Xalkori 50 mg granules in capsules for opening

Patient Information Leaflet

Introduction

Patient Information Leaflet

XALKORI 20 mg granules in capsules for opening

XALKORI 50 mg granules in capsules for opening

XALKORI 150 mg granules in capsules for opening

crizotinib

The terms "you" and "your" refer to both adult patients and caregivers of pediatric patients.

Read this entire leaflet carefully before starting to take this medicine, as it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• 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 harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if the reaction is not listed in this leaflet. See section 4.

Leaflet Contents

1. What XALKORI is and what it is used for
2. What you need to know before taking XALKORI
3. How to take XALKORI granules in capsules for opening
4. Possible side effects
5. How to store XALKORI
6. Contents of the pack and other information
7. Instructions for use

1. What XALKORI is and what it is used for

XALKORI is an anticancer medicine containing crizotinib as the active substance, used to treat adults with a type of lung cancer called non-small cell lung cancer that has a specific alteration or defect in a gene known as anaplastic lymphoma kinase (ALK) or in a gene called ROS1.

XALKORI may be prescribed as initial treatment if your lung cancer is at an advanced stage.

XALKORI may be prescribed if your disease is at an advanced stage and previous treatment has not helped to stop your disease.

XALKORI can slow down or stop the growth of lung cancer. This may help reduce the tumor.

XALKORI is used to treat children and adolescents (aged ≥ 1 to < 18 years) with a type of tumor called anaplastic large cell lymphoma (ALCL) or a type of tumor called inflammatory myofibroblastic tumor (IMT) that has a specific rearrangement or defect in a gene known as anaplastic lymphoma kinase (ALK).

XALKORI may be prescribed to children and adolescents to treat ALCL if previous treatment has not helped to stop the disease.

XALKORI may be prescribed to children and adolescents to treat IMT if surgical treatment has not helped to stop the disease. 77

You should only receive this medicine under the supervision of a doctor experienced in the treatment of cancer. If you have any questions about how XALKORI works or why it has been prescribed for you, consult your doctor.

2. What you need to know before starting XALKORI

Do not take XALKORI

• If you are allergic to crizotinib or to any of the other components of this medicine (listed in section 6, “Composition of XALKORI”).

Warnings and precautions

Talk to your doctor before starting XALKORI:

• If you have moderate or severe liver disease.
• If you have ever had any lung problems. Some lung problems may worsen during treatment with XALKORI, as XALKORI can cause lung inflammation during treatment. Contact your doctor immediately if you develop any new symptoms or if existing symptoms worsen, including difficulty breathing, shortness of breath, cough with or without mucus, or fever.
• If, after undergoing an electrocardiogram (ECG), you were informed that you have a heart condition known as QT interval prolongation.
• If you have a slow heart rate.
• If you have ever had stomach or intestinal problems, such as perforations (holes), or have had conditions causing inflammation inside the abdomen (diverticulitis), or if cancer has spread to the abdomen (metastases).
• If you have vision disturbances (such as seeing flashes of light, blurred vision, or double vision).
• If you have severe kidney disease.
• If you are currently being treated with any other medicine listed in the section “Other medicines and XALKORI”.

If any of the above situations apply to you, inform your doctor.

Contact your doctor immediately after taking XALKORI:

• If you experience severe stomach or abdominal pain, fever, chills, shortness of breath, rapid pulse, partial or complete loss of vision (in one or both eyes), or changes in bowel habits.

Children and adolescents

The indication for non-small cell lung cancer does not include children and adolescents. Do not administer this medicine to children under 1 year of age with ALK-positive ALCL or ALK-positive IMT. XALKORI should be administered to children and adolescents under adult supervision.

Other medicines and XALKORI

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including herbal medicines and medicines obtained without a prescription.

In particular, the following medicines may increase the risk of adverse effects with XALKORI:

• Clarithromycin, telithromycin, erythromycin, antibiotics used to treat bacterial infections.
• Ketoconazole, itraconazole, posaconazole, voriconazole, used to treat fungal infections.
• Atazanavir, ritonavir, cobicistat, used to treat HIV/AIDS infections.

The following medicines may reduce the effectiveness of XALKORI:

• Phenytoin, carbamazepine, or phenobarbital, antiepileptic medicines used to treat seizures or epileptic attacks.
• Rifabutin, rifampicin, used to treat tuberculosis.
• St. John’s wort (Hypericum perforatum), a herbal remedy used to treat depression.

