ELZONRIS 1 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

ELZONRIS 1 mg/ml concentrate for solution for infusion

tagraxofusp

This medicine is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of section 4 will tell you how to report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What is ELZONRIS and what is it used for
2. What you need to know before you are given ELZONRIS
3. How ELZONRIS is given
4. Possible side effects
5. Storage of ELZONRIS
6. Contents of the pack and other information

1. What is ELZONRIS and what is it used for

ELZONRIS contains the active substance tagraxofusp. Tagraxofusp, an anti-cancer medicine, is made up of two proteins from different sources. One of the proteins can destroy cancer cells. This protein is delivered to the cancer cell by the second protein.

ELZONRIS is used to treat adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

BPDCN is a rare type of cancer of the immune cells called 'plasmacytoid dendritic cells' that can affect many organs such as 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 any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Tell your doctor before you start using ELZONRIS and during treatment if:

• You suddenly gain weight after starting treatment, have new or worsening swelling of the face, or swelling of the arms or legs (edema) or dizziness (a symptom of low blood pressure). These may be signs of a potentially life-threatening condition known as capillary leak syndrome. For more information, see 'Capillary leak syndrome' in section 4.
• You have a whistling sound while breathing (wheezing) or have difficulty breathing, hives/rash, itching or swelling (signs of an allergic reaction).

• You have been told you have low platelet counts in your blood (thrombocytopenia).
• You have been told you have low levels of a type of white blood cell called neutrophil (neutropenia).
• You feel dizzy, have decreased urine output, confusion, vomiting, nausea, swelling, shortness of breath, or changes in heart rhythm (signs of tumor lysis syndrome).
• You have abnormal liver test results (possible sign of severe liver damage).
• You have hereditary fructose intolerance (HFI), a rare genetic disorder that means you cannot break down fructose from foods and drinks.
• You have kidney or liver problems.
• You start having headaches, or feelings of confusion or drowsiness; or you start having problems with speech, vision, or memory.
• You have been told you have cancer in the central nervous system (CNS). You will be given a different medicine to treat it.

Your doctor will monitor you and perform regular blood tests to make sure it is safe for you to take this medicine. If you have any problems, treatment may be temporarily stopped and restarted when you feel better.

Children and adolescents

ELZONRIS is not recommended for use in children and adolescents under 18 years of age, as there is not enough information on how it works in this age group.

Other medicines and ELZONRIS

Tell your doctor if you are taking or have recently taken or might take any other medicines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

You should not use this medicine if you are pregnant unless you and your doctor decide that the benefit outweighs the potential risk to the unborn baby.

You should not breastfeed during treatment with ELZONRIS and for at least 1 week after the last dose. It is not known if ELZONRIS passes into breast milk.

If you are a woman who could become pregnant, you will have a pregnancy test about 1 week before starting treatment with ELZONRIS.

You should continue to use contraception for at least 1 week after the last dose of ELZONRIS. Talk to your doctor about the contraception that is best for you and before stopping contraception.

Driving and using machines

Tagraxofusp is unlikely to affect your ability to drive or use machines.

ELZONRIS contains sorbitol (E420) and sodium

Sorbitol is a source of fructose. If you have hereditary fructose intolerance (HFI), a rare genetic disorder, you should not receive this medicine. Patients with HFI cannot break down fructose, which can cause serious side effects.

Talk to your doctor before receiving this medicine if you have HFI or if you can no longer take sweet foods or drinks because they make you feel unwell, vomit, or cause unpleasant effects such as bloating, stomach cramps, or diarrhea.

This medicine contains less than 1 mmol of sodium (23 mg) per ml, which is 'essentially sodium-free'.

3. How ELZONRIS is given

ELZONRIS will be given to you in a hospital or clinic under the supervision of a doctor.

About 1 hour before treatment starts, you will be given medicines to help you avoid an allergic reaction, such as antihistamines, a corticosteroid, and paracetamol.

The amount of ELZONRIS you will be given will depend on your body weight and will be calculated by your doctor. The recommended dose is 12 micrograms per kilogram of body weight. It will be given to you through a drip in a vein (intravenous infusion) over 15 minutes, once a day, for the first 5 days of a 21-day cycle.

