Patient Information Leaflet

XALKORI 200 mg hard capsules, 250 mg hard capsules

crizotinib
The terms "you" and "your" refer to both adult patients and caregivers of paediatric patients.
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet. 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 yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

What XALKORI is and what it is used for
What you need to know before taking XALKORI
How to take XALKORI 200 mg and 250 mg hard capsules
Possible side effects
How to store XALKORI
Contents of the pack and other information

1. What XALKORI is and what it is used for

XALKORI is an anticancer medicine containing the active substance crizotinib, used for the treatment of adult patients with a type of cancer called non-small cell lung cancer (NSCLC) that has a specific rearrangement or defect in the ALK (anaplastic lymphoma kinase) gene or the ROS1 gene.
XALKORI may be prescribed as initial treatment if the disease is advanced-stage lung cancer.
XALKORI may be prescribed if the disease is advanced and previous treatments have not been able to stop disease progression.
XALKORI can slow down or stop the growth of lung cancer and thereby help reduce tumor mass.
XALKORI is used for the treatment of children and adolescents (aged ≥ 1 to < 18 years) with a type of cancer called anaplastic large cell lymphoma (ALCL) or a type of tumor called inflammatory myofibroblastic tumor (IMT) that have a specific rearrangement or defect in the ALK (anaplastic lymphoma kinase) gene.
XALKORI may be prescribed for children and adolescents for the treatment of ALCL if previous treatment has not helped to stop the disease.
XALKORI may be prescribed for children and adolescents for the treatment of IMT if surgery has not helped to stop the disease.
This medicine must be administered only to you and under the supervision of a physician experienced in cancer treatment. If you have any doubts about how XALKORI works or why it has been prescribed for you, consult your doctor.

2. What you should know before taking XALKORI

Do not take XALKORI

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

Warnings and precautions
Talk to your doctor before taking XALKORI:

If you have moderate or severe liver disease.
If you have or have ever had any other lung problems. Some lung disorders may worsen during treatment with XALKORI, as XALKORI can cause lung inflammation during treatment. Symptoms may resemble those of lung cancer. Inform your doctor immediately if new symptoms occur or existing symptoms worsen during treatment with this medicine, including difficulty breathing, shortness of breath, cough with or without mucus, or fever.
If you have been diagnosed with an abnormal heart rhythm on electrocardiogram (ECG), known as QT interval prolongation.
If you have a slow heart rate.
If you have ever had stomach or intestinal problems, such as perforations, or if you have conditions causing inflammation in the abdomen (diverticulitis) or if the tumour has spread to the abdomen (metastases).
If you have vision disorders (seeing flashes of light, blurred vision, or double vision).
If you have severe kidney disease.
If you are currently being treated with any of the medicines listed in the section “Other medicines and XALKORI”.

If any of the above conditions apply to you, inform your doctor.
Inform your doctor immediately after taking XALKORI:

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

Most of the available information comes from adult patients with a specific type of
NSCLC histology (adenocarcinoma) positive for ALK or ROS1. Information on other histologies is limited.
Children and adolescents
The indication for non-small cell lung cancer does not apply to children and
adolescents. XALKORI should be administered to children and adolescents under the supervision of an
adult.
Other medicines and XALKORI
Inform your doctor or pharmacist if you are taking, have recently taken, or might take
any other medicines, including herbal preparations and medicines 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 convulsions.
Rifabutin, rifampicin, used to treat tuberculosis.
St. John’s wort (Hypericum perforatum), a herbal remedy used to treat depression.

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

Alfentanil and other short-acting opioids such as fentanyl (analgesics used during certain surgical procedures).
Quinidine, digoxin, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, verapamil, diltiazem, used to treat heart problems.
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 arrhythmia.
Cisapride, used to treat stomach problems.
Cyclosporine, sirolimus, and tacrolimus, used in transplant patients.
Ergot alkaloids (e.g., ergotamine, dihydroergotamine), used to treat migraine.
Dabigatran, an anticoagulant used to slow blood clotting.
Colchicine, used to treat gout.
Pravastatin, used to lower cholesterol levels.
Clonidine, guanfacine, used to treat hypertension.
Mefloquine, used to prevent malaria.
Pilocarpine, used to treat glaucoma (a serious eye condition).
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 smoking cessation.
Efavirenz, raltegravir, used to treat HIV infections.
Irinotecan, a chemotherapeutic agent used to treat colon and rectal cancer.
Morphine, used to treat acute pain and cancer pain.
Naloxone, used to treat opioid dependence and withdrawal.

