Label: information for the user

XALKORI200mg hard capsules

XALKORI250mg hard capsules

crizotinib

The words “you” and “your” are used to refer to both the adult patient and the caregiver of the pediatric patient.

Read this label carefully before starting to take this medicine, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you must not give it to other people 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 label. See section 4.

XALKORI is a cancer medication, which contains crizotinib as the active ingredient, used to treat adults with a type of lung cancer called non-microcitic lung cancer, which has a certain alteration or defect in a gene called anaplastic lymphoma kinase (ALK) or in a gene called ROS1.

XALKORI may be prescribed for initial treatment if your lung cancer is in an advanced stage.

XALKORI may be prescribed if your disease is in 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 the tumor to shrink.

XALKORI is used to treat children and adolescents (≥ 1 to < 18 years of age) with a type of tumor called anaplastic large cell lymphoma (LACG) or a type of tumor called inflammatory myofibroblastic tumor (TMI) that presents with a specific rearrangement or defect in a gene called anaplastic lymphoma kinase (ALK).

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

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

You should only receive this medication under the supervision of a doctor with experience in cancer treatment. If you have any doubts about how XALKORI works or why it has been prescribed to you, consult your doctor.

Do not take XALKORI

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

Warnings and precautions

Consult your doctor before starting XALKORI:

• If you have moderate or severe liver disease.

• If you have ever had any other lung problem. Some lung problems may worsen during treatment with XALKORI, as XALKORI may cause lung inflammation during treatment. These symptoms may be similar to lung cancer symptoms. Consult your doctor immediately if you have a new symptom or if any of your symptoms worsen, including difficulty breathing, shortness of breath, or cough with or without mucus, or fever.

• If, after an electrocardiogram (ECG), you have been informed that you have a heart condition known as QT interval prolongation.
• If you have bradycardia (slow heart rate).
• If you have ever had stomach or intestinal problems, such as perforation, or have had diseases that cause inflammation in the abdominal cavity (diverticulitis) or if the cancer has spread to the abdomen (metastasis).

• If you have vision problems (seeing flashes of light, blurry vision, or double vision).
• If you have severe kidney disease.
• If you are currently being treated with any other medication listed in the section “Taking XALKORI with other medications”.

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

Consult 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.

Most of the available information is for adult patients with one of the specific types of non-small cell lung cancer (adenocarcinoma) ALK-positive or ROS1-positive. Information for other histologies is limited.

Children and adolescents

The indication for non-small cell lung cancer does not include children or adolescents. XALKORI should be administered to children and adolescents under adult supervision.

Other medications and XALKORI

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including herbal supplements and over-the-counter medications.

Particularly, the following medications 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.

The following medications may reduce the effectiveness of XALKORI:

• Phenytoin, carbamazepine, or phenobarbital, antiepileptic medications used to treat seizures or epilepsy.
• Rifabutin, rifampicin, used to treat tuberculosis.
• St. John's Wort (Hypericum perforatum), a medicinal herb used to treat depression.

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

• Alfentanil and other short-acting opioids such as fentanyl (anesthetics used for surgical procedures).
• Quinidine, digoxin, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, verapamil, diltiazem, used to treat heart conditions.
• Beta-blockers, such as atenolol, propranolol, labetalol, used to treat hypertension.
• Pimozide, used to treat mental health conditions.
• Metformin, used to treat diabetes.
• Procainamide, used to treat arrhythmias.

• Cisapride, used to treat gastrointestinal conditions.
• Ciclosporin, 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 reduce cholesterol levels.
• Clonidine, guanfacine, used to treat hypertension.
• Mefloquine, used to prevent malaria.
• Pilocarpine, used to treat glaucoma (a serious eye condition).
• Cholinesterase inhibitors, used to restore muscle function.
• Antipsychotics, used to treat mental health conditions.
• 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/AIDS.
• Irinotecan, a chemotherapy medication used to treat colon and rectal cancer.
• Morphine, used to treat acute pain and cancer pain.
• Naloxone, used to treat opioid addiction and withdrawal.

These medications 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 beverages

XALKORI can be taken with or without food; however, you should avoid drinking grapefruit juice or eating grapefruit while taking XALKORI, as it may alter the amounts of XALKORI in your body.

