Elzonris: detailed information

Package leaflet: Information for the user

ELZONRIS 1 mg/mL concentrate for solution for infusion

tagraxofusp
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any adverse reactions you experience while taking this medicine. See the end of section 4 for information on how to report adverse reactions.
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or nurse.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

What is in this leaflet

What ELZONRIS is and what it is used for
What you should know before being given ELZONRIS
How ELZONRIS is administered
Possible side effects
How to store ELZONRIS
Contents of the pack and other information

1. What ELZONRIS is and what it is used for

ELZONRIS contains the active substance tagraxofusp. Tagraxofusp, an antineoplastic agent, is composed of two proteins derived from different sources, one of which can kill tumor cells. This protein is delivered to the tumor cell by the second protein. ELZONRIS is used to treat adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). BPDCN is a tumor of a rare type of immature immune cells called "plasmacytoid dendritic cells," which can affect multiple organs including the skin, bone marrow, and lymph nodes.

2. What you need to know before you are given ELZONRIS

Do not use ELZONRIS

if you are allergic to tagraxofusp or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before using ELZONRIS and during treatment if:

you experience sudden weight gain after starting treatment, new or worsening swelling of the face, limbs or joints (edema), or dizziness (a symptom of hypotension). These could be signs of a potentially life-threatening condition known as capillary leak syndrome. For more information, see “Capillary leak syndrome” in section 4;
you develop a whistling sound when breathing (wheezing) or have difficulty breathing, hives/rash, itching, or swelling (signs of an allergic reaction);
you have been told you have low platelet levels in your blood (thrombocytopenia);
you have been told you have low levels of a type of white blood cell called neutrophils (neutropenia);
you experience dizziness, reduced urination, confusion, vomiting, nausea, swelling, shortness of breath, or changes in heart rhythm (signs of tumor lysis syndrome);
you have abnormal liver function test results (possible signs of severe liver damage);
you have hereditary fructose intolerance (HFI), a rare genetic disorder that prevents you from breaking down the sugar found in foods and drinks;
you have kidney or liver problems;
you begin to have headaches or feel confused, drowsy, or have problems with speech, vision, or memory;
you have been diagnosed with a tumor in the central nervous system (CNS). You may be given a different medicine to treat this tumor.

Your doctor will monitor you and carry out regular blood tests to ensure that you can receive this medicine safely. If you experience any problems, treatment may be temporarily interrupted and resumed once you feel better.

Children and adolescents
ELZONRIS is not recommended in children and adolescents under 18 years of age, as information on the use of this medicine in this age group is limited.

Other medicines and ELZONRIS
Inform your doctor if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you might be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor for advice before receiving this medicine.
You must not use this medicine during pregnancy unless you and your doctor decide that the benefit to you outweighs the potential risk to the unborn child.
You must not breastfeed during treatment with ELZONRIS and for at least 1 week after the last dose. It is not known whether ELZONRIS is excreted in breast milk.
If you are a woman of childbearing potential, you will be tested for pregnancy approximately one week before starting treatment with ELZONRIS.
You must continue using contraception for at least 1 week after the last dose of ELZONRIS. Discuss with your doctor the most effective contraceptive method for you and before stopping contraception.

Driving and using machines
It is unlikely that tagraxofusp will affect your ability to drive or operate machinery.

ELZONRIS contains sorbitol (E420) and sodium
Sorbitol is a source of fructose. If your doctor has diagnosed you with hereditary fructose intolerance, a rare genetic disease, you must not take this medicine. Patients with hereditary fructose intolerance cannot metabolize fructose, and its accumulation may cause serious side effects.
Before taking this medicine, inform your doctor if you have hereditary fructose intolerance or if you feel unwell, vomit, or experience unpleasant reactions such as stomach bloating, cramps, or diarrhea after consuming sweetened foods or drinks.
This medicine contains less than 1 mmol (23 mg) of sodium per mL, i.e., essentially ‘sodium-free’.

