AKYNZEO 300 mg /0.50 Mg Kapsułka Twarda

Treść ulotki

1. Akynzeo 300 mg/0.5 mg hard capsules
   1. What is Akynzeo and what is it 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. Package contents and other information
2. Akynzeo 235 mg/0.25 mg powder for concentrate for infusion solution
   1. What is Akynzeo and what it is used for
   2. What you need to know before you receive Akynzeo
   3. How Akynzeo is administered
   4. Possible side effects
   5. How to store Akynzeo
   6. Contents of the pack and other information
3. Akynzeo 235 mg/0.25 mg concentrate for infusion solution
   1. What is Akynzeo and what it is used for
   2. What you need to know before you receive Akynzeo
   3. How Akynzeo is administered
   4. Possible side effects
   5. How to store Akynzeo
   6. Contents of the pack and other information

Akynzeo 300 mg/0.5 mg hard capsules

netupitant/palonosetron

Read this leaflet carefully before you start to take this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of 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 is Akynzeo and what is it used for

What is Akynzeo
Akynzeo contains two medicines (“active substances”), called:

• netupitant
• palonosetron.

What is Akynzeo used for
Akynzeo is used to help prevent nausea or vomiting in adult patients with cancer undergoing
cancer treatment, called “chemotherapy”.

How does Akynzeo work
The medicines used for chemotherapy can cause the body to release substances called
serotonin and substance P. This stimulates the vomiting center located in the brain, causing nausea
or vomiting. The medicines contained in Akynzeo bind to the receptors of the nervous system through
which serotonin and substance P act: netupitant (an NK receptor antagonist) blocks the
receptors for substance P, while palonosetron (a 5-HT receptor antagonist) blocks some
receptors for serotonin. By blocking the action of substance P and serotonin in this way, the
medicines help to prevent stimulation of the vomiting center and the resulting nausea and vomiting.

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 unsure, ask your doctor, pharmacist or nurse before taking this medicine
• if you are pregnant.

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

• if you have problems with your liver
• if you have a blockage in your intestine or have suffered from constipation in the past
• if you or a close family member has had a heart problem in the past called “prolongation of the QT interval”
• if you have any other heart problems
• if you have been diagnosed with an imbalance of minerals in your blood, such as potassium and magnesium, that has not been corrected.

If you are in any of the above situations (or if you are unsure), ask your doctor, pharmacist or nurse before taking Akynzeo.

Children and adolescents
Akynzeo should not be used in children and adolescents under the age of 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 reuptake inhibitors), such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram
• medicines for depression or anxiety, called SNRIs (serotonin-norepinephrine reuptake inhibitors), such as venlafaxine or duloxetine.

Also, tell your doctor, pharmacist or nurse if you are taking any of the following medicines, because it may be necessary for your doctor to adjust the dose of these other medicines:

• medicines that can cause an irregular heartbeat, such as amiodarone, nicardipine, quinidine, moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone
• medicines with a narrow therapeutic index metabolized primarily by CYP3A4, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, ergotamine, ergotamine, fentanyl or quinidine
• some chemotherapy medicines, such as docetaxel or etoposide
• erythromycin, for the treatment of bacterial infections
• midazolam, a sedative used for the treatment of anxiety
• dexamethasone, which can be used for the treatment of nausea and vomiting
• ketoconazole, for the treatment of Cushing's syndrome
• rifampicin, for the treatment of tuberculosis (TB) and other infections.

If you are in any of the above situations (or if you are unsure), ask your doctor, pharmacist or nurse before taking Akynzeo.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning a pregnancy, or if you are breastfeeding, 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 who is not using contraceptive measures.
Do not breastfeed while taking Akynzeo, as it is not known whether the medicine passes into breast milk.

Driving and using machines
After taking Akynzeo you may feel dizzy or tired. If this happens, do not drive vehicles and do not use tools or machines.

Akynzeo contains sucrose, sorbitol (E 420), sodium and may contain traces of soya.
If your doctor has told you that you have an intolerance to some sugars, contact your doctor before taking this medicine.
This medicine contains 7 mg of sorbitol (E 420) in each hard capsule.
This medicine contains less than 1 mmol (23 mg) of sodium per hard capsule, that is to say essentially ‘sodium-free’.
It may contain traces of lecithin, which is derived from soya. If you are allergic to peanuts or soya, do not use this medicine.

