Xalkori 200 mg/250 mg Capsules

XALKORI is an anticancer medicine. XALKORI is used to treat adults with a type of lung cancer called Non-Small Cell Lung Cancer (NSCLC), that is advanced or that has spread to other parts of the body. NSCLC presents with a specific rearrangement or defect in a gene called ALK (anaplastic lymphoma kinase) or c-Ros Oncogene 1 (ROS1).

Do not take XALKORI • if you are hypersensitive (allergic) to crizotinib, or any of the other ingredients of XALKORI (listed in section 6).

Warnings and precautions

Take special care with XALKORI: Before you take XALKORI, tell your doctor or health care provider • if you have liver problems • if you have a lung disease (interstitial lung disease/pneumonitis) • if you have heart problems, including a condition called QT interval prolongation • if you have an abnormally slow pulse rate (bradycardia) • if you have ever had stomach or intestine problems such as holes (perforation), or if you have conditions causing inflammation inside the abdomen (diverticulitis), or if you have spread of cancer inside the abdomen (metastasis) • if you have kidney problems • if you have vision problems

Talk to your doctor right away after having taken XALKORI: If you are experiencing severe stomach or abdominal pain, fever, chills, shortness of breath, fast heartbeat, partial or complete loss of vision (in one or both eyes) or changes in bowel habits.

Children and adolescents

The safety and efficacy of XALKORI in paediatric patients has not been established and is not recommended.

Other medicines and XALKORI

Always tell your health care provider if you are taking any other medicine. (This includes all complementary or traditional medicines.) If you are taking any of the following medicines, you should tell your doctor or health care provider, as the combined use can affect the way XALKORI or the other medicine works: • Atazanavir, indinavir, ritonavir, saquinavir and nelfinavir (used to treat HIV-AIDS) • Clarithromycin, telithromycin, erythromycin or troleandomycin (used to treat bacterial infections) • Itraconazole, ketoconazole, posaconazole or voriconazole (used to treat fungal infections) • Nefazodone, dihydroergotamine, ergotamine and pimozide (used to treat depression) • Carbamazepine, phenobarbital and phenytoin (used to treat seizures) • St. John’s wort (Hypericum perforatum) • Rifabutin and rifampicin (used to treat tuberculosis [TB]) • Alfentanil and fentanyl (anaesthetics) • Ciclosporin (used to treat rheumatoid arthritis, psoriasis and Crohn’s disease) • Quinidine (used to treat heart conditions) • Sirolimus and tacrolimus (used to prevent organ transplant rejections) • Midazolam (used in anaesthesia and sleep disorders)

XALKORI may increase side effects associated with the following medicines: • Alfentanil and other short acting opiates such as fentanyl (painkillers used for surgical procedures) • Quinidine, digoxin, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, verapamil, diltiazem used to treat heart problems • Medicines for high blood pressure called beta-blockers such as atenolol, propranolol, labetalol • Pimozide, used to treat mental illness • Metformin, used to treat diabetes • Procainamide, used to treat cardiac arrhythmia • Cisapride, used to treat stomach problems • Ciclosporin, sirolimus and tacrolimus used in transplant patients • Ergot alkaloids (e.g., ergotamine, dihydroergotamine), used to treat migraine • Dabigatran, anticoagulant used to slow down clotting of the blood • Colchicine, used to treat gout • Pravastatin, used to reduce cholesterol levels • Clonidine, guanfacine, used to treat hypertension • Mefloquine, used for the prevention of malaria • Pilocarpine, used to treat glaucoma (a severe eye disease) • Anticholinesterases, used to restore muscle function • Antipsychotics, used to treat mental illness • Moxifloxacine, used to treat bacterial infections • Methadone, used to treat pain and for the treatment of opioid dependence • Bupropion, used to treat depression and smoking cessation • Efavirenz, raltegravir, used to treat HIV infection • Irinotecan, a chemotherapy medicine used to treat cancer of the colon and rectum • Morphine, used to treat acute and cancer pain • Naloxone, used to treat opiate medicine addiction and withdrawal

These medicines should be avoided during your treatment with XALKORI

Oral contraceptives

If you take XALKORI whilst using oral contraceptives, the oral contraceptives may be ineffective.

