acalabrutinib: package leaflet

What Calquence is
- Calquence contains the active substance acalabrutinib.
- It belongs to a group of medicines called Bruton tyrosine kinase (BTK) inhibitors.

What Calquence is used for
Calquence is used to treat adults with chronic lymphocytic leukaemia (CLL).

CLL is a cancer of white blood cells called B-lymphocytes (or B-cells). These cells are part of the immune system (the body’s defences).

Calquence is used to treat adults with mantle cell lymphoma (MCL).

MCL is a type of blood cancer affecting the lymph nodes.

How Calquence works
Calquence works by blocking BTK, a protein in the body that helps these cancer cells grow and survive.
By blocking BTK, Calquence helps to kill and can reduce the number of cancer cells which can slow down the worsening of the disease.

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

Do not take Calquence if:
- you are allergic to acalabrutinib or any of the other ingredients of this medicine (listed in section 6).

If you are not sure, talk to your doctor, pharmacist or nurse before taking Calquence.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Calquence if you:
- have ever had unusual bruising or bleeding or are on any medicines that increase your risk of bleeding (see section 4 ‘Possible side effects’).
- have an infection (see section 4 “Possible side effects’)
- have recently had an operation or are about to have one. Your doctor may stop treatment with Calquence before and after a medical, surgical or dental procedure.
- have ever had hepatitis B (a liver infection) – this is because Calquence could cause hepatitis B to become active again and so that your doctor will look out for signs of this infection coming back (see section 4 ‘Possible side effects’).
- have or ever had irregular heart beat (see section 4 ‘Possible side effects’).

Talk to your doctor if you develop a new lesion or any change in the appearance of an area on the skin as you are at a high risk of developing skin cancer, see section 4. Use sun protection and make regular skin examination.

Your doctor will check your blood cell counts as needed during treatment.

Children and adolescents
Do not give this medicine to children or adolescents aged less than 18 years. This is because it has not been studied in this age group.

Other medicines and Calquence
Tell your doctor, pharmacist or nurse if you are taking or have recently taken or might take any other medicines, especially if you take any of the following:

• antibiotics for bacterial infections – such as clarithromycin
• medicines for fungal infections – such as posaconazole, itraconazole, voriconazole
• ketoconazole – a medicine for Cushing’s syndrome (a condition in which the body produces too much of the hormone cortisol)
• medicines for HIV infections – such as indinavir and ritonavir
• medicines for hepatitis C – such as telaprevir
• rifampicin – an antibiotic for bacterial infections (tuberculosis)
• ergotamine – a medicine for migraines
• conivaptan – a medicine for low blood sodium
• metformin – a medicine for high blood sugars
• cyclosporine – a medicine to prevent organ rejection
• medicines for fits (seizures) or epilepsy – such as carbamazepine and phenytoin
• pimozide – a medicine used for Tourette (condition which causes uncontrolled movements and outbursts of words and sounds)
• St. John’s wort – an herbal medicine for depression
• theophylline – a medicine used for wheezing, shortness of breath, and chest tightness
• medicines for reducing stomach acid:

o antacids – such as calcium carbonate. Take Calquence2 hours before or 2 hours after you take these medicines.
o histamine-2 receptor blockers – such as ranitidine and famotidine. Take Calquence 2 hours before or 10 hours after you take these medicines.
o proton pump inhibitors – such as omeprazole. Avoid taking these medicines while you are taking Calquence.
- methotrexate – a medicine for diseases such as rheumatoid arthritis, psoriasis and ulcerative colitis, which are caused by the immune system working incorrectly.
o
This medicine should be taken at least 6 hours before or after Calquence.

Medicines that increase your risk of bleeding
Calquence may make you bleed more easily. Tell your doctor, pharmacist, or nurse if you take other medicines that increase your risk of bleeding:
- Antiplatelets (medicines that act against blood clotting) such as acetylsalicylic acid and clopidogrel.
- Anticoagulants (blood thinners) such as warfarin or enoxaparin.

Pregnancy
Talk to your doctor before taking Calquence if you are pregnant, think you may be pregnant, or are planning on having a baby. This is because Calquence may harm your unborn baby.

Breast-feeding
Do not breast-feed during treatment with Calquence and for 2 days after your last dose of Calquence. It is not known if Calquence passes into your breast milk.

Driving and using machines
Calquence is unlikely to affect the ability to drive and use machines. However, if you feel dizzy, weak or tired while taking Calquence, you must not drive or use machines.

