B. PACKAGE LEAFLET

Package Leaflet: Information for the patient

Akynzeo 300 mg/0.5 mg hard capsules netupitant/pa­lonosetron

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Akynzeo is and what it is used for

• 2. What you need to know before you take Akynzeo

• 3. How to take Akynzeo

• 4. Possible side effects

• 5. How to store Akynzeo

• 6. Contents of the pack and other information

1. What Akynzeo is and what it is used for

What Akynzeo is

Akynzeo contains two medicines (‘active substances’) called:

• netupitant
• palonosetron.

What Akynzeo is used for

Akynzeo is used to help prevent adults with cancer feeling sick (nausea) or being sick (vomiting) while having cancer treatment called ‘chemotherapy’.

How Akynzeo works

Chemotherapy medicines can cause the body to release substances called serotonin and substance P. This stimulates the vomiting centre in the brain, making you feel or be sick. The medicines in Akynzeo attach to the receptors in the nervous system through which serotonin and substance P work: netupitant (an NK1 receptor antagonist) blocks the receptors for substance P, and palonosetron (a 5-HT3 receptor antagonist) blocks certain receptors for serotonin. By blocking the actions of substance P and serotonin in this way, the medicines help prevent the stimulation of the vomiting centre and the resulting sickness.

2. What you need to know before you take Akynzeo

Do not take Akynzeo if:

• you are allergic to netupitant or palonosetron, 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 this medicine.

• you are pregnant.

Warnings and precautions

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

• you have liver problems
• you have a blockage in your gut, or you have had constipation in the past
• you or one of your close relatives has ever had a heart problem called ‘QT interval

prolongation’

• you have any other heart problems
• you have been told you have an imbalance of minerals in your blood such as potassium and

magnesium that has not been corrected.

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

Children and adolescents

Akynzeo should not be taken by children and adolescents under 18 years.

Other medicines and Akynzeo

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

In particular tell your doctor, pharmacist or nurse if you are taking any of the following medicines:

• medicines for depression or anxiety called SSRIs (selective serotonin re-uptake inhibitors) –

such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram

• medicines for depression or anxiety called SNRIs (serotonin noradrenaline re-uptake inhibitors)

– such as venlafaxine or duloxetine.

Also tell your doctor, pharmacist or nurse if you are taking any of the following medicines as your doctor may need to change the dose of these other medicines:

• medicines that might cause abnormal heartbeat such as amiodarone, nicardipine, quinidine,

moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone

• medicines with a narrow therapeutic range that are primarily metabolised by CYP3A4, such as

cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, or quinidine

• some chemotherapy medicines – such as docetaxel or etoposide
• erythromycin – to treat bacterial infections
• midazolam – a sedative used to treat anxiety
• dexamethasone – can be used to treat feeling and being sick
• ketoconazole – to treat Cushing's syndrome
• rifampicin – to treat tuberculosis (TB) and other infections.

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

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Do not take Akynzeo if you are pregnant or if you are a woman of childbearing potential not using contraception.

Do not breast-feed if you are taking Akynzeo. This is because it is not known whether the medicine passes into breast milk.

Driving and using machines

You may feel dizzy or tired after taking Akynzeo. If this happens, do not drive or use any tools or machines.

Akynzeo contains sucrose, sorbitol (E420), sodium and may contain traces of soya

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine contains 7 mg of sorbitol (E420) in each hard capsule.

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

It may contain traces of lecithin – which comes from soya. If you are allergic to peanut or soya, do not use this medicinal product.

3. How to take Akynzeo

Always take this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

How much to take

• The recommended dose is one capsule (each capsule contains 300 mg of netupitant and 0.5 mg

of palonosetron).

• Take the capsule about 1 hour before you start your chemotherapy cycle.
• You can take Akynzeo with or without food.

Akynzeo is taken before the chemotherapy to prevent sickness and feelings of sickness from developing. Do not take Akynzeo in the days after you have chemotherapy – unless you are about to have another chemotherapy cycle.

If you take more Akynzeo than you should

The usual dose is 1 capsule. If you think you may have taken more than you should, tell your doctor straight away. The symptoms of overdose may include headache, dizziness, constipation, anxiety, palpitations, euphoric mood and pain in the legs.

If you forget to take Akynzeo

If you think you have forgotten to take your dose, tell your doctor straight away.

If you stop taking Akynzeo

Akynzeo is taken to help prevent you feeling and being sick when you are having chemotherapy. If you do not want to take Akynzeo, discuss this with your doctor. If you decide not to take Akynzeo (or another similar medicine), your chemotherapy is likely to make you feel sick and be sick.

If you have any further questions on the use of 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.

Serious side effects

Stop taking Akynzeo and tell your doctor straight away if you notice the following serious side effect -you may need urgent medical treatment:

Very rare: may affect up to 1 in 10,000 people

• severe allergic reaction signs include hives, skin rash, itching, difficulty breathing or swallowing, swollen mouth, face, lips, tongue or throat and sometimes a drop in blood pressure.

Other side effects

Tell your doctor, pharmacist or nurse if you notice any of the following side effects:

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

• headache
• constipation
• feeling tired.

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

• hair loss
• lack of energy (feeling weak)
• decreased appetite
• high blood pressure
• raised, itchy rash on the skin (hives)
• problems with the muscles in your heart (cardiomyopathy)
• spinning sensation (vertigo), feeling dizzy or trouble sleeping (insomnia)
• stomach problems including stomach discomfort, feeling bloated, nausea, pain, indigestion,

hiccups, wind or diarrhoea

• high levels of certain enzymes, including blood alkaline phosphatase and liver transaminases

(shown in blood tests)

• high levels of creatinine – which measures kidney function (shown in blood tests)
• ECG (electrocardiogram) problems (called ‘QT and PR interval prolongation’, ‘conduction

disorder’, ‘tachycardia’ and ‘atrioventricular block first degree’)

• low levels of ‘neutrophils’ – a kind of white blood cell which fight infections (shown in blood

tests)

• high level of white blood cells (shown in blood tests).

Rare: (may affect up to 1 in 1 000 people)

• back pain, joint pain
• feeling hot, reddening of the face or other areas of the skin (feeling flushed)
• itchy skin rash
• feeling drowsy
• sleep problems
• ring in the ear
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, change in mood
• infection and inflammation in the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (shown in blood tests)
• modifications (or disturbances) in heart rhythm
• heart valve disorder (mitral valve incompetence)
• coating of the tongue, difficulty swallowing, dry mouth, belching, abnormal taste after medicine

intake

• decreased blood flow to the heart muscle (myocardial ischemia)
• high levels of creatine phosphokinase/ creatine phosphokinase MB – which indicates sudden

decreased blood flow to the heart muscle (shown in blood tests)

• high levels of troponin – which indicates heart muscle dysfunction (shown in blood tests)
• high levels of the pigment bilirubin – which indicates liver dysfunction (shown in blood tests)
• high levels of myoglobin – which indicates muscle injury (shown in blood tests)
• high levels of blood urea – which indicates kidney dysfunction (shown in blood tests)
• high level of ‘lymphocytes’- type of white blood cell which help the body fight disease (shown

in blood tests)

• low level of white blood cells (shown in blood tests)
• ECG (electrocardiogram) problems (called ‘ST segment depression’, ‘ST-T segment abnormal’

‘bundle branch block right/left’, and ‘atrioventricular block second degree’)

Reporting of side effects

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 via the national reporting system listed inBy reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Akynzeo

• 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 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 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.

