ENRYLAZE 10 mg/0.5 ml INJECTABLE SOLUTION AND PERFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Enrylaze 10 mg/0.5 ml Solution for Injection and Infusion

Recombinant crisantaspase

This medicinal product is subject to additional monitoring, which will allow for the quick identification of new safety information. You can help by reporting any side effects you may get. The last section of the leaflet contains information on how to report side effects.

Read all of this leaflet carefully before you start receiving 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 pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Enrylaze and what is it used for

Enrylaze contains the active substance recombinant crisantaspase. It is a medicine used with other medicines to treat acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL). Enrylaze can be given to patients from 1 month of age.

Enrylaze contains a protein that is produced in a laboratory using DNA recombinant technology. This protein works by reducing the amount of a protein called asparagine. This protein is necessary for the survival of ALL and LBL cancer cells.

2. What you need to know before you use Enrylaze

You should not receive Enrylaze

• if you have a severe allergic reaction to Enrylaze.
• if you have an allergic reaction to any of the other ingredients of this medicine (listed in section 6).
• if you currently have severe pancreatitis (inflammation of the pancreas).
• if you have had severe pancreatitis after treatment with asparaginase therapies.
• if you have had severe blood clots after treatment with asparaginase therapies.
• if you have had severe bleeding events after treatment with asparaginase therapies.

Warnings and precautions

Talk to your doctor or pharmacist before you start receiving Enrylaze.

The following problems may occur during treatment with Enrylaze:

• severe allergic reactions that can be life-threatening. The hospital will make sure they are prepared to deal with allergic reactions that may occur during treatment.

• pancreatitis. Discomfort or pain in the stomach or back area may be a sign of pancreatitis and should be reported to your doctor immediately.
• changes in the body's ability to control blood sugar levels. Your doctor should monitor your glucose levels during treatment and provide insulin if necessary.
• bleeding or blood clotting events. If any of these events occur, your doctor will stop treatment until they are resolved.
• liver problems. Your doctor will monitor you to identify if you are experiencing any liver-related problems and treat them as necessary.
• central nervous system toxicity, such as seizures and neurological dysfunction. Additionally, cases of posterior reversible encephalopathy syndrome (characterized by headache, confusion, seizures, and vision loss) may require medication to reduce blood pressure in case of seizure, and treatment with anti-epileptic drugs.

Monitoring during treatment with Enrylaze

You will be monitored during and after treatment with Enrylaze for:

• allergic reactions
• pancreas and liver function
• blood sugar levels

Other medicines and Enrylaze

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. In particular, tell your doctor or pharmacist if you have taken or are taking:

• methotrexate or cytarabine, used to treat cancer. The use of these medicines immediately before Enrylaze may increase their effect.
• vincristine, used to treat cancer. The use of vincristine with Enrylaze may increase the toxicity of vincristine.
• glucocorticoids, used as anti-inflammatory medicines. The use of these medicines immediately before Enrylaze may increase the formation of blood clots.

Pregnancy

Enrylaze is not recommended during pregnancy. Women should make sure they are not pregnant before starting treatment. If you are pregnant or think you may be pregnant, talk to your doctor or pharmacist before receiving this medicine.

Breast-feeding

Do not breast-feed during treatment and for 2 weeks after treatment with Enrylaze, as it may pose a risk to the baby.

Family planning

Men and women should use a contraceptive method to avoid conceiving a child during treatment with Enrylaze and for 3 months after the last administration of Enrylaze. Hormonal contraceptives are not recommended for women treated with Enrylaze.

A pregnancy test should be performed in women before starting treatment.

Driving and using machines

Enrylaze may cause you discomfort and headache. This may affect your ability to drive and use machines.

Enrylaze contains sodium

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

3. How to use Enrylaze

Your doctor will decide on the dose and whether it will be given through a vein or by intramuscular injection. You may also be given other medicines before starting Enrylaze, such as paracetamol, H1, and H2 blockers.

The dose and method of administration will depend on your specific condition, body surface area, and response to treatment.

If you are given Enrylaze through a vein, it will be administered over 2 hours. If you are given Enrylaze by intramuscular injection, several injection sites may be used.

If you think you have been given too much Enrylaze

If you have any doubts, contact your doctor or healthcare professional immediately.

If you think you have missed a dose of Enrylaze

If you have any doubts, contact your doctor or healthcare professional immediately.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects have been reported in patients treated with Enrylaze.

