for at least 24 hours after the last infusion to monitor for any immediate reactions or side effects.

Mechanism of action Tagraxofusp (Elzonris):

• Tagraxofusp is a unique medication designed to target a specific protein called CD123.
• It's made up of two parts: human interleukin-3 (IL-3) and truncated diphtheria toxin (DT).
• When Tagraxofusp binds to CD123 on the surface of certain cells, it gets taken inside those cells.
• Once inside, it disrupts the cell's ability to make proteins, ultimately leading to the death of the cell.
• This mechanism of action helps in treating conditions where CD123 plays a role in the disease, such as certain blood disorders.

Distribution:

• The volume of distribution of Tagraxofusp is 5.1 liters in general.
• However, in patients who already have antibodies against the drug, the volume of distribution increases to 21.2 liters.
• This means that in patients with preexisting anti-drug antibodies, Tagraxofusp may be distributed more widely in the body.

Half-life elimination:

• The half-life of Tagraxofusp is relatively short at 0.7 hours.
• This means that it takes approximately 0.7 hours for half of the drug to be eliminated from the body.
• A short half-life suggests that the drug is cleared relatively quickly.

Excretion:

• The clearance of Tagraxofusp is 7.1 liters per hour in general.
• However, in patients with preexisting anti-drug antibodies, the clearance increases to 13.9 liters per hour.
• Clearance is a measure of how quickly the drug is removed from the bloodstream.
• In patients with preexisting antibodies, Tagraxofusp is cleared from the body at a faster rate.

International Brands of Tagraxofusp:

• Elzonris

Elzonris (Tagraxofusp) Brands in Pakistan:

Not available.