Xalkori 20 mg granules in capsules for opening

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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 the entire leaflet carefully before you start taking 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, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions 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 that contains crizotinib as the active substance. It is used to treat adults with a type of lung cancer called non-small cell lung cancer that has a specific genetic abnormality or alteration in a gene known as anaplastic lymphoma kinase (ALK) or in a gene called ROS1.

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 called anaplastic lymphoma kinase (ALK).

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

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

This medicine should only be received 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, please 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, “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 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 holes (perforations), or have had conditions causing inflammation inside the abdomen (diverticulitis), or if cancer has spread to the abdomen (metastases).
• If you experience 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 vision loss (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 medicine 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 disorders.

• 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 stop 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 the 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 are advised to 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 nursing infant.

If you are pregnant or breastfeeding, think you may 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 informed you that you have an intolerance to certain sugars, consult with 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 ALCL or ALK-positive IMT 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 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 times each day.
• The granules must be administered into the mouth and must not be crushed, chewed, or dispersed onto food.
• The capsule shell must not be swallowed.

Method of administration

For detailed instructions on administering 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 into 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 dosing cup and then pour them into the child's mouth.
• Tap the open capsule to ensure that all the 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 the granules have been swallowed.
• After the child has swallowed the granules, you may give other liquids or food, except grapefruit and grapefruit juice.

If necessary, your doctor may reduce the oral dose to be taken. Your doctor may decide to permanently discontinue treatment with XALKORI if you cannot 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 forget to take a capsule 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 forgotten 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 that you take XALKORI every day for as long as your doctor has prescribed it. If you are unable to take this medicine as prescribed by your doctor, 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 experiences them.

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects 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 you start taking XALKORI”):

• Hepatic 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 develop itching or bruise more easily than normal. Your doctor may perform blood tests to check your liver function, and if the results are abnormal, your doctor may reduce the dose of XALKORI 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, your doctor may decide to reduce the dose of XALKORI.

• 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 abnormal heart rhythm. Your doctor may perform electrocardiograms to monitor for heart problems during treatment with XALKORI.

• Partial or complete loss of vision in one or both eyes

Contact your doctor immediately if you experience new vision problems, vision loss, or any changes in vision, such as difficulty seeing with one or both eyes. Your doctor may discontinue or permanently stop treatment with XALKORI 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 treatment with XALKORI and within 1 month after starting treatment with XALKORI to detect vision problems. An ophthalmological examination should be performed every 3 months during treatment with XALKORI, 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 treatment with XALKORI. 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.
• Abnormalities in liver function tests in blood tests.
• Decreased appetite.
• Fatigue.
• Dizziness.
• Neuropathy (numbness or tingling sensation in joints or extremities).
• Altered sense of taste.
• Abdominal pain.
• Reduction in the number of red blood cells in the blood (anemia).
• Skin 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 (indicator of organ dysfunction or injury, especially of 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)

• Abnormalities in 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 in the blood).
• 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 of the liver, pancreas, bones, thyroid gland, or gallbladder).
• Neuropathy (numbness or tingling sensation in joints or extremities).
• 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)

• Skin 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 they are possible adverse effects 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 should not be disposed of via wastewater or household waste. Empty XALKORI (oral granules) capsule shells may be discarded in domestic waste. Ask your pharmacist how to dispose of any unused medicines and packaging. 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 contents: 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 in colour and are contained in opening capsules.

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.

Available in plastic bottles containing 60 opening capsules.

Marketing Authorisation 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 medicine, please contact the local representative of the Marketing Authorisation Holder:

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

Other sources of information

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

Detailed information on 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 granules in capsules for opening.

Items required for administration of XALKORI:

• XALKORI granules in capsules, as prescribed by your doctor.
• Optionally, a spoon or dosing cup provided by the user.

Preparation of XALKORI granules (steps 1 to 3):

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

Once step 4 is completed, you may give the child other liquids or food, 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.