Patient Information Leaflet

Piqray 50 mg film-coated tablets, 150 mg film-coated tablets, 200 mg film-coated tablets

alpelisib
Please read this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Piqray is and what it is used for
What you need to know before taking Piqray
How to take Piqray
Possible side effects
How to store Piqray
Contents of the pack and other information

1. What Piqray is and what it is used for

What Piqray is
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 hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast carcinoma. Piqray is used in combination with fulvestrant, a hormonal anticancer therapy, in patients whose cancer has not responded to other hormonal treatments and who have certain alterations (mutations) in a gene called PIK3CA.
Your doctor will take a sample of your blood and/or tumour tissue to test for PIK3CA mutations. If the result is positive, it is likely that the tumour 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 tumour cells grow and multiply. By blocking their activity, Piqray can reduce cancer growth and spread and help destroy cancer cells.
If you have questions about how Piqray works or want to know why this medicine has been prescribed for you, consult your doctor, pharmacist, or nurse.

2. What you should know before taking Piqray

Carefully follow all instructions given by your doctor, which may differ from the general information contained in this leaflet. If you have any doubts, consult your doctor.
Do not take Piqray

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Piqray.
Inform your doctor or pharmacist if any of the following apply to you before starting treatment with Piqray:

if you currently have or have previously had high blood sugar levels or diabetes (or signs of high blood sugar such as excessive thirst and dry mouth, need to urinate more frequently than normal, increased urine output, fatigue, nausea, increased appetite with weight loss);
if you have previously experienced Stevens-Johnson syndrome (SJS, a very serious reaction with flu-like symptoms and a painful rash affecting the skin, mouth, eyes, and genitals), erythema multiforme (EM, a skin reaction causing red spots or patches on the skin, which may resemble a target or “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 swelling, swollen lymph nodes, and kidney or liver damage), or toxic epidermal necrolysis (TEN, a severe skin reaction with skin redness, blistering/vesicles on lips, eyes or mouth, skin peeling, with or without fever, rash);
if you have severe bone disease affecting the jaw (osteonecrosis of the jaw, ONJ).

Inform your doctor or pharmacist immediately if any of the following occur while you are being treated with Piqray:

rash, itching, hives, shortness of breath, difficulty breathing, wheezing, cough, feeling of light-headedness, dizziness, altered consciousness, low blood pressure, skin redness, facial or throat swelling, bluish discoloration of lips, tongue or skin (possible signs of severe allergic reactions);
new or worsening breathing problems such as difficulty or pain when breathing, cough, rapid breathing, bluish discoloration of lips, tongue or skin, hiccups (possible signs of non-infectious pneumonia or pneumonitis);
increased thirst and dry mouth, need to urinate more frequently than normal, fatigue, increased appetite with weight loss, confusion, nausea, vomiting, fruity breath odor, difficulty breathing, dry or red skin, which may be signs of elevated blood sugar levels (hyperglycemia) and its complications;
skin rash, skin redness, blistering/vesicles on lips, eyes or mouth, skin peeling, sometimes accompanied by fever (possible signs of one of the following skin conditions: Stevens-Johnson syndrome (SJS), erythema multiforme (EM), drug reaction with eosinophilia and systemic symptoms (DRESS), or toxic epidermal necrolysis (TEN));
new or worsening symptoms affecting the mouth (such as tooth loss, pain or swelling, failure of mouth sores to heal, or discharge);
severe diarrhea or severe abdominal pain or mucus or blood in the stool, which may be signs of intestinal inflammation (colitis). Your doctor may need to treat these symptoms, temporarily interrupt treatment, reduce the dose, or permanently discontinue treatment with Piqray.

Blood tests required before and during treatment with Piqray
Your doctor will perform blood tests before and regularly 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 lower your blood sugar levels. If needed, 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.
Perform regular blood sugar level tests before starting treatment,
during treatment, and after completing treatment with Piqray.

