Venclixto

Patient Information Leaflet

Venclyxto 10 mg film-coated tablets, 50 mg film-coated tablets, 100 mg film-coated tablets

venetoclax
Please read all of 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.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Venclyxto is and what it is used for

What Venclyxto is
Venclyxto is an anticancer medicine that contains the active substance venetoclax. It belongs to a
group of medicines called “BCL-2 inhibitors”.
What Venclyxto is used for
Venclyxto is used to treat adults with:

• chronic lymphocytic leukemia (CLL). Venclyxto may be taken in combination with other medicines or alone.
• acute myeloid leukemia (AML). Venclyxto will be taken in combination with other medicines.

CLL is a type of cancer affecting white blood cells called lymphocytes and the lymph nodes. In CLL,
lymphocytes multiply too quickly and live too long, resulting in high levels of lymphocytes in the blood.
AML is a type of cancer affecting white blood cells called myeloid cells. In AML, myeloid blood cells
multiply and grow very rapidly in the bone marrow and blood; this leads to an excess of these cells in the
blood and an insufficient number of red blood cells.
How Venclyxto works
Venclyxto works by blocking a protein in the body called “BCL-2”. This protein is present in high amounts
in certain cancer cells and helps cancer cells survive. Blocking this protein helps kill cancer cells and
reduce their numbers, and also slows down disease progression.

2. What you need to know before taking Venclyxto

Do not take Venclyxto if:

• you are allergic to the active substance venetoclax or to any of the other ingredients of this medicine (listed in section 6).
• you have CLL and are taking any of the following medicines when starting treatment and while the dose is being gradually increased (usually over 5 weeks). This is because serious and potentially fatal reactions may occur when Venclyxto is taken with these medicines:
  • itraconazole, ketoconazole, posaconazole, or voriconazole for fungal infections
  • clarithromycin for bacterial infections
  • ritonavir for HIV infection.

Once the dose of Venclyxto has been increased to the full standard dose, consult your doctor to find out whether you may resume taking these medicines.

• you are taking a herbal medicine called St. John’s wort, used for depression. If in doubt, speak to your doctor, pharmacist, or nurse before taking Venclyxto.

It is important to inform your doctor, pharmacist, or nurse if you are taking any medicines, including prescription or over-the-counter medicines, vitamins, and herbal supplements. Your doctor may ask you to stop taking certain medicines when you start taking Venclyxto and during the first days or weeks, while the dose is being increased to the full standard dose.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Venclyxto if:

• you have kidney problems, as this may increase the risk of an unwanted effect called tumour lysis syndrome
• you have liver problems, as this may increase the risk of side effects. Your doctor may need to reduce your dose of Venclyxto.
• you think you may have an infection or have had a long-lasting or repeated infection
• you need to have a vaccination.

If any of the situations described above apply to you or if you have any doubts, speak to your doctor, pharmacist, or nurse before taking this medicine.

Tumour lysis syndrome
Some people may develop abnormal levels of electrolytes (such as potassium and uric acid) in the blood due to the rapid breakdown of tumour cells during treatment. This can cause changes in kidney function, abnormal heartbeat, or seizures, and is known as tumour lysis syndrome (TLS). The risk of tumour lysis syndrome occurs during the first days or weeks of treatment with Venclyxto, when the dose is being increased.

If you have CLL
Your doctor, pharmacist, or nurse will perform blood tests to monitor for tumour lysis syndrome.
Your doctor will prescribe medicines to help prevent the build-up of uric acid in your body before you start treatment with Venclyxto.
Drink plenty of water, at least 1.5–2 litres per day, to help remove the breakdown products of tumour cells through the urine and reduce the risk of developing tumour lysis syndrome (see section 3).
Immediately inform your doctor, pharmacist, or nurse if you develop any of the symptoms of tumour lysis syndrome listed in section 4.
If you are at risk of tumour lysis syndrome, you may be treated in hospital so that you can receive intravenous fluids if needed, have more frequent blood tests, and be monitored for any side effects. This will help determine whether you can continue taking this medicine safely.

If you have AML
You may be treated in hospital and your doctor or nurse will ensure you receive an adequate amount of water/fluids, give you medicines to prevent the build-up of uric acid in your body, and perform blood tests before starting treatment with Venclyxto, during the dose-escalation phase, and when you begin taking the full dose.

Children and adolescents
Venclyxto must not be used in children and adolescents.

