Active Ingredient: Tagraxofusp
ELZONRIS is indicated as monotherapy for the first-line treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, 12 micrograms tagraxofusp per kilogram of body weight, once daily, 5 doses in total, over the duration of 21 days.
The recommended dose is 12 mcg/kg tagraxofusp administered as an intravenous infusion over 15 minutes, once daily, on days 1-5 of a 21-day cycle. The dosing period may be extended for dose delays up to day 10 of the cycle. Treatment should be continued until disease progression or unacceptable toxicity.
The first cycle of tagraxofusp should be administered in the in-patient setting. Patients should be monitored for signs and symptoms of hypersensitivity or capillary leak syndrome until at least 24 hours after the last infusion.
Tagraxofusp can be administered in the in-patient setting or in a suitable out-patient ambulatory care setting that is equipped for intensive monitoring of patients with haematopoietic malignancies undergoing treatment.
Patients should be pre-medicated with a H1-histamine antagonist (e.g. diphenhydramine hydrochloride), a H2-histamine antagonist, a corticosteroid (e.g. 50 mg intravenous methylprednisolone or equivalent) and paracetamol approximately 60 minutes prior to the start of infusion.
Vital signs should be monitored and albumin, transaminases, and creatinine checked prior to preparing each dose of tagraxofusp. See Table 1 for recommended dose modifications and Table 2 for capillary leak syndrome (CLS) management guidelines.
Vital signs should be monitored frequently during dosing.
Table 1. Recommended tagraxofusp dosing regimen modifications:
| Parameter | Severity criteria | Dose modification |
|---|---|---|
| Serum albumin | Serum albumin < 3.5 g/dL or reduced ≥ 0.5 g/dL from value measured prior to initiation of the current cycle | See CLS Management Guidelines (Table 2) |
| Body weight | Body weight increase ≥ 1.5 kg over pre- treatment weight on prior treatment day | See CLS Management Guidelines (Table 2) |
| Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) | ALT or AST increase > 5 times the upper limit of normal | Withhold treatment until transaminase elevations are ≤ 2.5 times the upper limit of normal. |
| Serum creatinine | Serum creatinine > 1.8 mg/dL (159 micromol/L) or creatinine clearance < 60 mL/minute | Withhold treatment until serum creatinine resolves to ≤ 1.8 mg/dL (159 micromol/L) or creatinine clearance ≥ 60 mL/minute. |
| Systolic blood pressure | Systolic blood pressure ≥ 160 mmHg or ≤ 80 mmHg | Withhold treatment until systolic blood pressure is < 160 mmHg or > 80 mmHg. |
| Heart rate | Heart rate ≥ 130 bpm or ≤ 40 bpm | Withhold treatment until heart rate is < 130 bpm or > 40 bpm. |
| Body temperature | Body temperature ≥ 38°C | Withhold treatment until body temperature is < 38°C. |
| Hypersensitivity reactions | Mild or moderate | Withhold treatment until resolution of any mild or moderate hypersensitivity reaction. Resume tagraxofusp at the same infusion rate. |
Table 2. CLS management guidelines:
| Time of Presentation | CLS Sign/Symptom | Recommended Action | Tagraxofusp Dosing Management |
|---|---|---|---|
| Prior to first dose of tagraxofusp in cycle 1 | Serum albumin < 3.2 g/dL | Administer tagraxofusp when serum albumin ≥ 3.2 g/dL | |
| During tagraxofusp dosing | Serum albumin < 3.5 g/dL | Administer 25 g intravenous albumin every 12 hours (or more frequently as practical) until serum albumin is ≥ 3.5 g/dL AND not reduced by ≥ 0.5 g/dL from the value measured prior to dosing initiation of the current cycle | Hold dosing until the relevant CLS sign/symptom has resolved1 |
| Serum albumin reduced by ≥ 0.5 g/dL from the albumin value measured prior to tagraxofusp dosing initiation of the current cycle | |||
| A pre-dose body weight that is increased by ≥ 1.5 kg over the previous day's pre-dose weight | Administer 25 g intravenous albumin (every 12 hours or more frequently as practical), and manage fluid status as indicated clinically (e.g., generally with intravenous fluids and vasopressors if hypotensive and with diuretics if normotensive or hypertensive), until body weight increase has resolved (i.e. the increase is no longer ≥ 1.5 kg greater than the previous day's pre-dose weight). | ||
| Oedema, fluid overload and/or hypotension | Administer 25 g intravenous albumin (every 12 hours, or more frequently as practical) until serum albumin is ≥ 3.5 g/dL. Administer 1 mg/kg of methylprednisolone (or an equivalent) per day, until resolution of CLS sign/symptom or as indicated clinically. Aggressive management of fluid status and hypotension if present, which could include intravenous fluids and/or diuretics or other blood pressure management, until resolution of CLS sign/symptom or as clinically indicated. | ||
1 If tagraxofusp dose is held:
* Tagraxofusp administration may resume in the same cycle if all CLS signs/symptoms have resolved and the patient did not require measures to treat haemodynamic instability.
* Administration should be held for the remainder of the cycle if CLS signs/symptoms have not resolved or the patient required measures to treat haemodynamic instability (e.g., required administration of intravenous fluids and/or vasopressors to treat hypotension) (even if resolved).
* Administration may only resume in the next cycle if all CLS signs/symptoms have resolved, and the patient is haemodynamically stable.
Tagraxofusp is for intravenous use.
The prepared dose of diluted tagraxofusp should be administered via an infusion syringe pump over 15 minutes. The total infusion time should be controlled using an infusion syringe pump to deliver the entire dose and the sodium chloride 9 mg/mL (0.9%) solution for injection within 15 minutes.
Tagraxofusp must not be administered as an intravenous push or bolus. It should be administered through a dedicated intravenous line and it must not be mixed with other medicinal products.
Prior to infusion, venous access should be established and maintained with sodium chloride 9 mg/mL (0.9%) solution for injection.
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