Package Insert: Information for the Patient

Akynzeo 300 mg/0.5 mg Hard Capsules

netupitant/palonosetron

Read this entire package insert carefully before starting to take this medication, as it contains important information for you.

- Keep this package insert, as you may need to refer to it again.

- If you have any questions, consult your doctor, pharmacist, or nurse.

-This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

- If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

1. What is Akynzeo and how is it used

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

3. How to take Akynzeo

4. Possible adverse effects

5. Storage of Akynzeo

6. Contents of the package and additional information

What is Akynzeo

Akynzeo contains two medications (“active principles”) called:

• netupitant;

• palonosetrón.

What is Akynzeo used for

Akynzeo is used to help prevent nausea or vomiting in adults with cancer while they receive a cancer treatment called “chemotherapy”.

How Akynzeo works

Chemotherapy medications can make the body release substances called serotonin and substance P. These substances stimulate the vomiting center in the brain, causing nausea or vomiting. The medications contained in Akynzeo bind to the nervous system receptors through which serotonin and substance P function: netupitant (an NK1receptor antagonist) blocks substance P receptors and palonosetrón (a 5-HT3receptor antagonist) blocks certain serotonin receptors. By blocking these actions of substance P and serotonin, the medications help prevent stimulation of the vomiting center and the resulting nausea.

Do not take Akynzeo:

•if you are allergic to netupitant or palonosetron or any of the other ingredients in this medicine (listed in section 6). If in doubt, ask your doctor, pharmacist, or nurse before starting this medicine;

• if you are pregnant.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Akynzeo:

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

If any of the above points apply to you (or if in doubt), consult your doctor, pharmacist, or nurse before taking Akynzeo.

Children and adolescents

Children and adolescents under 18 years old should not take Akynzeo.

Other medicines and Akynzeo

Inform your doctor, pharmacist, or nurse if you are taking, have taken recently, or may need to take any other medicine.

Specifically, inform your doctor, pharmacist, or nurse if you are taking any of the following medicines:

•medicines to treat depression or anxiety called SSRIs (selective serotonin reuptake inhibitors), such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, or escitalopram;

•medicines to treat depression or anxiety called SNRIs (serotonin and noradrenaline reuptake inhibitors), such as venlafaxine and duloxetine.

Consult 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 medicines:

•medicines that can cause an abnormal heart rhythm, such as amiodarone, nicardipine, quinidine, moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine, or domperidone;

• medicines with a narrow therapeutic margin that are metabolized mainly by CYP3A4, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, dihydroergotamine, 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, which can be used to treat nausea and vomiting;

• ketoconazole, to treat Cushing's syndrome;

• rifampicin, to treat tuberculosis (TB) and other infections.

If any of the above points apply to you (or if in doubt), consult your doctor, pharmacist, or nurse before taking Akynzeo.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

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

Do not breastfeed while taking Akynzeo. This is because it is unknown whether the medicine passes into breast milk.

Driving and operating machinery

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

Akynzeo contains saccharose, sorbitol, and sodium, and may contain soy residues

If your doctor has told you that you have a certain sugar intolerance, consult your doctor before taking this medicine.

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

This medicine contains less than 1 mmol of sodium (23 mg) per capsule; this is essentially “sodium-free”.

Akynzeo may contain soy residues. If you are allergic to peanuts or soy, go immediately to your doctor if you notice signs of an allergic reaction. The signs may include urticaria, skin rash, itching, difficulty breathing or swallowing, swelling of the mouth, face, lips, tongue, or throat, and sometimes a drop in blood pressure.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor, pharmacist, or nurse again.

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 approximately 1 hour before starting chemotherapy.

• Akynzeo can be taken with or without food.

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

If you take more Akynzeo than you should

The usual dose is 1 capsule. If you think you may have taken too much, inform your doctor immediately.The symptoms of an overdose may include headache, dizziness, constipation, anxiety, palpitations, euphoria, and leg pain.

If you forget to take Akynzeo

If you think you may have forgotten to take your dose, inform your doctor immediately.

If you interrupt treatment with Akynzeo

Akynzeo is taken to help prevent nausea and vomiting when receiving chemotherapy. If you do not want to take Akynzeo, consult your doctor. If you decide not to take Akynzeo (or another similar medication), it is likely that chemotherapy will cause nausea and vomiting.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

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

Severe side effects

Stop taking Akynzeo and inform your doctor immediately if you observe the following severe side effect; you may need emergency medical treatment:

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

•severe allergic reaction: symptoms include urticaria, skin rash, itching, difficulty breathing or swallowing, swelling of the mouth, face, lips, tongue, or throat, and sometimes low blood pressure.