Other medicines and Venclyxto
Tell your doctor or pharmacist if you are taking any of the following medicines, as they may increase or decrease the amount of venetoclax in your blood:

• medicines for fungal infections – fluconazole, itraconazole, ketoconazole, posaconazole, or voriconazole
• antibiotics for bacterial infections – ciprofloxacin, clarithromycin, erythromycin, nafcillin, or rifampicin
• medicines for preventing seizures or treating epilepsy – carbamazepine, phenytoin
• medicines for HIV infection – efavirenz, etravirine, ritonavir
• medicines for high blood pressure or angina – diltiazem, verapamil
• medicines to lower cholesterol levels in the blood – colestyramine, colestipol, colesevelam
• a medicine used to treat a lung condition called pulmonary arterial hypertension – bosentan
• a medicine for sleep disorders (narcolepsy) called modafinil
• a herbal medicine called St. John’s wort

Your doctor may adjust the dose of Venclyxto.

Tell your doctor if you are taking any of the following medicines, as Venclyxto may affect their action:

• medicines that prevent blood clotting, such as warfarin, dabigatran
• a medicine used to treat heart problems called digoxin
• a cancer medicine called everolimus
• a medicine used to prevent organ rejection called sirolimus
• medicines to reduce cholesterol levels in the blood, known as statins

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines without a prescription, herbal medicines, and supplements. Venclyxto may affect how other medicines work. In addition, some other medicines may affect how Venclyxto works.

Venclyxto with food and drink
Do not consume grapefruit, bitter oranges (often used in marmalades), or starfruit during treatment with Venclyxto. This includes eating them, drinking their juice, or taking a supplement that may contain them. These may increase the amount of venetoclax in your blood.

Pregnancy

• Do not become pregnant while taking this medicine. If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor, pharmacist, or nurse before taking this medicine.
• Venclyxto must not be used during pregnancy. There is no information on the safety of venetoclax in pregnant women.

Contraception

• Women of childbearing potential must use a highly effective method of contraception during treatment and for at least 30 days after taking Venclyxto, to avoid pregnancy.
• If you are using oral contraceptives or hormonal contraceptive devices, you must also use a barrier method of contraception (such as condoms), because the effectiveness of oral contraceptives or hormonal contraceptive devices may be affected by Venclyxto.
• Inform your doctor immediately if you become pregnant while taking this medicine.

Breastfeeding
Do not breastfeed while taking this medicine. It is not known whether the active substance of Venclyxto is excreted in breast milk.

Fertility
Based on results in animals, Venclyxto may cause male infertility (low or absent sperm count). This may affect the ability to have children. Ask your doctor about sperm preservation before starting treatment with Venclyxto.

Driving and using machines
You may feel tired or dizzy after taking Venclyxto, which could affect your ability to drive or operate machinery. If this occurs, do not drive and do not use tools or machines.

Venclyxto contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Venclyxto

Take this medicine exactly as instructed by your doctor, pharmacist, or nurse. If you have any doubts, please consult your doctor, pharmacist, or nurse.

How much medicine to take

If you have CLL

You will start treatment with Venclyxto at a low dose for 1 week. Your doctor will gradually increase the dose over the next 4 weeks until you reach the full standard dose. During the first 4 weeks, you will receive a new pack each week.

• The starting dose is 20 mg (two 10 mg tablets) once daily for 7 days.

• The dose will be increased to 50 mg (one 50 mg tablet) once daily for 7 days.

• The dose will be increased to 100 mg (one 100 mg tablet) once daily for 7 days.

• The dose will be increased to 200 mg (two 100 mg tablets) once daily for 7 days.

• The dose will be increased to 400 mg (four 100 mg tablets) once daily for 7 days.

• When taking Venclyxto as monotherapy, you will remain on the standard daily dose of 400 mg for as long as needed.

• When taking Venclyxto in combination with rituximab, you will receive 400 mg daily for 24 months.

• When taking Venclyxto in combination with obinutuzumab, you will receive 400 mg daily for approximately 10 months.

Dose adjustments may be necessary if you experience side effects. Your doctor will advise you on the appropriate dose.

If you have AML

You will start treatment with Venclyxto at a lower dose. Your doctor will gradually increase the dose each day during the first 3 days. After 3 days, you will take the full standard dose. The dose (tablets) should be taken once daily.

The doses are listed in the table below

Your doctor will give you Venclyxto in combination with another medicine (azacitidine or decitabine).
You will continue taking Venclyxto at the full dose until there is a worsening of AML or until you are unable to continue treatment with Venclyxto due to severe side effects.
How to take Venclyxto

• Take the tablets with food, approximately at the same time each day
• Swallow the tablets whole with a glass of water
• Do not chew, crush, or break the tablets
• During the first days or weeks of treatment when the dose is being increased, you should take the tablets in the morning to facilitate blood tests if necessary.