Calquence contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

Calquence will only be prescribed to you by a doctor with experience in the use of medicines for cancer.
Always take Calquence exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

Depending on your type of cancer, Calquence may be given in combination with other anticancer medicines.

How much to take
- The usual dose is one capsule (100 mg) twice a day. Take doses about 12 hours apart.

How to take
- Swallow the capsule whole with water at about the same time each day.
- Do not chew, dissolve or open the capsules as this may change how quickly the medicine gets into your body.
- You can take Calquence with food or between meals.

• You can check when you last took a capsule of Calquence by looking on the blister. Pictures on the blister will help you to take your dose at the right time — the sun for the morning dose and the moon for the evening dose.

If you take more Calquence than you should
If you have taken more Calquence than you should, see a doctor or go to the nearest hospital straight away. Take the capsules and this leaflet with you.

If you forget to take a dose
- If less than 3 hours have passed after your usual time for taking a dose, take the missed dose right away. Take the next dose at your usual time.
- If more than 3 hours have passed after your usual time for taking a dose, skip the missed dose. Take the next dose at your usual time.
- Do not take a double dose of Calquence to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Calquence and contact a doctor or go to your nearest emergency department immediately if you experience any of the following symptoms:

Very common serious side effects (may affect more than 1 in 10 people):
- Bleeding in different sites, including skin, gut and brain. Symptoms may be black stools or stools with blood, pink or brown urine, nosebleeds, bruising, unexpected bleeding, vomiting or coughing up blood, dizziness, weakness, confusion.
- Infections. Signs may include fever, chills, feeling weak or confused, cough, shortness of breath [Pneumonia, a very common side effect (may affect more than 1 in 10 people) or Aspergillus infections, an uncommon side effect (may affect up to 1 in 100 people)].

Common serious side effects (may affect up to 1 in 10 people):
- fast heart rate, missed heart beats, weak or uneven pulse, dizziness, feeling faint, chest discomfort or shortness of breath (signs of heart rhythm problems known as atrial fibrillation and atrial flutter).
- fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain. This can be symptoms of tumour lysis syndrome (TLS) – a condition caused by the fast breakdown of cancer cells.

Other side effects:

Very common (may affect more than 1 in 10 people):
- muscle or joint pain
- headache
- rash
- feeling tired (fatigue), weakness or lack of energy
- feeling sick to your stomach (nausea),vomiting, stomach pain, constipation (infrequent or hard to pass stool), diarrhoea (frequent or loose stools)
- decreased number of red blood cells, decreased number of neutrophils (a type of white blood cells) or decreased number of cells that help blood clot (platelets)

• swelling especially of the ankles and feet
• dizziness
• high blood pressure
• headache, pressure in the eyes, nose or cheek area (sinusitis)
• sore throat and runny nose (nasopharyngitis)
• upper respiratory tract infection
• urinary tract infection (pain or burning feeling when passing urine).
• new cancers, including cancers of the skin, may happen during treatment with Calquence (see Section 2 ‘What you need to know before you take Calquence’)
• herpes

Common (may affect up to 1 in 10 people):
- increased levels of the liver enzymes (aspartate aminotransferase and alanine aminotransferase) in blood tests [when used in combination with certain medicines to treat mantle cell lymphoma (MCL)].
- bronchitis
- fever, chills, weakness, confusion, being sick and yellowing of the skin or eyeballs (jaundice) – these may be signs of hepatitis B (a liver infection) becoming active again.
- inflammation of the lungs (pneumonitis)

Uncommon side effects (may affect up to 1 in 100 people):
- memory loss, trouble thinking, difficulty walking or sight loss – these may be signs of a serious brain infection (Progressive Multifocal Leukoencephalopathy or PML).
- lymphocytosis (a higher than normal amount of lymphocytes, a type of white blood cells, in the blood).

Reporting of side effects
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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 foil and carton after EXP. The expiry date refers to the last day of that month.

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.

What Calquence contains
The active substance is acalabrutinib. Each hard capsule contains 100 mg of acalabrutinib.

The other ingredients are:

• Capsule content: microcrystalline cellulose, colloidal anhydrous silica, partially pregelatinised maize starch , magnesium stearate (E470b) and sodium starch glycollate (see section 2 “Calquence contains sodium”).
• Capsule shell: gelatine, titanium dioxide (E171), yellow iron oxide (E172) and indigo carmine (E132).
• Printing ink: shellac, black iron oxide (E172), propylene glycol (E1520) and ammonium hydroxide.