Sun protection

Avoid spending too much time in the sun. XALKORI may make your skin more sensitive to the sun (photosensitivity), and you may burn more easily. Wear protective clothing and/or sunscreen that covers your skin to protect yourself 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 medication.

It is recommended that women avoid becoming pregnant and that men not father children during treatment with XALKORI, as this medication may harm the fetus. A suitable contraceptive method should be used during treatment and for at least 90 days after completing treatment, if there is any possibility that the person taking this medication may become pregnant or conceive a child, as oral contraceptives may be ineffective while taking XALKORI.

Do not breastfeed during treatment with XALKORI. XALKORI may harm the breastfeeding infant.

If you are pregnant or breastfeeding, believe you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

Be extra cautious when driving or operating machinery, as patients taking XALKORI may experience visual disturbances, dizziness, and fatigue.

XALKORI contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 200 mg or 250 mg hard capsule; this is essentially “sodium-free”.

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

• The recommended dose for adults with CPNM is a 250 mg capsule, taken orally, twice a day (total dose 500 mg).
• The recommended dose for children and adolescents with LACG ALK-positive or TMI ALK-positive is 280 mg/m2 taken orally twice a day. The doctor will calculate the dose and it will depend on the child's body surface area (BSA). The maximum daily dose in children and adolescents should not exceed 1,000 mg. XALKORI should be administered under adult supervision.
• Take the recommended dose once in the morning and once at night.
• Take the capsules approximately at the same hours every day.
• You can take the capsules with or without food, always avoiding grapefruit.
• The capsules should be swallowed whole, without crushing, dissolving, or opening them.

If necessary, your doctor may reduce the dose to be taken orally. Your doctor may decide to permanently discontinue XALKORI treatment if you cannot tolerate XALKORI.

If you take more XALKORI than you should

If you accidentally take more capsules, consult your doctor or pharmacist immediately.You may require medical attention.

If you forgot to take XALKORI

The procedure to follow if you forgot to take a capsule depends on how much time is left until the next dose:

• If the next dose is within6 hours or more, take the missed capsule as soon as possible.Then take the next capsule at the usual time.
• If the next dose is withinless than 6 hours, do not take the missed capsule. Then 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 (two capsules at the same time) to compensate for the missed dose.

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 interrupt treatment with XALKORI

It is essential to take XALKORI every day, for the time your doctor prescribed. If you are unable to take this medication as your doctor prescribed, or think you no longer need it, contact your doctor immediately.

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

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

If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are side effects that do not appear in this leaflet.

Although not all side effects identified in adults withCPNMhave been observed in children and adolescents withLACGorTMI, the same side effects should be considered for adult patients with lung cancer and for children and adolescents withLACGorTMI.

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

• Liver failure

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

• Pulmonary inflammation

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

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

Consult your doctor immediately if you experiencefever 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

Consult your doctor immediately if you experience any of these symptoms, as they may be signs of changes in electrical activity (seen on an electrocardiogram) or an abnormal heart rhythm. Your doctor may perform electrocardiograms to check that there are no problems with your heart during treatment with XALKORI.

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

Consult your doctor immediatelyif you experience new visual problems, loss of vision, or any change in vision, such as difficulty seeing with one or both eyes. Your doctor may discontinue or permanently interrupt treatment with XALKORI and refer you to an ophthalmologist.

For children and adolescents who receive XALKORI for the treatment ofLACG ALK‑positive or TMI ALK‑positive: your doctor must refer you to an ophthalmologist before starting treatment with XALKORI, and within 1month of starting treatment with XALKORI to detect visual problems. An ophthalmological examination should be performed every 3months during treatment with XALKORI and more often if new visual problems occur.

• Severe gastrointestinal and intestinal problems (gastrointestinal) in children and adolescents with LACG ALK‑positive or TMI ALK‑positive

XALKORI may cause severe diarrhea, nausea, or vomiting. Inform your doctor immediately if you experience problems 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 that you drink more fluids or prescribe electrolyte supplements or other types of nutritional support if severe symptoms occur.