If you vomit after taking Venclyxto, do not take an additional dose that day. Take your next dose the following day at your usual time. If you have difficulty taking this medicine, talk to your doctor.
Drink plenty of water
If you have CLL
It is very important to drink plenty of water when taking Venclyxto during the first 5 weeks of treatment. This will help remove the breakdown products of cancer cells from the blood through urine.
You must start drinking at least 1.5–2 litres of water per day two days before starting Venclyxto. You may include other non-alcoholic and caffeine-free beverages in this amount, but you must exclude grapefruit juice, bitter orange juice, and starfruit. You must continue to drink at least 1.5–2 litres of water on the day you start taking Venclyxto. Drink the same amount of water (at least 1.5–2 litres per day) two days before and on the day your dose is increased.
If your doctor considers you to be at risk of tumour lysis syndrome, you may be treated in hospital so that you can receive additional fluids if needed, have more frequent blood tests, and be monitored for any side effects. This is to determine whether you can continue taking this medicine safely.
If you have AML
It is very important that you drink plenty of water when taking Venclyxto, especially when starting treatment and during the dose-escalation phase. Drinking water will help remove the breakdown products of tumour cells from the blood through urine. If necessary, your doctor or nurse will give you intravenous fluids while you are in hospital to ensure adequate removal of these breakdown products.
If you take more Venclyxto than you should
If you take more Venclyxto than you should, contact your doctor, pharmacist, or nurse immediately or go to hospital straight away. Take the tablets and this leaflet with you.
If you forget to take Venclyxto

• If less than 8 hours have passed since your usual dosing time, take the missed dose as soon as possible.
• If more than 8 hours have passed since your usual dosing time, do not take the missed dose that day. Resume your regular dosing schedule the next day.
• Do not take a double dose to make up for a forgotten dose.
• If you have any doubts, consult your doctor, pharmacist, or nurse.

Do not stop taking Venclyxto
Do not stop taking this medicine unless your doctor tells you to. If you have any questions about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following serious side effects may occur with this medicine:

Tumour lysis syndrome (common – may affect up to 1 in 10 people)
Stop taking Venclyxto and contact your doctor immediately if you experience any of the following symptoms of tumour lysis syndrome:

• fever or chills
• feeling unwell or malaise (nausea or vomiting)
• feeling confused
• shortness of breath
• irregular heartbeat
• dark or cloudy urine
• unusual tiredness
• muscle pain or joint discomfort
• seizures or convulsions
• abdominal pain and swelling

Low white blood cell count (neutropenia) and infections (very common – may affect more than 1 in 10 people)
Your doctor will monitor your blood counts during treatment with Venclyxto. A low white blood cell count may also increase the risk of infections. Signs may include fever, chills, feeling weak or confused, cough, pain or burning sensation when urinating. Some infections, such as lung infection or blood infection (sepsis), can be severe and may be fatal. Inform your doctor immediately if you develop signs of infection while taking this medicine.

Inform your doctor if you experience any of the following side effects:

If you have CLL

Very common (may affect more than 1 in 10 people)

• pneumonia
• upper respiratory tract infection – signs include runny nose, sore throat or cough
• diarrhoea
• feeling unwell or malaise (nausea or vomiting)
• constipation
• feeling tired

Blood tests may also show:

• low number of red blood cells
• low number of white blood cells called lymphocytes
• increased potassium levels
• higher levels of a salt (electrolyte) in the body called phosphate
• decreased calcium levels

Common (may affect up to 1 in 10 people)

• severe blood infection (sepsis)
• urinary tract infection
• low white blood cell count with fever (febrile neutropenia)

Blood tests may also show:

• increased creatinine levels
• increased urea levels

If you have AML

Very common (may affect more than 1 in 10 people)

• feeling unwell or malaise (nausea or vomiting)
• diarrhoea
• mouth ulcers
• feeling tired or weak
• lung or blood infection
• decreased appetite
• joint pain
• dizziness or fainting
• headache
• shortness of breath
• bleeding
• low blood pressure
• urinary tract infection
• weight loss
• stomach pain (abdominal pain)

Blood tests may also show:

• low platelet count (thrombocytopenia)
• low white blood cell count with fever (febrile neutropenia)
• low red blood cell count (anaemia)
• elevated total bilirubin levels
• low potassium levels in the blood

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

• gallstones or gallbladder infection

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

5. How to store Venclyxto

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister after EXP on the label
and on the carton after Exp.
This medicine requires no special storage conditions.
Do not dispose of any medicine 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 Venclyxto contains
The active substance is venetoclax.

• Venclyxto 10 mg film-coated tablets: each film-coated tablet contains 10 mg of venetoclax.
• Venclyxto 50 mg film-coated tablets: each film-coated tablet contains 50 mg of venetoclax.
• Venclyxto 100 mg film-coated tablets: each film-coated tablet contains 100 mg of venetoclax.