These medicines must be avoided during treatment with XALKORI.
Oral contraceptives
If you take XALKORI while using oral contraceptives, the oral contraceptives may
be ineffective.
XALKORI with food and drink
You may take XALKORI with or without food; however, grapefruit or grapefruit juice should be avoided during treatment with XALKORI, as it may alter the amount of XALKORI in your body.
Sun protection
Avoid prolonged exposure to sunlight. XALKORI may make your skin sensitive to sunlight (photosensitivity) and more prone to sunburn. If you need to be exposed to sunlight during treatment with XALKORI, wear protective clothing and/or use a sunscreen that protects your skin from sunburn.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Women are advised not to become pregnant and men are advised to avoid fathering a child during treatment with XALKORI, as this medicine may harm the unborn child. If there is any possibility that the person taking this medicine could become pregnant or father a child, a reliable method of contraception must be used throughout the treatment period and for at least 90 days after completion of therapy, as oral contraceptives may not be effective when taken with XALKORI.
Do not breastfeed during treatment with XALKORI.
XALKORI may harm the breastfed infant.
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
Exercise particular caution when driving or operating machinery, as patients taking XALKORI may experience visual disturbances, dizziness, and fatigue.
XALKORI contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 200 mg or 250 mg hard capsule,
i.e., essentially ‘sodium-free’.

3. How to take XALKORI 200 mg and 250 mg hard capsules

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

The recommended dose for adults with NSCLC is one 250 mg capsule taken orally twice daily (for a total of 500 mg).
The recommended dose for children and adolescents with ALK-positive ALCL or ALK-positive IMT is 280 mg/m² taken orally twice daily. The recommended dose will be calculated by the patient's doctor and depends on the patient's body surface area (BSA). The maximum daily dose in children and adolescents must not exceed 1,000 mg. XALKORI must be administered under the supervision of an adult.
Take the recommended dose once in the morning and once in the evening.
Take the capsules at approximately the same time each day.
You may take the capsules with or without food, but always avoid grapefruit juice.
Swallow the capsules whole, without breaking, dissolving, or opening them.

If necessary, your doctor may decide to reduce the oral dose. Your doctor may decide to permanently discontinue treatment if you do not tolerate XALKORI.

If you take more XALKORI than you should
If you accidentally take too many capsules, contact your doctor or pharmacist immediately. Medical intervention may be necessary.

If you forget to take XALKORI
If you forget to take a capsule, the action you should take depends on how long it is until your next dose.

If your next dose is due 6 hours or more away, take the missed capsule as soon as you remember. Then take the next capsule at your usual time.
If your next dose is due within 6 hours, do not take the missed capsule. Take the next capsule at your usual time.

At your next appointment, inform your doctor that you missed a dose.
Do not take a double dose (two capsules at the same time) to make up for a forgotten dose.
If you vomit after taking a dose of XALKORI, do not take another dose: take your next dose at the regular time.

If you stop taking XALKORI
It is important to take XALKORI every day for the entire duration prescribed by your doctor. If you are unable to take the medicine your doctor has prescribed, or if you think you no longer need it, contact your doctor immediately.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
Although not all adverse reactions identified in adults with NSCLC have been observed in children and adolescents with ALCL or IMT, the same side effects observed in adult patients with lung cancer should be considered in children and adolescents with ALCL or IMT.
Some side effects may be serious. Contact your doctor immediately if you experience any of the following serious side effects (see also section 2 "What you need to know before taking XALKORI"):

Liver failure Inform 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-coloured), if you develop nausea, vomiting or loss of appetite, if you have pain in the right side of your stomach, if you have itching, or if you notice an increased tendency to bruise. Your doctor may perform blood tests to monitor your liver function, and if the results are abnormal, may decide to reduce the dose of XALKORI or stop treatment.
Lung inflammation Inform your doctor immediately if you have difficulty breathing, especially if associated with cough or fever.
Reduction in white blood cell count (including neutrophils) Inform your doctor immediately if you develop fever or infection. Your doctor may perform a blood test and, if the results are abnormal, may decide to reduce the dose of XALKORI.
Mental confusion, fainting or chest discomfort Inform your doctor immediately if you experience these symptoms, which may indicate changes in electrical activity (seen on electrocardiogram) or changes in heart rhythm. Your doctor may perform an electrocardiogram to check for heart problems during treatment with XALKORI.
Complete or partial loss of vision in one or both eyes Inform your doctor immediately if you develop new vision problems, loss of vision, or any change in vision such as difficulty seeing with one or both eyes. Your doctor may suspend or permanently discontinue treatment with XALKORI and refer you to an ophthalmologist.