XALKORI may increase the adverse effects associated with the following medicines:

• Alfentanil and other short-acting opioids such as fentanyl (analgesics used during surgical procedures).

• Quinidine, digoxin, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, verapamil, diltiazem, used to treat heart conditions.

• Blood pressure medicines called beta-blockers, such as atenolol, propranolol, labetalol.

• Pimozide, used to treat mental illnesses.

• Metformin, used to treat diabetes.

• Procainamide, used to treat cardiac arrhythmias.

• Cisapride, used to treat gastric conditions.

• Cyclosporine, sirolimus, and tacrolimus, used in transplant patients.

• Ergot alkaloids (e.g., ergotamine, dihydroergotamine) used to treat migraines.

• Dabigatran, an anticoagulant used to reduce blood clotting.

• Colchicine, used to treat gout.

• Pravastatin, used to lower cholesterol levels.

• Clonidine, guanfacine, used to treat hypertension.

• Mefloquine, used for prevention of malaria.

• Pilocarpine, used to treat glaucoma (a serious eye disease).

• Anticholinesterases, used to restore muscle function.

• Antipsychotics, used to treat mental illnesses.

• Moxifloxacin, used to treat bacterial infections.

• Methadone, used to treat pain and opioid dependence.

• Bupropion, used to treat depression and to help quit smoking.

• Efavirenz, raltegravir, used to treat HIV infection.

• Irinotecan, a chemotherapeutic agent used to treat colon and rectal cancer.

• Morphine, used to treat acute and cancer-related pain.

• Naloxone, used to treat opioid addiction and withdrawal.

These medicines should be avoided during treatment with XALKORI.

Oral contraceptives

If you are taking oral contraceptives while taking XALKORI, the oral contraceptives may be ineffective.

Taking XALKORI with food and drinks

XALKORI may be taken after a meal or on an empty stomach. Do not disperse XALKORI granules in food. You should avoid drinking grapefruit juice or eating grapefruit while being treated with XALKORI, as they may alter the levels of XALKORI in your body.

Sun protection

Avoid spending too much time in sunlight. XALKORI may make your skin sensitive to sunlight (photosensitivity), increasing your risk of sunburn. Wear protective clothing and/or sunscreen to protect your skin from sunburn if you need to be exposed to sunlight during treatment with XALKORI.

Pregnancy and breastfeeding

If you are pregnant, may become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Women should avoid becoming pregnant and men should avoid fathering a child during treatment with XALKORI, as this medicine may harm the unborn baby. An effective method of contraception should be used during treatment and for at least 90 days after completing treatment, if there is any possibility that the person taking this medicine could become pregnant or conceive a child, since oral contraceptives may be ineffective while taking XALKORI.

Do not breastfeed during treatment with XALKORI. XALKORI could harm the breastfed infant.

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

Exercise caution when driving or operating machinery, as patients receiving XALKORI may experience visual disturbances, dizziness, and fatigue.

XALKORI contains sucrose

If your doctor has diagnosed you with an intolerance to certain sugars, consult him before taking this medicine.

3. How to take XALKORI capsules with granules for opening

Follow exactly the instructions for taking this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again.

• The recommended dose for children and adolescents with ALK-positive NSCLC or ALK-positive ROS1-positive cancers is 280 mg/m² orally twice daily. The recommended dose will be calculated by the child's doctor and will depend on the child's weight and height (body surface area, BSA). The maximum daily dose in children and adolescents must not exceed 1,000 mg. XALKORI should be administered under adult supervision.
• Administer the recommended dose once in the morning and once in the evening.
• Administer the capsules at approximately the same times each day.
• The granules must be administered into the mouth and must not be crushed, chewed, or sprinkled onto food.
• The capsule shell must not be swallowed.

Method of administration

For detailed instructions on how to administer XALKORI granules, see section 7 “Instructions for use” at the end of this leaflet.

• Hold the capsule with the text “Pfizer” on top, and tap the capsule gently so that all the granules fall to the lower half of the capsule.
• Carefully squeeze the lower part of the capsule.
• Twist and remove the capsule cap.
• Pour the granules directly into the child’s mouth, OR first pour the granules into a spoon or medicine cup and then administer into the child’s mouth.
• Tap the open capsule to ensure all granules have been administered.
• If the full dose cannot be administered at once, divide it into portions until the complete dose has been given.
• Immediately after administration, give the child a glass of water to ensure that all granules have been swallowed.
• After the child has swallowed the granules, other liquids or food may be given, except grapefruit and grapefruit juice.