3. How ELZONRIS is administered

ELZONRIS will be administered to you in a hospital or clinic under the supervision of a physician.
Approximately one hour before the start of treatment, you will be given medications to help prevent
an allergic reaction, including antihistamines, a corticosteroid, and paracetamol.
The amount of ELZONRIS given to you will be calculated by your doctor based on your body weight.
The recommended daily dose is 12 micrograms per kilogram of body weight.
It is administered as a 15-minute intravenous infusion (IV infusion) once daily for the first 5 days of a 21-day cycle.
The first cycle will be administered in the hospital. You will be monitored during treatment for any adverse effects and for at least 24 hours after the last dose.
More than one treatment cycle is usually performed. Your doctor will decide the number of cycles you will receive.
If the first cycle does not cause harmful side effects, subsequent treatment cycles may be administered in a clinic. You will be monitored during treatment.
If you miss a dose of ELZONRIS
It is very important that you do not miss any doses of ELZONRIS. If you miss a dose, ask your doctor when to schedule the next dose.
If you stop treatment with ELZONRIS
Do not stop treatment with ELZONRIS without first speaking to your doctor. Stopping treatment may worsen your condition.
If you have further questions about the use of this medicine, please consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Contact your doctor immediately if you experience any of the following side effects, as you may require urgent medical treatment:

any one or a combination of the following: weight gain, swelling or puffiness, which may be associated with reduced passage of fluid, difficulty breathing, abdominal swelling and feeling full, general feeling of tiredness. These symptoms usually develop rapidly. They could be symptoms of a condition called "capillary leak syndrome," which causes blood to leak out of small blood vessels in the body and requires urgent medical attention.

Other side effects
Inform your doctor if you notice any of the following side effects:
Very common (may affect more than 1 in 10 people):

abnormalities in blood tests (decrease in platelets [thrombocytopenia]; red blood cells [anaemia]; decrease in blood albumin [hypoalbuminaemia])
low blood pressure (hypotension)
feeling unwell or nausea (nausea; vomiting)
fever (pyrexia)
chills
tiredness (fatigue)
swelling of limbs and/or joints (peripheral oedema)
abnormal liver function tests (increase in aspartate aminotransferase; increase in alanine aminotransferase)
weight gain

Common (may affect up to 1 in 10 people):

skin infection (cellulitis)
decrease in white blood cells with or without fever (neutropenia, leucopenia, lymphopenia; febrile neutropenia)
complications from breakdown of tumour cells (tumour lysis syndrome)
reaction to treatment [including fever, feeling unwell, headache, rash, rapid heartbeat] (cytokine release syndrome)
abnormalities in blood tests [increase in white blood cells (leucocytosis), increase in blood uric acid (hyperuricaemia); decrease in blood calcium (hypocalcaemia); decrease in blood magnesium (hypomagnesaemia); decrease in blood sodium (hyponatraemia); decrease in blood potassium (hypokalaemia), increase in blood potassium (hyperkalaemia), increase in blood phosphates (hyperphosphataemia), increase in bile pigment in blood (hyperbilirubinaemia), increase in blood sugar level (hyperglycaemia)], prolonged blood clotting time (prolonged activated partial thromboplastin time, increased international normalized ratio)
decreased appetite
feeling confused
fainting (syncope)
headache
dizziness
blurred vision
fluid around the heart (pericardial effusion)
irregular or rapid heartbeat (tachycardia, sinus tachycardia)
redness (flushing)
decreased oxygen levels in the body (hypoxia)
fluid in the lungs (pulmonary oedema)
fluid accumulation around the lungs which may cause shortness of breath (pleural effusion)
difficulty breathing (dyspnoea)
nosebleed (epistaxis)
cough
difficulty swallowing (dysphagia)
diarrhoea
constipation
dry mouth or swollen, sore mouth (stomatitis)
indigestion (dyspepsia)
itchy skin (pruritus)
skin rashes
excessive sweating (hyperhidrosis)
tiny purple, red or brown spots on the skin (petechiae)
pain in shoulders, neck, wrists, legs and/or arms (limb pain), chest, back, joints (arthralgia), muscles (myalgia) or bones
muscle weakness
sudden kidney failure (acute kidney injury) and/or abnormal kidney function tests (increased blood creatinine)
flu-like symptoms such as aches, fever and shivering
abdominal pain
general feeling of being unwell (malaise)
abnormal heart rhythm (QT interval prolongation on electrocardiogram)
increased levels of enzymes in the blood found in blood tests (lactate dehydrogenase, alkaline phosphatase and creatine phosphokinase)
flushing, chills, seizures, fever, breathing difficulties, low blood pressure, rapid heartbeat, sudden swelling of the face, tongue or difficulty swallowing during or after infusion on the first day of treatment (infusion-related reaction)
bruising (contusions)