The first cycle will be given to you in the hospital. You will be monitored for any side effects during treatment and for at least 24 hours after the last dose.

You will normally have more than one treatment cycle. Your doctor will decide how many treatments you will have.

If the first cycle does not cause you any problematic side effects, the next cycle of treatment may be given to you in a clinic. You will be monitored during treatment.

If you miss a dose of ELZONRIS

It is very important that you attend all appointments to receive ELZONRIS. If you miss an appointment, ask your doctor when to schedule the next dose.

If you stop treatment with ELZONRIS

Do not stop treatment with ELZONRIS without talking to your doctor first. Stopping treatment may make your disease worse.

If you have any other questions about the use of this medicine, ask 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:

If you experience any of the following side effects, tell your doctor immediately; you may need urgent medical attention:

• any or a combination of: weight gain, swelling, or edema, which may be related to less frequent fluid expulsion; difficulty breathing, abdominal swelling, and feeling of fullness, as well as a general feeling of tiredness. These symptoms usually develop rapidly. This may be a sign of a condition called 'capillary leak syndrome', which causes blood to leak from the capillaries into the body and requires urgent medical attention.

Other side effects:

Tell your doctor if you notice any of the following side effects:

Very common (may affect more than 1 in 10 people):

• abnormal tests (decrease in platelets [thrombocytopenia]; red blood cells [anemia]; decrease in albumin in blood [hypoalbuminemia])
• low blood pressure (hypotension)
• feeling unwell or sick (nausea, vomiting)
• fever (pyrexia)
• chills

• fatigue (fatigue)
• swelling of the arms or legs (peripheral edema)
• 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 the breakdown of cancer cells (tumor lysis syndrome)
• reaction to treatment [such as fever, feeling unwell, headache, rash, rapid heartbeat] (cytokine release syndrome)
• abnormal tests (increase in white blood cells [leucocytosis], increase in uric acid in blood [hyperuricemia]; decrease in calcium in blood [hypocalcemia]; decrease in magnesium in blood [hypomagnesemia]; decrease in sodium in blood [hyponatremia]; decrease in potassium in blood [hypokalemia]; increase in potassium in blood [hyperkalemia]; increase in phosphate in blood [hyperphosphatemia]; increase in bilirubin in blood [hyperbilirubinemia]; increase in blood sugar levels [hyperglycemia]; increase in blood coagulation 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)
• abnormal or rapid heartbeat (tachycardia, sinus tachycardia)
• flushing
• decrease in oxygen levels in the blood (hypoxia)
• fluid in the lungs (pulmonary edema)
• fluid accumulation around the lungs, which can cause shortness of breath (pleural effusion)
• difficulty breathing (dyspnea)
• nosebleeds (epistaxis)
• cough
• difficulty swallowing (dysphagia)
• diarrhea
• constipation
• dry mouth or swelling and pain in the mouth (stomatitis)
• indigestion (dyspepsia)
• itching (pruritus)
• skin rash
• excessive sweating (hyperhidrosis)
• small purple, red, or brown spots on the skin (petechiae)
• pain in the shoulders, neck, wrists, legs, or arms (pain in the limbs), chest, back, joints (arthralgia), muscles (myalgia), or bones.
• muscle weakness
• sudden loss of kidney function (acute kidney injury) or abnormal kidney function tests (increase in creatinine in blood)
• flu-like symptoms, such as pain, fever, and chills
• chest pain
• general feeling of being unwell
• abnormal heart rhythm (prolonged QT interval on electrocardiogram)

• increase in enzyme levels in the blood as shown by blood tests (lactate dehydrogenase, alkaline phosphatase, and creatine phosphokinase)
• flushing, chills, seizures, fever, difficulty breathing, 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)
• bruises (contusions)

