XALKORI 200 mg HARD CAPSULES

Introduction

Package Leaflet: 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 pediatric patient’s caregiver.

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is XALKORI and what is it used for
2. What you need to know before you take XALKORI
3. How to take XALKORI 200 mg and 250 mg hard capsules
4. Possible side effects
5. Storage of XALKORI
6. Contents of the pack and other information

1. What is XALKORI and what is it used for

XALKORI is a cancer medicine that contains crizotinib as the active substance, used to treat adults with a type of lung cancer called non-small cell lung cancer (NSCLC), which has a specific 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 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 may slow down or stop the growth of lung cancer. This can help the tumor shrink.

XALKORI is used to treat children and adolescents (from ≥ 1 to <18 years of age) with a type tumor called anaplastic large cell lymphoma (alcl) or inflammatory myofibroblastic (imt) that has specific rearrangement defect in gene kinase (alk).< p>

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.

You should only take this medicine under the supervision of a doctor with experience in the treatment of cancer. If you have any questions about how XALKORI works or why you have been prescribed it, ask your doctor.

2. What you need to know before you take XALKORI

Do not take XALKORI

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

Warnings and precautions

Talk to your doctor before starting to take XALKORI:

• If you have moderate or severe liver disease.

• If you have ever had any other lung problems. Some lung problems can get worse during treatment with XALKORI, as XALKORI can cause lung inflammation during treatment. These symptoms can be similar to those of lung cancer. Tell your doctor right away if you have a new symptom or if any of your symptoms get worse, including difficulty breathing, shortness of breath, or cough with or without mucus, or fever.

• If you have been told that you have a heart problem called QT interval prolongation after having an electrocardiogram (ECG).
• If you have a slow heart rate.
• If you have ever had stomach or intestinal problems, such as holes (perforation), or have had diseases that cause inflammation in the abdomen (diverticulitis) or if the cancer has spread to the abdomen (metastasis).

• If you have vision problems (see flashes of light, blurred vision, or double vision).
• If you have severe kidney disease.
• If you are currently being treated with any other medicine, including those listed in the section “Taking XALKORI with other medicines”.

If any of the above applies to you, tell your doctor.

Tell your doctor right away 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 information available is for adult patients with specific types of non-small cell lung cancer (adenocarcinoma) ALK-positive or ROS1-positive. The information available 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 medicines and XALKORI

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including herbal medicines and medicines bought 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.

The following medicines may decrease the effectiveness of XALKORI:

• Phenytoin, carbamazepine, or phenobarbital, antiepileptics used to treat seizures or epilepsy.
• Rifabutin, rifampicin, used to treat tuberculosis.
• St. John's Wort (Hypericum perforatum), a herbal medicine used to treat depression.

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

• Alfentanil and other short-acting opioids like fentanyl (pain relievers used for surgical procedures).
• Quinidine, digoxin, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, verapamil, diltiazem, used to treat heart diseases.
• 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 heart arrhythmias.

• Cisapride, used to treat stomach diseases.
• Cyclosporin, 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 high blood pressure.
• Mefloquine, used to prevent 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 for opioid dependence treatment.
• Bupropion, used to treat depression and to help quit smoking.
• Efavirenz, raltegravir, used to treat HIV infection.
• Irinotecan, a chemotherapy medicine used to treat colon and rectal cancer.
• Morphine, used to treat acute and cancer pain.
• Naloxone, used to treat opioid addiction and withdrawal.

These medicines should be avoidedduring treatment with XALKORI.

Oral contraceptives

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

Taking XALKORI with food and drinks

XALKORI can be taken with or without food; however, you should avoid drinking grapefruit juice or eating grapefruit while being treated with XALKORI, as they 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 get sunburned more easily. Use protective clothing and/or sunscreen that covers your skin to protect yourself against sunburn if you need to be exposed to the sun during treatment with XALKORI.

Pregnancy and breastfeeding

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

Women are advised to avoid becoming pregnant and men are advised not to father a child during treatment with XALKORI, as this medicine may harm the fetus. An adequate 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 using this medicine 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 breastfed baby.

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

Driving and using machines

Be careful when driving or using machines, as patients treated with XALKORI may experience visual disturbances, dizziness, and fatigue.

XALKORI contains sodium

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

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

Follow exactly the instructions of your doctor for taking this medicine. If you are unsure, ask your doctor or pharmacist again.

• The recommended dose for adults with NSCLC is one 250 mg capsule, orally, twice a day (total dose 500 mg).
• The recommended dose for children and adolescents with ALK-positive ALCL or IMT is 280 mg/m2 orally, twice a day. The recommended dose will be calculated by the child’s doctor and will depend on the child’s body surface area (BSA). The maximum daily dose in children and adolescents should not exceed 1000 mg. XALKORI should be administered under adult supervision.
• Take the recommended dose once in the morning and once in the evening.
• Take the capsules at approximately the same times each day.
• You can take the capsules with or without food, always avoiding grapefruit.
• The capsules should be swallowed whole, without being crushed, dissolved, or opened.

