Enrylaze

Package leaflet: Information for the patient

Enrylaze 10 mg/0.5 mL solution for injection or infusion

recombinant crisantaspase
This medicinal product is subject to additional monitoring. This will allow rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Enrylaze is and what it is used for

Enrylaze contains the active substance crisantaspase recombinant. It is a medicine used in combination with other medicines for the treatment of acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LL).
Enrylaze may be given to patients aged 1 month and older.
Enrylaze contains a protein produced in the laboratory using recombinant DNA technology.
This protein works by reducing the amount of a protein called asparagine. Asparagine is required by cancer cells in ALL and LL to survive.

2. What you should know before using Enrylaze

Do not use Enrylaze

• if you experience a severe allergic reaction to Enrylaze.
• if you are allergic 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 previously had severe pancreatitis after treatment with asparaginase-based therapies.
• if you have experienced severe blood clots after treatment with asparaginase-based therapies.
• if you have experienced severe bleeding events after treatment with asparaginase-based therapies.

Warnings and precautions
Talk to your doctor or pharmacist before using Enrylaze.
The following problems may occur during treatment with Enrylaze:

• severe allergic reactions, which may be life-threatening. The hospital will ensure it is prepared to manage any allergic reactions that may occur during treatment.

• inflammation of the pancreas. Discomfort or pain in the abdominal or back area may be a sign of pancreatitis and must be reported to your doctor immediately.

• changes in your body’s ability to regulate blood sugar levels. Your doctor will monitor your glucose levels during treatment and provide insulin if necessary.

• unusual bleeding or blood clotting events. If any of these occur, your doctor will suspend treatment until they resolve.

• liver problems. Your doctor will monitor you for signs of liver issues and treat them as needed.

• central nervous system toxicity, such as seizures and neurological impairment. Cases of reversible posterior encephalopathy syndrome (characterized by headache, confusion, seizures, and vision loss) may require medications to lower blood pressure and, in the case of seizures, treatment with antiepileptic medicines.

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

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

Other medicines and Enrylaze
Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. In particular, inform your doctor or pharmacist if you have used or are using:

• methotrexate or cytarabine, used in cancer treatment. Using these medicines immediately before Enrylaze may enhance their effect.
• vincristine, used in cancer treatment. Using vincristine with Enrylaze may increase vincristine toxicity.
• glucocorticoids, used as anti-inflammatory medicines. Using these medicines immediately before Enrylaze may increase the risk of blood clot formation.

Pregnancy
Enrylaze must not be used during pregnancy, and women must confirm they are not pregnant before starting treatment. If you are pregnant or suspect you may be pregnant, consult your doctor or pharmacist before using this medicine.
Breastfeeding
You must not breastfeed during treatment and for two weeks after treatment with Enrylaze, as there may be a risk to the breastfed infant.
Fertility planning
Both men and women must use contraception and avoid conceiving a child during treatment with Enrylaze and for 3 months after the last dose of Enrylaze. The use of hormonal contraceptives is not recommended in women during treatment with Enrylaze.
Women must undergo pregnancy testing before starting treatment.
Driving and using machines
Enrylaze may cause nausea and headache, which may affect your ability to drive and use machinery.
Enrylaze contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose unit, i.e., essentially ‘sodium-free’.

3. How to use Enrylaze

Your doctor will determine the dose to be administered and whether Enrylaze will be given as an intravenous infusion or as an intramuscular injection. You may also be prescribed other medicines before starting Enrylaze, such as paracetamol and H1 and H2 receptor blockers.
The dose and method of administration may vary depending on your specific condition, body surface area, and response to therapy.
If Enrylaze is administered intravenously, it will be given over a period of 2 hours. If Enrylaze is administered intramuscularly, different injection sites may be used.
If you use more Enrylaze than you should
If in doubt, contact your doctor or any other healthcare professional immediately.
If you forget to use Enrylaze
If in doubt, contact your doctor or any other healthcare professional immediately.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone 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, shortness of breath, hay fever-like symptoms, rash, chills, wheezing, flushing, vomiting, or high or low blood pressure. In more severe cases, anaphylaxis may occur (a sudden and severe allergic reaction with difficulty breathing, swelling, mild confusion, rapid heartbeat, sweating, and loss of consciousness).

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

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

Other side effects
Talk to your doctor if you experience any of the following:

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

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

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

• blood poisoning (sepsis)
• sudden and severe allergic reaction with difficulty breathing, swelling, mild confusion, rapid heartbeat, sweating, and loss of consciousness (anaphylactic reaction)
• skin rash characterised by flat, discoloured spots (macules) and red raised areas (papules) (maculopapular rash)
• rash with redness and inflammation (erythematous rash)
• hives
• itchy skin (pruritus)
• inflammation of the pancreas (pancreatitis)
• injection site pain
• injection site reaction
• infusion-related reactions
• abnormal levels of blood clotting factors (prolonged activated partial thromboplastin time, decreased antithrombin III, decreased blood fibrinogen)
• abnormal kidney function (increased blood creatinine)
• low blood sugar levels (hypoglycaemia)
• low blood pressure (hypotension)
• blood clots, including in blood vessels of the lungs and brain
• irritability
• dizziness

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

• blood clot in one of the major veins of the brain (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 get any side effects, including any not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Enrylaze

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/EXP. The expiry date refers to the last day of that month.
Store unopened vials in the refrigerator (2 °C – 8 °C) in an upright position. Do not freeze.
Keep the vial tightly closed to protect the medicine from light.
After preparing a dose in a syringe, Enrylaze can be stored for up to 8 hours at
room temperature (15 °C – 25 °C) or 24 hours in the refrigerator (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 in the refrigerator (2 °C – 8 °C). The storage period
starts from the moment the solution has been withdrawn from unopened vials.
Do not use this medicine if you notice the presence of particles in the solution.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines you
no longer use. This will help protect the environment.

6. Package contents and other information

What Enrylaze contains

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

Description of the appearance of Enrylaze and package contents
Enrylaze is a clear to slightly yellow solution for injection or infusion, free from particulate matter.
One package contains 3 glass vials, each with 0.5 mL of solution for injection or 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
E-mail: [email protected]

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.
This leaflet is available in all languages of the European Union/European Economic Area on the European Medicines Agency website.