Other side effects with XALKORI in adults with CPNM may include:

Frequent side effects(may affect more than 1 in 10 people)

• Visual effects (seeing flashes of light, blurred vision, light sensitivity, seeing spotsor double vision, usually appear soon after starting treatment with XALKORI).
• Gastrointestinal problems, including vomiting, diarrhea, nausea.
• Edema (excess fluid in the body tissue that causes inflammation of the hands and feet).
• Constipation.
• Abnormal liver function tests in blood tests.
• Loss of appetite.
• Tiredness.
• Dizziness.
• Neuropathy (sensation of numbness or tingling in the joints or extremities).
• Alteration of taste.
• Abdominal pain.
• Anemia (reduction in the number of red blood cells in the blood).
• Rash.
• Bradycardia (reduction in heart rate).

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

• Indigestion.
• Increased levels of creatinine in the blood (may indicate that the kidneys are not functioning properly).
• Increased levels of the enzyme alkaline phosphatase in the blood (indicator of a dysfunction or injury to an organ, especially the liver, pancreas, bones, thyroid gland, or bile duct).
• Hypophosphatemia (low levels of phosphate in the blood that may cause confusion or muscle weakness).
• Cysts in the kidneys.
• Fainting.
• Esophagitis (inflammation of the esophagus).
• Decreased levels of testosterone, a male sex hormone.
• Heart failure.

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

• Perforation (hole) in the stomach or intestine.

• Sensitivity to sunlight (photosensitivity).
• High levels in blood tests to check for muscle damage (high levels of creatine phosphokinase).

Other side effects of XALKORI in children and adolescents withLACGALK‑positive or TMI ALK‑positive may include:

Frequent side effects(may affect more than1 in 10people)

• Abnormal liver function tests in blood tests.
• Visual effects (seeing flashes of light, blurred vision, light sensitivity, seeing spotsor double vision, usually appear soon after starting treatment with XALKORI).
• Abdominal pain.
• Increasedlevels of creatinine in the blood (may indicate that the kidneys are not functioning properly).
• 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).
• Tiredness.
• Loss of appetite.
• Constipation.
• Edema (excess fluid in the body tissue that causes inflammation of the hands and feet).
• Increased levels of the enzyme alkaline phosphatase in the blood (indicator of a dysfunction or injury to an organ, especially the liver, pancreas, bones, thyroid gland, or bile duct).
• Neuropathy (sensation of numbness or tingling in the joints or extremities).
• Dizziness.
• Indigestion.
• Alteration of taste.
• Hypophosphatemia (low levels of phosphate in the blood that may cause confusion or muscle weakness).

Common side effects(may affect up to1 in 10people)

• Rash.

• Esophagitis (inflammation of the esophagus).

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. 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 vial, in the blister pack, or in the case after “EXP”. The expiration date is the last day of the month indicated.
• This medication does not require special storage conditions..
• Do not use this medication if it is damaged or shows signs of deterioration.

Medications 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.This will help protect the environment.

Composition ofXALKORI

• The active ingredient ofXALKORIis crizotinib.

XALKORI200mg hard capsules: each capsule contains 200mg of crizotinib

XALKORI250mg hard capsules: each capsule contains 250mg of crizotinib

• The other components are (see also section2 “XALKORI contains sodium”):

Capule content:colloidal anhydrous silica, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, sodium carboxymethylcellulose (typeA), magnesium stearate.

Capule:gelatin, titanium dioxide (E171) and iron oxide red (E172).

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

Appearance of the product and contents of the pack

XALKORI 200mg is presented in the form of hard gelatin capsules with a pink cap and a white body, with “Pfizer” printed in black ink on the cap and“CRZ200” in the body.

XALKORI 250mg is presented in the form of hard gelatin capsules with a pink cap and body, with “Pfizer” printed in black ink on the cap and“CRZ250” in the body.

They are available in packs of 60 hard capsules and in plastic bottles of 60 hard capsules.

Only some pack sizes may be marketed.

Marketing authorisation holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer responsible

Pfizer Manufacturing Deutschland GmbH

Betriebsstätte Freiburg

Mooswaldallee 1

79090 Freiburg

Germany

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of the summary of product characteristics:11/2024.

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