Venclyxto is a cancer medicine that contains the active substance venetoclax. It belongs to a group of medicines called “BCL-2 inhibitors”. 

Venclyxto is a cancer medicine that contains the active substance venetoclax. It belongs to a group of medicines called “BCL-2 inhibitors.

Venclyxto works by blocking a protein in the body called “BCL-2”. This protein is present in highamounts in some cancer cells and helps cancer cells survive. Blocking this protein helps to kill and lower the number of cancer cells. It also slows down the worsening of the disease.

• If you are allergic to the active substance venetoclax or any of the other ingredients of this medicine (listed in section 6).
• If you have CLL and are taking any of the medicines listed below when you start your treatment and while your dose is gradually being increased (usually over 5 weeks). This is because serious and life-threatening effects can occur when Venclyxto^® is taken with these medicines:
  • itraconazole ketoconazole, posaconazole, or voriconazole for fungal infections
  • clarithromycin for bacterial infections
  • ritonavir for HIV infection
• When your Venclyxto dose has been increased to the full standard dose, check with your doctor if you can start taking these medicines again.
  
• If you are taking a herbal medicine called St. John’s wort, used for depression. If you are not sure about this, talk to your doctor, pharmacist or nurse before taking Venclyxto.
• It is important that you tell your doctor, pharmacist, or nurse about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your doctor may need to stop certain medicines when you first start taking Venclyxto and during the first days or weeks when your dose is increased to the full standard dose. 

Talk to your doctor, pharmacist, or nurse before taking Venclyxto® if:

• you have any kidney problems as your risk for a side effect called tumour lysis syndrome may increase
  
• you have liver problems as this may increase your risk for 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 are due to have a vaccine. 

If any of the above apply to you, or you are not sure, talk to your doctor, pharmacist, or nurse before taking this medicine.

Tumour Lysis Syndrome:

Some people may develop unusual levels of some body salts (such as potassium and uric acid) in the blood caused by the fast breakdown of cancer cells during treatment. This may lead to changes in kidney function, abnormal heartbeat, or seizures. This is called tumour lysis syndrome (TLS). The risk for TLS is in the first days or weeks of treatment with Venclyxto^®, as you increase your dose.

Your doctor, pharmacist or nurse will do blood tests to check for TLS.

Your doctor will also give you medicines to help prevent the build-up of uric acid in your body before you start treatment with Venclyxto^®.

Drinking plenty of water, at least 1.5 to 2 litres per day, helps to remove cancer cell breakdown products from your body through urine and may decrease your risk of getting TLS (see section 3).

Tell your doctor, pharmacist or nurse immediately if you get any of the symptoms of TLS listed in section 4.

If you are at risk of TLS you may be treated in hospital so that you can be given fluids into the vein if needed, have blood tests done more often and to check for side effects. This is to see if you can continue to take this medicine safely.

Children and adolescents:

Venclyxto^® should not be used in children and adolescents.

Other medicines and Venclyxto^®

Tell your doctor or pharmacist if you take any of the following medicines as they can increase or decrease the amount of venetoclax in your blood:

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

Your doctor may change your dose of Venclyxto^®.

Tell your doctor if you take any of the following medicines as Venclyxto^® may affect how they work:

• medicines that prevent blood clots, warfarin, dabigatran
  
• a medicine used to treat heart problems known as digoxin
• a medicine for cancer known as everolimus
• a medicine used to prevent organ rejection known as sirolimus
• medicines to lower 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 obtained without a prescription, herbal medicines and supplements. This is because Venclyxto^® may affect the way some other medicines work. Also, some other medicines can affect the way Venclyxto^® works.

Venclyxto^® with food and drink:

Do not eat grapefruit products, Seville oranges (bitter oranges, often used in marmalades), or starfruit (carambola) while you are taking Venclyxto^® – this includes eating them, drinking the juice or taking a supplement that might contain them. This is because they can increase the amount of venetoclax in your blood.

Pregnancy:

- Do not get pregnant while you are taking this medicine. If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist, or nurse for advice before taking this medicine.

- Venclyxto^® should not be used during pregnancy. There is no information about the safety of venetoclax in pregnant women.

Contraception:

- Women of childbearing age must use a highly effective method of contraception during treatment and for at least 30 days after receiving Venclyxto^® to avoid becoming pregnant. If you are using hormonal contraceptive pills or devices, you must also use a barrier method of contraception (such as condoms) as the effect of hormonal contraceptive pills or devices may be affected by Venclyxto^®.

- Tell your doctor immediately if you become pregnant while you are taking this medicine.

Breast-feeding

Do not breast-feed while you are taking this medicine. It is not known whether the active substance in Venclyxto^® passes into breast milk.

Fertility

Based on findings in animals, Venclyxto^® may cause male infertility (low or no sperm count). This may affect your ability to father a child. Ask your doctor for advice on sperm storage before starting treatment with Venclyxto^®.

Driving and using machines:

You may feel tired or dizzy after taking Venclyxto^®, which may affect your ability to drive or use tools or machines. If this happens, do not drive or use any tools or machines.

Venclyxto^® contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially “sodium free”.

