Product Information for the Patient

Piqray 50 mg Film-Coated Tablets

Piqray 150 mg Film-Coated Tablets

Piqray 200 mg Film-Coated Tablets

alpelisib

Read this entire product information carefully before starting to take this medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist or nurse.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist or nurse, even if they are not listed in this product information. See section 4.

What is Piqray

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

How is Piqray used

Piqray is used to treat postmenopausal women and men with a type of breast cancer called advanced hormone receptor-positive (HR) breast cancer, human epidermal growth factor receptor 2 (HER2) negative. Piqray is used in combination with fulvestrant, a hormone treatment for cancer, in patients whose cancer has not responded to other hormone 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 analyzed 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 doubts about how Piqray works or why you have been prescribed this medication, ask your doctor, pharmacist, or nurse.

Follow your doctor's instructions carefully, as they may be different from the general information contained in this prospectus. Consult with your doctor if you have any doubts.

Do not take Piqray

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

Warnings and precautions

Consult your doctor or pharmacist before taking Piqray.

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

• if you have or have had high blood sugar levels or diabetes (or signs of high blood sugar, such as excessive thirst and dry mouth, frequent urination, increased urination, fatigue, nausea, increased appetite with weight loss).
• if you have ever had Stevens-Johnson syndrome (SSJ, a severe reaction with symptoms similar to the flu 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 resemble a bullseye 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, facial hives, swollen lymph nodes, and kidney or liver damage) or toxic epidermal necrolysis (NET, 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, inform your doctor or pharmacist immediately:

• hives, itching, rashes, rapid breathing, difficulty breathing, wheezing, cough, fainting, dizziness, changes in level of consciousness, low blood pressure, skin redness, facial or throat swelling, blue discoloration of the lips, tongue, or skin (possible signs of severe allergic reactions).
• new-onset respiratory problems or changes in existing ones, such as difficult or painful breathing, cough, rapid breathing, blue discoloration of lips, tongue, or skin, hiccups (possible signs of non-infectious pneumonitis or pneumonia).
• increased thirst and dry mouth, frequent urination, fatigue, increased appetite with weight loss, confusion, nausea, vomiting, fruity breath odor, difficulty breathing, and dry or red skin, which may be signs of high blood sugar (hyperglycemia) and its complications.
• rash, skin redness, blisters on the lips, eyes, or mouth, skin peeling, sometimes with fever (possible signs of one of the following skin changes: Stevens-Johnson syndrome (SSJ), erythema multiforme (EM), drug reaction with eosinophilia and systemic symptoms (DRESS), or toxic epidermal necrolysis (NET)).
• appearance or worsening of symptoms affecting the mouth (such as loose teeth, pain or swelling, lack of wound healing, or discharge).
• severe diarrhea or severe abdominal pain or bloody stools, which may be signs of intestinal inflammation (colitis).

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

Blood tests before and after treatment with Piqray

Your doctor will perform blood tests before and periodically during treatment with Piqray to monitor your blood sugar levels. Based on the results, your doctor will take necessary actions, such as prescribing a medication 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 to regularly monitor your blood sugar levels before starting treatment, during treatment, and after stopping treatment with Piqray.

• Your doctor will inform you when and where to perform the blood tests. Treatment with Piqray can only be initiated if the tests show that you have adequate blood sugar levels. This is because Piqray can cause high blood sugar (hyperglycemia), which can be severe and require treatment. Your doctor can only determine if you are developing hyperglycemia with regular blood tests in the fasting state.
• Your doctor will inform you exactly when and where to perform the blood sugar test. This will be more frequent during the first 4 weeks of treatment and especially the first 2 weeks of treatment with Piqray. Subsequently, blood tests will be required at least once a month, depending on blood sugar levels.

Children and adolescents

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

Other medications and Piqray

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. This includes, in particular:

• eltrombopag, a medication used to treat low platelet counts.
• medications used to treat breast cancer (such as lapatinib, ribociclib).
• everolimus, apalutamida, enzalutamida, and mitotano, medications used to treat certain types of cancer.
• pantoprazol, a medication used to treat acid reflux and reduce stomach acid production.
• midazolam, a medication used for sedation or sleep disorders.
• rifampicina, a medication used to treat tuberculosis or other severe infections.
• carbamazepina and phenytoin, medications used to treat seizures.
• St. John's Wort, a herbal product used to treat depression and other conditions.
• encorafenib, a medication used to treat a type of skin cancer.
• warfarina, a medication used to reduce blood clotting.

Consult your doctor or pharmacist if you are unsure if your medication is listed above.

Pregnancy, breastfeeding, and fertility

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

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

Women who may become pregnant should use an effective method of birth control during treatment and for at least 1 week after stopping treatment with Piqray. Consult your doctor about the most suitable methods. If you think you may become pregnant after starting treatment with Piqray, inform your doctor immediately.

During treatment and for at least 1 week after stopping treatment, male patients should use condoms for sexual intercourse with women who may become pregnant. If a male patient's partner suspects she may be pregnant during this time, she should inform the doctor immediately.

Driving and operating machinery

Treatment with Piqray may cause fatigue or blurred vision. Therefore, you should exercise caution when driving or operating machinery during treatment with Piqray.

Piqray contains sodium

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

Follow exactly the administration instructions of this medication as indicated by your doctor.

In case of doubt, consult 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 is the appropriate dose for you.

Depending on the dose prescribed, you will 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 experience some side effects, your doctor may tell you to change to a lower dose, to interrupt treatment for a time, or to discontinue treatment.

Your doctor will establish the dose of fulvestrant that you should receive and when you should receive it.