If necessary, your doctor may reduce the oral dose. Your doctor may decide to permanently discontinue treatment with XALKORI if you are unable to tolerate it.

If you take more XALKORI than you should

If you accidentally take more capsules, contact your doctor or pharmacist immediately. Medical attention may be required.

If you forget to take XALKORI

The course of action if you miss a dose depends on how long it is until the next dose:

• If the next dose is 6 hours or more away, take the missed capsule as soon as possible. Then take the next capsule at the usual time.
• If the next dose is less than 6 hours away, do not take the missed capsule. Take the next capsule at the usual time.

Inform your doctor about the missed dose at your next visit.

Do not take a double dose to make up for a missed capsule.

If you vomit after taking a dose of XALKORI, do not take an additional dose; take the next dose at the usual time.

If you stop taking XALKORI

It is important to take XALKORI every day for as long as your doctor has prescribed it. If you are unable to take this medicine as prescribed, or if you think you no longer need it, contact your doctor immediately.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

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

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if these adverse effects are not listed in this leaflet.

Although not all adverse effects identified in adults with NSCLC have been observed in children and adolescents with ALK-positive ALCL or ALK-positive IMT, the same adverse effects should be considered for adult patients with lung cancer and for children and adolescents with ALK-positive ALCL or ALK-positive IMT.

Some adverse effects may be serious. You must contact your doctor immediately if you experience any of the following serious adverse effects (see also section 2, “What you need to know before starting XALKORI”):

• Liver failure

Contact your doctor immediately if you feel more tired than usual, if your skin or the whites of your eyes turn yellow, if your urine becomes dark or brown (tea-colored), if you have nausea, vomiting, or loss of appetite, if you have pain in the right side of your stomach, or if you experience itching or bruise more easily than normal. Your doctor may perform blood tests to check your liver function, and if the results are abnormal, may reduce your XALKORI dose or discontinue treatment.

• Lung inflammation

Contact your doctor immediately if you experience difficulty breathing, especially if associated with cough or fever.

• Reduction in the number of white blood cells (including neutrophils)

Contact your doctor immediately if you develop fever or infection. Your doctor may perform blood tests, and if the results are abnormal, may decide to reduce your XALKORI dose.

• Dizziness, fainting, or chest pain

Contact your doctor immediately if you experience any of these symptoms, as they could be signs of changes in electrical activity (seen on an electrocardiogram) or an abnormal heart rhythm. Your doctor may perform electrocardiograms to monitor for heart problems during XALKORI treatment.

• Partial or complete vision loss in one or both eyes

Contact your doctor immediately if you experience new vision problems, vision loss, or any change in vision, such as difficulty seeing with one or both eyes. Your doctor may suspend or permanently discontinue XALKORI treatment and refer you to an ophthalmologist.

For children and adolescents receiving XALKORI for the treatment of ALK-positive ALCL or ALK-positive IMT: your doctor should refer you to an ophthalmologist before starting XALKORI treatment, and within 1 month after starting XALKORI treatment to detect vision problems. An ophthalmological examination should be performed every 3 months during XALKORI treatment, and more frequently if new vision problems occur.

• Severe gastrointestinal problems in children and adolescents with ALK-positive ALCL or ALK-positive IMT

XALKORI may cause severe diarrhea, nausea, or vomiting. Inform your doctor immediately if you experience difficulty swallowing, vomiting, or diarrhea during XALKORI treatment. Your doctor may prescribe medications as needed to prevent or treat diarrhea, nausea, and vomiting. Your doctor may recommend drinking more fluids or prescribe electrolyte supplements or other forms of nutritional support if severe symptoms occur.

Other adverse effects with XALKORI in adults with NSCLC may include:

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

• Visual disturbances (seeing flashes of light, blurred vision, light sensitivity, seeing floaters, or double vision, usually occurring soon after starting XALKORI treatment).
• Gastrointestinal problems, including vomiting, diarrhea, nausea.
• Edema (excess fluid in body tissues causing swelling of hands and feet).
• Constipation.
• Abnormal liver function tests in blood tests.
• Decreased appetite.
• Fatigue.
• Dizziness.
• Neuropathy (numbness or tingling sensation in joints or limbs).
• Altered sense of taste.
• Abdominal pain.
• Reduction in red blood cells (anemia).
• Rash.
• Slowed heart rate.