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

If you take more XALKORI than you should

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

If you forget to take XALKORI

The way to proceed if you forget to take a capsule depends on how much time is left until the next dose:

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

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

Do not take a double dose (two capsules at the same time) to make up for the 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 that you take XALKORI every day, for as long as your doctor has prescribed it. If you are not able to take this medicine as your doctor has prescribed, or if you think you no longer need it, contact your doctor immediately.

If you have any other 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 all people suffer from them.

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

Although not all adverse effects identified in adults with CPNM have been observed in children and adolescents with LACG or TMI, the same adverse effects should be considered for adult patients with lung cancer and for children and adolescents with LACG or TMI.

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

• Hepatic Insufficiency

Consult your doctor immediately if you feel more tired than usual, if your skin and the white areas of your eyes turn yellow, if your urine turns 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 bruising more easily than normal. Your doctor may perform blood tests to check your liver function, and if the results of these tests are abnormal, they may reduce the dose of XALKORI or suspend treatment.

• Pulmonary Inflammation

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

• Reduction in the Number of White Blood Cells (including Neutrophils)

Consult your doctor immediately if you experience 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.

• Feeling of Dizziness, Fainting, or Chest Pain

Consult your doctor immediately if you experience any of these symptoms, as they could be signs of changes in electrical activity (observed in 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 immediately if 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 suspend or permanently interrupt treatment with XALKORI and refer you to an ophthalmologist.

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

• Severe Gastrointestinal Problems in Children and Adolescents with ALK-positive LACG or TMI

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 give you medications as needed to prevent or treat diarrhea, nausea, and vomiting. Your doctor may recommend drinking more liquids or prescribing electrolyte supplements or other types of nutritional support if severe symptoms occur.

Other Adverse Effects of XALKORI in Adults with CPNM may Include:

Very Common Adverse Effects(may affect more than 1 in 10 people)

• Visual effects (seeing flashes of light, blurred vision, sensitivity to light, seeing spots or double vision, usually appearing 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.
• Abnormalities in liver tests in blood tests.
• Decreased appetite.
• Fatigue.
• Dizziness.
• Neuropathies (feeling of numbness or tingling in the joints or extremities).
• Alteration of the sense of taste.
• Abdominal pain.
• Reduction in the number of red blood cells (anemia).
• Rash.
• Decreased heart rate.

Common Adverse Effects(may affect up to 1 in 10 people)

• Indigestion.
• Increased levels of creatinine in blood (may indicate that the kidneys are not functioning properly).
• Increased levels of alkaline phosphatase enzyme in blood (indicator of dysfunction or injury to an organ, especially the liver, pancreas, bones, thyroid gland, or gallbladder).
• Hypophosphatemia (low levels of phosphate in blood that can cause confusion or muscle weakness).
• Fluid-filled cysts in the kidneys.
• Fainting.
• Inflammation of the esophagus (swallowing tube).
• Decreased levels of testosterone, a male sex hormone.
• Heart failure.

Uncommon Adverse Effects(may affect up to 1 in 100 people)

• Hole (perforation) in the stomach or intestine.
• Sensitivity to sunlight (photosensitivity).
• Elevated results in blood tests to check for muscle damage (high levels of creatine phosphokinase).

Other Adverse Effects of XALKORI in Children and Adolescents with ALK-positive LACG or TMI may Include:

Very Common Adverse Effects(may affect more than 1 in 10 people)

• Abnormalities in liver tests in blood tests.
• Visual effects (seeing flashes of light, blurred vision, sensitivity to light, seeing spots or double vision, usually appearing soon after starting treatment with XALKORI).
• Abdominal pain.
• Increased levels of creatinine in blood (may indicate that the kidneys are not functioning properly).
• 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 the body tissue that causes inflammation of the hands and feet).
• Increased levels of alkaline phosphatase enzyme in blood (indicator of dysfunction or injury to an organ, especially the liver, pancreas, bones, thyroid gland, or gallbladder).
• Neuropathy (feeling of numbness or tingling in the joints or extremities).
• Dizziness.
• Indigestion.
• Alteration of the sense of taste.
• Hypophosphatemia (low levels of phosphate in blood that can cause confusion or muscle weakness).

Common Adverse Effects(may affect up to 1 in 10 people)

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

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing 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 expiration date that appears on the bottle, blister, or carton after "EXP". The expiration date is the last day of the month indicated.
• This medicine does not require special storage conditions.
• Do not use this medicine if it is damaged or shows signs of deterioration.

Medicines should not be thrown away in drains or trash. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of XALKORI

• The active ingredient of 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 content: colloidal anhydrous silica, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, sodium carboxymethyl cellulose (type A), magnesium stearate.

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

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

Appearance of the Product and Package Contents

XALKORI 200 mg 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 "CRZ 200" on the body.

XALKORI 250 mg 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 "CRZ 250" on the body.

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

Only some package sizes may be marketed.

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Brussels

Belgium

Manufacturer

Pfizer Manufacturing Deutschland GmbH

Betriebsstätte Freiburg

Mooswaldallee 1

79090 Freiburg

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet:11/2024.

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