Serious Warnings and Precautions

Xtandi should only be prescribed by a doctor experienced with the treatment of prostate cancer.

Clinically significant adverse events:

• Seizures (see Seizures: section, below).
• Posterior Reversible Encephalopathy Syndrome (PRES, see Posterior Reversible Encephalopathy Syndrome (PRES):section, below)

Be careful if you are engaging in activities that require mental concentration or where sudden loss of consciousness could cause serious harm to others (e.g driving or operating tools or machines).

BEFORE you use Xtandi talk to your doctor or pharmacist:

• If you have history of seizures or are at a high risk of seizures (see below paragraph on situations in which you may have a higher risk of seizures).
• If you have problems with your liver or kidneys.
• If you have any heart disorder, including an irregular heartbeat, an abnormal electrical signal called “prolongation of the QT interval” or a known history of QT interval prolongation.
• If you have high blood pressure. Xtandi can raise blood pressure. Your doctor will measure your blood pressure before starting treatment with Xtandi and periodically during treatment.
• If you have a personal history of fainting spells.
• If you have electrolyte disturbances (e.g. low blood potassium or magnesium levels) or conditions that could lead to electrolyte disturbances (e.g. vomiting, diarrhea, dehydration, eating disorder).
• About all medicines (including natural health products) you have recently taken or are currently taking.

You should not start or stop Xtandi before you talk to your healthcare provider that prescribed you Xtandi.

Men who are sexually active with a pregnant woman must use a condom during and for three months after treatment with Xtandi. If their sexual partner may become pregnant, a condom and another form of birth control must be used during and for three months after treatment.

Xtandi should not be given to patients less than 18 years of age.

Seizures:

Xtandi has been shown to cause seizures in about 9 of every 1000 people who had received prior cancer treatment with docetaxel, and in about 1 of every 1000 people who had not received chemotherapy.

Posterior Reversible Encephalopathy Syndrome (PRES):

Reversible swelling in the rear part of the brain that can be associated with high blood pressure and can lead to headache, loss of speech or vision, confusion and/or seizure.

Tell your doctor, pharmacist or nurse if you are taking any of the following medicines. When taken at the same time as Xtandi, these medicines may increase the risk of a seizure:

• Certain medicines used to treat asthma and other respiratory diseases (e.g. aminophylline, theophylline)
• Medicines used to treat certain psychiatric disorders such as depression and schizophrenia (e.g. clozapine, olanzapine, risperidone, ziprasidone, bupropion, lithium, chlorpromazine, mesoridazine, thioridazine, amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine, venlafaxine)
• Certain medicines for the treatment of pain (e.g. meperidine)

Some situations in which you may have a higher risk of seizures include:

• If you had earlier episodes of seizures
• If you drink very large amounts of alcohol either regularly or from time to time
• If you have had a serious head injury or a history of head trauma
• If you have had certain kinds of stroke
• If you have had a brain tumour or metastases of cancer in the brain
• If you are taking a medicine that can cause seizures or medicines that can lower the susceptibility for having seizures

If you have a seizure during treatment: Stop taking Xtandi and see your doctor, pharmacist or nurse as soon as possible.