Other side effects

Inform your doctor, pharmacist, or nurse if you observe any of the following side effects:

Common(may affect up to 1 in 10 people)

• headache;

• constipation;

• fatigue.

Uncommon(may affect up to 1 in 100 people)

• hair loss;

• lack of energy (weakness);

• decreased appetite;

• high blood pressure;

• skin rash with itching and raised hives (hives);

• problems with the heart muscle (myocarditis);

• sensation of rotational movement (dizziness), dizziness, or difficulty sleeping (insomnia);

•gastrointestinal problems that include stomach discomfort,swelling,nausea, pain, indigestion, hiccups, gas, or diarrhea;

•high levels of certain enzymes, includingalkaline phosphatase and liver transaminases in the blood(detected in blood tests);

• high levels of creatinine, which measures kidney function (detected in blood tests);

• ECG abnormalities (“prolongation of the QTand 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 levels of white blood cells (detected in blood tests).

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

• back pain, joint pain;
• sensation of heat, flushing of the face or other areas of the skin (hot flashes);
• skin rash with itching;
• drowsiness;
• difficulty sleeping;
• tinnitus;
• vomiting;
• low blood pressure;
• chest pain (not related to the heart);
• numbness, blurred vision;
• sudden nervous crisis, change in mood;
• urinary tract infection and inflammation (cystitis);
• hemorrhoids;
• conjunctivitis (a type of eye inflammation);
• low levels of potassium (detected in blood tests);
• heart rhythm disturbances;
• mitral valve insufficiency (trouble with the heart valves);
• sluggish tongue, difficulty swallowing,dry mouth, belching,unpleasant taste after taking the medicine;
• decreased blood flow to the heart muscle (myocardial ischemia);
• high levels ofcreatine phosphokinase/creatine phosphokinase MB, indicating a sudden decrease in blood flow to the heart muscle (detected in blood tests);
• high levels of troponin, indicating heart muscle insufficiency (detected in blood tests);
• high levels of bilirubin pigment, indicating liver insufficiency(detected in blood tests);
• high levels of myoglobin, indicating muscle damage (detected in blood tests);
• high levels of urea in the blood, indicating kidney insufficiency (detected in blood tests);
• high levels of “lymphocytes”, a type of white blood cell that helps the body fight diseases (detected in blood tests);
• low levels of white blood cells (detected in blood tests);
• ECG abnormalities (“ST segment depression”, “ST-T segment anomaly”, “right/left branch block”, and “second-degree atrioventricular block”).

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

• Keep this medication out of the sight and reach of children.

•Do not use this medication after the expiration date that appears on the box and on the blister pack after CAD. The expiration date is the last day of the month indicated.

• No special storage conditions are required.

•Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medication that you no longer need. In this way, you will help protect the environment.

Composition of Akynzeo

• The active principles are palonosetron and netupitant. Each capsuleduracontains three tablets (300 mg of netupitant) and one hard capsule (palonosetron hydrochloride equivalent to 0.5 milligrams of palonosetron).
• The other components are microcrystalline cellulose (E460), sucrose esters and lauric acid, povidone K-30, sodium croscarmellose, hydrated colloidal silica, sodium stearate fumarate, magnesium stearate, monocaprylate/monocaprate of glycerin (type I), glycerin, polyglycerol oleate, purified water, butylhydroxyanisole (E320), gelatin, sorbitol, 1,4 sorbitan, titanium dioxide (E171), partially esterified shellac, yellow, red, and black iron oxide (E172), propylene glycol (E1520).

This medicine containssucrose, sorbitol, and sodium,and may contain soy; see section 2 for more information.

Appearance of the product and contents of the pack

The hard capsules are opaque with a white body and a caramel-colored cap with “HE1” printed on the body. Pack size containing 1 capsule in an aluminium blister or4 x 1 hard capsules in perforated unit dose blisters. Only some pack sizes may be marketed.

Marketing Authorization Holder and Responsible Person for Manufacturing

Helsinn Birex Pharmaceuticals Ltd.

Damastown

Mulhuddart

Dublin 15

Ireland

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicineis available on the website of the European Medicines Agency:http://www.ema.europa.eu.