6. Contents of the pack and other information

What Akynzeo contains

• The active substances are palonosetron and netupitant. Each hard capsule contains three tablets

(300 mg of netupitant), and one soft capsule (palonosetron hydrochloride equivalent to 0.5 milligrams of palonosetron).

• The other ingredients are microcrystalline cellulose (E460), sucrose lauric acid esters, povidone

K-30, croscarmellose sodium, colloidal hydrated silica, sodium stearyl fumarate, magnesium stearate, glycerol monocaprylocaproate (type I), glycerol, polyglyceryl oleate, purified water, butylhydroxyanisole (E320), gelatin, sorbitol (E420), 1,4 sorbitan, titanium dioxide (E171), shellac glaze (partially esterified), yellow, red and black iron oxide (E172), propylene glycol (E1520).

This medicine contains sucrose, sorbitol (E420), sodium and may contain soya – see section 2 for more information.

What Akynzeo looks like and contents of the pack

The hard capsules are opaque with a white body and a caramel cap with ‘HE1’ printed on the body. Pack size containing 1 capsule in an aluminium blister or 4 × 1 hard capsules in aluminium perforated unit dose blisters. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:

Helsinn Birex Pharmaceuticals Ltd.

Damastown

Mulhuddart

Dublin 15

Ireland

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

Belgie/Belgiqu­e/Belgien

Vifor Pharma

Tél/Tel: +32(0)32 182070

Etnrapua

Angelini Pharma Bulgaria EOOD

Ten.: +359 2 975 13 95

Česká republika

Angelini Pharma Česká republika s.r.o.

Tel: (+420) 546 123 111

Danmark

Swedish Orphan Biovitrum A/S

Tlf: + 45 32 96 68 69

Deutschland

Esteve Pharmaceuticals GmbH

Tel: + 49 30 338427–0

Eesti

PharmaSwiss

Tel: +372 6827 400

EXXáSa

Galenica A.E.

Tql: +30 210 52 81 700

España

Vifor Pharma España, S.L.

Tel: +34 902 121 111

France

Vifor France

Tél: +33 (0)1 41 06 58 90

Hrvatska

PharmaSwiss

Tel: +385 1 6311 833

Ireland

Chugai Pharma France

Tel: +33 1 79 36 36 18

Ísland

Swedish Orphan Biovitrum A/S

Tlf: + 45 32 96 68 69

Italia

Italfarmaco

Tel: + 39 02 64431

Kúnpog

Galenica A.E.

Tql: +30 210 52 81 700

Latvija

PharmaSwiss

PharmaSwiss

Tel: +370 5 279 07 62

Luxembourg/Lu­xemburg

Vifor Pharma

Tél/Tel: +32(0)32 182070

Magyarország

Angelini Pharma Magyarország Kft

Tel.: + 36 1 336 1614

Malta

Helsinn Birex Pharmaceuticals Ltd.

Tel.: + 353 1 822 5404

Nederland

Vifor Pharma

Tel: +31(0)88 8484300

Norge

Swedish Orphan Biovitrum AS

Tlf: +47 66 82 34 00

Österreich

Angelini Pharma Österreich GmbH

Tel: +43–5–9–606–0

Polska

Angelini Pharma Polska Sp. z o.o.

Tel: +48 22 70 28 200

Portugal

Vifor Pharma Portugal, S.A.

Tel: +351 21 470 85 00

Romania

Angelini Pharmaceuticals Romania Srl

Tel: +40 21 331 67 67

Slovenija

PharmaSwiss

Tel: +386 1 2364 700

Slovenská republika

Angelini Pharma Slovenská republika s.r.o.

Tel: +421 2 5920 7320

Suomi/Finland

Oy Swedish Orphan Biovitrum Ab

Puh./Tel: +358 201 558 840

Sverige

Swedish Orphan Biovitrum AB (publ)

Tel: +46 8 697 20 00

United Kingdom (Northern Ireland)

Chugai Pharma France

Tel: +371 6750 2185

Tel: +33 1 79 36 36 18

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency website

Package Leaflet: Information for the patient

Akynzeo 235 mg/0.25 mg powder for concentrate for solution for infusion fosnetupitant/pa­lonosetron

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Akynzeo is and what it is used for

• 2. What you need to know before you are given Akynzeo

• 3. How Akynzeo is given

• 4. Possible side effects

• 5. How Akynzeo is stored

• 6. Contents of the pack and other information

1. What Akynzeo is and what it is used for

What Akynzeo is

Akynzeo contains two medicines (‘active substances’) called:

• fosnetupitant
• palonosetron.

What Akynzeo is used for

Akynzeo is used to help prevent adults with cancer feeling sick (nausea) or being sick (vomiting) while having cancer treatment called ‘chemotherapy’.

How Akynzeo works

Chemotherapy medicines can cause the body to release substances called serotonin and substance P. This stimulates the vomiting centre in the brain, making you feel or be sick. The medicines in Akynzeo attach to the receptors in the nervous system through which serotonin and substance P work: fosnetupitant which is converted to netupitant (an NK1 receptor antagonist) in your body blocks the receptors for substance P, and palonosetron (a 5-HT3 receptor antagonist) blocks certain receptors for serotonin. By blocking the actions of substance P and serotonin in this way, the medicines help prevent the stimulation of the vomiting centre and the resulting sickness.

2. What you need to know before you are given Akynzeo

You should not be given Akynzeo if:

• you are allergic to fosnetupitant, netupitant or palonosetron, 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 you are given this medicine.

• you are pregnant.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before being given Akynzeo if:

• you have liver problems
• you have a blockage in your gut or you have had constipation in the past
• you or one of your close relatives has ever had a heart problem called ‘QT interval

prolongation’

• you have any other heart problems
• you have been told you have an imbalance of minerals in your blood such as potassium and

magnesium that has not been corrected.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Children and adolescents

Akynzeo should not be given to children and adolescents under 18 years.

Other medicines and Akynzeo

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

In particular tell your doctor, pharmacist or nurse if you are taking any of the following medicines:

• medicines for depression or anxiety called SSRIs (selective serotonin re-uptake inhibitors) –

such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram

• medicines for depression or anxiety called SNRIs (serotonin noradrenaline re-uptake inhibitors)

– such as venlafaxine or duloxetine.

