Akynzeo 300 mg/0.5 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Akynzeo 300 mg/0.5 mg hard capsules

netupitant/palonosetron

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Akynzeo is and what it is used for

What Akynzeo is

Akynzeo contains two medicines ("active substances") called:

• netupitant;
• palonosetron.

What Akynzeo is used for

Akynzeo is used to help prevent nausea or vomiting in adults with cancer while they are receiving cancer treatment known as "chemotherapy".

How Akynzeo works

Chemotherapy medicines can cause the body to release substances called serotonin and substance P. These substances stimulate the vomiting center in the brain, leading to nausea or vomiting. The medicines in Akynzeo bind to nervous system receptors through which serotonin and substance P act: netupitant (an NK1 receptor antagonist) blocks substance P receptors, and palonosetron (a 5-HT3 receptor antagonist) blocks certain serotonin receptors. By blocking the actions of substance P and serotonin in this way, the medicines help prevent stimulation of the vomiting center and thereby prevent nausea and vomiting.

2. What you need to 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 in doubt, ask your doctor, pharmacist, or nurse before starting 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 intestinal obstruction or a history of constipation;
• if you or a close family member has ever had a heart problem called “QT interval prolongation”;
• if you have other heart problems;
• if you have been told you have an imbalance of certain blood minerals, 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 taking Akynzeo.

Children and adolescents

Akynzeo must not be used in 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 need to take any other medicines.

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

• medicines used to treat depression or anxiety called SSRIs (selective serotonin reuptake inhibitors), such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, or escitalopram;
• medicines used to treat depression or anxiety called SNRIs (serotonin-norepinephrine reuptake inhibitors), such as venlafaxine and duloxetine.

Also consult 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 medicines:

• medicines that may cause abnormal heartbeats, such as amiodarone, nicardipine, quinidine, moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine, or domperidone;

  • medicines with a narrow therapeutic index that are primarily metabolized by CYP3A4, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, dihydroergotamine, ergotamine, fentanyl, or quinidine;

• certain chemotherapy medicines, 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 taking Akynzeo.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning 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 potential and are not using contraceptive methods.

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

Driving and using machines

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

Akynzeo contains sucrose, sorbitol, and sodium, and may contain traces of soy

If your doctor has told you that you have an intolerance to certain sugars, 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, which is essentially “sodium-free”.

It may contain traces of lecithin derived from soy. If you are allergic to peanuts or soy, seek immediate medical attention if you notice signs of an allergic reaction. Signs may include hives, rash, itching, difficulty breathing or swallowing, swelling of the mouth, face, lips, tongue, or throat, and sometimes a drop in blood pressure.

3. How to take Akynzeo

Follow exactly the instructions given by your doctor for taking this medicine. 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 your chemotherapy cycle.
• Akynzeo may be taken with or without food.

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

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. 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 have missed a 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 further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Serious adverse effects

Stop taking Akynzeo and contact your doctor immediately if you experience the following serious adverse effect; you may require urgent medical treatment:

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 adverse effects

Inform your doctor, pharmacist, or nurse if you experience any of the following adverse 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;
• itchy rash with raised red spots (urticaria);
• heart muscle problems (cardiomyopathy);
• sensation of spinning (vertigo), dizziness, or difficulty sleeping (insomnia);
• stomach problems including stomach discomfort, bloating, nausea, pain, indigestion, hiccups, gas, or diarrhea;
• elevated levels of certain enzymes, including alkaline phosphatase and liver transaminases in the blood (detected in blood tests);
• elevated creatinine levels, which measure kidney function (detected in blood tests);
• abnormalities in the ECG (electrocardiogram) (“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 levels of white blood cells (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 skin (flushing);
• itchy rash;
• drowsiness;
• difficulty sleeping;
• ringing in the ears;
• vomiting;
• low blood pressure;
• chest pain (not related to the heart);
• numbness, blurred vision;
• sudden nervous episode, change in mood;
• infection and inflammation of the bladder (cystitis);
• hemorrhoids;
• conjunctivitis (a type of eye inflammation);
• low potassium levels (detected in blood tests);
• disturbances (or disorders) of heart rhythm;
• heart valve disorder (mitral insufficiency);
• slurred speech, difficulty swallowing, dry mouth, burping, abnormal taste after taking the medicine;
• reduced blood flow to the heart muscle (myocardial ischemia);
• elevated creatine phosphokinase/creatine phosphokinase MB levels, indicating sudden reduced blood flow to the heart muscle (detected in blood tests);
• elevated troponin levels, indicating heart muscle dysfunction (detected in blood tests);
• elevated levels of the pigment bilirubin, indicating liver failure (detected in blood tests);
• elevated myoglobin levels, indicating muscle damage (detected in blood tests);
• elevated blood urea levels, indicating kidney failure (detected in blood tests);
• elevated levels of “lymphocytes”, a type of white blood cell that helps the body fight disease (detected in blood tests);
• low levels of white blood cells (detected in blood tests);
• abnormalities in the ECG (electrocardiogram) (“ST segment depression”, “ST-T segment abnormality”, “right/left bundle branch block”, and “second-degree atrioventricular block”).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Akynzeo

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and on the blister after EXP. The expiry date refers to the last day of the month indicated.
• No special storage conditions are required.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Akynzeo

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

This medicine contains sucrose, sorbitol and sodium, and may contain soya; 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 sizes containing 1 capsule in an aluminum blister or 4 x 1 hard capsules in perforated unit-dose blisters. Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Helsinn Birex Pharmaceuticals Ltd.

Damastown

Mulhuddart

Dublin 15

Ireland

Further information on this medicine can be obtained by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.