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

• lung infection (pneumonia)
• urinary tract infection
• gum disease (gingivitis) such as gum bleeding
• abnormal tests (decrease in phosphate in blood [hypophosphatemia], increase in lactic acid in the blood [lactic acidosis], decrease in blood clotting protein levels [decrease in fibrinogen in blood])
• unusual mood changes such as depression and anxiety
• difficulty sleeping (insomnia)
• brain disorders (encephalopathy/metabolic encephalopathy)
• stroke
• loss of mobility in the face (facial paralysis)
• persistent bad taste in the mouth (dysgeusia)
• worsening of multiple sclerosis (relapse)
• drowsiness (somnolence)
• tingling or numbness (paresthesia, peripheral sensory neuropathy)
• muscle weakness (peripheral motor neuropathy)
• bleeding in the white part of the eye (conjunctival hemorrhage)
• eye redness (ocular hyperemia)
• floaters
• irregular heartbeats that can cause the heart to stop (supraventricular extrasystoles, ventricular fibrillation, atrial fibrillation)
• slow heart rate (bradycardia)
• heart attack
• high blood pressure (hypertension)
• lung malfunction, which can cause shortness of breath (respiratory failure)
• wheezing
• pain in the mouth or throat (oropharyngeal pain)
• rapid breathing (tachypnea)
• swollen and painful stomach
• mouth ulcers
• blood blisters on the tongue (tongue hematoma)
• swelling of the face, tongue, arms, or legs (angioedema)
• redness, swelling, and pain in the palms of the hands or soles of the feet (palmar-plantar erythrodysesthesia syndrome)

• hives
• hair loss (alopecia)
• skin pain
• dry, red, itchy skin or pain on the lower legs (stasis dermatitis)
• cold sweats
• dry skin
• pain in the joints, muscles, or bones, including the tailbone (musculoskeletal pain, coccydynia)
• muscle spasms
• pain, muscle weakness, dark or brown urine (rhabdomyolysis)
• kidney failure
• difficulty urinating
• pain in the lower back/abdomen or pain when urinating (pain in the urinary tract)
• frequent urination during the day (pollakiuria)
• abnormal blood test (increase in protein [proteinuria])

• inability to tolerate the side effects of this medicine (drug intolerance)
• low body temperature (hypothermia)
• fever or low body temperature, increased heart rate, increased breathing rate (systemic inflammatory response syndrome)
• increase in the time it takes for the blood to clot (as shown by blood tests)
• positive bacterial test
• weight loss

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of ELZONRIS

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the vial and carton after EXP. The expiry date is the last day of the month shown.

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. Do not re-freeze once thawed.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Additional Information

Composition of ELZONRIS

• The active ingredient is tagraxofusp. Each vial contains 1 mg of tagraxofusp in 1 ml of concentrate.
• The other excipients are trometamol, sodium chloride, sorbitol (E420), and water for injectable preparations (see section 2 'ELZONRIS contains sorbitol (E420) and sodium').

Appearance of ELZONRIS and Package Contents

The concentrate for solution for infusion (sterile concentrate) ELZONRIS is a clear, colorless liquid. It may present some white to translucent particles.

The package size is 1 glass vial per box.

Marketing Authorization Holder

Stemline Therapeutics B.V.

Basisweg 10,

1043 AP Amsterdam

Netherlands

Manufacturer

Stemline Therapeutics B.V.

Basisweg 10,

1043 AP Amsterdam

Netherlands

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet

This medicine has been authorized under 'exceptional circumstances'. This means that due to the rarity of this disease, it has not been possible to obtain complete information on this medicine.

The European Medicines Agency will review any new information on this medicine that may become available annually, and this leaflet will be updated as necessary.

Other Sources of Information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

The European Medicines Agency website can be found in all languages of the European Union/European Economic Area.

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This information is intended only for healthcare professionals:

General Precautions

Proper handling procedures should be followed, including personal protective equipment (e.g., gloves), and disposal of anticancer medicines.

The solution for infusion should be prepared by a medical professional using an appropriate aseptic technique throughout handling of this medicine.

Preparation and Administration

Preparation of the Infusion

Ensure you have the following necessary components for preparation and administration of the dose before thawing ELZONRIS:

• A syringe pump for infusion
• A 10 ml empty sterile vial
• Solution for injection of 9 mg/ml (0.9%) sodium chloride
• Three 10 ml sterile syringes
• A 1 ml sterile syringe
• A Mini-Bifuse Y-connector
• Microbore tubing
• A 0.2 µm low-protein-binding in-line polyethersulfone filter

Use only if the solution is clear and colorless or has some white to translucent particles.