For children and adolescents taking XALKORI for the treatment of ALK-positive ALCL or ALK-positive IMT: your doctor should refer you to an ophthalmologist before starting treatment with XALKORI and within 1 month after starting XALKORI to check for vision problems. You should have an eye examination every 3 months during treatment with XALKORI, and more frequently if new vision problems occur.

Severe stomach and intestinal (gastrointestinal) problems in children and adolescents with ALK-positive ALCL or ALK-positive IMT XALKORI may cause severe diarrhoea, nausea or vomiting. Inform your doctor immediately if you develop difficulty swallowing, vomiting or diarrhoea during treatment with XALKORI. Your doctor may prescribe medications as needed to prevent or treat diarrhoea, nausea and vomiting. If you develop severe symptoms, your doctor may recommend drinking more fluids or may prescribe electrolyte supplements or other types of nutritional support.

Other side effects of XALKORI in adults with NSCLC may include:
Very common side effects (may affect more than 1 in 10 people)

Vision disorders (flashes of light, blurred vision, light sensitivity, floaters or double vision, which often occur soon after starting treatment with XALKORI).
Stomach problems, including vomiting, diarrhoea, nausea.
Swelling of hands and feet (oedema).
Constipation.
Abnormal liver function tests.
Decreased appetite.
Tiredness.
Dizziness.
Neuropathy (numbness or pins and needles sensation in joints or extremities).
Altered sense of taste.
Abdominal pain.
Reduction in red blood cells (anaemia).
Rash.
Decreased heart rate.

Common side 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 (an indicator of organ dysfunction or injury, particularly of the liver, pancreas, bones, thyroid or gallbladder).
Hypophosphataemia (low phosphate levels in the blood, which may cause confusion or muscle weakness).
Fluid-filled sacs in the kidneys (renal cysts).
Fainting.
Inflammation of the oesophagus.
Decreased testosterone levels, a male sex hormone.
Heart failure.

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

Perforation of the stomach or intestine.
Sensitivity to sunlight (photosensitivity).
Increased blood levels in tests indicating muscle damage (elevated creatine phosphokinase levels).

Other side effects of XALKORI in children and adolescents with ALK-positive ALCL or ALK-positive IMT may include:
Very common side effects (may affect more than 1 in 10 people)

Abnormal blood tests for liver function.
Vision disorders (flashes of light, blurred vision, light sensitivity, floaters or double vision), which often occur soon after starting treatment with XALKORI.
Abdominal pain.
Increased blood creatinine levels (may indicate impaired kidney function).
Anaemia (reduction in red blood cell count).
Low platelet count in blood tests (may increase the risk of bleeding and bruising).
Tiredness.
Loss of appetite.
Constipation.
Oedema (excess fluid in body tissues causing swelling of hands and feet).
Increased blood alkaline phosphatase enzyme levels (an indicator of organ dysfunction or injury, particularly of the liver, pancreas, bones, thyroid or gallbladder).
Neuropathy (numbness or pins and needles sensation in joints or extremities).
Dizziness.
Indigestion.
Altered sense of taste.
Hypophosphataemia (low phosphate levels in the blood, which may cause confusion or muscle weakness).

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

Rash.
Inflammation of the oesophagus.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. 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 XALKORI

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, blister pack label, or bottle after “EXP”. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.

Do not dispose of any medicine via wastewater or household waste. 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 XALKORI contains
The active substance in XALKORI is crizotinib.
XALKORI 200 mg hard capsules: each capsule contains 200 mg of crizotinib.
XALKORI 250 mg hard capsules: each capsule contains 250 mg of crizotinib.
The other components are (see also section 2 “XALKORI contains sodium”):
Capsule contents: anhydrous colloidal silica, microcrystalline cellulose, anhydrous dibasic calcium phosphate, sodium starch glycolate (Type A), magnesium stearate.
Capsule shell: gelatin, titanium dioxide (E171), red iron oxide (E172).
Ink: shellac (E904), propylene glycol (E1520), potassium hydroxide (E525), black iron oxide (E172).