Also tell your doctor, pharmacist or nurse if you are taking any of the following medicines as your doctor may need to change the dose of these other medicines:

• medicines that might cause abnormal heartbeat such as amiodarone, nicardipine, quinidine,

moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone

• medicines with a narrow therapeutic range that are primarily metabolised by CYP3A4, such as

cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, or quinidine

• some chemotherapy medicines – such as docetaxel or etoposide
• erythromycin – to treat bacterial infections
• midazolam – a sedative used to treat anxiety
• dexamethasone – can be used to treat feeling and being sick
• ketoconazole – to treat Cushing's syndrome
• rifampicin – to treat tuberculosis (TB) and other infections.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before being given this medicine.

You should not be given Akynzeo if you are pregnant or if you are a woman of childbearing potential not using contraception.

Do not breast-feed if you are being given Akynzeo. This is because it is not known whether the medicine passes into breast milk.

Driving and using machines

You may feel dizzy or tired after being given Akynzeo. If this happens, do not drive or use any tools or machines.

Akynzeo contains sodium

This medicine contains 24.8 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.24% of the recommended maximum daily dietary intake of sodium for an adult.

If reconstituted and diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, the final solution contains approximately 202 mg of sodium per dose. This is equivalent to 10.1% of the recommended maximum daily dietary intake of sodium for an adult.

• 3. How Akynzeo is given

The recommended dose of Akynzeo is one vial (each vial contains 235 mg of fosnetupitant and

0.25 mg of palonosetron) on Day 1 of your chemotherapy.

• The powder is reconstituted and diluted before use.
• Akynzeo is given to you by a doctor or nurse
• Akynzeo is given as a drip into a vein (intravenous infusion) about 30 minutes before you start your chemotherapy treatment.

Your doctor will ask you to take other medicines including a corticosteroid (such as dexamethasone) to prevent you feeling and being sick. Check with your doctor or nurse if you are not sure.

If you stop being given Akynzeo

Akynzeo is given to help prevent you feeling and being sick when you are having chemotherapy. If you do not want to be given Akynzeo, discuss this with your doctor. If you decide not to be given Akynzeo (or another similar medicine), your chemotherapy is likely to make you feel and be sick.

If you have any further questions on the use of 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.

Serious side effects

Stop being given Akynzeo and tell your doctor straight away if you notice the following serious side effect – you may need urgent medical treatment:

Very rare (may affect up to 1 in 10 000 people)

• severe allergic reaction – signs include hives, skin rash, itching, difficulty breathing or

swallowing, swollen mouth, face, lips, tongue or throat and sometimes a drop in blood pressure.

Other side effects

Tell your doctor, pharmacist or nurse if you notice any of the following side effects:

Common (may affect up to 1 in 10 people)

• headache
• constipation
• feeling tired.

Uncommon (may affect up to 1 in 100 people)

• hair loss
• lack of energy (feeling weak)
• decreased appetite
• high blood pressure
• raised, itchy rash on the skin (hives)
• problems with the muscles in your heart (cardiomyopathy)
• spinning sensation (vertigo), feeling dizzy or trouble sleeping (insomnia) stomach problems including stomach discomfort, feeling bloated, nausea, pain, indigestion, hiccups, wind or diarrhoea

high levels of certain enzymes, including blood alkaline phosphatase and liver transaminases (shown in blood tests)

high levels of creatinine – which measures kidney function (shown in blood tests)

ECG (electrocardiogram) problems (called ‘QT and PR interval prolongation’, ‘conduction

disorder’, ‘tachycardia’ and ‘atrioventricular block first degree’)

low levels of ‘neutrophils’ – a kind of white blood cell which fight infections (shown in blood tests)

high level of white blood cells (shown in blood tests).

Rare (may affect up to 1 in 1 000 people)

• back pain, joint pain
• feeling hot, reddening of the face or other areas of the skin (feeling flushed)
• itchy skin rash
• feeling drowsy
• sleep problems
• ring in the ear
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, change in mood
• infection and inflammation in the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (shown in blood tests)
• modifications (or disturbances) in heart rhythm
• heart valve disorder (mitral valve incompetence)
• coating of the tongue, difficulty swallowing, dry mouth, belching, abnormal taste after medicine

intake

• decreased blood flow to the heart muscle (myocardial ischemia)
• high levels of creatine phosphokinase//cre­atine phosphokinase MB – which indicates sudden

decreased blood flow to the heart muscle (shown in blood tests)

• high levels of troponin – which indicates heart muscle dysfunction (shown in blood tests)
• high levels of the pigment bilirubin – which indicates liver dysfunction (shown in blood tests)
• high levels of myoglobin – which indicates muscle injury (shown in blood tests)
• high levels of blood urea – which indicates kidney dysfunction (shown in blood tests)
• high level of ‘lymphocytes’- type of white blood cell which help the body fight disease (shown

in blood tests)

• low level of white blood cells (shown in blood tests)
• ECG (electrocardiogram) problems (called ‘ST segment depression’, ‘ST-T segment abnormal’ ‘bundle branch block right/left’, and ‘atrioventricular block second degree’)

Reporting of side effects

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 via the national reporting system listed inBy reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Akynzeo

• 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 carton and vial after ‘EXP’. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C – 8°C).

Keep the vial in the outer carton in order to protect from light.

The total time from reconstitution to the start of the infusion should not exceed 24 hours. Store the reconstituted solution and the final diluted solution below 25°C.

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.

6. Contents of the pack and other information

What Akynzeo contains

• The active substances are fosnetupitant and palonosetron. Each vial contains 235 mg of

fosnetupitant and 0.25 milligrams of palonosetron.

• The other ingredients are mannitol, disodium edetate (E386), sodium hydroxide (E524),

hydrochloric acid diluted (E507) (for pH adjustment).

This medicine contains sodium, see section 2 for more information.

What Akynzeo looks like and contents of the pack

Akynzeo powder for concentrate for solution for infusion is a sterile, white to off-white lyophilised powder and is supplied in a pack of one Type I glass vial with rubber stopper and aluminium cap. Each vial contains one dose.

Pack of 1 vial.

Marketing Authorisation Holder and Manufacturer:

Helsinn Birex Pharmaceuticals Ltd.