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

• Indigestion.
• Increased blood creatinine levels (may indicate impaired kidney function).
• Increased blood alkaline phosphatase enzyme levels (a sign of organ dysfunction or injury, especially in the liver, pancreas, bones, thyroid gland, or gallbladder).
• Hypophosphatemia (low blood phosphate levels that may cause confusion or muscle weakness).
• Fluid-filled sac within the kidney (renal cysts).
• Fainting.
• Inflammation of the esophagus (swallowing tube).
• Decreased testosterone levels, a male sex hormone.
• Heart failure.

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

• Perforation (hole) in the stomach or intestine.
• Sensitivity to sunlight (photosensitivity).
• Elevated blood test results indicating muscle damage (high levels of creatine phosphokinase).

Other adverse effects of XALKORI in children and adolescents with ALK-positive ALCL or ALK-positive IMT may include:

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

• Abnormal liver function tests in blood tests.
• Visual disturbances (seeing flashes of light, blurred vision, light sensitivity, seeing floaters, or double vision, usually occurring soon after starting XALKORI treatment).
• Abdominal pain.
• Increased blood creatinine levels (may indicate impaired kidney function).
• Anemia (reduction in the number of red blood cells).
• Low platelet count in blood tests (may increase the risk of bleeding and bruising).
• Fatigue.
• Decreased appetite.
• Constipation.
• Edema (excess fluid in body tissues causing swelling of hands and feet).
• Increased blood alkaline phosphatase enzyme levels (indicator of organ dysfunction or injury, especially in the liver, pancreas, bones, thyroid gland, or gallbladder).
• Neuropathy (numbness or tingling sensation in joints or limbs).
• Dizziness.
• Indigestion.
• Altered sense of taste.
• Hypophosphatemia (low blood phosphate levels that may cause confusion or muscle weakness).

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

• Rash.
• Inflammation of the esophagus (swallowing tube).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of XALKORI

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the bottle and carton after "EXP". The expiry date is the last day of the month indicated.
• Store below 25°C.
• Do not use this medicine if it is damaged or shows signs of deterioration.

Medicines must not be disposed of via wastewater or household waste. Empty XALKORI capsule shells (oral granules) may be discarded in domestic waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of XALKORI

• The active substance in XALKORI is crizotinib.

XALKORI 20 mg granules in capsules for opening: each capsule contains 20 mg of crizotinib

XALKORI 50 mg granules in capsules for opening: each capsule contains 50 mg of crizotinib

XALKORI 150 mg granules in capsules for opening: each capsule contains 150 mg of crizotinib

• The other components are (see also section 2 “XALKORI contains sucrose”):

Granule content: stearyl alcohol, poloxamer, sucrose, talc (E553b), hypromellose (E464), macrogol (E1521), glycerol monostearate (E471), medium-chain triglycerides.

Capsule: gelatin, titanium dioxide (E171), brilliant blue (E133) or iron oxide black (E172).

Printing ink: shellac (E904), propylene glycol (E1520), potassium hydroxide (E525), iron oxide black (E172).

Appearance of the product and contents of the pack

XALKORI granules are white to off-white and contained in an opening capsule.

XALKORI 20 mg granules in opening capsules are capsules with a light blue cap printed with the word “Pfizer” in black ink and a white body printed with “CRZ 20” in black ink.

XALKORI 50 mg granules in opening capsules are capsules with a grey cap printed with the word “Pfizer” in black ink and a light grey body printed with “CRZ 50” in black ink.

XALKORI 150 mg granules in opening capsules are capsules with a light blue cap printed with the word “Pfizer” in black ink and a light blue body printed with “CRZ 150” in black ink.

It is available in plastic bottles containing 60 opening capsules.

