Akynzeo: detailed information

Package leaflet: Information for the patient

Akynzeo 300 mg/0.5 mg hard capsules

netupitant/palonosetron
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

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

Contents of this leaflet

What Akynzeo is and what it is used for
What you need to know before taking Akynzeo
How to take Akynzeo
Possible side effects
How to store Akynzeo
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 nausea or vomiting in adults with cancer who are receiving
cancer treatment known as "chemotherapy".

How Akynzeo works
Chemotherapy medicines can cause the body to release substances called serotonin and substance P.
This stimulates the vomiting centre located in the brain, leading to nausea or vomiting. The medicines in Akynzeo bind to nerve system receptors through which serotonin and substance P act: netupitant (an NK receptor antagonist) blocks receptors for substance P, while palonosetron (a 5-HT receptor antagonist) blocks certain receptors for serotonin. By blocking the action of substance P and serotonin in this way, the medicines help prevent stimulation of the vomiting centre and thereby prevent nausea and vomiting.

2. What you should know before taking Akynzeo

Do not take Akynzeo

if you are allergic to netupitant or palonosetron or to any of the other ingredients of this medicine (listed in section 6). If you are unsure, consult 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 liver problems
if you have a bowel obstruction or have previously suffered from constipation
if you or one of your close relatives has previously had a heart problem called "QT interval prolongation"
if you have any other heart problems
if you have been diagnosed with an imbalance of minerals in the blood, such as potassium or magnesium, which has not been corrected.

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before taking Akynzeo.
Children and adolescents
Akynzeo must not be used in children and adolescents under 18 years of age.
Other medicines and Akynzeo
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform 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.

Additionally, inform your doctor, pharmacist, or nurse if you are taking any of the following medicines, as your doctor may need to adjust the dose of these other medicines:

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

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before taking Akynzeo.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or 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 or operate tools or machinery.
Akynzeo contains sucrose, sorbitol (E 420), sodium, and may contain traces of soy.
If your doctor has diagnosed you with an intolerance to certain sugars, contact them 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, i.e., essentially 'sodium-free'.
It may contain traces of lecithin, which is derived from soy. If you are allergic to peanuts or soy, do not use this medicine.

3. How to take Akynzeo

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

Dosage

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 your chemotherapy session.
You may take Akynzeo with or without food.

Akynzeo is taken before chemotherapy to prevent the development of nausea and vomiting. Do not take Akynzeo on 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 your dose, inform your doctor immediately.

If you stop taking Akynzeo
Akynzeo is taken to help prevent nausea and vomiting during chemotherapy. If you do not wish to take Akynzeo, discuss this with your doctor. If you decide not to take Akynzeo (or a similar medicine), you are likely to experience nausea and vomiting during chemotherapy.

If you have any questions 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 gets 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

severe allergic reaction; signs include hives, 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)
heart muscle problems (cardiomyopathy)
sensation of spinning (dizziness), feeling lightheaded, or difficulty sleeping (insomnia)
stomach problems, including stomach discomfort, feeling of abdominal bloating, nausea, pain, indigestion, hiccup, flatulence or diarrhoea
high levels of certain enzymes, including alkaline phosphatase in the blood and liver transaminases (detected in blood tests)
high levels of creatinine, which measures kidney function (detected in blood tests)
ECG (electrocardiogram) abnormalities (called “prolongation of QT and PR intervals”, “conduction disorder”, “tachycardia”, and “first-degree atrioventricular block”)
low levels of “neutrophils”, a type of white blood cell that fights infections (detected in blood tests)
high white blood cell count (detected in blood tests).

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

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

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to 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 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 dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What 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 mg of palonosetron).
The other components are microcrystalline cellulose (E 460), sucrose esters of lauric acid, povidone K-30, croscarmellose sodium, hydrated colloidal silica, sodium stearate fumarate, magnesium stearate, glycerol monocaprylocaprate (type I), glycerol, polyglyceryl 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 oxides (E 172), propylene glycol (E 1520).