3. How to take Akynzeo

Take this medicine following exactly the instructions of your doctor. If you have any doubts, consult your
doctor, pharmacist or nurse.

Dosage to be taken

• The recommended dose is one capsule (each capsule contains 300 mg of netupitant and 0.5 mg of palonosetron).
• Take the capsule approximately 1 hour before starting the chemotherapy cycle.
• You can take Akynzeo with or without food.

Akynzeo is taken before chemotherapy, to prevent the development of nausea and vomiting. Do not
take Akynzeo in the days following chemotherapy, unless you are about to undergo another
chemotherapy cycle.

If you take more Akynzeo than you should
The usual dose is 1 capsule. If you think you have taken more medicine than you should, inform your
doctor immediately. Symptoms of overdose may include headache, dizziness,
constipation, anxiety, palpitations, euphoric mood and leg pain.

If you forget to take Akynzeo
If you think you have forgotten to take the dose, inform your doctor immediately.

If you stop taking Akynzeo
Akynzeo is taken to help prevent nausea and vomiting when you undergo
chemotherapy. If you do not want to take Akynzeo, discuss it with your doctor. If you decide not to take
Akynzeo (or another similar medicine), it is likely that chemotherapy will cause you nausea and vomiting.
If you have any doubts about 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 everyone will experience them.

Serious side effects
Stop taking Akynzeo and tell your doctor immediately if you notice the following serious side effect – urgent medical treatment may be needed:

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

• serious allergic reaction; signs include hives, skin rash, itching, difficulty breathing or swallowing, swelling of the 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
• itchy, raised rash on the skin (urticaria)
• problems with the heart muscle (cardiomyopathy)
• feeling dizzy, lightheaded or difficulty sleeping (insomnia)
• problems with the stomach, including stomach discomfort, feeling bloated, nausea, pain, indigestion, hiccups, flatulence or diarrhoea
• high levels of certain enzymes, including alkaline phosphatase in the blood and transaminases in the liver (found in blood tests)
• high levels of creatinine, which measures kidney function (found in blood tests)
• problems with the ECG (electrocardiogram) (called “QT and PR prolongation”, “conduction disturbance”, “tachycardia” and “first-degree atrioventricular block”)
• low levels of “neutrophils”, a type of white blood cell that fights infections (found in blood tests)
• high level of white blood cells (found in blood tests).

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

• back pain, joint pain
• feeling of warmth, redness of the face or other areas of the skin (flushing)
• skin rash with itching
• feeling sleepy
• problems with sleeping
• ringing in the ears
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, mood changes
• infection and inflammation of the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (found in blood tests)
• changes (or disturbances) in heart rhythm
• heart valve problem (mitral valve insufficiency)
• coated tongue, difficulty swallowing, dry mouth, belching, abnormal taste after taking the medicine
• decreased blood flow to the heart muscle (myocardial ischemia)
• high levels of creatine phosphokinase/creatine phosphokinase MB, which indicates a sudden decrease in blood flow to the heart muscle (found in blood tests)
• high levels of troponin, which indicate heart muscle dysfunction (found in blood tests)
• high levels of bilirubin, a pigment, which indicates liver dysfunction (found in blood tests)
• high levels of myoglobin, which indicates muscle damage (found in blood tests)
• high levels of azotemia, which indicates kidney dysfunction (found in blood tests)
• high level of “lymphocytes”, a type of white blood cell that helps the body fight disease (found in blood tests)
• low level of white blood cells (found in blood tests)
• problems with the ECG (electrocardiogram) (called “ST segment depression”, “abnormal ST-T segment”, “right/left bundle branch block” and “second-degree atrioventricular block”)

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

5. How to store 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 box and blister after “Exp”. The expiry date refers to the last day of that month.
• This medicine does not require any particular storage conditions.
• Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Akynzeo contains

• The active ingredients are palonosetron and netupitant. Each hard capsule contains three tablets (300 mg of netupitant) and one soft capsule (palonosetron hydrochloride equivalent to 0.5 mg of palonosetron).
• The other ingredients are microcrystalline cellulose (E 460), lauric acid sucroesters, povidone K-30, sodium croscarmellose, hydrated colloidal silica, sodium stearyl fumarate, magnesium stearate, glycerol monocaprylocaprate (Type I), glycerol, polyglycerol oleate, purified water, butylated hydroxyanisole (E 320), gelatin, sorbitol (E 420), 1,4 sorbitan, titanium dioxide (E 171), shellac (partially esterified), yellow, red and black iron oxide (E 172), propylene glycol (E 1520).