Damastown

Mulhuddart

Dublin 15

Ireland

Deutschland

Esteve Pharmaceuticals GmbH

Tel: + 49 30 338427–0

Eesti PharmaSwiss Tel: +372 6827 400	Norge Swedish Orphan Biovitrum AS Tlf: +47 66 82 34 00
EkXáSa Galenica A.E. Tql: +30 210 52 81 700	Österreich Angelini Pharma Österreich GmbH Tel: +43–5–9–606–0
España Vifor Pharma España, S.L. Tel: +34 902 121 111	Polska Angelini Pharma Polska Sp. z o.o. Tel: +48 22 70 28 200
France Vifor France Tél: +33 (0)1 41 06 58 90	Portugal Vifor Pharma Portugal, S.A. Tel: +351 21 470 85 00
Hrvatska PharmaSwiss Tel: +385 1 6311 833	Romania Angelini Pharmaceuticals Romania Srl Tel: +40 21 331 67 67
Ireland Chugai Pharma France Tel: +33 1 79 36 36 18	Slovenija PharmaSwiss Tel: +386 1 2364 700
Ísland Swedish Orphan Biovitrum A/S Tlf: + 45 32 96 68 69	Slovenská republika Angelini Pharma Slovenská republika s.r.o Tel: +421 2 5920 7320
Italia Italfarmaco Tel: + 39 02 64431	Suomi/Finland Oy Swedish Orphan Biovitrum Ab Puh./Tel: +358 201 558 840
Kúnpog Galenica A.E. Tql: +30 210 52 81 700	Sverige Swedish Orphan Biovitrum AB (publ) Tel: +46 8 697 20 00
Latvija PharmaSwiss Tel: +371 6750 2185	United Kingdom (Northern Ireland) Chugai Pharma France Tel: +33 1 79 36 36 18

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website

The following information is intended for medical or healthcare professionals only:

Instructions of how to reconstitute and dilute AKYNZEO 235 mg/0.25 mg

Preparation of Akynzeo

Step 1	Aseptically inject 20 mL 5% glucose injection or sodium chloride 9 mg/ml (0.9%) solution for injection, into the vial. Ensure the solvent is added to the vial along the vial wall and not jetted in order to prevent foaming. Swirl the vial gently for 3 minutes. The powder should be dissolved before the solution is diluted in the infusion bag.
Step 2	Aseptically prepare an infusion vial or bag filled with 30 mL of 5% glucose injection, or sodium chloride 9 mg/ml (0.9%) solution for injection.
Step 3	Dilution should occur immediately after reconstitution (according to Step 1). Aseptically withdraw the entire volume of reconstituted solution from the AKYNZEO vial and transfer it into the infusion vial or bag containing 30 mL of 5% glucose injection or sodium chloride 9 mg/ml (0.9%) solution for injection to yield a total volume of 50 mL.
Step 4	Gently invert the vial or bag until complete dissolution.
Step 5	Before administration, inspect the final diluted solution for particulate matter and discolouration. Discard the vial or bag if particulates and/or discolouration are observed.

The reconstituted and diluted final solution is stable for 24 hours at 25°C.

Parenteral medicines should be inspected visually for particulate matter and discolouration before administration whenever solution and container permit.

The appearance of the reconstituted solution is the same as the appearance of the diluent.

Discard any remaining solution and waste material. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

The medicinal product must not be reconstituted or mixed with solutions for which physical and chemical compatibility has not been established (see Summary of Product Characteristic (SmPC), section 6.2).

Package Leaflet: Information for the patient

Akynzeo 235 mg/0.25 mg concentrate for solution for infusion fosnetupitant/pa­lonosetron

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Akynzeo is and what it is used for

• 2. What you need to know before you are given Akynzeo

• 3. How Akynzeo is given

• 4. Possible side effects

• 5. How Akynzeo is stored

• 6. Contents of the pack and other information

1. What Akynzeo is and what it is used for

What Akynzeo is

Akynzeo contains two medicines (‘active substances’) called:

• fosnetupitant
• palonosetron.

What Akynzeo is used for

Akynzeo is used to help prevent adults with cancer feeling sick (nausea) or being sick (vomiting) while having cancer treatment called ‘chemotherapy’.

How Akynzeo works

Chemotherapy medicines can cause the body to release substances called serotonin and substance P. This stimulates the vomiting centre in the brain, making you feel or be sick. The medicines in Akynzeo attach to the receptors in the nervous system through which serotonin and substance P work: fosnetupitant which is converted to netupitant (an NK1 receptor antagonist) in your body blocks the receptors for substance P, and palonosetron (a 5-HT3 receptor antagonist) blocks certain receptors for serotonin. By blocking the actions of substance P and serotonin in this way, the medicines help prevent the stimulation of the vomiting centre and the resulting sickness.

2. What you need to know before you are given Akynzeo

You should not be given Akynzeo if:

• you are allergic to fosnetupitant, netupitant or palonosetron, 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 you are given this medicine.

• you are pregnant.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before being given Akynzeo if:

• you have liver problems
• you have a blockage in your gut or you have had constipation in the past
• you or one of your close relatives has ever had a heart problem called ‘QT interval

prolongation’

• you have any other heart problems
• you have been told you have an imbalance of minerals in your blood such as potassium and

magnesium that has not been corrected.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Children and adolescents

Akynzeo should not be given to children and adolescents under 18 years.

Other medicines and Akynzeo

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

In particular tell your doctor, pharmacist or nurse if you are taking any of the following medicines:

• medicines for depression or anxiety called SSRIs (selective serotonin re-uptake inhibitors) –

such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram

• medicines for depression or anxiety called SNRIs (serotonin noradrenaline re-uptake inhibitors)

– such as venlafaxine or duloxetine.

Also tell your doctor, pharmacist or nurse if you are taking any of the following medicines as your doctor may need to change the dose of these other medicines:

• medicines that might cause abnormal heartbeat such as amiodarone, nicardipine, quinidine,

moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone

• medicines with a narrow therapeutic range that are primarily metabolised by CYP3A4, such as

cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, or quinidine

• some chemotherapy medicines – such as docetaxel or etoposide
• erythromycin – to treat bacterial infections
• midazolam – a sedative used to treat anxiety
• dexamethasone – can be used to treat feeling and being sick
• ketoconazole – to treat Cushing's syndrome
• rifampicin – to treat tuberculosis (TB) and other infections.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before being given this medicine.

You should not be given Akynzeo if you are pregnant or if you are a woman of childbearing potential not using contraception.

Do not breast-feed if you are being given Akynzeo. This is because it is not known whether the medicine passes into breast milk.

Driving and using machines

You may feel dizzy or tired after being given Akynzeo. If this happens, do not drive or use any tools or machines.

Akynzeo contains sodium

This medicine contains 24.4 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.22% of the recommended maximum daily dietary intake of sodium for an adult.

If diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, the final solution contains approximately 202 mg of sodium per dose. This is equivalent to 10.1% of the recommended maximum daily dietary intake of sodium for an adult.

• 3. How Akynzeo is given

The recommended dose of Akynzeo is one vial (each vial contains 235 mg of fosnetupitant and

0.25 mg of palonosetron) on Day 1 of your chemotherapy.