This medicinal product contains sucrose, sorbitol (E 420), sodium and may contain soya; see
section 2 for further information.
Description of the appearance of Akynzeo and pack contents
The hard capsules are opaque, with a white body and caramel-coloured cap, marked with “HE1” on the body. Pack containing 1 capsule in an aluminium blister; 4 x 1 hard capsules in aluminium blisters divisible for single dose. Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Helsinn Birex Pharmaceuticals Ltd.
Damastown
Mulhuddart
Dublin 15
Ireland
For further information on this medicinal product, contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Immedica Pharma AB Farma Mondo
Tél/Tel: + 46(0)8 533 39 500 Tel: + 370 698 36600
България Luxembourg/Luxemburg
Angelini Pharma Bulgaria EOOD Immedica Pharma AB
Teл.: +359 2 975 13 95 Tél/Tel: + 46(0)8 533 39 500
Česká republika Magyarország
Angelini Pharma Česká republika s.r.o. Angelini Pharma Magyarország Kft
Tel: (+420) 546 123 111 Tel.: +36 1 336 1614
Danmark Malta
Swedish Orphan Biovitrum A/S Helsinn Birex Pharmaceuticals Ltd.
Tlf: + 45 32 96 68 69 Tel.: + 353 1 822 5404
Deutschland Nederland
Esteve Pharmaceuticals GmbH Immedica Pharma AB
Tel: + 49 30 338427-0 Tel: + 46(0)8 533 39 500
Eesti Norge
Farma Mondo Swedish Orphan Biovitrum AS
Tel: + 370 698 36600 Tlf: +47 66 82 34 00
Ελλάδα Österreich
Galenica A.E. Angelini Pharma Österreich GmbH
Τηλ: +30 210 52 81 700 Tel: +43-5-9-606-0
España Polska
Immedica Pharma AB Angelini Pharma Polska Sp. z o.o.
Tel: + 34(0)9 373 70 164 Tel: +48 22 70 28 200
France Portugal
Immedica Pharma France SARL Immedica Pharma AB
Tél: + 33(0)148 014 711 Tel: + 46(0)8 533 39 500
Hrvatska România
Bausch Health Poland sp. z o.o., Podružnica Zagreb Angelini Pharmaceuticals Romania Srl
Tel: +385 1 670 0750 Tel: +40 21 331 67 67
Ireland Slovenija
Chugai Pharma France PharmaSwiss
Tel: +33 1 79 36 36 18 Tel: +386 1 2364 700
Ísland Slovenská republika
Swedish Orphan Biovitrum A/S Angelini Pharma Slovenská republika s.r.o.
Símí : + 45 32 96 68 69 Tel: +421 2 5920 7320
Italia Suomi/Finland
Italfarmaco Oy Swedish Orphan Biovitrum Ab
Tel: + 39 02 64431 Puh./Tel: +358 201 558 840
Κύπρος Sverige
Galenica A.E. Swedish Orphan Biovitrum AB (publ)
Τηλ: +30 210 52 81 700 Tel: +46 8 697 20 00
Latvija
Farma Mondo
Tel: + 370 398 36600
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu .

Patient information leaflet: information for the patient

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

fosnetupitant/palonosetron
Please read this leaflet carefully before receiving 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.
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Akynzeo is and what it is used for
What you need to know before receiving Akynzeo
How Akynzeo is administered
Possible side effects
How to store Akynzeo
Package contents 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 nausea or vomiting in adults with cancer undergoing anticancer treatment known as "chemotherapy".

How Akynzeo works
Chemotherapy medicines can cause the body to release substances called serotonin and substance P. These stimulate the vomiting centre located in the brain, leading to nausea or vomiting. The medicines in Akynzeo bind to nerve system receptors through which serotonin and substance P act: fosnetupitant, which is converted in the body to netupitant (an NK receptor antagonist), blocks the receptors for substance P, while palonosetron (a 5-HT receptor antagonist) blocks certain receptors for serotonin. By blocking the action of substance P and serotonin in this way, the medicines help prevent stimulation of the vomiting centre and thereby prevent nausea and vomiting.

2. What you should know before receiving Akynzeo

Do 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 in doubt, consult your doctor, pharmacist, or nurse before receiving this medicine
if you are pregnant.

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

if you have liver problems
if you have a bowel obstruction or have previously suffered from constipation
if you or a close family member have ever had a heart problem called "QT interval prolongation"
if you have any other heart problems
if you have been diagnosed with an imbalance of minerals in your blood, such as potassium or magnesium, that has not been corrected.

If any of the above apply to you (or if you are in doubt), consult 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
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform 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, inform your doctor, pharmacist, or nurse if you are taking any of the following medicines, as your doctor may need to adjust the dose of these other medicines:

medicines that may cause irregular heartbeat, such as amiodarone, nicardipine, quinidine, moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine, or domperidone
medicines with a narrow therapeutic index primarily metabolized by CYP3A4, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, dihydroergotamine, ergotamine, fentanyl, or quinidine
certain chemotherapeutic agents, such as docetaxel or etoposide
erythromycin, used to treat bacterial infections
midazolam, a sedative used to treat anxiety
dexamethasone, which may be used to treat nausea and vomiting
ketoconazole, used to treat Cushing's syndrome
rifampicin, used to treat tuberculosis (TB) and other infections.

If any of the above apply to you (or if you are in doubt), consult your doctor, pharmacist, or nurse before receiving Akynzeo.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or 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 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 occurs, do not drive or operate tools or machinery.
Akynzeo contains sodium
This medicine contains 24.8 mg of sodium (a main component of table salt) per vial. This corresponds to 1.24% of the maximum daily dietary intake recommended for an adult.
If reconstituted and diluted with 9 mg/mL (0.9%) sodium chloride injection solution, the final solution contains approximately 202 mg of sodium per dose. This corresponds to 10.1% of the maximum daily dietary intake recommended 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 is reconstituted and diluted before use.
Akynzeo is administered by a doctor or a nurse.
Akynzeo is given intravenously as an infusion (intravenous infusion) approximately 30 minutes before starting chemotherapy treatment.

Your doctor will ask you to take other medicines, including a corticosteroid (such as dexamethasone), to prevent nausea and vomiting. If you have any doubts, consult your doctor or nurse.
If you interrupt treatment with Akynzeo
Akynzeo is administered to help prevent nausea and vomiting during chemotherapy. If you do not wish to receive Akynzeo, discuss this with your doctor. If you decide not to receive Akynzeo (or a similar medicine), it is likely that your chemotherapy will cause nausea and vomiting.
If you have any questions about the use of this medicine, consult 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 receiving Akynzeo and inform your doctor immediately if you notice the following serious side effect – urgent medical treatment may be required:

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

severe allergic reaction; signs include hives, 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)
heart muscle problems (cardiomyopathy)
dizziness, lightheadedness or difficulty sleeping (insomnia)
stomach problems, including stomach discomfort, bloated feeling, nausea, pain, indigestion, hiccups, flatulence or diarrhoea
high levels of certain enzymes, including alkaline phosphatase in the blood and transaminases in the liver (detected in blood tests)
high levels of creatinine, which measures kidney function (detected in blood tests)
ECG (electrocardiogram) abnormalities (called “prolongation of QT and PR intervals”, “conduction disorder”, “tachycardia” and “first-degree atrioventricular block”)
low levels of “neutrophils”, a type of white blood cell that fights infections (detected in blood tests)
high white blood cell count (detected 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)
rash accompanied by itching
drowsiness
sleep problems
ringing in the ears
vomiting
low blood pressure
chest pain (not heart-related)
numbness, blurred vision
sudden nervous collapse, mood changes
infection and inflammation of the bladder (cystitis)
haemorrhoids
conjunctivitis (a type of eye inflammation)
low potassium levels (detected in blood tests)
changes (or disturbances) in heart rhythm
heart valve disorder (mitral valve insufficiency)
coated tongue, difficulty swallowing, dry mouth, burping, altered taste after taking the medicine
reduced blood flow to the heart muscle (myocardial ischaemia)
high levels of creatine phosphokinase/creatine phosphokinase MB, indicating a sudden reduction in blood flow to the heart muscle (detected in blood tests)
high troponin levels, indicating heart muscle dysfunction (detected in blood tests)
high bilirubin levels, a pigment indicating liver dysfunction (detected in blood tests)
high myoglobin levels, indicating muscle damage (detected in blood tests)
high blood urea levels, indicating kidney dysfunction (detected in blood tests)
high levels of “lymphocytes”, a type of white blood cell that helps the body fight disease (detected in blood tests)
low white blood cell count (detected in blood tests)
ECG (electrocardiogram) abnormalities (called “ST segment depression”, “abnormal ST-T segment”, “right/left bundle branch block” and “second-degree atrioventricular block”)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system referred to 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 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 packaging to protect the medicine from light.
The total time between reconstitution and the start of 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 medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This 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 components are mannitol, disodium edetate (E 386), sodium hydroxide (E 524), and diluted hydrochloric acid (E 507) (for pH adjustment). This medicinal product contains sodium. For more information, see section 2.