When to take Piqray

Piqray tablets are supplied in blister packs. Each blister pack shows the tablets that you should take each day of the week. Follow the instructions indicated on the blister pack.

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 medication.

How to take Piqray

Piqray tablets should be swallowed whole, do not crush, break, or split 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 tablets, do not take any more tablets until the next scheduled dose.

How long to take Piqray

Take Piqray for the time that your doctor tells you.

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

If you have any doubts about how long you should take Piqray, consult your doctor or pharmacist.

If you take more Piqray than you should

People who have taken too many Piqray tablets have experienced side 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 medication accidentally, contact a doctor or go to a hospital immediately. You may need medical treatment.

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 when you should have taken it. If you realize more than 9 hours after when 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 the missed doses.

If you interrupt treatment with Piqray

Interrupting your treatment with Piqray may cause a worsening of your situation. Do not interrupt treatment with Piqray unless your doctor tells you to.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

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

Some side effects could be serious

If you experience any serious side effect,stop taking the medicine and inform your doctor immediately.

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

• Feeling very thirsty, 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, also known as hyperglycemia)
• Fever, cough, runny nose, swollen lymph nodes, painful joints, rash, night sweats, weight loss (possible symptoms of low lymphocyte count, a type of white blood cell)

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

• Rash, itching, hives, rapid breathing, difficulty breathing, wheezing, cough, fainting, dizziness, changes in level of consciousness, low blood pressure, skin redness, facial and/or throat swelling, blue discoloration of lips, tongue, or skin (possible signs of severe allergic reactions)
• Difficulty breathing, headache, nausea, vomiting (possible symptoms of a condition called ketoacidosis, which involves high levels of acids in the blood)
• Respiratory problems that include difficulty breathing and painful breathing, cough, rapid breathing, blue discoloration of 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 legs, ankles, and around the eyes, fatigue, confusion, nausea, seizures, chest pain (possible symptoms of acute renal failure)
• Toothache, swelling, or numbness of the jaw, a feeling of heaviness in the jaw or tooth loss (possible symptoms of jaw osteonecrosis)
• Rash, skin redness, blisters on lips, eyes, or mouth, skin peeling (possible symptoms of erythema multiforme)

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

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

Frequency not known(cannot be estimated from available data):

• Diarrhea, increased bowel movements, blood in stool, or dark-colored stool, stomach pain or discomfort (possible symptoms of colitis, inflammation of the intestines)
• Confusion, dry mouth, dry skin, nausea, vomiting, fatigue, frequent urination, thirst (possible symptoms of hyperglycemic hyperosmolar non-ketotic syndrome (HHNS))
• Swelling in the face or throat and difficulty breathing (possible symptoms of angioedema, a severe adverse reaction)
• Rash, fever (possible symptoms of a rash with eosinophilia and systemic symptoms (RESS))
• Eye redness, eye pain, light sensitivity, dark spots in the field of vision, blurred vision, decreased vision, small pupil (possible symptoms of uveitis)

Other possible side effects

Other possible side effects include the following. If these side effects become serious, inform your doctor, pharmacist, or nurse.

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

• Frequent urination and painful urination (possible symptom of urinary tract infection)
• Fatigue, pale skin (possible symptoms of anemia, a condition with low red blood cell count)
• Spontaneous bleeding or bruises (signs of low platelet count in the blood)
• Loss of appetite
• Headache
• Strange taste in the mouth (dysgeusia)
• Diarrhea
• Nausea
• Vomiting
• Mouth sores or ulcers with inflamed gums (stomatitis)
• Abdominal pain
• Discomfort in the stomach, indigestion (dyspepsia)
• Rash
• Hair loss or weakened hair (alopecia)
• Itching (pruritus)
• Dry skin
• Fatigue (fatigue)
• Pain, redness, and swelling of the airways or digestive tract or genital mucosa (inflammation of mucous membranes)
• Swelling in hands, ankles, or feet (peripheral edema)
• Fever (pyrexia)
• Mucous dryness
• Weight loss
• Low calcium levels in the blood, which can cause muscle cramps (hypocalcemia)
• Low potassium levels 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 falling asleep (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, skin thickening, and recurrent infections (possible symptoms of lymphedema)
• Toothache
• Bleeding, sensitive or swollen gums (signs of gum inflammation)
• Cracked lips (cheilitis)
• Gum pain
• Erythema
• Dermatitis (inflammation of the skin with rash)
• Redness and/or swelling and possibly peeling on the palms of the hands and soles of the feet, which may be accompanied by a feeling of tingling and burning pain (possible symptoms of hand-foot syndrome)
• Muscle spasms
• Muscle pain (myalgia)
• Generalized swelling (edema)

During treatment with Piqray, some blood test results may be altered, including 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 levels of creatinine and/or calcium in the blood
• Low lymphocyte, platelet, sugar, hemoglobin, and/or albumin levels in the blood
• Increased prothrombin time (a measure of blood coagulation ability)

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

• High hemoglobin A1c level in the blood (a marker of blood sugar level over the last 8 to 12 weeks)

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

This medication does not require special storage conditions.

Do not take this medication if you notice any damage to the packaging or if you see any signs of tampering.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Composition of Piqray

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

Appearance of Piqray and contents of the pack

Piqray 50 mg film-coated tablets are pale 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 pale 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:

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

Only some pack sizes may be marketed.

Marketing authorisation holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible for manufacturing

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Germany

Lek Pharmaceuticals d.d.

VerovškovaUlica 57

1526 Ljubljana

Slovenia

Novartis Pharmaceutical Manufacturing LLC

Verovskovaulica 57

1000 Ljubljana

Slovenia

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu