PIQRAY 200 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Piqray 50 mg film-coated tablets

Piqray 150 mg film-coated tablets

Piqray 200 mg film-coated tablets

alpelisib

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 get 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 Piqray and what is it used for
2. What you need to know before you take Piqray
3. How to take Piqray
4. Possible side effects
5. Storage of Piqray
6. Contents of the pack and other information

1. What is Piqray and what is it used for

What is Piqray

Piqray contains the active substance alpelisib, which belongs to a group of medicines called phosphatidylinositol 3-kinase (PI3K) inhibitors.

What Piqray is used for

Piqray is used to treat postmenopausal women and men with a type of breast cancer called advanced hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) breast cancer. Piqray is used in combination with fulvestrant, a hormonal treatment for cancer, in patients who have not responded to other hormonal treatments and who have changes (mutations) in a gene called PIK3CA.

Your doctor will take a blood sample and/or a tumor tissue sample, which will be tested to detect these mutations in PIK3CA. If the result is positive, it is likely that the cancer will respond to treatment with Piqray.

How Piqray works

Piqray works by blocking the effects of enzymes called phosphatidylinositol-3 kinases (PI3K). These enzymes help cancer cells grow and multiply. By blocking their action, Piqray can reduce the growth and spread of cancer and help destroy cancer cells.

If you have any questions about how Piqray works or why you have been prescribed this medicine, ask your doctor, pharmacist, or nurse.

2. What you need to know before you take Piqray

Follow your doctor's instructions carefully, as they may be different from the general information contained in this leaflet. If you have any questions, ask your doctor.

Do not take Piqray

• if you are allergic to alpelisib or any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic, talk to your doctor.

Warnings and precautions

Talk to your doctor or pharmacist before taking Piqray.

If you are in any of the following situations before taking Piqray, tell your doctor or pharmacist:

• if you have or have ever had high blood sugar levels or diabetes (or signs of high blood sugar levels, such as excessive thirst and dry mouth, need to urinate more often than usual, production of a larger amount of urine than usual, fatigue, nausea, increased appetite with weight loss).
• if you have ever had Stevens-Johnson syndrome (SJS, a severe reaction with flu-like symptoms and a painful rash that affects the skin, mouth, eyes, and genitals), erythema multiforme (EM, a skin reaction that causes red spots or patches on the skin, which may look like a target or a "bull's eye" with a dark red center surrounded by lighter red rings), drug reaction with eosinophilia and systemic symptoms (DRESS, a skin reaction combined with fever, swelling of the face, increased size of the lymph nodes, and kidney or liver problems) or toxic epidermal necrolysis (TEN, a severe skin reaction with redness of the skin, blisters on the lips, eyes, or mouth, skin peeling, with or without fever, rash).
• If you have a severe bone disease that affects the jaw (osteonecrosis of the jaw, ONJ).

If you are in any of the following situations during treatment with Piqray, tell your doctor or pharmacist immediately:

• Rash, itching, hives, wheezing, difficulty breathing, wheezing, cough, fainting, dizziness, changes in level of consciousness, low blood pressure, redness of the skin, swelling of the face or throat, blue discoloration of the lips, tongue, or skin (possible signs of severe allergic reactions).
• New or worsening respiratory problems, such as difficult or painful breathing, cough, rapid breathing, blue discoloration of the lips, tongue, or skin, hiccups (possible signs of non-infectious pneumonitis or pneumonia).
• Increased thirst and dry mouth, need to urinate more often than usual, fatigue, increased appetite with weight loss, confusion, nausea, vomiting, fruity odor of the breath, difficulty breathing, and dry or red skin, which may be signs of high blood sugar levels (hyperglycemia) and its complications.
• Rash, redness of the skin, blisters on the lips, eyes, or mouth, skin peeling, sometimes with fever (possible signs of skin disorders: Stevens-Johnson syndrome (SJS), erythema multiforme (EM), drug reaction with eosinophilia and systemic symptoms (DRESS) or toxic epidermal necrolysis (TEN)).
• Appearance or worsening of symptoms that affect the mouth (such as loose teeth, pain or swelling, poor healing of mouth sores, or discharge).
• Severe diarrhea or severe abdominal pain or stools with mucus or blood, which may be signs of intestinal inflammation (colitis).

Your doctor may need to treat these symptoms and temporarily interrupt your treatment, reduce the dose, or permanently discontinue your treatment with Piqray.

Blood tests before and after your treatment with Piqray

Your doctor will perform blood tests before and periodically during treatment with Piqray to check your blood sugar levels. Based on the results, your doctor will take the necessary actions, such as prescribing a medicine to reduce blood sugar levels. If necessary, your doctor may decide to temporarily interrupt treatment with Piqray or reduce the dose of Piqray to allow blood sugar levels to decrease. Your doctor may also decide to permanently discontinue treatment with Piqray.

Make sure you regularly check your blood sugar levels before starting treatment, during treatment, and after stopping treatment with Piqray.

• Your doctor will tell you when and where you should have blood tests. Treatment with Piqray can only be started if the tests show that you have adequate blood sugar levels. This is because Piqray can cause high blood sugar levels (hyperglycemia), which can be serious and require treatment. Your doctor can only know if you are developing hyperglycemia with regular fasting blood tests.
• Your doctor will tell you exactly when and where you should have your blood sugar test. This will be more frequent during the first 4 weeks of treatment and especially during the first 2 weeks of treatment with Piqray. After that, blood tests will be needed at least once a month, depending on your blood sugar levels.

Children and adolescents

Piqray should not be used in children and adolescents under 18 years of age.

Other medicines and Piqray

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes, in particular:

• eltrombopag, a medicine used to treat low platelet count
• medicines used to treat breast cancer (such as lapatinib, ribociclib)
• everolimus, apalutamide, enzalutamide, and mitotane, medicines used to treat certain types of cancer
• pantoprazole, a medicine used to treat acidity and reduce the amount of acid produced in the stomach
• midazolam, a medicine used for sedation or sleep disorders
• rifampicin, a medicine used to treat tuberculosis or other serious infections
• carbamazepine and phenytoin, medicines used to treat seizures
• St. John's Wort, a herbal product used to treat depression and other problems
• encorafenib, a medicine used to treat a type of skin cancer
• warfarin, a medicine used to reduce blood clotting

Ask your doctor or pharmacist if you are not sure if your medicine is one of those listed above.

Pregnancy, breastfeeding, and fertility

Piqray should not be used in women who are or may be pregnant or breastfeeding. Piqray may harm your fetus. If you think you may be pregnant or plan to become pregnant, talk to your doctor or pharmacist before using this medicine. Women should not breastfeed during treatment and for at least 1 week after the last dose of Piqray. Your doctor will discuss with you the possible risks of taking Piqray during pregnancy or breastfeeding.

If you are a woman who could become pregnant, your doctor must rule out pregnancy before starting treatment with Piqray. This may include a pregnancy test.

Women who could become pregnant must use an effective method of birth control during treatment and for at least 1 week after finishing treatment with Piqray. Talk to your doctor about the most suitable methods. If you think you may be pregnant after starting treatment with Piqray, tell your doctor immediately.

During treatment and for at least 1 week after finishing treatment, male patients must use condoms when having sex with women who could become pregnant. If the partner of a male patient suspects that she has become pregnant during this time, she should tell her doctor immediately.

Driving and using machines

Treatment with Piqray may cause fatigue or blurred vision. Therefore, you should be careful when driving or using machines during treatment with Piqray.

Piqray contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet; it is essentially "sodium-free".

3. How to take Piqray

Follow the instructions for administration of this medicine exactly as told by your doctor.

If you are unsure, talk to your doctor again.

How much Piqray to take

The usual starting dose of Piqray is 300 mg once a day. Your doctor will decide what dose is right for you.

Depending on the dose you have been prescribed, you should take this number of tablets:

• Dose of 300 mg: two 150 mg tablets
• Dose of 250 mg: one 200 mg tablet and one 50 mg tablet
• Dose of 200 mg: one 200 mg tablet

Depending on how you respond to treatment with Piqray, your doctor may adjust the dose of Piqray. It is very important to follow your doctor's instructions. If you have any side effects, your doctor may tell you to switch to a lower dose, interrupt treatment for a while, or stop treatment.

Your doctor will decide what dose of fulvestrant you should receive and when you should receive it.

When to take Piqray

Piqray tablets are supplied in packs that contain blisters. Each blister shows the tablet(s) to be taken each day of the week. Follow the instructions indicated on the blister.

Take Piqray once a day, immediately after a meal. Taking Piqray at the same time each day will help you remember when to take your medicine.

How to take Piqray

Piqray tablets should be swallowed whole, do not chew, crush, or break them before swallowing. Do not take any tablets that are broken, fractured, or damaged, as you may not be taking the full dose.

If you vomit after taking the Piqray tablet(s), do not take any more tablets until your next scheduled dose.

How long to take Piqray

Take Piqray for as long as your doctor tells you.

This is a long-term treatment, possibly for months or years. Your doctor will regularly review your situation to check that the treatment is having the desired effect.