You will begin treatment with Venclyxto^® at a low-dose for 1 week. Your doctor will gradually increase the dose over the next 4 weeks to the full standard dose. For the first 4 weeks you will get a new pack each week. 

• the starting dose is 20 mg (two 10 mg tablets) once a day for 7 days.
• the dose will be increased to 50 mg (one 50 mg tablet) once a day for 7 days.
• the dose will be increased to 100 mg (one 100 mg tablet) once a day for 7 days.
• the dose will be increased to 200 mg (two 100 mg tablets) once a day for 7 days.
• the dose will be increased to 400 mg (four 100 mg tablets) once a day for 7 days.
• When you are receiving Venclyxto^® therapy alone, you will stay on the 400 mg daily dose, which is the standard dose, for as long as necessary.
• When you are receiving Venclyxto^® therapy in combination with rituximab, you will receive the 400 mg daily dose for 24 months.
• When you are receiving Venclyxto^® therapy in combination with obinutuzumab, you will receive the 400 mg daily dose for approximately 10 months. 

Your dose may need to be adjusted for side effects. Your doctor will advise what your dose should be.

It is very important that you drink plenty of water when taking Venclyxto^® during the first 5 weeks of

treatment. This will help to remove cancer cell breakdown products from your blood through your urine.

You should start drinking at least 1.5 to 2 litres of water daily two days before starting Venclyxto^®. You may also include non-alcoholic and non-caffeinated drinks in this amount, but exclude grapefruit, Seville orange, or starfruit (carambola) juices. You should continue to drink at least 1.5 to 2 litres of water on the day you start Venclyxto^®. Drink the same amount of water (at least 1.5 to 2 litres daily) two days before and on the day that your dose is increased.

If your doctor thinks that you are at risk of TLS, you may be treated in the hospital so that you can be

given extra fluids into the vein if needed, have your blood tests more often and be checked for side

effects. This is to see if you can continue to take this medicine safely.

If you take more Venclyxto^® than you should, talk to your doctor, pharmacist, or nurse or go to hospital immediately. Take the tablets and this leaflet with you. 

• If it is less than 8 hours since the time you usually take your dose, take it as soon as possible.
• If it is more than 8 hours since the time you usually take your dose, do not take the dose that day. Return to your normal dose schedule the next day.
• Do not take a double dose to make up for a forgotten dose.
• If you are not sure talk to your doctor, pharmacist or nurse. 

Do not stop taking this medicine unless your doctor tells you to. If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

Tumour lysis syndrome (common – may affect up to 1 in 10 people)

Stop taking Venclyxto^® and seek medical attention immediately if you notice any of the symptoms of

TLS:

• fever or chills
• feeling or being sick (nausea or vomiting)
• feeling confused
• feeling short of breath
• irregular heart beat
• dark or cloudy urine
• feeling unusually tired
• muscle pain or uncomfortable joints
• fits or seizures
• abdominal pain and distension

Low white blood cell count (neutropenia) and infections (very common – may affect more than 1 in 10 people)

Your doctor will check your blood count during treatment with Venclyxto^®. Low white blood cell count can increase your risk for infection. Signs may include fever, chills, feeling weak or confused, cough, pain or burning feeling when passing urine. Some infections such as pneumonia or blood infection (sepsis) can be serious and may lead to death. Tell your doctor immediately if you have signs of an infection while taking this medicine.

Tell your doctor if you notice 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 or being sick (nausea or vomiting)
• constipation
• feeling tired

Blood tests may also show

• lower number of red blood cells
• lower number of white blood cells called lymphocytes
• higher level of potassium
• higher level of a body salt (electrolyte) called phosphate
• lower level of calcium

Common (may affect up to 1 in 10 people)

• severe infection in the blood (sepsis)
• urinary tract infection
• low number of white blood cells with fever (febrile neutropenia) Blood tests may also show:
  • higher level of creatinine
  • higher level of urea

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

HPRA Pharmacovigilance

Website: www.hpra.ie

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the blister label and carton after EXP. This medicine does not require any special storage conditions.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment. 

The active substance is venetoclax.

• Venclyxto^® 10 mg film-coated tablets: Each film-coated tablet contains 10 mg venetoclax.
• Venclyxto^® 50 mg film-coated tablets: Each film-coated tablet contains 50 mg venetoclax.
• Venclyxto^® 100 mg film-coated tablets: Each film-coated tablet contains 100 mg venetoclax.

Venclyxto^® 10 mg film-coated tablet is pale yellow, round 6 mm diameter, with V on one side and 10 on the other.

Venclyxto^® 50 mg film-coated tablet is beige, oblong 14 mm long, with V on one side and 50 on the other.

Venclyxto^® 100 mg film-coated tablet is pale yellow, oblong 17.2 mm long with V on one side and 100 on the other.

Venclyxto^® tablets are provided in blisters or bottles which are packed in cartons as follows:

Venclyxto^® 10 mg film-coated tablets:

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

Venclyxto^® 50 mg film-coated tablets:

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

Venclyxto^® 100 mg film-coated tablets:

• 7 tablets (7 blisters each with 1 tablet)
• 14 tablets (7 blisters each with 2 tablets)
• 112 (4 x 28) tablets (4 cartons of 7 blisters each with 4 tablets)  360 tablets (3 bottles each with 120 tablets).