This medicine contains sucrose, sorbitol (E 420), sodium and may contain soy; see
section 2 for more information.

Description of Akynzeo and package contents
The hard capsules are opaque, with a white body and caramel-colored head, with “HE1” imprinted on the
body. Pack containing 1 capsule in an aluminum blister 4 x 1 hard capsules in aluminum blisters
divisible per unit dose. Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer
Helsinn Birex Pharmaceuticals Ltd.
Damastown
Mulhuddart
Dublin 15
Ireland
For further information on this medicine, contact the local representative of the marketing
authorization holder:

België/Belgique/Belgien
Immedica Pharma AB
Tel: + 46(0)8 533 39 500

Lietuva
Farma Mondo
Tel: + 370 698 36600

България
Angelini Pharma Bulgaria EOOD
Тел.: +359 2 975 13 95

Luxembourg/Luxemburg
Immedica Pharma AB
Tél/Tel: + 46(0)8 533 39 500

Česká republika
Angelini Pharma Česká republika s.r.o.
Tel: (+420) 546 123 111

Magyarország
Angelini Pharma Magyarország Kft
Tel.: +36 1 336 1614

Danmark
Swedish Orphan Biovitrum A/S
Tlf: + 45 32 96 68 69

Malta
Helsinn Birex Pharmaceuticals Ltd.
Tel.: + 353 1 822 5404

Deutschland
Esteve Pharmaceuticals GmbH
Tel: + 49 30 338427-0

Nederland
Immedica Pharma AB
Tel: + 46(0)8 533 39 500

Eesti
Farma Mondo
Tel: + 370 698 36600

Norge
Swedish Orphan Biovitrum AS
Tlf: +47 66 82 34 00

Ελλάδα
Galenica A.E.
Τηλ: +30 210 52 81 700

Österreich
Angelini Pharma Österreich GmbH
Tel: +43-5-9-606-0

España
Immedica Pharma AB
Tel: + 34(0)9 373 70 164

Polska
Angelini Pharma Polska Sp. z o.o.
Tel: +48 22 70 28 200

France
Immedica Pharma France SARL
Tél: + 33(0)148 014 711

Portugal
Immedica Pharma AB
Tel: + 46(0)8 533 39 500

Hrvatska
Bausch Health Poland sp. z o.o., Podružnica Zagreb
Tel: +385 1 670 0750

România
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
Símí : + 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

Κύπρος
Galenica A.E.
Τηλ: +30 210 52 81 700

Sverige
Swedish Orphan Biovitrum AB (publ)
Tel: +46 8 697 20 00

Latvija
Farma Mondo
Tel: + 370 398 36600
More detailed information on this medicine is available on the website of the European Medicines Agency, http://www.ema.europa.eu .

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

fosnetupitant/palonosetron

Read this leaflet carefully before you receive this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If any side effects occur, including those not listed in this leaflet, ask your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is Akynzeo and what it is used for

What is Akynzeo
Akynzeo contains two medicines (“active substances”), called:

• fosnetupitant
• palonosetron.

What is Akynzeo used for
Akynzeo is used to help prevent nausea or vomiting in adult patients with cancer undergoing
cancer treatment, called “chemotherapy”.

How Akynzeo works
The medicines used for chemotherapy can cause the body to release substances called
serotonin and substance P. This stimulates the vomiting center located in the brain, causing nausea
or vomiting. The medicines contained in Akynzeo bind to the receptors of the nervous system through
which serotonin and substance P act: fosnetupitant, which is converted into netupitant (a
receptor NK antagonist) in the body, blocks the receptors for substance P, while palonosetron
(a 5-HT receptor antagonist) blocks some receptors for serotonin. By blocking the action of
substance P and serotonin in this way, the medicines help to prevent stimulation of the vomiting center and the resulting nausea and vomiting.