Your doctor will inform you exactly when and where to have blood tests performed. Treatment with Piqray can only be started if these tests show that your blood sugar levels are within normal limits. This is because Piqray can increase blood sugar levels (hyperglycemia), a condition that can be serious and require treatment. Only regular fasting blood tests will allow your doctor to detect whether you are developing hyperglycemia.
Your doctor will inform you exactly when and where to check your blood sugar levels. This type of monitoring may need to be performed more frequently during the first 4 weeks of treatment, especially during the first 2 weeks of treatment with Piqray. Afterwards, blood tests will be required at least once a month, depending on your blood sugar levels.

Children and adolescents
Piqray must not be used in children and adolescents under 18 years of age.
Other medicines and Piqray
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, especially:

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 heartburn and reduce stomach acid production
midazolam, a medicine used for sedation or sleep disorders
rifampicin, a medicine used to treat tuberculosis and certain other serious infections
carbamazepine and phenytoin, medicines used to treat seizures or convulsions
St John’s wort, a herbal product used to treat depression and other conditions
encorafenib, a medicine used to treat a certain type of skin cancer
warfarin, a medicine used to reduce blood clotting ability

Consult your doctor or pharmacist if you are unsure whether a medicine you are taking is included among those listed above.
Pregnancy, breastfeeding and fertility
Piqray must not be used in women who are pregnant or suspect they may be pregnant or during breastfeeding. Piqray may harm the unborn baby. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medicine. Women must not breastfeed during treatment and for at least 1 week after the last dose of Piqray. Your doctor will explain the potential risks of taking Piqray during pregnancy or breastfeeding.
If you are a woman of childbearing potential, your doctor must confirm that you are not pregnant before starting treatment with Piqray. This includes the possibility of performing a pregnancy test.
Women of childbearing potential must use an effective method of contraception during treatment and for at least 1 week after the end of treatment with Piqray. Ask your doctor which contraceptive methods are appropriate. If you think you may be pregnant after starting treatment with Piqray, inform your doctor immediately.
During treatment and for at least 1 week after the end of treatment, male patients must use a condom during sexual intercourse with female partners of childbearing potential. If a male patient’s partner suspects she may be pregnant during this period, she must inform the doctor immediately.
Driving and using machines
Treatment with Piqray may cause fatigue or blurred vision; therefore, caution is advised when driving or operating machinery during treatment with Piqray.
Piqray contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per film-coated tablet, i.e. essentially ‘sodium-free’.

3. How to take Piqray

Always follow exactly your doctor's instructions when taking this medicine. If you have any doubts, consult your doctor.

How much Piqray to take
The usual starting dose of Piqray is 300 mg once daily. Your doctor will decide the right dose for you.
Depending on the prescribed dose, the number of tablets to take is as follows:

300 mg dose: two 150 mg tablets
250 mg dose: one 200 mg tablet and one 50 mg tablet
200 mg dose: one 200 mg tablet

Depending on how your body responds to treatment with Piqray, your doctor may decide to adjust the dose of Piqray. It is very important that you follow your doctor's instructions. If certain side effects occur, your doctor may modify or reduce the dose, or temporarily or permanently stop treatment.

Your doctor will determine the dose of fulvestrant you should take and when to take it.

When to take Piqray
Piqray tablets are supplied in packages containing blister packs. Each blister indicates which tablet(s) to take each day of the week. Follow the instructions printed on the blister.

Take Piqray once daily, immediately after eating food. Taking Piqray at the same time each day will help you remember when to take the medicine.

How to take Piqray
Piqray tablets must be swallowed whole, without chewing, crushing, or dividing before ingestion. Do not swallow broken, cracked, or otherwise damaged tablets, as you may not receive the full dose of Piqray.

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

How long to take Piqray
Take Piqray for as long as your doctor tells you to.
This is a long-term treatment, which may last for months or years. Your doctor will regularly monitor your condition to check that the treatment is working as expected.
For any questions about the duration of Piqray therapy, consult your doctor or pharmacist.

If you take more Piqray than you should
People who have taken too many Piqray tablets have experienced effects that are known side effects of Piqray, including high blood sugar levels, nausea, fatigue, and skin rash. If you accidentally take too many tablets, or if someone else accidentally takes your medicine, seek immediate medical help from a doctor or hospital. Medical treatment may be necessary.