If you are unsure how long you should take Piqray, talk to your doctor or pharmacist.

If you take more Piqray than you should

People who have taken too many Piqray tablets have had effects that are known side effects of Piqray, including high blood sugar levels, nausea, fatigue, and rash. If you accidentally take too many tablets, or if someone else takes your medicine accidentally, contact a doctor or go to a hospital immediately. Medical treatment may be necessary.

If you forget to take Piqray

If you forget to take a dose of Piqray, you can take it immediately after a meal, up to 9 hours after the time you should have taken it. If you realize more than 9 hours after the time you should have taken it, do not take the dose for that day. The next day, take the dose at the usual time. Do not take a double dose to make up for forgotten doses.

If you stop taking Piqray

Stopping your treatment with Piqray may cause your condition to worsen. Do not stop taking Piqray unless your doctor tells you to.

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.

Some adverse effects could be serious

If you experience any serious adverse effect, stop treatment with the medicine and inform yourdoctor immediately.

Very Common(may affect more than 1 in 10patients):

• Feeling of excessive thirst, urinating more frequently than usual or urinating a larger amount of urine than usual, increased appetite with weight loss (possible symptoms of high blood sugar levels, also called hyperglycemia)
• Fever, cough, rhinitis, enlarged lymph nodes, painful joints, rash, night sweats, weight loss (possible symptoms of a low level of lymphocytes, a type of white blood cell)

Common(may affect up to 1 in 10patients):

• Rash, itching, hives, wheezing, difficulty breathing, wheezing, cough, fainting, dizziness, changes in level of consciousness, low blood pressure, skin redness, swelling of the face and/or throat, blue discoloration of the lips, tongue or skin (possible signs of severe allergic reactions)
• Difficulty breathing, headache, nausea, vomiting, (possible symptoms of a situation called ketoacidosis, which involves a high level of acids in the blood)
• Respiratory problems including difficult and painful breathing, cough, rapid breathing, blue discoloration of the lips, tongue or skin, hiccups (possible symptoms of pneumonitis)
• Urinating less frequently than usual or urinating a smaller amount of urine than usual, swelling in the legs, ankles, and around the eyes, fatigue, confusion, nausea, seizures, chest pain (possible symptoms of acute kidney failure)
• Pain, swelling or numbness of the jaw, a feeling of heaviness in the jaw or loss of a tooth (possible symptoms of jaw osteonecrosis)
• Rash, skin redness, blisters on the lips, eyes or mouth, skin peeling (possible symptoms of erythema multiforme)

Uncommon(may affect up to 1 in 100patients):

• Severe pain in the upper abdomen (possible symptom of pancreatitis)
• Rash, skin redness, blisters on the lips, eyes or mouth, skin peeling, fever (possible symptoms of Stevens-Johnson syndrome)

Frequency Not Known(cannot be estimated from the available data):

• Diarrhea, increased number of bowel movements compared to usual, blood in the stool or darker-colored stool, pain or sensitivity in the stomach area (possible symptoms of colitis, inflammation of the intestines)
• Confusion, dry mouth, dry or red skin, nausea, vomiting, fatigue, need to urinate more frequently, thirst (possible symptoms of hyperglycemic hyperosmolar non-ketotic syndrome (HHNS))
• Swelling in the face or throat and difficulty breathing (possible symptoms of angioedema, a type of severe adverse reaction)
• Rash, fever (possible symptoms of a rash with eosinophilia and systemic symptoms (RESS)).
• Redness of the eyes, eye pain, sensitivity to light, dark floating bodies in the field of vision, blurred vision, decreased vision, small pupil (possible symptoms of uveitis)

Other Possible Adverse Effects

Other possible effects include those listed below. If these adverse effects become serious, inform your doctor, pharmacist or nurse.

Very Common(may affect more than 1 in 10patients):

• Frequent and painful urination (possible symptom of urinary tract infection)
• Fatigue, pale skin (possible symptoms of anemia, a situation with a low level of red blood cells)
• Spontaneous bleeding or bruising (signs of a low level of platelets in the blood)
• Lack of appetite
• Headache
• Unusual taste in the mouth (dysgeusia)
• Diarrhea
• Nausea
• Vomiting
• Sores or ulcers in the mouth with gum inflammation (stomatitis)
• Abdominal pain
• Stomach discomfort, indigestion (dyspepsia)
• Rash
• Hair loss or hair weakening (alopecia)
• Itching (pruritus)
• Dry skin
• Fatigue (fatigue)
• Pain, redness and swelling of the airways or the digestive tube or the genital mucosa (mucosal inflammation)
• Swelling in the hands, ankles or feet (peripheral edema)
• Fever (pyrexia)
• Dryness of mucous membranes
• Weight loss
• Low calcium level in the blood, which can cause cramps (hypocalcemia)
• Low potassium level in the blood, associated with muscle weakness, muscle spasms and/or abnormal heart rhythm (hypokalemia)
• Headache, dizziness (possible symptoms of high blood pressure)