The other components are:

• In the tablet core: copovidone (K 28), polysorbate 80 (E433), anhydrous colloidal silica (E551), anhydrous dibasic calcium phosphate (E341 (ii)), sodium stearyl fumarate.

In the film coating:

• Venclyxto 10 mg film-coated tablets: yellow iron oxide (E172), polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol 3350 (E1521), talc (E553b).
• Venclyxto 50 mg film-coated tablets: yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172), polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol 3350 (E1521), talc (E553b).
• Venclyxto 100 mg film-coated tablets: yellow iron oxide (E172), polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol 3350 (E1521), talc (E553b).

Description of the appearance of Venclyxto and contents of the pack
The 10 mg film-coated tablet of Venclyxto is pale yellow, round, with a diameter of 6 mm, marked with "V" on one side and "10" on the other.
The 50 mg film-coated tablet of Venclyxto is beige, oblong, with a length of 14 mm, marked with "V" on one side and "50" on the other.
The 100 mg film-coated tablet of Venclyxto is pale yellow, oblong, with a length of 17.2 mm, marked with "V" on one side and "100" on the other.
Venclyxto tablets are supplied in blisters or bottles packed in cartons as follows:
Venclyxto 10 mg film-coated tablets:

• 10 tablets (5 blisters containing 2 tablets each)
• 14 tablets (7 blisters containing 2 tablets each)

Venclyxto 50 mg film-coated tablets:

• 5 tablets (5 blisters containing 1 tablet each)
• 7 tablets (7 blisters containing 1 tablet each)

Venclyxto 100 mg film-coated tablets:

• 7 tablets (7 blisters containing 1 tablet each)
• 14 tablets (7 blisters containing 2 tablets each)
• 112 (4x28) tablets (4 cartons containing 7 blisters with 4 tablets each)
• 360 tablets (3 bottles containing 120 tablets each)

Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
AbbVie Deutschland GmbH & Co. KG
Knollstrasse
67061 Ludwigshafen
Germany
F.
AbbVie S.r.l.
S.R. 148 Pontina, km 52 SNC
04011 Campoverde di Aprilia (Latina)
Italy
For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
AbbVie SA AbbVie UAB
Tél/Tel: +32 10 477811 Tel: +370 5 205 3023
България Luxembourg/Luxemburg
АбВи ЕООД AbbVie SA
Тел.: +359 2 90 30 430 Belgique/Belgien
Tél/Tel: +32 10 477811
Česká republika Magyarország
AbbVie s.r.o. AbbVie Kft.
Tel: +420 233 098 111 Tel:+36 1 455 8600
Danmark Malta
AbbVie A/S V.J.Salomone Pharma Limited
Tlf: +45 72 30-20-28 Tel: +356 22983201
Deutschland Nederland
AbbVie Deutschland GmbH & Co. KG AbbVie B.V.
Tel: 00800 222843 33 (toll-free) Tel: +31 (0)88 322 2843
Tel: +49 (0) 611 / 1720-0
Eesti Norge
AbbVie OÜ AbbVie AS
Tel: +372 623 1011 Tlf: +47 67 81 80 00
Ελλάδα Österreich
AbbVie ΦΑΡΜΑΚΕΥΤΙΚΗ Α.Ε. AbbVie GmbH
Τηλ: +30 214 4165 555 Tel: +43 1 20589-0
España Polska
AbbVie Spain, S.L.U. AbbVie Sp. z o.o.
Tel: +34 91 384 09 10 Tel.: +48 22 372 78 00
France Portugal
AbbVie AbbVie, Lda.
Tél: +33 (0)1 45 60 13 00 Tel: +351 (0)21 1908400
Hrvatska România
AbbVie d.o.o. AbbVie S.R.L.
Tel: + 385 (0)1 5625 501 Tel: +40 21 529 30 35
Ireland Slovenija
AbbVie Limited AbbVie Biofarmacevtska družba d.o.o.
Tel: +353 (0)1 4287900 Tel: +386 (1)32 08 060
Ísland Slovenská republika
Vistor hf. AbbVie s.r.o.
Tel: +354 535 7000 Tel: +421 2 5050 0777
Italia Suomi/Finland
AbbVie S.r.l. AbbVie Oy
Tel: +39 06 928921 Puh/Tel: +358 (0)10 2411 200
Κύπρος Sverige
Lifepharma (Z.A.M.) Ltd AbbVie AB
Τηλ: +357 22 34 74 40 Tel: +46 (0)8 684 44 600
Latvija
AbbVie SIA
Tel: +371 67605000

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.
To listen to or request a copy of this package leaflet in large print or audio format, please contact the local representative of the Marketing Authorisation Holder.