2. What you need to know before you receive Akynzeo

You must not receive Akynzeo

• if you are allergic to fosnetupitant, netupitant or palonosetron or to any of the other ingredients of this medicine (listed in section 6). If you have any doubts, ask your doctor, pharmacist or nurse before receiving this medicine
• if you are pregnant.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you receive Akynzeo:

• if you have problems with your liver
• if you have a blockage in your intestine or have suffered from constipation in the past
• if you or a close relative has had a heart problem in the past called “prolongation of the QT interval”
• if you have any other heart problems
• if you have been diagnosed with an imbalance of minerals in your blood, such as potassium and magnesium, that has not been corrected.

If you fall into any of the above categories (or if you are unsure), ask your doctor, pharmacist or
nurse before receiving Akynzeo.

Children and adolescents
Akynzeo must not be given to children and adolescents under 18 years of age.

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 reuptake inhibitors), such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram
• medicines for depression or anxiety, called SNRIs (serotonin-noradrenaline reuptake inhibitors), such as venlafaxine or duloxetine.

Also, tell your doctor, pharmacist or nurse if you are taking any of the following
medicines, because it may be necessary for your doctor to adjust the dose of these other medicines:

• medicines that can cause an irregular heartbeat, such as amiodarone, nicardipine, quinidine, moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone
• medicines with a narrow therapeutic index metabolised mainly by CYP3A4, such as ciclosporin, tacrolimus, sirolimus, everolimus, alfentanil, ergotamine, dihydroergotamine, fentanyl or quinidine
• some chemotherapy medicines, such as docetaxel or etoposide
• erythromycin, for the treatment of bacterial infections
• midazolam, a sedative used for the treatment of anxiety
• dexamethasone, which can be used for the treatment of nausea and vomiting
• ketoconazole, for the treatment of Cushing's syndrome
• rifampicin, for the treatment of tuberculosis (TB) and other infections.

If you fall into any of the above categories (or if you are unsure), ask your doctor, pharmacist or
nurse before receiving Akynzeo.

Pregnancy and breastfeeding
If you are pregnant, if you suspect you might be pregnant or if you are planning a pregnancy, or if you are
breastfeeding, ask your doctor for advice before receiving this medicine.
You must not receive Akynzeo if you are pregnant or if you are a woman of childbearing potential who is not using
contraception.
Do not breastfeed while you are receiving Akynzeo, as it is not known whether the medicine passes into
breast milk.

Driving and using machines
After receiving Akynzeo you may feel dizzy or tired. If this happens, do not drive vehicles and
do not use tools or machines.

Akynzeo contains sodium
This medicine contains 24.8 mg of sodium (the main component of table salt) per
vial. This is equivalent to 1.24% of the recommended maximum daily intake of sodium with the diet
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 intake of sodium with the diet for an adult.

3. How Akynzeo is administered

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 chemotherapy.

• The powder must be reconstituted and diluted before use.
• Akynzeo is administered by a doctor or nurse
• Akynzeo is administered intravenously as an infusion approximately 30 minutes before starting chemotherapy treatment.

The doctor will ask you to take other medications, including a corticosteroid (such as dexamethasone) to
prevent nausea and vomiting. If you have any doubts, consult your doctor or nurse.

If you stop taking Akynzeo
Akynzeo is administered to help prevent nausea and vomiting when you undergo
chemotherapy. If you do not wish to receive Akynzeo, discuss this with your doctor. If you decide not to receive
Akynzeo (or another similar medication), it is likely that chemotherapy will cause you nausea and vomiting.
If you have any questions about the use of this medication, 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 receiving Akynzeo and tell your doctor immediately if you notice the following serious side effect – urgent medical treatment may be needed:

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

• serious allergic reaction; signs include hives, skin rash, itching, difficulty breathing or swallowing, swelling of the 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
• itchy raised bumps on the skin (urticaria)
• problems with the heart muscle (cardiomyopathy)
• feeling dizzy, lightheaded or difficulty sleeping (insomnia)
• problems with the stomach, including stomach discomfort, feeling bloated, nausea, pain, indigestion, hiccups, flatulence or diarrhoea
• high levels of certain enzymes, including alkaline phosphatase in the blood and transaminases in the liver (shown in blood tests)
• high levels of creatinine, which measures kidney function (shown in blood tests)
• problems with the ECG (electrocardiogram) (called “QT and PR prolongation”, “conduction disturbance”, “tachycardia” and “first-degree atrioventricular block”)
• low levels of “neutrophils”, a type of white blood cell that fights 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 of warmth, redness of the face or other areas of the skin (flushing)
• skin rash with itching
• feeling sleepy
• sleep problems
• ringing in the ears
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, mood changes
• infection and inflammation of the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (shown in blood tests)
• changes (or disturbances) in heart rhythm
• heart valve problem (mitral valve insufficiency)
• coated tongue, difficulty swallowing, dry mouth, belching, unusual taste after taking the medicine
• decreased blood flow to the heart muscle (myocardial ischemia)
• high levels of creatine phosphokinase/creatine phosphokinase MB, which indicates a sudden decrease in 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 bilirubin, a pigment, which indicates liver dysfunction (shown in blood tests)
• high levels of myoglobin, which indicates muscle damage (shown in blood tests)
• high levels of azotemia, which indicates kidney dysfunction (shown in blood tests)
• high level of “lymphocytes”, a type of white blood cell that helps the body fight disease (shown in blood tests)
• low level of white blood cells (shown in blood tests)
• problems with the ECG (electrocardiogram) (called “ST segment depression”, “abnormal ST-T segment”, “right/left bundle branch block” and “second-degree atrioventricular block”)

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

5. How to store 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 pack 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 packaging to protect the medicine from light.
• The total time between reconstitution and the start of the infusion must not exceed 24 hours. Store the reconstituted solution and the final diluted solution at a temperature below 25°C.
• Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Akynzeo contains

• The active ingredients are fosnetupitant and palonosetron. Each vial contains 235 mg of fosnetupitant and 0.25 milligrams of palonosetron.
• The other ingredients are mannitol, disodium edetate (E 386), sodium hydroxide (E 524) and diluted hydrochloric acid (E 507) (for pH adjustment). This medicine contains sodium, for more information see section 2.

Description of Akynzeo and contents of the pack
Akynzeo powder for concentrate for solution for infusion is a sterile, lyophilized powder, of
colour from white to off-white, supplied in a pack containing a glass vial of type I, with
rubber stopper and aluminium crimp cap. Each vial contains one dose.
Pack size of 1 vial.

Marketing authorisation holder and manufacturer:
Helsinn Birex Pharmaceuticals Ltd.
Damastown
Mulhuddart
Dublin 15
Ireland
For further information on this medicine, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Immedica Pharma AB
Tél/Tel: + 46(0)8 533 39 500

