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 infusion syringe pump
- One empty 10 mL sterile vial
- 0.9% Sodium Chloride Injection, USP
- 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 to be used to flush the administration set once the ELZONRIS dose is delivered.
- Label the 0.9% Sodium Chloride Injection, USP flush syringe.
- Connect the 0.9% Sodium Chloride Injection, USP 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 0.9% Sodium Chloride Injection, USP flush syringe. Prime the Y-connector up to the intersection (do not prime the full infusion set with 0.9% Sodium Chloride Injection, USP). Re-clamp the Y-connector line on the 0.9% Sodium Chloride Injection, USP 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.
- 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 0.9% Sodium Chloride Injection, USP 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 0.9% Sodium Chloride Injection, USP flush syringe in the syringe pump.
- Open the clamp on the 0.9% Sodium Chloride Injection, USP 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.
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 53% (65/122), including Grade 1 or 2 in 43% (52/122) of patients, Grade 3 in 7% (8/122) of patients, Grade 4 in 1% (1/122) of patients, and four fatalities (3%) [see Adverse Reactions (6.1)]. The median time to onset was 4 days (range — 1 to 46 days), and all but 5 patients experienced an event in Cycle 1.
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 Dosage and Administration (2.2)].
5.2 Hypersensitivity Reactions
ELZONRIS can cause severe hypersensitivity reactions. In patients receiving ELZONRIS in clinical trials, hypersensitivity reactions were reported in 43% (53/122) of patients treated with ELZONRIS and were Grade ≥ 3 in 7% (9/122) [see Adverse Reactions (6.1)]. Manifestations of hypersensitivity reported in ≥ 5% of patients include rash, pruritus, and stomatitis. 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 Dosage and Administration (2.2)].
Treatment with ELZONRIS was associated with elevations in liver enzymes. In patients receiving ELZONRIS in clinical trials, elevations in ALT occurred in 79% (96/122) and elevations in AST occurred in 76% (93/122) [see Adverse Reactions (6.1)]. Grade 3 ALT elevations were reported in 26% (32/122) of patients. Grade 3 AST elevations were reported in 30% (36/122) and Grade 4 AST elevations were reported in 3% (4/122) of patients. Elevated liver enzymes occurred in the majority of patients in Cycle 1 and were reversible following dose interruption.
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 Dosage and Administration (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 122 adults with newly-diagnosed or relapsed/refractory myeloid malignancies, including 86 with BPDCN, treated with ELZONRIS 12 mcg/kg daily for 5 days of a 21-day cycle. The overall median number of cycles started was 2.5 (range, 1-76), and 4 in patients with BPDCN (range, 1-76).
Four (3%) patients (4/122) had fatal adverse reactions, all of which were related to capillary leak syndrome. Overall, 8% (10/122) of patients discontinued treatment with ELZONRIS due to an adverse reaction; the most common adverse reactions resulting in treatment discontinuation were hepatic toxicities, hypoalbuminemia and CLS (2% each).
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.
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).
|All Grades %||Grade ≥ 3 %|
|Capillary leak syndrome1||53||11|
|General disorders and administration site conditions|
|Nervous system disorders|
|Metabolism and nutrition disorders|
|Respiratory, thoracic and mediastinal disorders|
|Blood and lymphatic system disorders|
|Musculoskeletal and connective tissue disorders|
|Pain in extremity||10||2|
|Skin and subcutaneous tissue disorders|
Table 4 summarizes the clinically-important laboratory abnormalities that occurred in ≥ 10% patients with myeloid malignancies treated with ELZONRIS.
|Treatment-Emergent Laboratory Abnormalities|
|All Grades %||Grade ≥ 3 %|
|Alkaline phosphatase increase||22||1|
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