Uncommon (may affect up to 1 in 100 people):

lung infection (pneumonia)
urinary tract infection
gum disease (gingivitis), including bleeding gums
blood test abnormalities, decrease in blood phosphates (hypophosphataemia), increase in blood lactic acid (lactic acidosis/acidosis), decrease in levels of a blood clotting protein (decrease in blood fibrinogen)]
unusual mood changes, including depression and anxiety
sleep problems (insomnia)
brain function disorders (encephalopathy/metabolic encephalopathy)
stroke
loss of facial movement (facial paralysis)
persistent bad taste in mouth (dysgeusia)
worsening of multiple sclerosis (relapse)
drowsiness
tingling or numbness (paralysis, peripheral sensory neuropathy)
muscle weakness (peripheral motor neuropathy)
bleeding in the white part of the eye (conjunctival haemorrhage)
redness of the eyes (ocular hyperaemia)
floaters in the eye (eye floaters)
irregular heartbeat that may lead to cardiac arrest (supraventricular extrasystoles, ventricular fibrillation, atrial fibrillation)
slow heart rate (bradycardia)
heart attack (myocardial infarction)
high blood pressure (hypertension)
lungs not working properly, causing shortness of breath (respiratory failure)
noisy breathing (wheezing)
pain in mouth and/or throat (oropharyngeal pain)
rapid breathing (tachypnoea)
stomach swelling and stomach ache
blisters on the tongue
blood blister on the tongue (tongue haematoma)
swelling of face, tongue, limbs or joints (angioedema)
redness, swelling and pain on palms of hands and/or soles of feet (palmar-plantar erythrodysesthesia syndrome)
hives
hair loss (alopecia)
skin pain
dry, red, itchy skin or sores on lower legs (stasis dermatitis)
cold sweating
dry skin
joint, muscle and/or bone pain including tailbone (musculoskeletal pain, coccygodynia)
muscle spasm
muscle pain, weakness, dark or brown urine (rhabdomyolysis)
kidney failure
difficulty urinating
back/abdominal pain and/or painful urination (urinary tract pain)
frequent urination during the day (pollakiuria)
abnormal urine test [increased protein (proteinuria)]
inability to tolerate side effects of this medicine (drug intolerance)
low body temperature (hypothermia)
fever or low body temperature, increased heart rate, increased breathing (systemic inflammatory response syndrome)
prolonged blood clotting time (shown in blood tests)
positive bacterial test
weight loss

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store ELZONRIS

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after
Exp. The expiry date refers to the last day of that month.
Unopened vial: store and transport frozen (-20 °C±5 °C).
Keep the vial in the outer packaging to protect it from light.
Diluted solution: use immediately or store below 25 °C and use within 4 hours.
Once thawed, do not refreeze.
Do not dispose of any medicine via wastewater or household waste. Healthcare professionals will dispose of medicines that are no longer used. This will help protect the environment.

6. Package contents and other information

What ELZONRIS contains

The active substance is tagraxofusp. Each vial contains 1 mg of tagraxofusp in 1 mL of concentrate.
The other ingredients are tromethamine, sodium chloride, sorbitol (E420) and water for injections (see section 2 “ELZONRIS contains sorbitol (E420) and sodium”).

Description of the appearance of ELZONRIS and contents of the pack
ELZONRIS concentrate for solution for infusion (sterile concentrate) is a clear, colourless liquid.
White to translucent particles may be present.
Pack size: 1 glass vial per carton.

Marketing Authorisation Holder
Stemline Therapeutics B.V.
Basisweg 10,
1043 AP Amsterdam
The Netherlands

Manufacturer
Stemline Therapeutics B.V.
Basisweg 10,
1043 AP Amsterdam
The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien; България; Italia
Česká republika; Danmark; Eesti; Menarini Stemline Italia S.r.l.
Ελλάδα; Hrvatska; Ireland; Ísland; Tel: +39 800776814
Κύπρος; Latvija; Lietuva; [email protected]
Luxembourg/Luxemburg;
Magyarország; Malta; Nederland;
Norge; Polska; Portugal; România;
Slovenija; Slovenská republika;
Suomi/Finland; Sverige
Stemline Therapeutics B.V.
Tel: +44 (0)800 047 8675
[email protected]

Deutschland Österreich
Menarini Stemline Deutschland GmbH Stemline Therapeutics B.V.
Tel: +49 (0)800 0008974 Tel: +43 (0)800 297 649
[email protected] [email protected]

España
Menarini Stemline España, S.L.U.
Tel: +34919490327
[email protected]

France
Stemline Therapeutics B.V.
Tél: +33 (0)800 991014
[email protected]

This medicinal product has been granted a marketing authorisation under exceptional circumstances. This means that, due to the rarity of the disease, it has not been possible to obtain complete information about this medicinal product. The European Medicines Agency will review annually any new information on this medicinal product, and this package leaflet will be updated if necessary.