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Brussels

Belgium

Manufacturer

Pfizer Service Company BV

Hermeslaan 11

1932 Zaventem

Belgium

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

Belgium/Belgium/Belgium Luxembourg/Luxembourg Pfizer S.A./N.V. Tel/Tel: + 32 (0)2 554 62 11	Latvia Pfizer Luxembourg SARL filiale Latvija Tel.: + 371 670 35 775
	Lithuania Pfizer Luxembourg SARL filialas Lietuvoje Tel: +370 52 51 4000
Czech Republic Pfizer, spol. s r.o. Tel: + 420 283 004 111	Hungary Pfizer Kft Tel: +36 1 488 3700
Denmark Pfizer ApS Tlf: + 45 44 201 100	Malta Vivian Corporation Ltd. Tel: + 35621 344610
Germany Pfizer Pharma GmbH Tel: + 49 (0)30 550055-51000	Netherlands Pfizer BV Tel: +31 (0)800 63 34 636
Estonia Pfizer Luxembourg SARL Eesti filiaal Tel.: +372 666 7500	Norway Pfizer AS Tlf: +47 67 52 61 00
Greece Pfizer Ελλάς A.E. Tel.: +30 210 6785 800	Austria Pfizer Corporation Austria Ges.m.b.H Tel: + 43 (0)1 521 15-0
Spain Pfizer, S.L. Tel+34914909900	Poland Pfizer Polska Sp. z o.o. Tel.: +48 22 335 61 00
France Pfizer Tel +33 1 58 07 34 40	Portugal Laboratórios Pfizer, Lda. Tel: (+351) 21 423 55 00
Croatia Pfizer Croatia d.o.o. Tel: + 385 1 3908 777	Romania Pfizer Romania S.R.L Tel: +40 (0) 21 207 28 00
Ireland Pfizer Healthcare Ireland Tel: 1800 633 363 (toll free) +44 (0)1304 616161	Slovenia Pfizer Luxembourg SARL Pfizer, podružnica za svetovanje s podrocja farmacevtske dejavnosti, Ljubljana Tel.: + 386 (0)1 52 11 400
Iceland Icepharma hf Simi: + 354 540 8000	Slovakia Pfizer Luxembourg SARL, organizačná zložka Tel: + 421 2 3355 5500
Italy Pfizer s.r.l Tel: +39 06 33 18 21	Finland Pfizer Oy Puh/Tel: +358 (0)9 430 040
Cyprus Pfizer Ελλάς Α.Ε. (Cyprus Branch) Tel: +357 22 817690	Sweden Pfizer AB Tel: +46 (0)8 550 520 00

Date of the most recent revision of this leaflet: {MM/YYYY}.

Other sources of information

Detailed information about this medicine and information in different languages is available by scanning the QR code on the carton with a mobile device.

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

1. Instructions for use

Read section 7 in full before using XALKORI capsules with granules to open.

Items required for administration of XALKORI:

• XALKORI capsules with granules, prescribed by your doctor.
• Optionally, a spoon or measuring cup provided by the user.

Preparation of XALKORI granules (steps 1 to 3):

Step 1	Remove the number of capsules required for the prescribed dose of XALKORI granules from the corresponding bottle(s).
Step 2	Hold a capsule with the text "Pfizer" on top. Tap the capsule gently so that all the granules fall to the bottom part of the capsule. Carefully squeeze the bottom part of the capsule to loosen the top part.
Step 3	Hold the top and bottom parts of the capsule and twist them in opposite directions to separate and open the capsule.

Administration of XALKORI granules (step 4): There are 2 options for administering the granules orally to the child.

Step 4	Option 1 (pour granules directly into the child's mouth)	Pour the entire contents of 1 capsule directly into the child's mouth. Gently tap the capsule with a finger to release all the granules. Immediately after administering XALKORI granules, give the child a sufficient amount of water to ensure that all granules have been swallowed. If more than 1 capsule is required to achieve the prescribed dose, repeat the administration of granules from each opened capsule, followed by water.
Option 2 (pour granules from an administration device)	Pour the granules from the capsules corresponding to the prescribed dose into a dry administration device. Pour the granules from the administration device into the child's mouth. Immediately after administering XALKORI granules, give the child a sufficient amount of water to ensure that all granules are swallowed. If the child cannot take the prescribed dose in a single administration, divide the granules into portions as needed and administer them sequentially, each followed by water, until the full prescribed dose has been given.

Once step 4 is completed, you may give the child other liquids or foods, except grapefruit and grapefruit juice.

Consult your doctor or pharmacist if you are unsure how to prepare or administer the prescribed dose of XALKORI granules to the child.