What Calquence looks like and contents of the pack
Calquence is a 20 mm hard gelatine capsule with a yellow body and blue cap, marked with “ACA 100 mg” in black.

Calquence is supplied in aluminium blisters containing either 6 or 8 hard capsules. Each carton contains either 56 or 60 hard capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer
AstraZeneca AB
Gärtunavägen
SE-152 57 Södertälje
Sweden

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел: +359 24455000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf.: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 40 809034100

Nederland
AstraZeneca BV
Tel: +31 85 808 9900

Eesti
AstraZeneca
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0

España
AstraZeneca Farmacéutica Spain, S.A.
Tel: +34 91 301 91 00

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel: +48 22 245 73 00

France
AstraZeneca
Tél: +33 1 41 29 40 00

Portugal
AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
AstraZeneca Pharmaceuticals (Ireland)
DAC
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
AstraZeneca S.p.A.
Tel: +39 02 00704500

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu

What Calquence is
- Calquence contains the active substance acalabrutinib.
- It belongs to a group of medicines called Bruton tyrosine kinase (BTK) inhibitors.

What Calquence is used for
Calquence is used to treat adults with chronic lymphocytic leukaemia (CLL).

CLL is a cancer of white blood cells called B-lymphocytes (or B-cells). These cells are part of the immune system (the body’s defences).

Calquence is used to treat adults with mantle cell lymphoma (MCL).

MCL is a type of blood cancer affecting the lymph nodes.

How Calquence works
Calquence works by blocking BTK, a protein in the body that helps these cancer cells grow and survive.
By blocking BTK, Calquence helps to kill and can reduce the number of cancer cells which can slow down the worsening of the disease.

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

Do not take Calquence if:
- you are allergic to acalabrutinib or any of the other ingredients of this medicine (listed in section 6).

If you are not sure, talk to your doctor, pharmacist or nurse before taking Calquence.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Calquence if you:
- have ever had unusual bruising or bleeding or are on any medicines that increase your risk of bleeding (see section 4 ‘Possible side effects’).
- have an infection (see section 4 ‘Possible side effects’)
- have recently had an operation or are about to have one. Your doctor may stop treatment with Calquence before and after a medical, surgical or dental procedure.
- have ever had hepatitis B (a liver infection) – this is because Calquence could cause hepatitis B to become active again and so that your doctor will look out for signs of this infection coming back (see section 4 ‘Possible side effects’).
- have or ever had irregular heart beat (see section 4 ‘Possible side effects’).

Talk to your doctor if you develop a new lesion or any change in the appearance of an area on the skin as you are at a high risk of developing skin cancer, see section 4. Use sun protection and make regular skin examination.

Your doctor will check your blood cell counts as needed during treatment.

Children and adolescents
Do not give this medicine to children or adolescents aged less than 18 years. This is because it has not been studied in this age group.

Other medicines and Calquence
Tell your doctor, pharmacist or nurse if you are taking or have recently taken or might take any other medicines, especially if you take any of the following:

• antibiotics for bacterial infections – such as clarithromycin
• medicines for fungal infections – such as posaconazole, itraconazole, voriconazole
• ketoconazole – a medicine for Cushing’s syndrome (a condition in which the body produces too much of the hormone cortisol)
• medicines for HIV infections – such as indinavir and ritonavir
• medicines for hepatitis C – such as telaprevir
• rifampicin – an antibiotic for bacterial infections (tuberculosis)
• ergotamine – a medicine for migraines
• conivaptan – a medicine for low blood sodium
• metformin – a medicine for high blood sugars
• cyclosporine – a medicine to prevent organ rejection
• medicines for fits (seizures) or epilepsy – such as carbamazepine and phenytoin
• pimozide – a medicine used for Tourette (condition which causes uncontrolled movements and outbursts of words and sounds)
• St. John’s wort – an herbal medicine for depression
• theophylline – a medicine used for wheezing, shortness of breath, and chest tightness

- methotrexate – a medicine for diseases such as rheumatoid arthritis, psoriasis and ulcerative colitis, which are caused by the immune system working incorrectly.
o
This medicine should be taken at least 6 hours before or after Calquence.

You can take stomach acid reducing medicines such as antacids (calcium carbonate), histamine-2 receptor blockers (ranitidine and famotidine) and proton pump inhibitors (omeprazole) with Calquence tablets.

Medicines that increase your risk of bleeding
Calquence may make you bleed more easily. Tell your doctor, pharmacist, or nurse if you take other medicines that increase your risk of bleeding:
- Antiplatelets (medicines that act against blood clotting) such as acetylsalicylic acid and clopidogrel.
- Anticoagulants (blood thinners) such as warfarin or enoxaparin.