Lietuva
Farma Mondo
Tel: + 370 698 36600

България
Angelini Pharma Bulgaria EOOD
Teл.: +359 2 975 13 95

Luxembourg/Luxemburg
Immedica Pharma AB
Tél/Tel: + 46(0)8 533 39 500

Česká republika
Angelini Pharma Česká republika s.r.o.
Tel: (+420) 546 123 111

Magyarország
Angelini Pharma Magyarország Kft
Tel.: + 36 1 336 1614

Danmark
Swedish Orphan Biovitrum A/S
Tlf: + 45 32 96 68 69

Malta
Helsinn Birex Pharmaceuticals Ltd.
Tel.: + 353 1 822 5404

Deutschland
Esteve Pharmaceuticals GmbH
Tel: + 49 30 338427-0

Nederland
Immedica Pharma AB
Tel: + 46(0)8 533 39 500

Eesti
Farma Mondo
Tel: + 370 698 36600

Norge
Swedish Orphan Biovitrum AS
Tlf: +47 66 82 34 00

Ελλάδα
Galenica A.E.
Τηλ: +30 210 52 81 700

Österreich
Angelini Pharma Österreich GmbH
Tel: +43-5-9-606-0

España
Immedica Pharma AB
Tel: + 34(0)9 373 70 164

Polska
Angelini Pharma Polska Sp. z o.o.
Tel: +48 22 70 28 200

France
Immedica Pharma France SARL
Tél: + 33(0)148 014 711

Portugal
Immedica Pharma AB
Tel: + 46(0)8 533 39 500

Hrvatska
Bausch Health Poland sp. z o.o., Podružnica Zagreb
Tel: +385 1 670 0750

România
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

Κύπρος
Galenica A.E.
Τηλ: +30 210 52 81 700

Sverige
Swedish Orphan Biovitrum AB (publ)
Tel: +46 8 697 20 00

Latvija
Farma Mondo
Tel: + 370 698 36600

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines
Agency, http://www.ema.europa.eu .
The following information is intended exclusively for healthcare professionals:
Instructions for reconstitution and dilution of AKYNZEO 235 mg/0.25 mg

Preparation of Akynzeo

The final reconstituted and diluted solution is stable for 24 hours at 25 °C.
If the solution and container allow, parenteral medicines should be visually inspected
for the presence of particulate matter and colour changes before administration.
The appearance of the reconstituted solution is identical to that of the diluent.
Dispose of any remaining solution and waste materials. Unused medicine and waste materials
from this medicine must be disposed of in accordance with local regulations.
The medicine must not be reconstituted or mixed with solutions for which physical and chemical
compatibility has not been established (see summary of product characteristics, section 6.2).

Akynzeo 235 mg/0.25 mg concentrate for infusion solution

fosnetupitant/palonosetron

Read this leaflet carefully before receiving this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If any side effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is Akynzeo and what it is used for

What is Akynzeo
Akynzeo contains two medicines (“active substances”), called:

• fosnetupitant
• palonosetron.

What is Akynzeo used for
Akynzeo is used to help prevent nausea or vomiting in adult patients with cancer undergoing
cancer treatment, called “chemotherapy”.

How Akynzeo works
The medicines used for chemotherapy can cause the body to release substances called
serotonin and substance P. This stimulates the vomiting center located in the brain, causing nausea
or vomiting. The medicines contained in Akynzeo bind to the receptors of the nervous system through
which serotonin and substance P act: fosnetupitant, which is converted into netupitant (a
receptor NK antagonist) in the body, blocks the receptors for substance P, while palonosetron
(a 5-HT receptor antagonist) blocks some receptors for serotonin. By blocking the action of
substance P and serotonin in this way, the medicines help to prevent stimulation of the vomiting
center and the resulting nausea and vomiting.

2. What you need to know before you receive Akynzeo

You must not receive Akynzeo

• if you are allergic to fosnetupitant, netupitant or palonosetron or to any of the other ingredients of this medicine (listed in section 6). If you have any doubts, ask your doctor, pharmacist or nurse before receiving this medicine
• if you are pregnant.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before you receive Akynzeo:

• if you have problems with your liver
• if you have a blockage in your intestine or have suffered from constipation in the past
• if you or a close family member has had a heart problem in the past called “prolongation of the QT interval”
• if you have any other heart problems
• if you have been diagnosed with an imbalance of minerals in your blood, such as potassium and magnesium, that has not been corrected.

If you fall into any of the above categories (or if you are unsure), ask your doctor, pharmacist or
nurse before receiving Akynzeo.

Children and adolescents
Akynzeo must not be given to children and adolescents under 18 years of age.

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 reuptake inhibitors), such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram
• medicines for depression or anxiety, called SNRIs (serotonin-noradrenaline reuptake inhibitors), such as venlafaxine or duloxetine.

Also, tell your doctor, pharmacist or nurse if you are taking any of the following
medicines, because it may be necessary for your doctor to adjust the dose of these other medicines:

• medicines that can cause an irregular heartbeat, such as amiodarone, nicardipine, quinidine, moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone
• medicines with a narrow therapeutic index metabolised mainly by CYP3A4, such as ciclosporin, tacrolimus, sirolimus, everolimus, alfentanil, ergotamine, dihydroergotamine, fentanyl or quinidine
• some chemotherapy medicines, such as docetaxel or etoposide
• erythromycin, for the treatment of bacterial infections
• midazolam, a sedative used for the treatment of anxiety
• dexamethasone, which can be used for the treatment of nausea and vomiting
• ketoconazole, for the treatment of Cushing's syndrome
• rifampicin, for the treatment of tuberculosis (TB) and other infections.