Description of the appearance of Akynzeo and contents of the pack
Akynzeo powder for concentrate for solution for infusion is a sterile, lyophilized powder, white to off-white in colour, supplied in a pack containing one type I glass vial with a rubber stopper and aluminium seal. 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 about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Immedica Pharma AB Farma Mondo
Tél/Tel: + 46(0)8 533 39 500 Tel: + 370 698 36600

България Luxembourg/Luxemburg
Angelini Pharma Bulgaria EOOD Immedica Pharma AB
Teл.: +359 2 975 13 95 Tél/Tel: + 46(0)8 533 39 500

Česká republika Magyarország
Angelini Pharma Česká republika s.r.o. Angelini Pharma Magyarország Kft
Tel: (+420) 546 123 111 Tel.: + 36 1 336 1614

Malta
Danmark Helsinn Birex Pharmaceuticals Ltd.
Swedish Orphan Biovitrum A/S Tel.: + 353 1 822 5404
Tlf: + 45 32 96 68 69

Deutschland Nederland
Esteve Pharmaceuticals GmbH Immedica Pharma AB
Tel: + 49 30 338427-0 Tel: + 46(0)8 533 39 500

Eesti Norge
Farma Mondo Swedish Orphan Biovitrum AS
Tel: + 370 698 36600 Tlf: +47 66 82 34 00

Ελλάδα Österreich
Galenica A.E. Angelini Pharma Österreich GmbH
Τηλ: +30 210 52 81 700 Tel: +43-5-9-606-0

España Polska
Immedica Pharma AB Angelini Pharma Polska Sp. z o.o.
Tel: + 34(0)9 373 70 164 Tel: +48 22 70 28 200

France Portugal
Immedica Pharma France SARL Immedica Pharma AB
Tél: + 33(0)148 014 711 Tel: + 46(0)8 533 39 500

Hrvatska România
Bausch Health Poland sp. z o.o., Podružnica Zagreb Angelini Pharmaceuticals Romania Srl
Tel: +385 1 670 0750 Tel: +40 21 331 67 67

Ireland Slovenija
Chugai Pharma France PharmaSwiss
Tel: +33 1 79 36 36 18 Tel: +386 1 2364 700

Ísland Slovenská republika
Swedish Orphan Biovitrum A/S Angelini Pharma Slovenská republika s.r.o.
Tlf: + 45 32 96 68 69 Tel: +421 2 5920 7320

Italia Suomi/Finland
Italfarmaco Oy Swedish Orphan Biovitrum Ab
Tel: + 39 02 64431 Puh./Tel: +358 201 558 840

Κύπρος Sverige
Galenica A.E. Swedish Orphan Biovitrum AB (publ)
Τηλ: +30 210 52 81 700 Tel: +46 8 697 20 00

Latvija
Farma Mondo
Tel: + 370 698 36600

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

The following information is intended for healthcare professionals only:
Instructions for reconstitution and dilution of AKYNZEO 235 mg/0.25 mg
Preparation of Akynzeo