If you forget to take Piqray
If you forget to take a dose of Piqray, you may still take it immediately after eating food, up to 9 hours after the time you were supposed to take it. If you remember more than 9 hours after the scheduled time, skip the dose for that day. Take your next dose at the usual time the following day. Do not take a double dose to make up for a forgotten dose.

If you stop taking Piqray
Stopping treatment with Piqray may cause your condition to worsen. Do not stop taking Piqray unless your doctor tells you to.
If you have any questions about using Piqray, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some side effects could be serious
If you experience serious side effects, stop taking this medicine and contact your doctor
immediately.
Very common (may affect more than 1 in 10 people):

excessive thirst, need to urinate more often than usual or production of larger amounts of urine than usual, increased appetite with weight loss (possible symptoms of elevated blood sugar levels, also called hyperglycaemia)
fever, cough, runny nose, swollen lymph nodes, joint pain, skin rash, night sweats, weight loss (possible symptoms of low lymphocyte levels, a type of white blood cells in the blood).

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

skin rash, itching, hives, shortness of breath, difficulty breathing, wheezing, cough, feeling of light-headedness, dizziness, altered state of consciousness, low blood pressure, skin redness, swelling of the face and/or throat, bluish discoloration of lips, tongue or skin (possible signs of severe allergic reactions)
breathing difficulties, headache, nausea, vomiting (possible symptoms of a condition called ketoacidosis, which involves high levels of acids in the blood)
breathing problems, including difficulty or pain when breathing, cough, rapid breathing, bluish discoloration of lips, tongue or skin, hiccups (possible symptoms of pneumonia)
need to urinate less often than usual or production of smaller amounts of urine than usual, swelling in legs, ankles and around the eyes, fatigue, confusion, nausea, seizures, chest pain (possible symptoms of acute kidney failure)
pain, swelling or numbness in the jaw, feeling of heaviness in the jaw or loosening of a tooth (possible symptoms of osteonecrosis of the jaw)
skin rash, skin redness, formation of blisters/vesicles on lips, eyes or mouth, skin peeling (possible symptoms of erythema multiforme).

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

severe pain in the upper abdomen (possible symptom of pancreatitis)
skin rash, skin redening, formation of blisters/vesicles on lips, eyes or mouth, skin peeling, fever (possible symptoms of Stevens-Johnson syndrome).

Not known (frequency cannot be estimated from the available data):

Diarrhoea, increased number of bowel movements compared to usual, blood in the stool or stools of darker colour, pain or tenderness in the stomach area (possible symptoms of colitis, inflammation of the intestine)
Confusion, dry mouth, dry or red skin, nausea, vomiting, fatigue, frequent need to urinate, thirst (possible symptoms of hyperosmolar hyperglycaemic non-ketotic syndrome (HHNKS))
Swelling of the face or throat and breathing difficulties (possible symptoms of angioedema, a type of severe allergic reaction)
Skin rash, fever (possible symptoms of drug rash with eosinophilia and systemic symptoms (DRESS))
Eye redness, eye pain, sensitivity to light, dark floating spots in the visual field, blurred vision, decreased vision, narrowing of the pupil (possible symptoms of uveitis)

Other possible side effects
Other side effects include those listed below. If these side effects worsen, contact your doctor, pharmacist or nurse.
Very common (may affect more than 1 in 10 people):

painful and frequent urination (possible symptoms of urinary tract infection)
fatigue, pale skin (possible symptoms of anaemia, a condition involving low levels of red blood cells)
spontaneous bleeding or bruising (signs of low platelet count in the blood, also called thrombocytes)
loss of appetite
headache
altered taste in the mouth (dysgeusia)
diarrhoea
nausea
vomiting
mouth sores or ulcers with inflammation of the gums (stomatitis)
abdominal pain
stomach ache, indigestion (dyspepsia)
skin rash
hair loss or thinning (alopecia)
itching
dry skin
fatigue (tiredness)
pain, redness and swelling in the respiratory tract, pharynx or genital mucosa (mucosal inflammation)
swollen hands, ankles or feet (peripheral oedema)
fever (pyrexia)
dryness of mucous membranes
weight reduction
reduced calcium levels in the blood, which may sometimes cause cramps (hypocalcaemia)
reduced potassium levels in the blood, associated with muscle weakness, muscle spasms and/or abnormal heart rhythm (hypokalaemia)
headache, dizziness (possible symptoms of high blood pressure)