Allow the vials to thaw at 25°C or less for a maximum of 1 hour in the outer packaging. Do not refreeze the vial once thawed.

Determining the Dose Quantity

Calculation to determine the total dose of ELZONRIS (ml) to be administered (see Summary of Product Characteristics or Package Leaflet, section 4.2):

A 2-step process is required to prepare the final dose of ELZONRIS:

Step 1: Prepare 10 ml of 100 mcg/ml ELZONRIS

• Using a 10 ml sterile syringe, transfer 9 ml of the solution for injection of 9 mg/ml (0.9%) sodium chloride to a 10 ml empty sterile vial.
• Gently swirl the ELZONRIS vial, remove the cap, and with a 1 ml sterile syringe, withdraw 1 ml of thawed ELZONRIS from the product vial.
• Transfer this 1 ml of ELZONRIS to the 10 ml vial containing 9 ml of solution for injection of 9 mg/ml (0.9%) sodium chloride. Gently invert the vial at least 3 times to mix the contents. Do not shake vigorously.
• After dilution, the final concentration of ELZONRIS is 100 mcg/ml.

Step 2: Prepare the ELZONRIS Infusion Kit

• Calculate the required volume of diluted ELZONRIS (100 mcg/ml) based on the patient's weight.
• Prepare the required volume in a new syringe (if more than 10 ml of diluted ELZONRIS [100 mcg/ml] is needed for the patient's calculated dose, repeat step 1 with a second vial of ELZONRIS). Label the ELZONRIS syringe.
• Prepare a separate syringe with at least 3 ml of solution for injection of 9 mg/ml (0.9%) sodium chloride to flush the administration kit after ELZONRIS administration.
• Label the syringe for flushing the solution for injection of 9 mg/ml (0.9%) sodium chloride.

• Connect the flushing syringe of solution for injection of 9 mg/ml (0.9%) sodium chloride to one of the inputs of the Y-connector and ensure the clamp is closed.
• Connect the drug syringe to the other input 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 µm filter and attach it to the terminal end of the Microbore tubing.
• Release the input of the Y-connector connected to the flushing syringe of solution for injection of 9 mg/ml (0.9%) sodium chloride. Flush the Y-connector up to the intersection (do not flush the entire infusion kit with the solution for injection of 9 mg/ml [0.9%] sodium chloride). Reclamp the Y-connector line at the input of the flushing syringe of solution for injection of 9 mg/ml (0.9%) sodium chloride.
• Remove the cap from the terminal end of the 0.2 µm filter and set it aside. Release the input of the Y-connector connected to the drug syringe and flush the entire infusion kit, including the filter. Replace the cap on the filter and re-clamp the Y-connector line on the drug side. The infusion kit is now ready for administration of the dose.

The diluted solution should be used immediately once prepared.

Administration

1. Place the venous access and maintain the sterile solution for injection of 9 mg/ml (0.9%) sodium chloride.
2. Administer the prepared dose of ELZONRIS via infusion with a syringe pump for infusion over 15 minutes. The total infusion time will be controlled with a syringe pump for infusion to administer the complete dose and the flushing of the solution for injection of 9 mg/ml (0.9%) sodium chloride over 15 minutes.
3. Insert the ELZONRIS syringe into the syringe pump for infusion, open the clamp on the ELZONRIS side of the Y-connector, and administer the prepared dose of ELZONRIS.
4. Once the ELZONRIS syringe is empty, remove it from the syringe pump for infusion and place the flushing syringe of solution for injection of 9 mg/ml (0.9%) sodium chloride in the syringe pump for infusion.
5. Open the clamp on the flushing side of the solution for injection of 9 mg/ml (0.9%) sodium chloride of the Y-connector and resume infusion via the syringe pump for infusion at the pre-set rate to expel the remaining ELZONRIS dose from the infusion line to complete administration.