Pregnancy
Talk to your doctor before taking Calquence if you are pregnant, think you may be pregnant, or are planning on having a baby. This is because Calquence may harm your unborn baby.

Breast-feeding
Do not breast-feed during treatment with Calquence and for 2 days after your last dose of Calquence. It is not known if Calquence passes into your breast milk.

Driving and using machines
Calquence is unlikely to affect the ability to drive and use machines. However, if you feel dizzy, weak or tired while taking Calquence, you must not drive or use machines.

Calquence contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

Calquence will only be prescribed to you by a doctor with experience in the use of medicines for cancer.
Always take Calquence exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

Depending on your type of cancer, Calquence may be given in combination with other anticancer medicines.

How much to take
- The usual dose is one tablet (100 mg) twice a day. Take doses about 12 hours apart.

How to take
- Swallow the tablet whole with water at about the same time each day.
- Do not chew, crush, dissolve or divide the tablets.
- You can take Calquence with food or between meals.
- You can check when you last took a tablet of Calquence by looking on the blister. Pictures on the blister will help you to take your dose at the right time — the sun for the morning dose and the moon for the evening dose.

If you take more Calquence than you should
If you have taken more Calquence than you should, see a doctor or go to the nearest hospital straight away. Take the tablets and this leaflet with you.

If you forget to take a dose
- If less than 3 hours have passed after your usual time for taking a dose, take the missed dose right away. Take the next dose at your usual time.
- If more than 3 hours have passed after your usual time for taking a dose, skip the missed dose. Take the next dose at your usual time.
- Do not take a double dose of Calquence to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Calquence and contact a doctor or go to your nearest emergency department immediately if you experience any of the following symptoms:

Very common serious side effects (may affect more than 1 in 10 people):
- Bleeding in different sites, including skin, gut and brain. Symptoms may be black stools or stools with blood, pink or brown urine, nosebleeds, bruising, unexpected bleeding, vomiting or coughing up blood, dizziness, weakness, confusion.
- Infections. Signs may include fever, chills, feeling weak or confused, cough, shortness of breath [Pneumonia, a very common side effect (may affect more than 1 in 10 people) or Aspergillus infections, an uncommon side effect (may affect up to 1 in 100 people)].

Common serious side effects (may affect up to 1 in 10 people):
- fast heart rate, missed heart beats, weak or uneven pulse, dizziness, feeling faint, chest discomfort or shortness of breath (signs of heart rhythm problems known as atrial fibrillation and atrial flutter).
- fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain. This can be symptoms of tumor lysis syndrome (TLS) – a condition caused by the fast breakdown of cancer cells.

Other side effects:

Very common (may affect more than 1 in 10 people):
- muscle or joint pain
- headache
- rash
- feeling tired (fatigue), weakness or lack of energy
- feeling sick to your stomach (nausea),vomiting, stomach pain, constipation (infrequent or hard to pass stool), diarrhoea (frequent or loose stools)
- decreased number of red blood cells, decreased number of neutrophils (a type of white blood cells) or decreased number of cells that help blood clot (platelets)
- swelling especially of the ankles and feet
- dizziness
- high blood pressure
- headache, pressure in the eyes, nose or cheek area (sinusitis)

• sore throat and runny nose (nasopharyngitis)
• upper respiratory tract infection
• urinary tract infection (pain or burning feeling when passing urine)
• new cancers, including cancers of the skin, may happen during treatment with Calquence (see section 2 ‘What you need to know before you take Calquence’)
• herpes

Common (may affect up to 1 in 10 people):
- increased levels of the liver enzymes (aspartate aminotransferase and alanine aminotransferase) in blood tests [when used in combination with certain medicines to treat mantle cell lymphoma (MCL)].
- bronchitis
- fever, chills, weakness, confusion, being sick and yellowing of the skin or eyeballs (jaundice) – these may be signs of hepatitis B (a liver infection) becoming active again.
- inflammation of the lungs (pneumonitis)

Uncommon side effects (may affect up to 1 in 100 people):
- memory loss, trouble thinking, difficulty walking or sight loss – these may be signs of a serious brain infection (Progressive Multifocal Leukoencephalopathy or PML).
- lymphocytosis (a higher than normal amount of lymphocytes, a type of white blood cells, in the blood).

Reporting of side effects
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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 foil and carton after EXP. The expiry date refers to the last day of that month.

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.