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu/.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

The following information is intended exclusively for healthcare professionals.

General precautions
Proper handling procedures must be followed, including the use of personal protective equipment (e.g., gloves) and the safe disposal of anticancer drugs.
The infusion solution must be prepared by a healthcare professional using an appropriate aseptic technique throughout the entire handling process of this medicinal product.

Preparation and administration
Infusion preparation
Before thawing ELZONRIS, ensure the following components required for dose preparation and administration are available:

a syringe infusion pump
one sterile empty 10 mL vial
sodium chloride 9 mg/mL (0.9%) injection solution
three sterile 10 mL syringes
one sterile 1 mL syringe
a mini Y-type connector
microbore tubing
a 0.2 µm low-protein-binding polyethersulfone in-line filter

Use only if the solution is clear and colourless or with a few white to translucent particles.
Allow vials to thaw at 25 °C or lower for up to 1 hour in the outer carton. Do not refreeze the vial once thawed.

Dose calculation
Calculation to determine the total dose of ELZONRIS (mL) to be administered (see Summary of Product Characteristics, section 4.2):
ELZONRIS dose (mcg/kg) x patient body weight (kg)
= Total dose (mL) to be administered
Diluted vial concentration (100 mcg/mL)

A two-step process is required to prepare the final dose of ELZONRIS.

Step 1 – Prepare 10 mL of 100 mcg/mL ELZONRIS

Using a sterile 10 mL syringe, transfer 9 mL of sodium chloride 9 mg/mL (0.9%) injection solution into a sterile empty 10 mL vial.
Gently swirl the ELZONRIS vial to mix its contents, remove the cap, and using a sterile 1 mL syringe, withdraw 1 mL of thawed ELZONRIS from the product vial.
Transfer 1 mL of ELZONRIS into the 10 mL vial containing 9 mL of sodium chloride 9 mg/mL (0.9%) injection solution. Gently invert the vial at least three times to mix. Do not shake vigorously.
After 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) based on the patient’s weight.
Transfer 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 using a second ELZONRIS vial.) Label the syringe as ELZONRIS.
Prepare a separate syringe containing at least 3 mL of sodium chloride 9 mg/mL (0.9%) injection solution to be used for flushing the administration set after ELZONRIS dose delivery.
Label the flushing syringe as sodium chloride 9 mg/mL (0.9%) injection solution.
Connect the sodium chloride 9 mg/mL (0.9%) injection solution flushing 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 distal end of the Y-connector to the microbore tubing.
Remove the cap from the inlet side of the 0.2 µm filter and attach it to the distal end of the microbore tubing.
Open the clamp on the Y-connector arm connected to the sodium chloride 9 mg/mL (0.9%) injection solution flushing syringe and prime the Y-connector up to the junction (do not prime the entire infusion set with sodium chloride 9 mg/mL (0.9%) injection solution). Close the Y-connector line on the sodium chloride 9 mg/mL (0.9%) injection solution flushing arm again.
Remove the cap from the distal end of the 0.2 µm filter and set it aside. Open the clamp on the Y-connector arm connected to the product syringe and prime the entire infusion set, including the filter. Close the filter and reconnect the Y-connector line on the product side. The infusion set is now ready for dose administration.

The diluted solution must be used immediately after preparation.

Administration

Establish venous access and maintain with sterile sodium chloride 9 mg/mL (0.9%) injection solution.
Administer the prepared ELZONRIS dose via syringe infusion pump over 15 minutes. The total infusion time will be controlled using a syringe infusion pump to deliver the full dose and the sodium chloride 9 mg/mL (0.9%) injection solution flush over 15 minutes.
Insert the ELZONRIS syringe into the syringe infusion pump, open the clamp on the ELZONRIS side of the Y-connector, and deliver the prepared ELZONRIS dose.
Once the ELZONRIS syringe is empty, remove it from the pump and place the sodium chloride 9 mg/mL (0.9%) injection solution flushing syringe into the syringe infusion pump.
Open the clamp on the sodium chloride 9 mg/mL (0.9%) injection solution flushing side of the Y-connector and resume infusion via the syringe pump at the pre-specified flow rate to flush the remaining ELZONRIS dose out of the infusion line, completing the delivery.