Package Insert: Information for the Patient

Xospata 40Film-Coated Tablets

Gilteritinib

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section4.

What is Xospata

Xospata belongs to a class of cancer medications called protein kinase inhibitors. The active ingredient it contains is gilteritinib.

What is Xospata used for

Xospata is used to treat adults with acute myeloid leukemia (AML), a cancer that affects certain white blood cells. Xospata is used if the AML is related to a mutation of a gene called FLT3 and is administered to patients whose disease has relapsed or not improved with previous treatment.

How Xospata works

In AML, patients develop an elevated number of abnormal white blood cells. Gilteritinib blocks the action of certain enzymes (kinases) that the abnormal cells need to multiply and grow, preventing cancer growth.

Do not take Xospata

• If you are allergic to gilteritinib or any of the other components of this medication (listed in section6).

Warnings and precautions

Consult your doctor, pharmacist, or nurse immediately:

• If you experience any of the following symptoms: fever, difficulty breathing, rash, dizziness, rapid weight gain, swelling of the arms or legs. These may be signsof a complication called differentiation syndrome (see section4‑Adverse reactions). Differentiation syndrome can occur from the first day after starting treatment with Xospata and at any time during the first 3months of treatment. If this occurs, your doctor will monitor your health and may prescribe a medication to treat this complication. Your doctor may also interrupt treatment with Xospata until your symptoms have improved. You can also find this information in the patient information leaflet included in the packaging. It is essential to carry this leaflet with you and show it to any healthcare professional who treats you.

• If you have a seizure or rapidly worsening symptoms, such as headache, decreased alertness, confusion, blurred vision, or other vision problems. These may be signs of a complication called SEPR (see section4. - Adverse reactions). To check if you have developed SEPR, your doctor may perform a test, and if SEPR is confirmed, your doctor will discontinue treatment with Xospata.

Consult your doctor, pharmacist, or nurse before starting Xospata:

• If you have a heart rhythm disorder, such as irregular heartbeat or a complication called QT interval prolongation (see section4. - Adverse reactions).
• If you have a history of low potassium or magnesium levels in your blood, as this may increase the risk of abnormal heart rhythm.
• If you experience severe upper abdominal and back pain, nausea, and vomiting. These may be signs of pancreatitis (inflammation of the pancreas).

Additional monitoring during treatment with Xospata

Your doctor will perform regular blood tests before and during treatment with Xospata. Your doctor will also regularly check your heart function before and during treatment.

Children and adolescents

Xospata should not be administered to children and adolescents under 18years of age because its safety and efficacy in this age group are unknown.

Other medications and Xospata

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take any other medication. Xospata may affect the functioning of other medications, or these medications may affect the functioning of Xospata.

Specifically, inform your doctor, pharmacist, or nurse if you are taking any of the following medications:

• Medications to treat certain types of cancer, such as mitoxantrone or methotrexate.
• Medications used to treat tuberculosis, such as rifampicin.
• Medications used to treat epilepsy, such as phenytoin.
• Medications used to treat fungal infections, such as voriconazole, posaconazole, or itraconazole.
• Medications used to treat bacterial infections, such as erythromycin, clarithromycin, or azithromycin.
• Medications used to treat high blood pressure (hypertension), such as captopril or carvedilol.
• Medications used to treat high blood sugar (hyperglycemia), such as metformin.
• Medications used to lower cholesterol levels, such as rosuvastatin.
• Medications used to treat HIV infection, such as ritonavir.
• Medications used to treat depression, such as escitalopram, fluoxetine, or sertraline.
• Medications used to treat heart problems, such as digoxin.
• Medications used to prevent blood clotting, such as dabigatran etexilate.
• St. John's Wort (also known asHypericum perforatum), a plant-based medication used to treat depression.

If you usually take any of these medications, your doctor may change your medication and prescribe a different one during treatment with Xospata.

Pregnancy and breastfeeding

Xospata may harm the fetus and should not be used during pregnancy. Women receiving Xospata who may become pregnant should use an effective contraceptive method during treatment with Xospata and for at least 6months after completing treatment with Xospata. If you use hormonal contraception, you should also use a barrier method, such as a condom or diaphragm. Men treated with Xospata whose partners may become pregnant should use an effective contraceptive method during treatment with Xospata and for at least 4months after completing treatment.

