Elzonris (Page 2 of 5)

2.3 Preparation for Administration

Assure the following components required for dose preparation and administration are available prior to thawing ELZONRIS:

  • One empty 10 mL sterile vial
  • 0.9% Sodium Chloride Injection, USP (sterile saline)
  • Three 10 mL sterile syringes
  • One 1 mL sterile syringe
  • One mini-bifuse Y-connector
  • Microbore tubing
  • One 0.2 micron polyethersulfone in-line filter
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Thawed ELZONRIS appearance should be a clear, colorless liquid that may contain a few white to translucent particles.
  • Prior to dose preparation thaw at room temperature, between 15°C and 25°C (59°F and 77°F), for 15 to 30 minutes in original carton, and verify thaw visually. Thawed vials may be held at room temperature for approximately 1 hour prior to dosage preparation. Do not force thaw. Do not refreeze vial once thawed.
  • Use aseptic technique for preparation of the ELZONRIS dose.
  • A 2-step process is required for preparation of the final ELZONRIS dose:
    Step 1 — Prepare 10 mL of 100 mcg/mL ELZONRIS
    Using a sterile 10 mL syringe, transfer 9 mL of 0.9% Sodium Chloride Injection, USP to an empty sterile 10 mL vial.
    Gently swirl the ELZONRIS vial to mix the contents, remove the cap, and using a sterile 1 mL syringe, withdraw 1 mL of thawed ELZONRIS from the product vial.
    Transfer the 1 mL of ELZONRIS into the 10 mL vial containing the 0.9% Sodium Chloride Injection. Gently invert the vial at least 3 times to mix the contents. Do not shake vigorously.
    Following dilution the final concentration of ELZONRIS is 100 mcg/mL.
    Step 2 – Prepare the ELZONRIS infusion set.
    Calculate the required volume of diluted ELZONRIS (100 mcg/mL) according to patient’s weight.
    Draw up the required volume into a new syringe (if more than 10 mL of diluted ELZONRIS (100 mcg/mL) is required for the calculated patient dose, repeat step 1 with a second vial of ELZONRIS). Label the ELZONRIS syringe.
    Prepare a separate syringe with at least 3 mL of 0.9% Sodium Chloride Injection, USP (saline flush) to be used to flush the administration set once the ELZONRIS dose is delivered.
    Label the saline flush syringe.
    Connect the saline flush syringe to one arm of the Y-connector and ensure the clamp is closed.
    Connect the product syringe to the other arm of the Y-connector and ensure the clamp is closed.
    Connect the terminal end of the Y-connector to the microbore tubing.
    Remove the cap from the supply side of the 0.2 micron filter and attach it to the terminal end of the microbore tubing.
    Unclamp the arm of the Y-connector connected to the saline flush syringe. Prime the Y-connector up to the intersection (do not prime the full infusion set with saline). Re-clamp the Y-connector line on the saline flush arm.
    Remove the cap on the terminal end of the 0.2 micron filter and set it aside. Unclamp the arm of the Y-connector connected to the product syringe, and prime the entire infusion set, including the filter. Recap the filter, and re-clamp the Y-connector line on the product side. The infusion set is now ready for delivery for dose administration.
  • Administer ELZONRIS within 4 hours. During this 4-hour window, the prepared dose should remain at room temperature.
  • Do not reuse excess ELZONRIS. Any excess material should be thrown away immediately following infusion.

2.4 Administration

  • Establish venous access and maintain with sterile 0.9% Sodium Chloride Injection, USP.
  • Administer the prepared ELZONRIS dose via infusion syringe pump over 15 minutes. The total infusion time will be controlled using a syringe pump to deliver the entire dose and the saline flush over 15 minutes.
  • Insert the ELZONRIS syringe into the syringe pump, open the clamp on the ELZONRIS side of the Y-connector and deliver the prepared ELZONRIS dose.
  • Once the ELZONRIS syringe has been emptied, remove it from the pump and place the saline flush syringe in the syringe pump.
  • Open the clamp on the saline flush side of the Y-connector and resume infusion via the syringe pump at the pre-specified flow to push remaining ELZONRIS dose out of the infusion line to complete delivery.

3 DOSAGE FORMS AND STRENGTHS

Injection: 1,000 mcg in 1 mL clear colorless solution in a single-dose vial.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Capillary Leak Syndrome

Capillary leak syndrome (CLS), including life-threatening and fatal cases, has been reported among patients treated with ELZONRIS. In patients receiving ELZONRIS in clinical trials, the overall incidence of CLS was 55% (52/94), including Grade 1 or 2 in 46% (43/94), Grade 3 in 6% (6/94), Grade 4 in 1% (1/94) and 2 fatal events (2/94, 2%). Common signs and symptoms (incidence ≥ 20%) associated with CLS that were reported during treatment with ELZONRIS include hypoalbuminemia, edema, weight gain, and hypotension.

Before initiating therapy with ELZONRIS, ensure that the patient has adequate cardiac function and serum albumin is greater than or equal to 3.2 g/dL. During treatment with ELZONRIS, monitor serum albumin levels prior to the initiation of each dose of ELZONRIS and as indicated clinically thereafter, and assess patients for other signs or symptoms of CLS, including weight gain, new onset or worsening edema, including pulmonary edema, hypotension or hemodynamic instability [see Dose Modifications (2.2)].

