ZYNLONTA- loncastuximab tesirine injection, powder, lyophilized, for solution
ADC Therapeutics America, Inc.
ZYNLONTA is indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma.
This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
ZYNLONTA as an intravenous infusion administered over 30 minutes on Day 1 of each cycle (every 3 weeks). Administer intravenous infusion as follows:
- 0.15 mg/kg every 3 weeks for 2 cycles.
- 0.075 mg/kg every 3 weeks for subsequent cycles.
Unless contraindicated, administer dexamethasone 4 mg orally or intravenously twice daily for 3 days beginning the day before administering ZYNLONTA. If dexamethasone administration does not begin the day before ZYNLONTA, dexamethasone should begin at least 2 hours prior to administration of ZYNLONTA.
|Adverse Reactions||Severity *||Dosage Modification|
|Hematologic Adverse Reactions|
|Neutropenia [see Warnings and Precautions (5.2)]||Absolute neutrophil count less than 1 × 109 /L||Withhold ZYNLONTA until neutrophil counts returns to 1 × 109 /L or higher|
|Thrombocytopenia [see Warnings and Precautions (5.2)]||Platelet count less than 50,000/mcL||Withhold ZYNLONTA until platelet count returns to 50,000/mcL or higher|
|Nonhematologic Adverse Reactions|
|Edema or Effusion [see Warnings and Precautions (5.1)]||Grade 2* or higher||Withhold ZYNLONTA until the toxicity resolves to Grade 1 or less|
|Other Adverse Reactions [see Warnings and Precautions (5.3), (5.4), Adverse Reactions (6.1)]||Grade 3* or higher||Withhold ZYNLONTA until the toxicity resolves to Grade 1 or less|
If dosing is delayed by more than 3 weeks due to toxicity related to ZYNLONTA, reduce subsequent doses by 50%. If toxicity reoccurs following dose reduction, consider discontinuation.
Note: If toxicity requires dose reduction following the second dose of 0.15 mg/kg (Cycle 2), the patient should receive the dose of 0.075 mg/kg for Cycle 3.
Reconstitute and further dilute ZYNLONTA prior to intravenous infusion. Use appropriate aseptic technique.
ZYNLONTA is a hazardous drug. Follow applicable special handling and disposal procedures.1
Calculate the total dose (mg) required based on the patient’s weight and prescribed dose [see Dosage and Administration (2.1)].
- For patients with a body mass index (BMI) ≥35 kg/m2 , calculate the dose based on an adjusted body weight (ABW) as follows: ABW in kg = 35 kg/m2 × (height in meters)2
- More than one vial may be needed to achieve the calculated dose.
- Convert the calculated dose (mg) to volume using 5 mg/mL, which is the concentration of ZYNLONTA after reconstitution.
Reconstitution of lyophilized ZYNLONTA
- Reconstitute each ZYNLONTA vial using 2.2 mL of Sterile Water for Injection, USP with the stream directed toward the inside wall of the vial to obtain a final concentration of 5 mg/mL.
- Swirl the vial gently until the powder is completely dissolved. Do not shake. Do not expose to direct sunlight.
- Inspect the reconstituted solution for particulate matter and discoloration. The solution should appear clear to slightly opalescent, colorless to slightly yellow. Do not use if the reconstituted solution is discolored, is cloudy, or contains visible particulates.
- Use reconstituted ZYNLONTA immediately. If not used immediately, store the reconstituted solution in the vial for up to 4 hours refrigerated at 2°C to 8°C (36°F to 46°F) or room temperature 20°C to 25°C (68°F to 77°F). Do not freeze.
- The product does not contain a preservative. Discard unused vial after reconstitution if the recommended storage time is exceeded.
Dilution in infusion bag
- Withdraw the required volume of reconstituted solution from the ZYNLONTA vial using a sterile syringe. Discard any unused portion left in the vial.
- Add the calculated dose volume of ZYNLONTA solution into a 50 mL infusion bag of 5% Dextrose Injection, USP.
- Gently mix the intravenous bag by slowly inverting the bag. Do not shake.
- If not used immediately, store the diluted ZYNLONTA infusion solution refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at room temperature 20°C to 25°C (68°F to 77°F) for up to 8 hours. Discard diluted infusion bag if storage time exceeds these limits. Do not freeze.
- No incompatibilities have been observed between ZYNLONTA and intravenous infusion bags with product-contacting materials of polyvinylchloride (PVC), polyolefin (PO), and PAB® (copolymer of ethylene and propylene).
- Administer by intravenous infusion over 30 minutes using a dedicated infusion line equipped with a sterile, non-pyrogenic, low-protein binding in-line or add-on filter (0.2- or 0.22-micron pore size) and catheter.
- Extravasation of ZYNLONTA has been associated with irritation, swelling, pain, and/or tissue damage, which may be severe [see Adverse Reactions (6.1)]. Monitor the infusion site for possible subcutaneous infiltration during drug administration.
- Do not mix ZYNLONTA with or administer as an infusion with other drugs.
For Injection: 10 mg of loncastuximab tesirine-lpyl as a white to off-white lyophilized powder in a single-dose vial for reconstitution and further dilution.
Serious effusion and edema occurred in patients treated with ZYNLONTA. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites) and Grade 3 pleural effusion occurred in 3% and Grade 3 or 4 pericardial effusion occurred in 1% [see Adverse Reactions (6.1)].
Monitor patients for new or worsening edema or effusions. Withhold ZYNLONTA for Grade 2 or greater edema or effusion until the toxicity resolves. Consider diagnostic imaging in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites such as swelling in the abdomen and bloating. Institute appropriate medical management for edema or effusions [see Dosage and Administration (2.3)].
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