If you fall into any of the above categories (or if you are unsure), ask your doctor, pharmacist or
nurse before receiving Akynzeo.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant or are breastfeeding with
breast milk, ask your doctor for advice before receiving this medicine.
You must not receive Akynzeo if you are pregnant or if you are a woman of childbearing potential who is not using
contraceptive measures.
Do not breastfeed while receiving Akynzeo, as it is not known whether the medicine passes into
breast milk.

Driving and using machines
After receiving Akynzeo you may feel dizzy or tired. If this happens, do not drive vehicles and
do not use tools or machines.

Akynzeo contains sodium
This medicine contains 24.4 mg of sodium (the main component of common table salt) per
vial. This is equivalent to 1.22% of the recommended maximum daily intake of sodium with the diet
for an adult.
If diluted with sodium chloride injection 9 mg/mL (0.9%), the final solution contains approximately
202 mg of sodium per dose. This is equivalent to 10.1% of the recommended maximum daily
intake of sodium with the diet for an adult.

3. How Akynzeo is administered

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 chemotherapy.

• The concentrate is diluted before use.
• Akynzeo is administered by a doctor or nurse
• Akynzeo is administered intravenously as an infusion (intravenous infusion) approximately 30 minutes before starting chemotherapy treatment.

The doctor will ask you to take other medications, including a corticosteroid (such as desamethasone) to
prevent nausea and vomiting. If you have any doubts, consult your doctor or nurse.

If you stop taking Akynzeo
Akynzeo is administered to help prevent nausea and vomiting when you undergo
chemotherapy. If you do not wish to receive Akynzeo, discuss this with your doctor. If you decide not to receive
Akynzeo (or another similar medication), it is likely that chemotherapy will cause you nausea and vomiting.
If you have any doubts about the use of this medication, consult 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 receiving Akynzeo and tell your doctor immediately if you notice the following serious side effect – urgent medical treatment may be needed:

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

• serious allergic reaction; signs include hives, skin rash, itching, difficulty breathing or swallowing, swelling of the 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
• itchy raised bumps on the skin (urticaria)
• problems with the heart muscle (cardiomyopathy)
• feeling dizzy, lightheaded or difficulty sleeping (insomnia)
• problems with the stomach, including stomach discomfort, feeling bloated, nausea, pain, indigestion, hiccups, flatulence or diarrhoea
• high levels of certain enzymes, including alkaline phosphatase in the blood and transaminases in the liver (seen in blood tests)
• high levels of creatinine, which measures kidney function (seen in blood tests)
• problems with the ECG (electrocardiogram) (called “QT and PR prolongation”, “conduction disturbance”, “tachycardia” and “first-degree atrioventricular block”)
• low levels of “neutrophils”, a type of white blood cell that fights infections (seen in blood tests)
• high level of white blood cells (seen in blood tests).

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

• back pain, joint pain
• feeling of warmth, redness of the face or other areas of the skin (flushing)
• skin rash with itching
• feeling sleepy
• problems with sleeping
• ringing in the ears
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, mood changes
• infection and inflammation of the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (seen in blood tests)
• changes (or disturbances) in heart rhythm
• heart valve disorder (mitral valve insufficiency)
• coated tongue, difficulty swallowing, dry mouth, belching, abnormal taste after taking the medicine
• reduced blood flow to the heart muscle (myocardial ischaemia)
• high levels of creatine phosphokinase/creatine phosphokinase MB, which indicates a sudden decrease in blood flow to the heart muscle (seen in blood tests)
• high levels of troponin, which indicates heart muscle dysfunction (seen in blood tests)
• high levels of bilirubin, a pigment, which indicates liver dysfunction (seen in blood tests)
• high levels of myoglobin, which indicates muscle damage (seen in blood tests)
• high levels of azotaemia, which indicates kidney dysfunction (seen in blood tests)
• high level of “lymphocytes”, a type of white blood cell that helps the body fight disease (seen in blood tests)
• low level of white blood cells (seen in blood tests)
• problems with the ECG (electrocardiogram) (called “ST segment depression”, “abnormal ST-T segment”, “right/left bundle branch block” and “second-degree atrioventricular block”)