What Calquence contains
The active substance is acalabrutinib. Each film-coated tablet contains 100 mg of acalabrutinib (as acalabrutinib maleate).

The other ingredients are:
- Tablet core: mannitol (E421), microcrystalline cellulose (E460), low-substituted hydroxypropyl cellulose (E463) and sodium stearyl fumarate (see section 2 ‘Calquence contains sodium’).
- Tablet coating: hypromellose (E464), copovidone, titanium dioxide (E171), macrogol, medium- chain triglycerides, iron oxide yellow (E172) and iron oxide red (E172).

What Calquence looks like and contents of the pack
Calquence is an orange, 7.5 x 13 mm, oval, biconvex tablet, debossed with ‘ACA 100’ on one side and plain on the reverse.

Calquence is supplied in aluminium blisters containing either 8 or 10 film-coated tablets. On each blister there are sun/moon symbols to help you to take your dose at the right time — the sun for the morning dose and the moon for the evening dose. Both the sun and the moon blisters contain the same medicine. Each carton contains either 56 or 60 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer
AstraZeneca AB
Gärtunavägen
SE-152 57 Södertälje
Sweden

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
AstraZeneca S.A./N.V.
Tel: +32 2 370 48 11

Lietuva
UAB AstraZeneca Lietuva
Tel: +370 5 2660550

България
АстраЗенека България ЕООД
Тел: +359 24455000

Luxembourg/Luxemburg
AstraZeneca S.A./N.V.
Tél/Tel: +32 2 370 48 11

Česká republika
AstraZeneca Czech Republic s.r.o.
Tel: +420 222 807 111

Magyarország
AstraZeneca Kft.
Tel: +36 1 883 6500

Danmark
AstraZeneca A/S
Tlf.: +45 43 66 64 62

Malta
Associated Drug Co. Ltd
Tel: +356 2277 8000

Deutschland
AstraZeneca GmbH
Tel: +49 40 809034100

Nederland
AstraZeneca BV
Tel: +31 85 808 9900

Eesti
AstraZeneca
Tel: +372 6549 600

Norge
AstraZeneca AS
Tlf: +47 21 00 64 00

Ελλάδα
AstraZeneca A.E.
Τηλ: +30 210 6871500

Österreich
AstraZeneca Österreich GmbH
Tel: +43 1 711 31 0

España
AstraZeneca Farmacéutica Spain, S.A.
Tel: +34 91 301 91 00

Polska
AstraZeneca Pharma Poland Sp. z o.o.
Tel: +48 22 245 73 00

France
AstraZeneca
Tél: +33 1 41 29 40 00

Portugal
AstraZeneca Produtos Farmacêuticos, Lda.
Tel: +351 21 434 61 00

Hrvatska
AstraZeneca d.o.o.
Tel: +385 1 4628 000

România
AstraZeneca Pharma SRL
Tel: +40 21 317 60 41

Ireland
AstraZeneca Pharmaceuticals (Ireland)
DAC
Tel: +353 1609 7100

Slovenija
AstraZeneca UK Limited
Tel: +386 1 51 35 600

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
AstraZeneca AB, o.z.
Tel: +421 2 5737 7777

Italia
AstraZeneca S.p.A.
Tel: +39 02 00704500

Suomi/Finland
AstraZeneca Oy
Puh/Tel: +358 10 23 010

Κύπρος
Αλέκτωρ Φαρµακευτική Λτδ
Τηλ: +357 22490305

Sverige
AstraZeneca AB
Tel: +46 8 553 26 000

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu

ANNEX IV
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF
THE MARKETING AUTHORISATION(S)

Scientific conclusions

Taking into account the PRAC Assessment Report on the PSUR(s) for acalabrutinib, the scientific conclusions of PRAC are as follows:

In view of available data on oedema peripheral from clinical trials and post-marketing reports including 69 cases with positive dechallenge and 3 cases with positive rechallenge as well as a potential class effect, the PRAC Rapporteur considers a causal relationship between acalabrutinib and oedema peripheral is at least a reasonable possibility. The PRAC Rapporteur concluded that the product information of products containing acalabrutinib should be amended accordingly.

Having reviewed the PRAC recommendation, the CHMP agrees with the PRAC overall conclusions and grounds for recommendation.

Grounds for the variation to the terms of the marketing authorisation(s)

On the basis of the scientific conclusions for acalabrutinib the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing acalabrutinib is unchanged subject to the proposed changes to the product information

The CHMP recommends that the terms of the marketing authorisation(s) should be varied.