• The concentrate is diluted before use.
• Akynzeo is given to you by a doctor or nurse
• Akynzeo is given as a drip into a vein (intravenous infusion) about 30 minutes before you start your chemotherapy treatment.

Your doctor will ask you to take other medicines including a corticosteroid (such as dexamethasone) to prevent you feeling and being sick. Check with your doctor or nurse if you are not sure.

If you stop being given Akynzeo

Akynzeo is given to help prevent you feeling and being sick when you are having chemotherapy. If you do not want to be given Akynzeo, discuss this with your doctor. If you decide not to be given Akynzeo (or another similar medicine), your chemotherapy is likely to make you feel and be sick.

If you have any further questions on the use of 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.

Serious side effects

Stop being given Akynzeo and tell your doctor straight away if you notice the following serious side effect – you may need urgent medical treatment:

Very rare (may affect up to 1 in 10 000 people)

• severe allergic reaction – signs include hives, skin rash, itching, difficulty breathing or

swallowing, swollen mouth, face, lips, tongue or throat and sometimes a drop in blood pressure.

Other side effects

Tell your doctor, pharmacist or nurse if you notice any of the following side effects:

Common (may affect up to 1 in 10 people)

• headache
• constipation
• feeling tired.

Uncommon (may affect up to 1 in 100 people)

• hair loss
• lack of energy (feeling weak)
• decreased appetite
• high blood pressure
• raised, itchy rash on the skin (hives)
• problems with the muscles in your heart (cardiomyopathy)
• spinning sensation (vertigo), feeling dizzy or trouble sleeping (insomnia) stomach problems including stomach discomfort, feeling bloated, nausea, pain, indigestion, hiccups, wind or diarrhoea

high levels of certain enzymes, including blood alkaline phosphatase and liver transaminases (shown in blood tests)

high levels of creatinine – which measures kidney function (shown in blood tests)

ECG (electrocardiogram) problems (called ‘QT and PR interval prolongation’, ‘conduction

disorder’, ‘tachycardia’ and ‘atrioventricular block first degree’)

low levels of ‘neutrophils’ – a kind of white blood cell which fight infections (shown in blood tests)

high level of white blood cells (shown in blood tests).

Rare (may affect up to 1 in 1 000 people)

• back pain, joint pain
• feeling hot, reddening of the face or other areas of the skin (feeling flushed)
• itchy skin rash
• feeling drowsy
• sleep problems
• ring in the ear
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, change in mood
• infection and inflammation in the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (shown in blood tests)
• modifications (or disturbances) in heart rhythm
• heart valve disorder (mitral valve incompetence)
• coating of the tongue, difficulty swallowing, dry mouth, belching, abnormal taste after medicine

intake

• decreased blood flow to the heart muscle (myocardial ischemia)
• high levels of creatine phosphokinase//cre­atine phosphokinase MB – which indicates sudden

decreased blood flow to the heart muscle (shown in blood tests)

• high levels of troponin – which indicates heart muscle dysfunction (shown in blood tests)
• high levels of the pigment bilirubin – which indicates liver dysfunction (shown in blood tests)
• high levels of myoglobin – which indicates muscle injury (shown in blood tests)
• high levels of blood urea – which indicates kidney dysfunction (shown in blood tests)
• high level of ‘lymphocytes’- type of white blood cell which help the body fight disease (shown

in blood tests)

• low level of white blood cells (shown in blood tests)
• ECG (electrocardiogram) problems (called ‘ST segment depression’, ‘ST-T segment abnormal’ ‘bundle branch block right/left’, and ‘atrioventricular block second degree’)

Reporting of side effects

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 via the national reporting system listed inBy reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Akynzeo

• 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 carton and vial after ‘EXP’.

The expiry date refers to the last day of that month.

• Store below 25°C.
• Keep the vial in the outer carton in order to protect from light.
• The total time from dilution to the start of the infusion should not exceed 24 hours. Store the

diluted solution below 25°C.

• 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.

6. Contents of the pack and other information

What Akynzeo contains

• The active substances are fosnetupitant and palonosetron. Each vial contains 235 mg of

fosnetupitant and 0.25 milligrams of palonosetron.

• The other ingredients are mannitol, disodium edetate (E386), sodium hydroxide (E524),

What Akynzeo looks like and contents of the pack

The hard capsules are opaque with a white body and a caramel cap with ‘HE1’ printed on the body. Pack size containing 1 capsule in an aluminium blister or 4 × 1 hard capsules in aluminium perforated unit dose blisters. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:

Helsinn Birex Pharmaceuticals Ltd.

Damastown

Mulhuddart

Dublin 15

Ireland

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

Belgie/Belgiqu­e/Belgien

Vifor Pharma

Tél/Tel: +32(0)32 182070

Etnrapua

Angelini Pharma Bulgaria EOOD

Ten.: +359 2 975 13 95

Česká republika

Angelini Pharma Česká republika s.r.o.

Tel: (+420) 546 123 111

Danmark

Swedish Orphan Biovitrum A/S

Tlf: + 45 32 96 68 69

Deutschland

Esteve Pharmaceuticals GmbH

Tel: + 49 30 338427–0

Eesti

PharmaSwiss

Tel: +372 6827 400

EXXáSa

Galenica A.E.

Tql: +30 210 52 81 700

España

Vifor Pharma España, S.L.

Tel: +34 902 121 111

France

Vifor France

Tél: +33 (0)1 41 06 58 90

Hrvatska

PharmaSwiss

Tel: +385 1 6311 833

Ireland

Chugai Pharma France

Tel: +33 1 79 36 36 18

Ísland

Swedish Orphan Biovitrum A/S

Tlf: + 45 32 96 68 69

Italia

Italfarmaco

Tel: + 39 02 64431

Kúnpog

Galenica A.E.

Tql: +30 210 52 81 700

Latvija

PharmaSwiss

PharmaSwiss

Tel: +370 5 279 07 62

Luxembourg/Lu­xemburg

Vifor Pharma

Tél/Tel: +32(0)32 182070

Magyarország

Angelini Pharma Magyarország Kft

Tel.: + 36 1 336 1614

Malta

Helsinn Birex Pharmaceuticals Ltd.

Tel.: + 353 1 822 5404

Nederland

Vifor Pharma

Tel: +31(0)88 8484300

Norge

Swedish Orphan Biovitrum AS

Tlf: +47 66 82 34 00

Österreich

Angelini Pharma Österreich GmbH

Tel: +43–5–9–606–0

Polska

Angelini Pharma Polska Sp. z o.o.

Tel: +48 22 70 28 200

Portugal

Vifor Pharma Portugal, S.A.

Tel: +351 21 470 85 00

Romania

Angelini Pharmaceuticals Romania Srl

Tel: +40 21 331 67 67

Slovenija

PharmaSwiss

Tel: +386 1 2364 700

Slovenská republika

Angelini Pharma Slovenská republika s.r.o.