Serious side effects

Tell your doctor immediately if you experience:

Symptoms of a severe allergic reaction, including swelling of the face, difficulty breathing, hay fever symptoms, rash, hives, itching, flushing, vomiting, high or low blood pressure. In severe cases, anaphylaxis (a severe, sudden allergic reaction with difficulty breathing, swelling, fainting, rapid heartbeat, sweating, and loss of consciousness) may also occur.

Symptoms of blood clots, including in the blood vessels of the lungs, which may present as sudden shortness of breath, chest pain, or coughing up blood, and in the blood vessels of the brain, which may present with symptoms such as weakness/numbness, seizure, difficulty speaking, or severe headache.

Symptoms of pancreatitis, including abdominal pain, nausea, vomiting, back pain, or loss of appetite.

Other side effects

Tell your doctor if you experience any of the following:

Very common side effects(may affect up to 1 in 10 people):

• allergic reaction, including rash, itching, and hives
• infections
• low red blood cell count (anaemia)
• low platelet count in the blood (thrombocytopenia)
• low white blood cell count (decreased white blood cell count)
• low levels of neutrophils, a type of white blood cell that fights infection (neutropenia)
• low levels of neutrophils (neutrophils) with fever due to infection (febrile neutropenia)
• low levels of lymphocytes, a type of white blood cell that fights infection (decreased lymphocyte count)
• stomach pain (abdominal pain)
• diarrhoea
• feeling sick (nausea)
• vomiting
• fatigue (fatigue)
• fever (pyrexia)
• high blood sugar levels (hyperglycaemia)
• pain in the limbs (limb pain)
• weight loss (decreased weight)
• headache
• decreased appetite
• abnormal liver function test (elevated transaminase, elevated bilirubin in blood)
• low albumin levels (a blood protein) (hypoalbuminaemia)
• anxiety
• bruising (contusion)

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

• blood poisoning (sepsis)
• severe allergic reaction, sudden difficulty breathing, swelling, fainting, rapid heartbeat, sweating, and loss of consciousness (anaphylactic reaction)
• rash characterized by flat, discoloured patches (macules) and red bumps (papules) (maculopapular rash)
• rash with redness and inflammation (erythematous rash)
• hives (urticaria)
• itching (pruritus)
• pancreatitis
• pain at the injection site
• injection site reaction
• infusion-related reactions
• abnormal blood clotting factor levels (prolonged activated partial thromboplastin time, decreased antithrombin III, decreased fibrinogen in blood)
• abnormal kidney function (elevated creatinine in blood)
• low blood sugar levels (hypoglycaemia)
• low blood pressure (hypotension)
• blood clots, including in the blood vessels of the lungs and brain
• irritability
• dizziness

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

• blood clot in a main brain vein (superior sagittal sinus thrombosis)
• blood clot in the neck vein (jugular vein thrombosis)
• blood clot in the veins of the limbs (deep vein thrombosis)

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects 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 Enrylaze

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 carton and vial after EXP. The expiry date is the last day of the month stated.

Store the unopened vials in a refrigerator (2°C - 8°C) in an upright position. Do not freeze. Keep the vial in the outer packaging to protect it from light.

After preparation of a dose in a syringe, Enrylaze can be stored for up to 8 hours at room temperature (15°C - 25°C) or 24 hours refrigerated (2°C - 8°C).

After dilution in an intravenous bag, Enrylaze can be stored for up to 12 hours at room temperature (15°C - 25°C) or 24 hours refrigerated (2°C - 8°C). The storage time starts once the solution is removed from the unopened vials.

Do not use this medicine if you notice any particles in the solution.

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. Contents of the pack and other information

Composition of Enrylaze

• The active substance is recombinant crisantaspase. Each vial contains 10 mg of recombinant crisantaspase in 0.5 ml of solution.
• The other ingredients are trehalose dihydrate, sodium chloride (see section 2 "Enrylaze contains sodium"), sodium hydroxide (for pH adjustment), disodium phosphate, sodium dihydrogen phosphate monohydrate, polysorbate 80, and water for injections.

Appearance of Enrylaze and contents of the pack

Enrylaze is a clear to slightly yellowish solution for injection and infusion, free from particles.

A carton contains 3 glass vials, each with 0.5 ml of solution for injection and infusion.

Marketing authorisation holder and manufacturer

Jazz Pharmaceuticals Ireland Ltd

5th Floor

Waterloo Exchange

Waterloo Road

Dublin 4

D04 E5W7

Ireland

Tel: +353 1 968 1631

Email: medinfo-int@jazzpharma.com

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

The leaflet for this medicine can be found on the European Medicines Agency website in all EU/EEA languages.