Step 1	Using aseptic technique, inject 20 mL of 5% glucose injection solution or 9 mg/mL (0.9%) sodium chloride injection solution into the vial. Ensure that the diluent is added along the wall of the vial, not as a jet, to avoid foaming. Gently rotate the vial for 3 minutes. The powder must be completely dissolved before further dilution in the infusion bag.
Step 2	Prepare, using aseptic technique, an infusion bag or vial containing 30 mL of 5% glucose injection solution or 9 mg/mL (0.9%) sodium chloride injection solution.
Step 3	Dilution must be performed immediately after reconstitution (according to Step 1). Using aseptic technique, withdraw the entire volume of reconstituted solution from the AKYNZEO vial and transfer it into the infusion bag or vial containing 30 mL of 5% glucose injection solution or 9 mg/mL (0.9%) sodium chloride injection solution, to obtain a total volume of 50 mL.
Step 4	Gently invert the vial or bag until complete dissolution is achieved.
Step 5	Prior to administration, inspect the final diluted solution for presence of particles and discoloration. Discard the vial or bag if particles and/or discoloration are observed.

The reconstituted and diluted solution is stable for 24 hours at 25 °C.
If the solution and container permit, parenteral medicines should be inspected visually for particulate matter and discoloration prior to administration.
The appearance of the reconstituted solution is identical to that of the diluent.
Discard any residual solution and waste materials. Unused medicine and waste materials derived 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).

Patient Information Leaflet

Akynzeo 235 mg/0.25 mg concentrate for solution for infusion

fosnetupitant/palonosetron
Please read this leaflet carefully before receiving 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.
If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

What Akynzeo is and what it is used for
What you need to know before receiving Akynzeo
How Akynzeo is administered
Possible side effects
How to store Akynzeo
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 nausea or vomiting in adults with cancer who are undergoing
cancer treatment known as "chemotherapy".

How Akynzeo works
Chemotherapy medicines can cause the body to release substances called serotonin and substance P.
This stimulates the vomiting centre located in the brain, leading to nausea or vomiting. The medicines in Akynzeo bind to nerve system receptors through which serotonin and substance P act: fosnetupitant, which is converted in the body to netupitant (an NK receptor antagonist), blocks receptors for substance P, while palonosetron (a 5-HT receptor antagonist) blocks certain receptors for serotonin. By blocking the action of substance P and serotonin in this way, the medicines help prevent stimulation of the vomiting centre and thereby prevent nausea and vomiting.

2. What you need to know before receiving Akynzeo

Do 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 are unsure, consult your doctor, pharmacist, or nurse before receiving this medicine
if you are pregnant.

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

if you have liver problems
if you have a bowel obstruction or have previously suffered from constipation
if you or one of your close relatives has ever had a heart problem called "QT interval prolongation"
if you have any other heart problems
if you have been diagnosed with an imbalance of minerals in the blood, such as potassium or magnesium, which has not been corrected.

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before receiving Akynzeo.
Children and adolescents
Akynzeo must not be administered to children and adolescents under 18 years of age.
Other medicines and Akynzeo
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform 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, inform your doctor, pharmacist, or nurse if you are taking any of the following medicines, as your doctor may need to adjust the dose of these other medicines:

medicines that may cause irregular heartbeat, such as amiodarone, nicardipine, quinidine, moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine, or domperidone
medicines with a narrow therapeutic index primarily metabolized by CYP3A4, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, dihydroergotamine, ergotamine, fentanyl, or quinidine
certain chemotherapeutic agents, such as docetaxel or etoposide
erythromycin, used to treat bacterial infections
midazolam, a sedative used to treat anxiety
dexamethasone, which may be used to treat nausea and vomiting
ketoconazole, used to treat Cushing's syndrome
rifampicin, used to treat tuberculosis (TB) and other infections.

If any of the above apply to you (or if you are unsure), consult your doctor, pharmacist, or nurse before receiving Akynzeo.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning to become pregnant, or 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 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 or operate tools or machinery.
Akynzeo contains sodium
This medicine contains 24.4 mg of sodium (a main component of table salt) per vial. This is equivalent to 1.22% of the maximum daily recommended dietary intake for an adult.
If diluted with 9 mg/mL (0.9%) sodium chloride injection solution, the final solution contains approximately 202 mg of sodium per dose. This is equivalent to 10.1% of the maximum daily recommended dietary intake 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 given intravenously as an infusion (intravenous infusion) approximately 30 minutes before starting chemotherapy treatment.