Tel: +421 2 5920 7320

Suomi/Finland

Oy Swedish Orphan Biovitrum Ab

Puh./Tel: +358 201 558 840

Sverige

Swedish Orphan Biovitrum AB (publ)

Tel: +46 8 697 20 00

United Kingdom (Northern Ireland)

Chugai Pharma France

Tel: +371 6750 2185

Tel: +33 1 79 36 36 18

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency website

Package Leaflet: Information for the patient

Akynzeo 235 mg/0.25 mg powder for concentrate for solution for infusion fosnetupitant/pa­lonosetron

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Akynzeo is and what it is used for

• 2. What you need to know before you are given Akynzeo

• 3. How Akynzeo is given

• 4. Possible side effects

• 5. How Akynzeo is stored

• 6. Contents of the pack and other information

1. What Akynzeo is and what it is used for

What Akynzeo is

Akynzeo contains two medicines (‘active substances’) called:

• fosnetupitant
• palonosetron.

What Akynzeo is used for

Akynzeo is used to help prevent adults with cancer feeling sick (nausea) or being sick (vomiting) while having cancer treatment called ‘chemotherapy’.

How Akynzeo works

Chemotherapy medicines can cause the body to release substances called serotonin and substance P. This stimulates the vomiting centre in the brain, making you feel or be sick. The medicines in Akynzeo attach to the receptors in the nervous system through which serotonin and substance P work: fosnetupitant which is converted to netupitant (an NK1 receptor antagonist) in your body blocks the receptors for substance P, and palonosetron (a 5-HT3 receptor antagonist) blocks certain receptors for serotonin. By blocking the actions of substance P and serotonin in this way, the medicines help prevent the stimulation of the vomiting centre and the resulting sickness.

2. What you need to know before you are given Akynzeo

You should not be given Akynzeo if:

• you are allergic to fosnetupitant, netupitant or palonosetron, 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 you are given this medicine.

• you are pregnant.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before being given Akynzeo if:

• you have liver problems
• you have a blockage in your gut or you have had constipation in the past
• you or one of your close relatives has ever had a heart problem called ‘QT interval

prolongation’

• you have any other heart problems
• you have been told you have an imbalance of minerals in your blood such as potassium and

magnesium that has not been corrected.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Children and adolescents

Akynzeo should not be given to children and adolescents under 18 years.

Other medicines and Akynzeo

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

In particular tell your doctor, pharmacist or nurse if you are taking any of the following medicines:

• medicines for depression or anxiety called SSRIs (selective serotonin re-uptake inhibitors) –

such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram

• medicines for depression or anxiety called SNRIs (serotonin noradrenaline re-uptake inhibitors)

– such as venlafaxine or duloxetine.

Also tell your doctor, pharmacist or nurse if you are taking any of the following medicines as your doctor may need to change the dose of these other medicines:

• medicines that might cause abnormal heartbeat such as amiodarone, nicardipine, quinidine,

moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone

• medicines with a narrow therapeutic range that are primarily metabolised by CYP3A4, such as

cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, or quinidine

• some chemotherapy medicines – such as docetaxel or etoposide
• erythromycin – to treat bacterial infections
• midazolam – a sedative used to treat anxiety
• dexamethasone – can be used to treat feeling and being sick
• ketoconazole – to treat Cushing's syndrome
• rifampicin – to treat tuberculosis (TB) and other infections.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before being given this medicine.

You should not be given Akynzeo if you are pregnant or if you are a woman of childbearing potential not using contraception.

Do not breast-feed if you are being given Akynzeo. This is because it is not known whether the medicine passes into breast milk.

Driving and using machines

You may feel dizzy or tired after being given Akynzeo. If this happens, do not drive or use any tools or machines.

Akynzeo contains sodium

This medicine contains 24.8 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.24% of the recommended maximum daily dietary intake of sodium for an adult.

If reconstituted and diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, the final solution contains approximately 202 mg of sodium per dose. This is equivalent to 10.1% of the recommended maximum daily dietary intake of sodium for an adult.

• 3. How Akynzeo is given

The recommended dose of Akynzeo is one vial (each vial contains 235 mg of fosnetupitant and

0.25 mg of palonosetron) on Day 1 of your chemotherapy.

• The powder is reconstituted and diluted before use.
• Akynzeo is given to you by a doctor or nurse
• Akynzeo is given as a drip into a vein (intravenous infusion) about 30 minutes before you start your chemotherapy treatment.

Your doctor will ask you to take other medicines including a corticosteroid (such as dexamethasone) to prevent you feeling and being sick. Check with your doctor or nurse if you are not sure.

If you stop being given Akynzeo

Akynzeo is given to help prevent you feeling and being sick when you are having chemotherapy. If you do not want to be given Akynzeo, discuss this with your doctor. If you decide not to be given Akynzeo (or another similar medicine), your chemotherapy is likely to make you feel and be sick.

If you have any further questions on the use of 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.

Serious side effects

Stop being given Akynzeo and tell your doctor straight away if you notice the following serious side effect – you may need urgent medical treatment:

Very rare (may affect up to 1 in 10 000 people)

• severe allergic reaction – signs include hives, skin rash, itching, difficulty breathing or

swallowing, swollen mouth, face, lips, tongue or throat and sometimes a drop in blood pressure.

Other side effects

Tell your doctor, pharmacist or nurse if you notice any of the following side effects:

Common (may affect up to 1 in 10 people)

• headache
• constipation
• feeling tired.

Uncommon (may affect up to 1 in 100 people)

• hair loss
• lack of energy (feeling weak)
• decreased appetite
• high blood pressure
• raised, itchy rash on the skin (hives)
• problems with the muscles in your heart (cardiomyopathy)
• spinning sensation (vertigo), feeling dizzy or trouble sleeping (insomnia) stomach problems including stomach discomfort, feeling bloated, nausea, pain, indigestion, hiccups, wind or diarrhoea

high levels of certain enzymes, including blood alkaline phosphatase and liver transaminases (shown in blood tests)

high levels of creatinine – which measures kidney function (shown in blood tests)

ECG (electrocardiogram) problems (called ‘QT and PR interval prolongation’, ‘conduction

disorder’, ‘tachycardia’ and ‘atrioventricular block first degree’)

low levels of ‘neutrophils’ – a kind of white blood cell which fight infections (shown in blood tests)

high level of white blood cells (shown in blood tests).