Description of the appearance of XALKORI and package contents
XALKORI 200 mg is available as hard gelatin capsules with a pink cap and a white body, printed in black ink with “Pfizer” on the cap and “CRZ 200” on the body.
XALKORI 250 mg is available as hard gelatin capsules with a pink cap and pink body, printed in black ink with “Pfizer” on the cap and “CRZ 250” on the body.
XALKORI is available in blister packs containing 60 hard capsules and in plastic bottles containing 60 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer
Pfizer Manufacturing Deutschland GmbH
Mooswaldallee 1
79108 Freiburg im Breisgau
Germany

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

België/Belgique/Belgien Latvija
Luxembourg/Luxemburg Pfizer Luxembourg SARL filiāle Latvijā
Pfizer NV/SA Tel: +371 670 35 775
Tél/Tel: +32 (0)2 554 62 11

България Lietuva
Пфайзер Люксембург САРЛ, Клон България Pfizer Luxembourg SARL filialas Lietuvoje
Тел.: +359 2 970 4333 Tel: +370 5 251 4000

Česká republika Magyarország
Pfizer, spol. s r.o. Pfizer Kft.
Tel: +420 283 004 111 Tel.: +36 1488 37 00

Danmark Malta
Pfizer ApS Vivian Corporation Ltd.
Tlf.: +45 44 20 11 00 Tel: +356 21344610

Deutschland Nederland
PFIZER PHARMA GmbH Pfizer bv
Tel: +49 (0)30 550055-51000 Tel: +31 (0)800 63 34 636

Eesti Norge
Pfizer Luxembourg SARL Eesti filiaal Pfizer AS
Tel: +372 666 7500 Tlf: +47 67 52 61 00

Ελλάδα Österreich
Pfizer Ελλάς A.E. Pfizer Corporation Austria Ges.m.b.H.
Τηλ: +30 210 6785800 Tel: +43 (0)1 521 15-0

España Polska
Pfizer, S.L. Pfizer Polska Sp. z o.o.
Tel: +34 91 490 99 00 Tel.: +48 22 335 61 00

France Portugal
Pfizer Laboratórios Pfizer, Lda.
Tél: +33 (0)1 58 07 34 40 Tel: +351 21 423 5500

Hrvatska România
Pfizer Croatia d.o.o. Pfizer Romania S.R.L.
Tel: +385 1 3908 777 Tel: +40 (0) 21 207 28 00

Ireland Slovenija
Pfizer Healthcare Ireland Unlimited Company Pfizer Luxembourg SARL
Tel: +1800 633 363 (toll free) Pfizer, podružnica za svetovanje s področja
Tel: +44 (0)1304 616161 farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Ísland Slovenská republika
Icepharma hf. Pfizer Luxembourg SARL, organizačná zložka
Sími: +354 540 8000 Tel: +421 2 3355 5500

Italia Suomi/Finland
Pfizer S.r.l. Pfizer Oy
Tel: +39 06 33 18 21 Puh/Tel: +358 (0)9 430 040

Kύπρος Sverige
Pfizer Ελλάς Α.Ε. (Cyprus Branch) Pfizer AB
Τηλ: +357 22817690 Tel: +46 (0)8 550 520 00

More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.

Package leaflet: information for the user

XALKORI 20 mg granules in openable capsules, 50 mg granules in openable capsules, 150 mg granules in openable capsules

crizotinib
The terms “you” and “your” refer to both the adult patient and the caregiver of the
pediatric patient.
Read this leaflet carefully before taking this medicine, as it contains
important information for you.