The safety of Xospata in breastfeeding women is unknown. Do not breastfeed during treatment with Xospata and for at least 2months after completing treatment.

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor, pharmacist, or nurse before using this medication.

Driving and operating machinery

You may feel dizzy after taking Xospata. If this happens, do not drive or operate machinery.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Xospata is administered orally, in the form of tablets.

Your doctor will tell you what dose of Xospata to take. The recommended dose is 120 mg (three tablets) once a day. Your doctor may decide to increase or decrease your dose or temporarily interrupt treatment. Take the treatment at the dose prescribed by your doctor.

How to Take Xospata

• Take Xospata once a day, at the same time each day.
• Swallow the tablets whole with water.
• Do not break or crush the tablets.
• Xospata can be taken with or without food.
• Take Xospata for the entire time that your doctor tells you to.

If You Take More Xospata Than You Should

If you take more tablets than you should, stop taking Xospata and consult your doctor.

If You Forget to Take Xospata

If you forget to take Xospata at the usual time, take your usual dose as soon as you remember and take the next dose at the usual time the next day. Do not take a double dose to make up for the missed doses.

If You Interrupt Treatment with Xospata

Do not stop taking this medication unless your doctor tells you to. The response may be delayed, so continue taking Xospata for the time that your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some possible side effects can be serious:

• Cell differentiation syndrome.Consult your doctor immediately if you have any of the following symptoms: fever, difficulty breathing, rash, dizziness, rapid weight gain, swelling of the arms or legs. These may be signs of a complication called cell differentiation syndrome (can affect up to 1 in 10 people).
• Reversible posterior leukoencephalopathy syndrome (RPLS).Consult your doctor immediately if you have a seizure, rapid worsening of headache, confusion, or vision problems. In patients treated with Xospata, there have been reported cases of a rare complication that affects the brain, called RPLS (can affect up to 1 in 100 people).
• Cardiac rhythm problems (QT interval prolongation).Consult your doctor immediately if you experience changes in your heart rhythm, or if you feel dizzy, lightheaded, or faint. Xospata can cause a heart problem called QT interval prolongation (can affect up to 1 in 10 people).

Other possible side effects

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

• diarrhea
• nausea
• constipation
• fatigue
• fluid retention (edema)
• lack of energy, weakness (asthenia)
• abnormal laboratory results: elevated levels of creatine phosphokinase (indicator of muscle or heart function), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or alkaline phosphatase (indicator of liver function)
• limb pain
• joint pain (arthralgia)
• muscle pain (myalgia)
• cough
• shortness of breath (dyspnea)
• dizziness
• low blood pressure (hypotension)

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

• fluid accumulation around the heart, which if severe can reduce the heart's ability to pump blood (pericardial effusion)
• a vague feeling of discomfort, not feeling well (general malaise)
• potentially life-threatening severe allergic reaction, e.g., swelling of the mouth, tongue, face, and throat, itching, hives (anaphylactic reaction)
• muscle stiffness
• reduced urine output, swelling of the legs (signs of sudden kidney injury)
• inflammation of the heart (pericarditis)
• heart failure

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is not listed in this leaflet. You can also report them directly through the national notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and on the blister pack after CAD. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from light.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Xospata

• The active ingredient is gilteritinib. Each film-coated tablet contains 40mg of gilteritinib (as fumarate).
• The other components are: mannitol (E421), hydroxypropylcellulose, hydroxypropylcellulose of low substitution, magnesium stearate, hypromellose, talc, macrogol, titanium dioxide, yellow iron oxide (E172).

Appearance of the product and contents of the pack

Xospata 40mg film-coated tablets (tablets) are round, yellowish-colored film-coated tablets, marked with the company logo and “235” on the same face of the tablet.

The tablets are in blisters and are available in packs of 84film-coated tablets (4blister packs of 21film-coated tablets).

Marketing Authorization Holder

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

Netherlands

Responsible Person for Manufacturing

Delpharm Meppel B.V.

Hogemaat 2

7942 JG Meppel

Netherlands

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of the summary of product characteristics: MM/YYYY

For detailed information about this medicinal product, please visit the website of the European Medicines Agency:http://www.ema.europa.eu