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

dehydration
difficulty falling asleep (insomnia)
dry eyes
blurred vision
swelling of part or all of the arm (including fingers) or leg (including toes), feeling of heaviness, limited movement, discomfort, thickening of the skin and recurrent infections (possible symptoms of lymphoedema)
toothache
bleeding, sensitive or swollen gums (signs of gum inflammation)
chapped lips (cheilitis)
gum pain
erythema
skin inflammation with rash (dermatitis)
redness and/or swelling and possible peeling on the palms of the hands and soles of the feet, which may be accompanied by tingling and painful burning sensation (signs of hand-foot syndrome)
muscle spasms
muscle pain (myalgia)
generalised swelling (oedema)

During treatment with Piqray, results of certain blood tests may be abnormal, as listed below:
Very common (may affect more than 1 in 10 people):

high blood levels of the following enzymes: gamma-glutamyltransferase, alanine aminotransferase, lipase
high blood sugar levels
high blood levels of creatinine and/or calcium
low blood levels of lymphocytes, platelets, glucose, haemoglobin and/or albumin
prolonged activated partial thromboplastin time (a measure of blood clotting ability)

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

high blood levels of glycated haemoglobin (a marker of blood sugar levels over the past 8–12 weeks)

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Piqray

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice any damage to the packaging or signs of tampering.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Piqray contains

The active substance in 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:
tablet core: microcrystalline cellulose, mannitol, sodium glycolate starch (see section 2 “Piqray contains sodium”), hypromellose, magnesium stearate.
coating material: hypromellose, red and black iron oxide (E172), titanium dioxide (E171), macrogol, talc.

Description of the appearance of Piqray and package contents
Piqray 50 mg film-coated tablets are round, light pink tablets, with “L7” engraved on one side and “NVR” on the other. Diameter approximately 7.2 mm.
Piqray 150 mg film-coated tablets are oval-shaped, pale red tablets, with “UL7” engraved on one side and “NVR” on the other. Approximate dimensions: 14.2 mm (length) and 5.7 mm (width).
Piqray 200 mg film-coated tablets are oval-shaped, light red tablets, with “YL7” engraved on one side and “NVR” on the other. Approximate dimensions: 16.2 mm (length) and 6.5 mm (width).
Piqray is supplied as film-coated tablets in blister packs. Piqray is available in the following pack sizes:

packs containing film-coated tablets of 50 mg and 200 mg (for patients taking a daily dose of 250 mg):
packs containing a 14-day supply: 28 film-coated tablets (14 of 50 mg and 14 of 200 mg)
packs containing a 28-day supply: 56 film-coated tablets (28 of 50 mg and 28 of 200 mg)
multiple packs containing 168 film-coated tablets (3 x 56, each comprising 28 tablets of 50 mg and 28 tablets of 200 mg)
packs containing film-coated tablets of 150 mg (for patients taking a daily dose of 300 mg):
packs containing a 14-day supply: 28 film-coated tablets
packs containing a 28-day supply: 56 film-coated tablets
multiple packs containing 168 (3 x 56) film-coated tablets
packs containing 200 mg film-coated tablets (for patients taking a daily dose of 200 mg):
packs containing a 14-day supply: 14 film-coated tablets
packs containing a 28-day supply: 28 film-coated tablets
multiple packs containing 84 (3 x 28) film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany
Lek Pharmaceuticals d.d.
Verovskova ulica 57
1526 Ljubljana
Slovenia
Novartis Pharmaceutical Manufacturing LLC
Verovskova ulica 57
1000 Ljubljana
Slovenia

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft.
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf.: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 111

Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00

Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570

España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600

Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01

Ireland Slovenija
Novartis Irlanda Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50

Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439

Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200

Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/