Keep this leaflet. 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 others, even if they have the same symptoms as you, because it may be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What XALKORI is and what it is used for
What you need to know before taking XALKORI
How to take XALKORI granules in openable capsules
Possible side effects
How to store XALKORI
Contents of the pack and other information
Instructions for use

1. What XALKORI is and what it is used for

XALKORI is an anticancer medicine containing the active substance crizotinib, used for the treatment of adult patients with a type of cancer called non-small cell lung cancer (NSCLC) that has a specific rearrangement or defect in the ALK (anaplastic lymphoma kinase) gene or the ROS1 gene.
XALKORI is used for the treatment of children and adolescents (aged ≥ 1 to < 18 years) with a type of cancer called anaplastic large cell lymphoma (ALCL) or a type of cancer called inflammatory myofibroblastic tumour (IMT), which have a specific rearrangement or defect in the ALK (anaplastic lymphoma kinase) gene.
XALKORI may be prescribed for children and adolescents for the treatment of ALCL if previous treatment has not helped to stop the disease.
XALKORI may be prescribed for children and adolescents for the treatment of IMT if surgery has not helped to stop the disease.
This medicine must be given only to you and 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 taking XALKORI

Do not take XALKORI

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

Warnings and precautions
Talk to your doctor before taking XALKORI:

If you have moderate or severe liver disease.
If you have or have ever had any other lung problems. Some lung disorders may worsen during treatment with XALKORI, as XALKORI can cause lung inflammation during treatment. Inform your doctor immediately if you develop new symptoms or if existing symptoms worsen, including difficulty breathing, shortness of breath, cough with or without mucus, or fever.
If you have been told you have an abnormal heart rhythm on electrocardiogram (ECG), known as QT interval prolongation.
If you have a slow heart rate.
If you have ever had stomach or intestinal problems, such as perforations, or if you have conditions causing inflammation in the abdomen (diverticulitis), or if the tumour has spread to the abdomen (metastases).
If you have vision disorders (such as seeing flashes of light, blurred vision, or double vision).
If you have severe kidney disease.
If you are currently taking any of the medicines listed in the section “Other medicines and XALKORI”. If any of the conditions listed above apply to you, inform your doctor.

Inform your doctor immediately after taking XALKORI:

If you experience severe stomach or abdominal pain, fever, chills, shortness of breath, rapid heartbeat, 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 apply to children and adolescents. Do not give 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 the supervision of an adult.

Other medicines and XALKORI
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including herbal preparations and those without a prescription.

In particular, the following medicines may increase the risk of side 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 convulsions.
Rifabutin, rifampicin, used to treat tuberculosis.
St. John’s wort (Hypericum perforatum), a herbal remedy used to treat depression.

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

Alfentanil and other short-acting opioids such as fentanyl (analgesics used during certain surgical procedures).
Quinidine, digoxin, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, verapamil, diltiazem, used to treat heart problems.
Blood pressure medicines called beta-blockers, such as atenolol, propranolol, labetalol.
Pimozide, used to treat mental disorders.
Metformin, used to treat diabetes.
Procainamide, used to treat cardiac arrhythmia.
Cisapride, used to treat stomach problems.
Cyclosporine, sirolimus, and tacrolimus, used in transplant patients.
Ergot alkaloids (e.g., ergotamine, dihydroergotamine), used to treat migraine.
Dabigatran, an anticoagulant used to slow blood clotting.
Colchicine, used to treat gout.
Pravastatin, used to reduce cholesterol levels.
Clonidine, guanfacine, used to treat hypertension.
Mefloquine, used to prevent malaria.
Pilocarpine, used to treat glaucoma (a serious eye condition).
Anticholinesterases, used to restore muscle function.
Antipsychotics, used to treat mental disorders.
Moxifloxacin, used to treat bacterial infections.
Methadone, used to treat pain and opioid dependence.
Bupropion, used to treat depression and smoking cessation.
Efavirenz, raltegravir, used to treat HIV infections.
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 dependence and withdrawal.

These medicines must be avoided during treatment with XALKORI.

Oral contraceptives
If you take XALKORI while using oral contraceptives, the contraceptives may become ineffective.

XALKORI with food and drink
You may take XALKORI with or without food; however, XALKORI granules must not be sprinkled on food. In addition, grapefruit or grapefruit juice should be avoided during treatment with XALKORI, as it may alter the amount of XALKORI in your body.

Sun protection
Avoid prolonged exposure to sunlight. XALKORI can make your skin sensitive to sunlight (photosensitivity) and more prone to sunburn. If you need to be exposed to sunlight during treatment with XALKORI, wear protective clothing and/or use a sunscreen that protects against sunburn.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Women are advised not to become pregnant and men are advised to avoid fathering a child during treatment with XALKORI, as this medicine may harm the unborn child. If there is any possibility that the person taking this medicine could become pregnant or father a child, a reliable method of contraception must be used throughout the treatment period and for at least 90 days after completion of therapy, as oral contraceptives may not be effective when taken with XALKORI.
Do not breastfeed during treatment with XALKORI. XALKORI may harm the breastfed newborn.