5.2 Hypersensitivity Reactions

ELZONRIS can cause severe hypersensitivity reactions. In patients receiving ELZONRIS in clinical trials, hypersensitivity reactions were reported in 46% (43/94) of patients treated with ELZONRIS and were Grade ≥ 3 in 10% (9/94). Manifestations of hypersensitivity reported in ≥ 5% of patients include rash, pruritus, stomatitis, and wheezing. Monitor patients for hypersensitivity reactions during treatment with ELZONRIS. Interrupt ELZONRIS infusion and provide supportive care as needed if a hypersensitivity reaction should occur [see Dose Modifications (2.2)].

5.3 Hepatotoxicity

Treatment with ELZONRIS was associated with elevations in liver enzymes. In patients receiving ELZONRIS in clinical trials, elevations in liver enzymes occurred in 88% (83/94) of patients, including Grade 1 or 2 in 48% (45/94), Grade 3 in 36% (34/94), and Grade 4 in 4% (4/94). Monitor alanine aminotransferase (ALT) and aspartate aminotransferase (AST) prior to each infusion with ELZONRIS. Withhold ELZONRIS temporarily if the transaminases rise to greater than 5 times the upper limit of normal and resume treatment upon normalization or when resolved [see Dose Modifications (2.2)].

6 ADVERSE REACTIONS

The following serious adverse drug reactions are described elsewhere in the labeling:

  • Capillary Leak Syndrome [see Warnings and Precautions (5.1) ]
  • Hypersensitivity Reactions [see Warnings and Precautions (5.2) ]
  • Hepatotoxicity [see Warnings and Precautions (5.3) ]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Safety of ELZONRIS was assessed in a single-arm clinical trial that included 94 adults with newly-diagnosed or relapsed/refractory myeloid malignancies, including 58 with BPDCN, treated with ELZONRIS 12 mcg/kg daily for 5 days of a 21-day cycle. The overall median number of cycles administered was 2 (range, 1-43), and 4 in patients with BPDCN (range, 1-43).

Two (2%) patients had fatal adverse reaction, both capillary leak syndrome. Overall, 10 (11%) patients discontinued treatment with ELZONRIS due to an adverse reaction; the most common adverse reactions resulting in treatment discontinuation were hepatic toxicities and CLS.

Table 3 summarizes the common (≥ 10%) adverse reactions with ELZONRIS in patients with myeloid malignancies. The rate of any given adverse reaction or lab abnormality was derived from all the reported events of that type.

Table 3. Adverse Reactions in ≥ 10% of Patients Receiving 12 mcg/kg of ELZONRIS

1 Capillary leak syndrome defined as any event reported as CLS during treatment with ELZONRIS or the occurrence of at least 2 of the following CLS manifestations within 7 days of each other: hypoalbuminemia (including albumin value less than 3.0 g/dL), edema (including weight increase of 5 kg or more), hypotension (including systolic blood pressure less than 90 mmHg).

N=94
All Grades % Grade ≥ 3 %
Vascular disorders
Capillary leak syndrome1 55 9
Hypotension 29 9
Hypertension 15 6
Gastrointestinal disorders
Nausea 49 0
Constipation 23 0
Vomiting 21 0
Diarrhea 20 0
General disorders and administration site conditions
Fatigue 45 7
Peripheral edema 43 1
Pyrexia 43 0
Chills 29 1
Investigations
Weight increase 31 0
Nervous system disorders
Headache 29 0
Dizziness 20 0
Metabolism and nutrition disorders
Decreased appetite 24 0
Blood and lymphatic system disorders
Febrile neutropenia 20 18
Musculoskeletal and connective tissue disorders
Back pain 20 2
Pain in extremity 10 2
Respiratory, thoracic and mediastinal disorders
Dyspnea 19 2
Cough 14 0
Epistaxis 14 1
Oropharyngeal pain 12 0
Psychiatric disorders
Insomnia 17 0
Anxiety 15 0
Confusional state 11 0
Cardiac disorders
Tachycardia 17 0
Skin and subcutaneous tissue disorders
Petechiae 10 0
Pruritus 10 0
Renal and urinary disorders
Hematuria 10 0

Table 4 summarizes the clinically-important laboratory abnormalities that occurred in ≥ 10% patients with myeloid malignancies treated with ELZONRIS.

Table 4. Selected Laboratory Abnormalities in Patients Receiving 12 mcg/kg of ELZONRIS
Treatment-Emergent Laboratory Abnormalities
All Grades % Grade ≥ 3 %
Hematology
Platelets decrease 67 53
Hemoglobin decrease 60 35
Neutrophils decrease 37 31
Chemistry
Glucose increase 87 20
ALT increase 82 30
AST increase 79 37
Albumin decrease 77 0
Calcium decrease 57 2
Sodium decrease 50 10
Potassium decrease 39 4
Phosphate decrease 30 11
Creatinine increase 27 0
Alkaline phosphatase increase 26 1
Potassium increase 21 2
Magnesium decrease 20 0
Magnesium increase 14 3
Bilirubin increase 14 0
Glucose decrease 11 0
Sodium increase 10 0

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