Rare (may affect up to 1 in 1 000 people)

• back pain, joint pain
• feeling hot, reddening of the face or other areas of the skin (feeling flushed)
• itchy skin rash
• feeling drowsy
• sleep problems
• ring in the ear
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, change in mood
• infection and inflammation in the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (shown in blood tests)
• modifications (or disturbances) in heart rhythm
• heart valve disorder (mitral valve incompetence)
• coating of the tongue, difficulty swallowing, dry mouth, belching, abnormal taste after medicine

intake

• decreased blood flow to the heart muscle (myocardial ischemia)
• high levels of creatine phosphokinase­creatine phosphokinase MB – which indicates sudden

decreased blood flow to the heart muscle (shown in blood tests)

• high levels of troponin – which indicates heart muscle dysfunction (shown in blood tests)
• high levels of the pigment bilirubin – which indicates liver dysfunction (shown in blood tests)
• high levels of myoglobin – which indicates muscle injury (shown in blood tests)
• high levels of blood urea – which indicates kidney dysfunction (shown in blood tests)
• high level of ‘lymphocytes’- type of white blood cell which help the body fight disease (shown

in blood tests)

• low level of white blood cells (shown in blood tests)
• ECG (electrocardiogram) problems (called ‘ST segment depression’, ‘ST-T segment abnormal’ ‘bundle branch block right/left’, and ‘atrioventricular block second degree’)

Reporting of side effects

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 via the national reporting system listed inBy reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Akynzeo

• 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 carton and vial after ‘EXP’. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C – 8°C).

Keep the vial in the outer carton in order to protect from light.

The total time from reconstitution to the start of the infusion should not exceed 24 hours. Store the reconstituted solution and the final diluted solution below 25°C.

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.

6. Contents of the pack and other information

What Akynzeo contains

• The active substances are fosnetupitant and palonosetron. Each vial contains 235 mg of

fosnetupitant and 0.25 milligrams of palonosetron.

• The other ingredients are mannitol, disodium edetate (E386), sodium hydroxide (E524),

hydrochloric acid diluted (E507) (for pH adjustment).

This medicine contains sodium, see section 2 for more information.

What Akynzeo looks like and contents of the pack

Akynzeo powder for concentrate for solution for infusion is a sterile, white to off-white lyophilised powder and is supplied in a pack of one Type I glass vial with rubber stopper and aluminium cap. Each vial contains one dose.

Pack of 1 vial.

Marketing Authorisation Holder and Manufacturer:

Helsinn Birex Pharmaceuticals Ltd.

Damastown

Mulhuddart

Dublin 15

Ireland

Deutschland

Esteve Pharmaceuticals GmbH

Tel: + 49 30 338427–0

Eesti PharmaSwiss Tel: +372 6827 400	Norge Swedish Orphan Biovitrum AS Tlf: +47 66 82 34 00
EkXáSa Galenica A.E. Tql: +30 210 52 81 700	Österreich Angelini Pharma Österreich GmbH Tel: +43–5–9–606–0
España Vifor Pharma España, S.L. Tel: +34 902 121 111	Polska Angelini Pharma Polska Sp. z o.o. Tel: +48 22 70 28 200
France Vifor France Tél: +33 (0)1 41 06 58 90	Portugal Vifor Pharma Portugal, S.A. Tel: +351 21 470 85 00
Hrvatska PharmaSwiss Tel: +385 1 6311 833	Romania Angelini Pharmaceuticals Romania Srl Tel: +40 21 331 67 67
Ireland Chugai Pharma France Tel: +33 1 79 36 36 18	Slovenija PharmaSwiss Tel: +386 1 2364 700
Ísland Swedish Orphan Biovitrum A/S Tlf: + 45 32 96 68 69	Slovenská republika Angelini Pharma Slovenská republika s.r.o Tel: +421 2 5920 7320
Italia Italfarmaco Tel: + 39 02 64431	Suomi/Finland Oy Swedish Orphan Biovitrum Ab Puh./Tel: +358 201 558 840
Kúnpog Galenica A.E. Tql: +30 210 52 81 700	Sverige Swedish Orphan Biovitrum AB (publ) Tel: +46 8 697 20 00
Latvija PharmaSwiss Tel: +371 6750 2185	United Kingdom (Northern Ireland) Chugai Pharma France Tel: +33 1 79 36 36 18

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website

The following information is intended for medical or healthcare professionals only:

Instructions of how to reconstitute and dilute AKYNZEO 235 mg/0.25 mg

Preparation of Akynzeo

Step 1	Aseptically inject 20 mL 5% glucose injection or sodium chloride 9 mg/ml (0.9%) solution for injection, into the vial. Ensure the solvent is added to the vial along the vial wall and not jetted in order to prevent foaming. Swirl the vial gently for 3 minutes. The powder should be dissolved before the solution is diluted in the infusion bag.
Step 2	Aseptically prepare an infusion vial or bag filled with 30 mL of 5% glucose injection, or sodium chloride 9 mg/ml (0.9%) solution for injection.
Step 3	Dilution should occur immediately after reconstitution (according to Step 1). Aseptically withdraw the entire volume of reconstituted solution from the AKYNZEO vial and transfer it into the infusion vial or bag containing 30 mL of 5% glucose injection or sodium chloride 9 mg/ml (0.9%) solution for injection to yield a total volume of 50 mL.
Step 4	Gently invert the vial or bag until complete dissolution.
Step 5	Before administration, inspect the final diluted solution for particulate matter and discolouration. Discard the vial or bag if particulates and/or discolouration are observed.

The reconstituted and diluted final solution is stable for 24 hours at 25°C.

Parenteral medicines should be inspected visually for particulate matter and discolouration before administration whenever solution and container permit.

The appearance of the reconstituted solution is the same as the appearance of the diluent.

Discard any remaining solution and waste material. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

The medicinal product must not be reconstituted or mixed with solutions for which physical and chemical compatibility has not been established (see Summary of Product Characteristic (SmPC), section 6.2).

Package Leaflet: Information for the patient

Akynzeo 235 mg/0.25 mg concentrate for solution for infusion fosnetupitant/pa­lonosetron

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Akynzeo is and what it is used for

• 2. What you need to know before you are given Akynzeo

• 3. How Akynzeo is given

• 4. Possible side effects

• 5. How Akynzeo is stored

• 6. Contents of the pack and other information

1. What Akynzeo is and what it is used for

What Akynzeo is

Akynzeo contains two medicines (‘active substances’) called:

• fosnetupitant
• palonosetron.

What Akynzeo is used for

Akynzeo is used to help prevent adults with cancer feeling sick (nausea) or being sick (vomiting) while having cancer treatment called ‘chemotherapy’.

How Akynzeo works

Chemotherapy medicines can cause the body to release substances called serotonin and substance P. This stimulates the vomiting centre in the brain, making you feel or be sick. The medicines in Akynzeo attach to the receptors in the nervous system through which serotonin and substance P work: fosnetupitant which is converted to netupitant (an NK1 receptor antagonist) in your body blocks the receptors for substance P, and palonosetron (a 5-HT3 receptor antagonist) blocks certain receptors for serotonin. By blocking the actions of substance P and serotonin in this way, the medicines help prevent the stimulation of the vomiting centre and the resulting sickness.

