Xalkori 250 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

XALKORI 200 mg hard capsules

XALKORI 250 mg hard capsules

crizotinib

The terms "you" and "your" are used to refer to both the adult patient and the caregiver of the pediatric patient.

Read the entire leaflet carefully before you start taking this medicine, because 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 may 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.

Contents of the leaflet

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

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 (NSCLC) that has a specific abnormality or defect in a gene known as anaplastic lymphoma kinase (ALK) or in a gene called ROS1.

XALKORI may be prescribed as initial treatment if your lung cancer is 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 reduce the size of the tumor.

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

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

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

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

2. What you need to know before taking XALKORI

Do not take XALKORI

• If you are allergic to crizotinib or any of the other ingredients of this medicine (listed in section 6, “Composition 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 may worsen during treatment with XALKORI, as XALKORI can cause lung inflammation during treatment. These symptoms may be similar to those of lung cancer. Contact your doctor immediately if you develop a new symptom or if any existing symptoms worsen, including difficulty breathing, shortness of breath, or cough with or without mucus, or fever.

• If, after undergoing an electrocardiogram (ECG), you have been informed that you have a heart condition known as QT interval prolongation.

• If you have a slow heart rate.

• If you have ever had stomach or intestinal problems, such as perforations (holes), or have suffered from conditions causing inflammation inside the abdomen (diverticulitis), or if cancer has spread to the abdomen (metastases).

• If you experience vision disturbances (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 “ Taking XALKORI with other medicines”.

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.

Most of the available information is for adult patients with specific histological types of non-small cell lung carcinoma (adenocarcinoma) that are ALK-positive or ROS1-positive. 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 the supervision of an adult.

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 over-the-counter medicines.

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 fits.
• 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 reduce 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 with or without food; however, 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), and you may burn more easily. Wear protective clothing and/or sunscreen to cover your skin and protect against 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 not father 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 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; therefore, it is essentially “sodium-free”.

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

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

• The recommended dose for adults with NSCLC is one 250 mg capsule taken orally twice daily (total amount 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 child's doctor and depends on the child's 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.
• Take the recommended dose once in the morning and once in the evening.
• Take the capsules at approximately the same times each day.
• You may take the capsules with or without food, but always avoid grapefruit.
• The capsules must be swallowed whole and must not be crushed, dissolved, or opened.

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

If you take more XALKORI than you should

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

If you forget to take XALKORI

The action to take if you miss a capsule depends on how long it is until your next dose:

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

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

If you stop taking XALKORI

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

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

4. Possible side effects

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

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

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

Some side effects may 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 you take XALKORI”):

• Liver failure

Contact your doctor immediately if you feel more tired than usual, if your skin or the whites of your eyes turn yellow, if your urine becomes dark or brown (tea-coloured), if you have nausea, vomiting, or loss of appetite, if you have pain in the right side of your stomach, or if you have 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 stop treatment.

• Lung inflammation

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

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

Contact your doctor immediately if you develop fever or infection. Your doctor may perform blood tests and, if the results are abnormal, may decide to reduce 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 an abnormal heart rhythm. Your doctor may perform electrocardiograms to monitor for heart problems during treatment with XALKORI.

• Partial or complete vision loss in one or both eyes

Contact your doctor immediately if you experience new vision problems, vision loss, or any change in vision, such as difficulty seeing with one or both eyes. Your doctor may stop or permanently discontinue 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 diarrhoea, nausea or vomiting. Inform your doctor immediately if you have difficulty swallowing, vomiting or diarrhoea during treatment with XALKORI. Your doctor may give you medications as needed to prevent or treat diarrhoea, 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 side effects with XALKORI in adults with NSCLC may include:

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

• Vision problems (seeing flashes of light, blurred vision, light sensitivity, seeing spots or double vision, usually occurring soon after starting XALKORI treatment).
• Stomach problems, including vomiting, diarrhoea, nausea.
• Oedema (excess fluid in body tissues causing swelling of hands and feet).
• Constipation.
• Abnormal liver function tests in blood tests.
• Loss of appetite.
• Tiredness.
• Dizziness.
• Neuropathy (numbness or tingling sensation in joints or limbs).
• Altered sense of taste.
• Abdominal pain.
• Reduction in the number of red blood cells (anaemia).
• Rash.
• Slowed heart rate.

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

• Indigestion.
• Increased levels of creatinine in blood (may indicate kidneys are not working properly).
• Increased levels of alkaline phosphatase enzyme in blood (indicator of organ dysfunction or injury, especially of the liver, pancreas, bones, thyroid gland or gallbladder).
• Hypophosphataemia (low levels of phosphate in blood which may cause confusion or muscle weakness).
• Fluid-filled sac within the kidney (renal cysts).
• Fainting.
• Inflammation of the oesophagus (swallowing tube).
• Decreased levels of testosterone, a male sex hormone.
• Heart failure.

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

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

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 function tests in blood tests.
• Vision problems (seeing flashes of light, blurred vision, light sensitivity, seeing spots or double vision, usually occurring soon after starting XALKORI treatment).
• Abdominal pain.
• Increased levels of creatinine in blood (may indicate kidneys are not working properly).
• Anaemia (reduction in the number of red blood cells).
• 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 levels of alkaline phosphatase enzyme in blood (indicator of organ dysfunction or injury, especially of the liver, pancreas, bones, thyroid gland or gallbladder).
• Neuropathy (numbness or tingling sensation in joints or limbs).
• Dizziness.
• Indigestion.
• Altered sense of taste.
• Hypophosphataemia (low levels of phosphate in blood which may cause confusion or muscle weakness).

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

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

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are possible side effects not listed in this leaflet. You can also report them directly via the national reporting system listed in Appendix V. By reporting side 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, blister pack, or carton, following “EXP”. The expiry date refers to the last day of the month indicated.
• This medicine does not require any special storage conditions.
• Do not use this medicine if it is damaged or shows signs of deterioration.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of XALKORI

• 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 calcium hydrogen phosphate, sodium carboxymethyl starch (type A), magnesium stearate.

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

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

Nature and contents of the container

XALKORI 200 mg is presented as 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 as hard gelatin capsules with both cap and body pink, with “Pfizer” printed in black ink on the cap and “CRZ 250” on the body.

Available in packs of 60 hard capsules and in plastic bottles containing 60 hard capsules.

Only certain pack sizes may be marketed.

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

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

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