Common(may affect up to 1 in 10patients):

• Dehydration
• Difficulty sleeping (insomnia)
• Dry eyes
• Blurred vision
• Swelling of a part or all of the arm (including fingers) or leg (including fingers), feeling of heaviness, restricted movement, discomfort, thickening of the skin and recurrent infections (possible symptoms of lymphedema)
• Toothache
• Bleeding, sensitive or swollen gums (signs of gum inflammation)
• Cracked lips (cheilitis)
• Gingival pain
• Erythema
• Skin inflammation with rash (dermatitis)
• Redness and/or swelling and possibly peeling on the palms of the hands and the soles of the feet, which may be accompanied by a tingling sensation and burning pain (signs of hand-foot syndrome)
• Muscle spasms
• Muscle pain (myalgia)
• Generalized swelling (edema)

During treatment with Piqray, the results of some blood tests may be altered, such as the following:

Very Common(may affect more than 1 in 10patients):

• High levels in the blood of the following enzymes: gamma glutamyl transferase, alanine aminotransferase, lipase
• High blood sugar level
• High creatinine and/or calcium level in the blood
• Low level of lymphocytes, platelets, sugar, hemoglobin and/or albumin in the blood
• Increased partial activated thromboplastin time (a measure of blood coagulation)

Common(may affect up to 1 in 10patients):

• High level of glycosylated hemoglobin in the blood (a marker of blood sugar level over the last 8 to 12 weeks)

Reporting of 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 is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Piqray

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the box and on the blister after "CAD" and "EXP". The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Do not take this medicine if you notice any damage to the packaging or if it shows any signs of tampering.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Piqray Composition

• The active ingredient of Piqray is alpelisib.
• Each Piqray 50 mg film-coated tablet contains 50 mg of alpelisib.
• Each Piqray 150 mg film-coated tablet contains 150 mg of alpelisib.
• Each Piqray 200 mg film-coated tablet contains 200 mg of alpelisib.
• The other components are:
• Core tablet: microcrystalline cellulose, mannitol, sodium glycolate starch (see section 2 "Piqray contains sodium"), hypromellose, magnesium stearate.
• Coating: Hypromellose, red and black iron oxide (E172), titanium dioxide (E171), macrogol, talc.

Piqray Appearance and Package Contents

Piqray 50 mg film-coated tablets are light pink, round tablets with the imprint "L7" on one side and "NVR" on the other side. Approximate diameter: 7.2 mm.

Piqray 150 mg film-coated tablets are pale red, ovaloid tablets with the imprint "UL7" on one side and "NVR" on the other side. Approximate size: 14.2 mm (length); 5.7 mm (width).

Piqray 200 mg film-coated tablets are light red, ovaloid tablets with the imprint "YL7" on one side and "NVR" on the other side. Approximate size: 16.2 mm (length); 6.5 mm (width).

Piqray is supplied as film-coated tablets in blisters. Piqray is available in the following formats:

• Packages containing 50 mg and 200 mg film-coated tablets (for patients with a daily dose of 250 mg):
• Packages containing a 14-day supply: 28 film-coated tablets (14 of 50 mg and 14 of 200 mg).
• Packages containing a 28-day supply: 56 film-coated tablets (28 of 50 mg and 28 of 200 mg).
• Multiple packages containing 168 film-coated tablets (3x 56, each with 28 tablets of 50 mg and 28 tablets of 200 mg).
• Packages containing 150 mg film-coated tablets (for patients with a daily dose of 300 mg):
• Packages containing a 14-day supply: 28 film-coated tablets.
• Packages containing a 28-day supply: 56 film-coated tablets.
• Multiple packages containing 168 film-coated tablets (3x 56).
• Packages containing 200 mg film-coated tablets (for patients with a daily dose of 200 mg):
• Packages containing a 14-day supply: 14 film-coated tablets.
• Packages containing a 28-day supply: 28 film-coated tablets.
• Multiple packages containing 84 film-coated tablets (3x 28).

Only some package sizes may be marketed.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Germany

Lek Pharmaceuticals d.d.

Verovškova Ulica 57

1526 Ljubljana

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovskova ulica 57

1000 Ljubljana

Slovenia

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

Date of Last Revision ofthis Prospectus:

Other Sources of Information

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