Your doctor will ask you to take other medicines, including a corticosteroid (such as dexamethasone), to prevent nausea and vomiting. If you have any doubts, consult your doctor or nurse.
If you interrupt treatment with Akynzeo
Akynzeo is administered to help prevent nausea and vomiting during chemotherapy. If you do not wish to receive Akynzeo, discuss this with your doctor. If you decide not to receive Akynzeo (or a similar medicine), it is likely that chemotherapy will cause you nausea and vomiting.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Serious side effects
Stop receiving Akynzeo and inform 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)

severe 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 of tiredness.

Uncommon (may affect up to 1 in 100 people)

hair loss
lack of energy (feeling weak)
decreased appetite
high blood pressure
itchy, raised skin rash (urticaria)
heart muscle problems (cardiomyopathy)
dizziness, feeling lightheaded or difficulty sleeping (insomnia)
stomach problems, including stomach discomfort, feeling of abdominal bloating, nausea, pain, indigestion, hiccup, 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)
ECG (electrocardiogram) abnormalities (called “prolongation of QT and PR intervals”, “conduction disorder”, “tachycardia” and “first-degree atrioventricular block”)
low levels of “neutrophils”, a type of white blood cell that fights infections (shown in blood tests)
high white blood cell count (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 accompanied by itching
drowsiness
sleep problems
ringing in the ears
vomiting
low blood pressure
chest pain (not heart-related)
numbness, blurred vision
sudden nervous collapse, mood change
infection and inflammation of the bladder (cystitis)
haemorrhoids
conjunctivitis (a type of eye inflammation)
low potassium levels (shown in blood tests)
changes (or disturbances) in heart rhythm
heart valve disorder (mitral valve insufficiency)
coated tongue, difficulty swallowing, dry mouth, belching, altered taste after taking the medicine
reduced blood flow to the heart muscle (myocardial ischaemia)
high levels of creatine phosphokinase/creatine phosphokinase MB, indicating a sudden reduction in blood flow to the heart muscle (shown in blood tests)
high troponin levels, indicating heart muscle dysfunction (shown in blood tests)
high bilirubin levels, a pigment indicating liver dysfunction (shown in blood tests)
high myoglobin levels, indicating muscle damage (shown in blood tests)
high blood urea nitrogen (BUN) levels, indicating kidney dysfunction (shown in blood tests)
high levels of “lymphocytes”, a type of white blood cell that helps the body fight disease (shown in blood tests)
low white blood cell count (shown in blood tests)
ECG (electrocardiogram) abnormalities (called “ST segment depression”, “ST-T abnormality”, “right/left bundle branch block” and “second-degree atrioventricular block”)

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to 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 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 packaging to protect the medicine from light.
The total time between dilution and the start of infusion must not exceed 24 hours. Store the final diluted solution below 25 °C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents 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 components are mannitol, edetate disodium (E 386), sodium hydroxide (E 524), diluted 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 clear, sterile, colourless to slightly yellow solution supplied in a pack containing one single-dose 20 mL glass vial of type I, with a rubber stopper and aluminium seal. Each vial contains one dose.
Pack: 1 vial.

Marketing Authorisation Holder and Manufacturer
Helsinn Birex Pharmaceuticals Ltd.
Damastown
Mulhuddart
Dublin 15
Ireland

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

België/Belgique/Belgien Lietuva
Immedica Pharma AB Farma Mondo
Tél/Tel: + 46(0)8 533 39 500 Tel: + 370 698 36600

България Luxembourg/Luxemburg
Angelini Pharma Bulgaria EOOD Immedica Pharma AB
Teл.: +359 2 975 13 95 Tél/Tel: + 46(0)8 533 39 500

Česká republika Magyarország
Angelini Pharma Česká republika s.r.o. Angelini Pharma Magyarország Kft
Tel: (+420) 546 123 111 Tel.: + 36 1 336 1614

Danmark Malta
Swedish Orphan Biovitrum A/S Helsinn Birex Pharmaceuticals Ltd.
Tlf: + 45 32 96 68 69 Tel.: + 353 1 822 5404