2. What you need to know before you are given Akynzeo

You should not be given Akynzeo if:

• you are allergic to fosnetupitant, netupitant or palonosetron, 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 you are given this medicine.

• you are pregnant.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before being given Akynzeo if:

• you have liver problems
• you have a blockage in your gut or you have had constipation in the past
• you or one of your close relatives has ever had a heart problem called ‘QT interval

prolongation’

• you have any other heart problems
• you have been told you have an imbalance of minerals in your blood such as potassium and

magnesium that has not been corrected.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Children and adolescents

Akynzeo should not be given to children and adolescents under 18 years.

Other medicines and Akynzeo

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.

In particular tell your doctor, pharmacist or nurse if you are taking any of the following medicines:

• medicines for depression or anxiety called SSRIs (selective serotonin re-uptake inhibitors) –

such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram

• medicines for depression or anxiety called SNRIs (serotonin noradrenaline re-uptake inhibitors)

– such as venlafaxine or duloxetine.

Also tell your doctor, pharmacist or nurse if you are taking any of the following medicines as your doctor may need to change the dose of these other medicines:

• medicines that might cause abnormal heartbeat such as amiodarone, nicardipine, quinidine,

moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone

• medicines with a narrow therapeutic range that are primarily metabolised by CYP3A4, such as

cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, ergotamine, fentanyl, or quinidine

• some chemotherapy medicines – such as docetaxel or etoposide
• erythromycin – to treat bacterial infections
• midazolam – a sedative used to treat anxiety
• dexamethasone – can be used to treat feeling and being sick
• ketoconazole – to treat Cushing's syndrome
• rifampicin – to treat tuberculosis (TB) and other infections.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before being given this medicine.

You should not be given Akynzeo if you are pregnant or if you are a woman of childbearing potential not using contraception.

Do not breast-feed if you are being given Akynzeo. This is because it is not known whether the medicine passes into breast milk.

Driving and using machines

You may feel dizzy or tired after being given Akynzeo. If this happens, do not drive or use any tools or machines.

Akynzeo contains sodium

This medicine contains 24.4 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.22% of the recommended maximum daily dietary intake of sodium for an adult.

If diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, the final solution contains approximately 202 mg of sodium per dose. This is equivalent to 10.1% of the recommended maximum daily dietary intake of sodium for an adult.

• 3. How Akynzeo is given

The recommended dose of Akynzeo is one vial (each vial contains 235 mg of fosnetupitant and

0.25 mg of palonosetron) on Day 1 of your chemotherapy.

• The concentrate is diluted before use.
• Akynzeo is given to you by a doctor or nurse
• Akynzeo is given as a drip into a vein (intravenous infusion) about 30 minutes before you start your chemotherapy treatment.

Your doctor will ask you to take other medicines including a corticosteroid (such as dexamethasone) to prevent you feeling and being sick. Check with your doctor or nurse if you are not sure.

If you stop being given Akynzeo

Akynzeo is given to help prevent you feeling and being sick when you are having chemotherapy. If you do not want to be given Akynzeo, discuss this with your doctor. If you decide not to be given Akynzeo (or another similar medicine), your chemotherapy is likely to make you feel and be sick.

If you have any further questions on the use of 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.

Serious side effects

Stop being given Akynzeo and tell your doctor straight away if you notice the following serious side effect – you may need urgent medical treatment:

Very rare (may affect up to 1 in 10 000 people)

• severe allergic reaction – signs include hives, skin rash, itching, difficulty breathing or

swallowing, swollen mouth, face, lips, tongue or throat and sometimes a drop in blood pressure.

Other side effects

Tell your doctor, pharmacist or nurse if you notice any of the following side effects:

Common (may affect up to 1 in 10 people)

• headache
• constipation
• feeling tired.

Uncommon (may affect up to 1 in 100 people)

• hair loss
• lack of energy (feeling weak)
• decreased appetite
• high blood pressure
• raised, itchy rash on the skin (hives)
• problems with the muscles in your heart (cardiomyopathy)
• spinning sensation (vertigo), feeling dizzy or trouble sleeping (insomnia) stomach problems including stomach discomfort, feeling bloated, nausea, pain, indigestion, hiccups, wind or diarrhoea

high levels of certain enzymes, including blood alkaline phosphatase and liver transaminases (shown in blood tests)

high levels of creatinine – which measures kidney function (shown in blood tests)

ECG (electrocardiogram) problems (called ‘QT and PR interval prolongation’, ‘conduction

disorder’, ‘tachycardia’ and ‘atrioventricular block first degree’)

low levels of ‘neutrophils’ – a kind of white blood cell which fight infections (shown in blood tests)

high level of white blood cells (shown in blood tests).

Rare (may affect up to 1 in 1 000 people)

• back pain, joint pain
• feeling hot, reddening of the face or other areas of the skin (feeling flushed)
• itchy skin rash
• feeling drowsy
• sleep problems
• ring in the ear
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, change in mood
• infection and inflammation in the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (shown in blood tests)
• modifications (or disturbances) in heart rhythm
• heart valve disorder (mitral valve incompetence)
• coating of the tongue, difficulty swallowing, dry mouth, belching, abnormal taste after medicine

intake

• decreased blood flow to the heart muscle (myocardial ischemia)
• high levels of creatine phosphokinase­creatine phosphokinase MB – which indicates sudden

decreased blood flow to the heart muscle (shown in blood tests)

• high levels of troponin – which indicates heart muscle dysfunction (shown in blood tests)
• high levels of the pigment bilirubin – which indicates liver dysfunction (shown in blood tests)
• high levels of myoglobin – which indicates muscle injury (shown in blood tests)
• high levels of blood urea – which indicates kidney dysfunction (shown in blood tests)
• high level of ‘lymphocytes’- type of white blood cell which help the body fight disease (shown

in blood tests)

• low level of white blood cells (shown in blood tests)
• ECG (electrocardiogram) problems (called ‘ST segment depression’, ‘ST-T segment abnormal’ ‘bundle branch block right/left’, and ‘atrioventricular block second degree’)

Reporting of side effects

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 via the national reporting system listed inBy reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Akynzeo

• 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 carton and vial after ‘EXP’.

The expiry date refers to the last day of that month.

• Store below 25°C.
• Keep the vial in the outer carton in order to protect from light.
• The total time from dilution to the start of the infusion should not exceed 24 hours. Store the

diluted solution below 25°C.

• 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.

6. Contents of the pack and other information

What Akynzeo contains

• The active substances are fosnetupitant and palonosetron. Each vial contains 235 mg of

fosnetupitant and 0.25 milligrams of palonosetron.

• The other ingredients are mannitol, disodium edetate (E386), sodium hydroxide (E524),