Sun exposure/protection

Avoid spending prolonged time in sunlight. XALKORI can make your skin sensitive to the sun (photosensitivity), and you may burn more easily. You should wear protective clothing and/or use sunscreen that covers your skin to help protect against sunburn if you have to be in the sunlight during treatment with XALKORI.

XALKORI with food and drink

You should not drink grapefruit juice or eat grapefruit during your treatment with XALKORI. It may make the amount of XALKORI in your blood increase to a harmful level.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist or health care provider for advice before taking this medicine. You should not take XALKORI if you are pregnant or breastfeeding your baby. XALKORI may cause foetal harm when administered to a pregnant woman. Therefore women of childbearing potential should be advised to avoid becoming pregnant while taking XALKORI. Women of childbearing potential who are taking XALKORI, or partners of women of childbearing potential taking XALKORI, should use adequate contraceptive methods during therapy and for at least 90 days after completing therapy. It is not known if XALKORI passes into your breast milk. Therefore, if you are breastfeeding or plan to breastfeed, discuss with your doctor or health care provider whether to discontinue breastfeeding or to discontinue this medicine.

Driving and using machines

XALKORI can cause dizziness, tiredness and changes in your vision. If you have these symptoms, use caution when driving a car, using machinery or doing anything that needs you to be alert. It is not always possible to predict to what extent XALKORI may interfere with the daily activities of a patient. Patients should ensure that they do not engage in the above activities until they are aware of the measure to which XALKORI affects them.

Do not share medicines prescribed for you with any other person. Always take XALKORI exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. The usual dose is 250 mg taken orally twice daily, however if required or if you have liver problems, your doctor may adjust the dosage. XALKORI capsules should be swallowed whole and may be taken with or without food. Your doctor will tell you how long your treatment with XALKORI will last. If you have the impression that the effect of XALKORI is too strong or too weak, tell your doctor or pharmacist.

If you take more XALKORI than you should

In the event that you take more capsules than your doctor prescribed, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison centre. Treatment of overdose with XALKORI should consist of general supportive measures.

If you forget to take XALKORI

If you miss a dose of XALKORI, take it as soon as you remember. If it is less than 6 hours until the next dose, then you should not take the missed dose. Do not take a double dose of XALKORI to make up for forgotten individual dose. If you vomit after taking a dose of XALKORI, do not take an extra dose; just take your next dose at your regular time.

XALKORI can have side effects. Not all side effects for XALKORI are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking XALKORI, please consult your health care provider for advice. The most serious side effects are liver damage (hepatotoxicity), lung disease (interstitial lung disease/pneumonitis), reduction in the number of white blood cells, light-headedness of chest discomfort, partial or complete loss of vision in one or both eyes, and abnormal heartbeat (QT interval prolongation). Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following: • your skin or the whites of your eyes turn yellow • your urine turns dark or brown (tea colour) • you have pain on the right side of your stomach • you bleed or bruise more easily than normal • you have itching • you have trouble breathing or shortness of breath • you have cough with or without mucous • you have fever • you have abnormal heartbeats • you feel dizzy or faint

Tell your doctor if you notice any of the following:

Frequent side effects

• abnormal white blood cell count
• decreased appetite
• decreased levels of phosphate in the blood
• nerve damage or disease (neuropathy) e.g. muscle weakness, skin burning sensation
• dizziness
• altered taste sensation
• vision disorders e.g. blurred vision, light hurting your eyes, flashes of light
• indigestion
• vomiting
• diarrhoea
• nausea
• constipation
• pain in the abdomen
• inflammation of the oesophagus (which may cause difficulty and pain upon swallowing)
• increased liver enzymes
• skin rash
• kidney growths (renal cysts)
• increased level of creatinine in your blood
• swelling of the hands and feet (oedema)
• fatigue or tiredness
• decreased testosterone (male hormone) in your body

Less frequent side effects

• hole (perforation) in stomach or intestine
• liver failure
• sensitivity to sunlight (photosensitivity)
• Increased blood levels of tests that check for muscle damage (high creatine phosphokinase levels)

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor or pharmacist or nurse. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of XALKORI.

• Store all medicines out of reach of children.
• Store at or below 25 °C.
• Keep the capsules in the original container and keep the container tightly closed. Do not remove blisters from the carton until required for use.
• Do not use XALKORI after the expiry date stated on the label and carton.
• Return all unused medicines to your pharmacist.
• Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).