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

5. How to store 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 package and the vial after “Exp”. The expiry date refers to the last day of that month.
• Store at a temperature below 25 °C.
• Keep the vial in the outer packaging to protect the medicine from light.
• The total time between dilution and the start of the infusion must not exceed 24 hours. Store the final diluted solution at a temperature below 25 °C.
• Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Akynzeo contains

• The active ingredients are fosnetupitant and palonosetron. Each vial contains 235 mg of fosnetupitant and 0.25 milligrams of palonosetron.
• The other ingredients are mannitol, disodium edetate (E 386), sodium hydroxide (E 524), dilute hydrochloric acid (E 507) (for pH adjustment) and water. This medicine contains sodium, for more information see section 2.

Description of the appearance of Akynzeo and contents of the pack
Akynzeo concentrate for solution for infusion is a sterile, clear solution, from colourless to
slightly yellow, supplied in a pack containing a single-dose vial of 20 mL, made of type I glass,
with a rubber stopper and an aluminium crimp cap. Each vial contains one dose.
Pack size: 1 vial.

Marketing authorisation holder and manufacturer
Helsinn Birex Pharmaceuticals Ltd.
Damastown
Mulhuddart
Dublin 15
Ireland
For further information on this medicine, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Immedica Pharma AB
Tél/Tel: + 46(0)8 533 39 500

Lietuva
Farma Mondo
Tel: + 370 698 36600

България
Angelini Pharma Bulgaria EOOD
Teл.: +359 2 975 13 95

Luxembourg/Luxemburg
Immedica Pharma AB
Tél/Tel: + 46(0)8 533 39 500

Česká republika
Angelini Pharma Česká republika s.r.o.
Tel: (+420) 546 123 111

Magyarország
Angelini Pharma Magyarország Kft
Tel.: + 36 1 336 1614

Danmark
Swedish Orphan Biovitrum A/S
Tlf: + 45 32 96 68 69

Malta
Helsinn Birex Pharmaceuticals Ltd.
Tel.: + 353 1 822 5404

Deutschland
Esteve Pharmaceuticals GmbH
Tel: + 49 30 338427-0

Nederland
Immedica Pharma AB
Tel: + 46(0)8 533 39 500

Eesti
Farma Mondo
Tel: + 370 698 36600

Norge
Swedish Orphan Biovitrum AS
Tlf: +47 66 82 34 00

Ελλάδα
Galenica A.E.
Τηλ: +30 210 52 81 700

Österreich
Angelini Pharma Österreich GmbH
Tel: +43-5-9-606-0

España
Immedica Pharma AB
Tel: + 34(0)9 373 70 164

Polska
Angelini Pharma Polska Sp. z o.o.
Tel: +48 22 70 28 200

France
Immedica Pharma France SARL
Tél: + 33(0)148 014 711

Portugal
Immedica Pharma AB
Tel: + 46(0)8 533 39 500

Hrvatska
Bausch Health Poland sp. z o.o., Podružnica Zagreb
Tel: +385 1 670 0750

România
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

Κύπρος
Galenica A.E.
Τηλ: +30 210 52 81 700

Sverige
Swedish Orphan Biovitrum AB (publ)
Tel: +46 8 697 20 00

Latvija
Farma Mondo
Tel: + 370 698 36600

Altre fonti d’informazioni
More detailed information on this medicine is available on the website of the European
Medicines Agency, http://www.ema.europa.eu .
The following information is intended exclusively for healthcare professionals:
Instructions for dilution of AKYNZEO 235 mg/0.25 mg

Preparation of Akynzeo

The final diluted solution is stable for 24 hours at 25 °C.
If the solution and container permit, parenteral medicines should be inspected
visually for the presence of particulate matter and colour changes before administration.
The appearance of the diluted solution is identical to that of the diluent.
Dispose of any remaining solution and waste materials. Unused medicine and waste
materials from this medicine must be disposed of in accordance with local regulations.
The medicine must not be diluted or mixed with solutions for which physical and chemical
compatibility has not been established (see summary of product characteristics, section 6.2).