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

Driving and using machines
Exercise caution when driving or operating machinery, as patients taking XALKORI may experience visual disturbances, dizziness, and fatigue.

XALKORI contains sucrose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

3. How to administer XALKORI granules in open capsules

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.

The recommended dose for children and adolescents with ALK-positive ALCL or ALK-positive IMT is 280 mg/m² orally twice daily. The recommended dose will be calculated by the patient's physician based on body surface area (BSA). The maximum daily dose in children and adolescents must not exceed 1,000 mg. XALKORI must be administered under the supervision of an adult.
Administer the recommended dose once in the morning and once in the evening.
Administer the capsules at approximately the same time each day.
The granules must be taken orally and must not be crushed, chewed, or sprinkled onto food.
The capsule shell must not be swallowed.

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

Hold the capsule with the “Pfizer” marking facing upwards and gently tap the capsule to ensure all granules have settled into the lower half.
Gently squeeze the bottom of the capsule.
Unscrew the top part of the capsule.
Pour the granules directly into the patient’s mouth OR into a spoon or dosing cup and then pour into the patient’s mouth.
Tap the open capsule gently to ensure all granules have been administered.
If it is not possible to take the entire dose at once, administer it in portions until the full dose has been taken.
Immediately after administration, give water to drink to ensure all granules are swallowed.
After the granules have been swallowed, other liquids or foods may be given, except grapefruit and grapefruit juice.

If necessary, your doctor may decide to reduce the orally administered dose. Your doctor may decide to permanently discontinue treatment with XALKORI if you do not tolerate it.

If you take more XALKORI than you should
If you accidentally take too many capsules, contact your doctor or pharmacist immediately. Medical intervention may be necessary.

If you forget to take XALKORI
If you forget to take a capsule, the action to take depends on how much time remains before the next scheduled dose.

If the next dose is due in 6 hours or more, take the missed capsule as soon as you remember. Then take the next capsule at the usual time.
If the next dose is due within 6 hours, do not take the missed capsule. Take the next capsule at the usual time.

At your next visit, inform your doctor that you missed a dose.
Do not take a double dose to make up for a forgotten dose.
If you vomit after taking a dose of XALKORI, do not take another dose: take the next dose at the regular time.

If you stop taking XALKORI
It is important to take XALKORI every day for the entire duration prescribed by your doctor. If you are unable to take the medicine as prescribed or if you think you no longer need it, contact your doctor immediately.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse.
Although not all adverse reactions identified in adults with NSCLC have been observed in children and adolescents with ALCL or IMT, the same side effects seen in adult patients with lung cancer should be considered relevant for children and adolescents with ALCL or IMT.
Some side effects can be serious. Contact your doctor immediately if you experience any of the following serious side effects (see also section 2 “What you should know before taking XALKORI”):

Liver failure Inform your doctor immediately if you feel more tired than usual, if you develop yellowing of the skin or the whites of the eyes, if your urine becomes dark or brown (tea-colored), if you experience nausea, vomiting, or loss of appetite, if you have pain in the right side of your abdomen, if you have itching, or if you notice an increased tendency to bruise. Your doctor may perform blood tests to monitor liver function, and if the results are abnormal, may decide to reduce the dose of XALKORI or stop treatment.
Lung inflammation Inform your doctor immediately if you have difficulty breathing, especially if associated with cough or fever.
Reduction in white blood cell count (including neutrophils) Inform your doctor immediately if you develop fever or signs of infection. Your doctor may perform a blood test, and if the results are abnormal, may decide to reduce the dose of XALKORI.
Mental confusion, fainting, or chest discomfort Inform your doctor immediately if you experience these symptoms, which may indicate changes in electrical activity (seen on electrocardiogram) or changes in heart rhythm. Your doctor may perform an electrocardiogram to check for cardiac problems during treatment with XALKORI.
Complete or partial loss of vision in one or both eyes Inform your doctor immediately if you develop new vision problems, loss of vision, or any changes in vision such as difficulty seeing in one or both eyes. Your doctor may suspend or permanently discontinue treatment with XALKORI and refer you to an ophthalmologist.

Severe stomach and intestinal (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 develop difficulty swallowing, vomiting, or diarrhea during treatment with XALKORI. Your doctor may prescribe medications as needed to prevent or treat diarrhea, nausea, and vomiting. If severe symptoms develop, your doctor may recommend drinking more fluids or may prescribe electrolyte supplements or other forms of nutritional support.

Other side effects of XALKORI in adults with NSCLC may include:
Very common side effects (may affect more than 1 in 10 people)

Visual disturbances (flashes of light, blurred vision, light sensitivity, floaters, or double vision, which often occur shortly after starting XALKORI treatment).
Stomach problems, including vomiting, diarrhea, nausea.
Edema (excess fluid in body tissues, causing swelling of the hands and feet).
Constipation.
Abnormal liver blood tests.
Decreased appetite.
Fatigue.
Dizziness.
Neuropathy (numbness or tingling sensations in joints or extremities).
Altered sense of taste.
Abdominal pain.
Reduction in red blood cell count (anemia).
Rash.
Slower heart rate.

Common side 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 (an indicator of organ dysfunction or injury, particularly of the liver, pancreas, bones, thyroid, or gallbladder).
Hypophosphatemia (low phosphate levels in the blood, which may cause confusion or muscle weakness).
Fluid-filled sacs in the kidneys (renal cysts).
Fainting.
Inflammation of the esophagus.
Decreased testosterone levels, a male sex hormone.
Heart failure.

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

Perforation of the stomach or intestine.
Increased sensitivity to sunlight (photosensitivity).
Increased blood levels in tests indicating muscle damage (elevated creatine phosphokinase levels).

Other side effects of XALKORI in children and adolescents with ALK-positive ALCL or ALK-positive IMT may include:
Very common side effects (may affect more than 1 in 10 people)

Abnormal liver blood tests.
Visual disturbances (flashes of light, blurred vision, light sensitivity, floaters, or double vision, which often occur shortly after starting XALKORI treatment).
Abdominal pain.
Increased blood creatinine levels (may indicate impaired kidney function).
Anemia (reduction in red blood cell count).
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 the hands and feet).
Increased blood alkaline phosphatase enzyme levels (an indicator of organ dysfunction or injury, particularly of the liver, pancreas, bones, thyroid, or gallbladder).
Neuropathy (numbness or tingling sensations in joints or extremities).
Dizziness.
Indigestion.
Altered sense of taste.
Hypophosphatemia (low phosphate levels in the blood, which may cause confusion or muscle weakness).

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

Rash.
Inflammation of the esophagus.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system listed in Annex V. Reporting side effects helps provide more information on the safety of this medicine.

5. How to store XALKORI

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and carton after “EXP”. The expiry date refers to the last day of that month.
Store below 25°C.
Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.

Do not dispose of any medicine via wastewater or household waste. Dispose of the empty XALKORI oral granule capsule containers in household waste. 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 XALKORI contains
The active substance in XALKORI is crizotinib.
XALKORI 20 mg granules in open capsules: each capsule contains 20 mg of crizotinib.
XALKORI 50 mg granules in open capsules: each capsule contains 50 mg of crizotinib.
XALKORI 150 mg granules in open capsules: each capsule contains 150 mg of crizotinib.
The other components are (see also section 2 “XALKORI contains sucrose”):
Granules content: stearyl alcohol, poloxamer, sucrose, talc (E553b), hypromellose (E464), macrogol (E1521), glycerol monostearate (E471), medium-chain triglycerides.
Capsule shell: 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).

Description of the appearance of XALKORI and package contents
XALKORI granules are white to off-white in open capsules.
XALKORI 20 mg granules in open capsules consist of a blue cap printed in black ink with “Pfizer” and a white body printed in black ink with “CRZ 20”.
XALKORI 50 mg granules in open capsules consist of a grey cap printed in black ink with “Pfizer” and a light grey body printed in black ink with “CRZ 50”.
XALKORI 150 mg granules in open capsules consist of a blue cap printed in black ink with “Pfizer” and a blue body printed in black ink with “CRZ 150”.
Available in plastic bottles containing 60 open 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 on this medicinal product, please contact the local representative of the Marketing Authorization Holder: