AKYNZEO 300 mg/0.5 mg HARD CAPSULES

2. What you need to know before you take Akynzeo

Do not take Akynzeo:

• if you are allergic to netupitant or palonosetron or any of the other ingredients of this medicine (listed in section 6). If you are not sure, ask your doctor, pharmacist, or nurse before taking this medicine;
• if you are pregnant.

Warnings and precautions

Tell your doctor, pharmacist, or nurse before taking Akynzeo:

• if you have liver problems;
• if you have a blockage in your intestine or a history of constipation;
• if you or a close family member have 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 minerals in your blood, such as potassium and magnesium, that has not been corrected.

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

Children and adolescents

Children and adolescents under 18 years should not take Akynzeo.

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 and norepinephrine reuptake inhibitors), such as venlafaxine and duloxetine.

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

• medicines that can cause abnormal heart rhythms, 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 chemotherapy medicines, such as docetaxel or etoposide;
• erythromycin, for treating bacterial infections;
• midazolam, a sedative used for treating anxiety;
• dexamethasone, which may be used for treating nausea and vomiting;
• ketoconazole, for treating Cushing's syndrome;
• rifampicin, for treating tuberculosis (TB) and other infections.

If any of the above applies to you (or if you are not sure), tell 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 have a baby, ask your doctor for advice before taking this medicine.

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

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

Driving and using machines

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

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

If your doctor has told you that you have an intolerance to some 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; this is essentially "sodium-free".

It may contain soy lecithin. If you are allergic to peanuts or soy, seek medical attention immediately if you notice signs of an allergic reaction. Signs may 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.

3. How to take Akynzeo

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor, pharmacist, or nurse.

How much to take

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

Akynzeo is taken before chemotherapy to prevent nausea and vomiting. Do not take Akynzeo on days after 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 more than you should, tell 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 forgotten to take your dose, tell your doctor immediately.

If you stop taking Akynzeo

Akynzeo is taken to help prevent nausea and vomiting when you receive chemotherapy. If you do not want to take Akynzeo, discuss this with your doctor. If you decide not to take Akynzeo (or a similar medicine), it is likely that chemotherapy will cause nausea and vomiting.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

Serious side effects

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

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

• severe allergic reaction: signs include hives, skin rash, itching, difficulty breathing or swallowing, 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;
• 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 bumps (hives);
• heart muscle problems (cardiomyopathy);
• feeling of spinning (vertigo), dizziness, or sleep problems (insomnia);
• stomach problems including stomach upset, feeling bloated, nausea, pain, indigestion, belching, gas, or diarrhea;
• high levels of certain enzymes, including alkaline phosphatase and liver transaminases (found in blood tests);
• high levels of creatinine, which measures kidney function (found in blood tests);
• abnormal electrocardiogram (ECG) ("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 infection (found in blood tests);
• high levels 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, flushing of the face or other areas of the skin (hot flashes);
• itchy skin rash;
• drowsiness;
• sleep problems;
• ringing in the ears;
• vomiting;
• low blood pressure;
• chest pain (not related to the heart);
• numbness, blurred vision;
• sudden nervous breakdown, mood change;
• bladder infection and inflammation (cystitis);
• hemorrhoids;
• conjunctivitis (a type of eye inflammation);
• low levels of potassium (found in blood tests);
• heart rhythm disorders;
• heart valve problems (mitral insufficiency);
• coated tongue, difficulty swallowing, dry mouth, belching, unusual taste after taking the medicine;
• reduced blood flow to the heart muscle (myocardial ischemia);
• high levels of creatine phosphokinase/creatine phosphokinase MB, indicating a sudden reduction in blood flow to the heart muscle (found in blood tests);
• high levels of troponin, indicating heart muscle failure (found in blood tests);
• high levels of bilirubin, indicating liver failure (found in blood tests);
• high levels of myoglobin, indicating muscle damage (found in blood tests);
• high levels of urea in the blood, indicating kidney failure (found in blood tests);
• high levels of "lymphocytes", a type of white blood cell that helps the body fight disease (found in blood tests);
• low levels of white blood cells (found in blood tests);
• abnormal electrocardiogram (ECG) ("ST segment depression", "ST-T segment abnormality", "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 possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side 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 blister after EXP. The expiry date refers to the last day of the month stated.
• 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 no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Akynzeo contains

• The active substances are palonosetron and netupitant. Each hard capsule contains three tablets (300 mg of netupitant) and one soft capsule (palonosetron hydrochloride equivalent to 0.5 mg of palonosetron).
• The other ingredients are microcrystalline cellulose (E460), sucrose esters of fatty acids, povidone K-30, croscarmellose sodium, colloidal anhydrous silica, sodium stearyl fumarate, magnesium stearate, glycerol monocaprylate/monoacrylate (type I), glycerol, polyglyceryl oleate, purified water, butylhydroxyanisole (E320), gelatin, sorbitol, 1,4 sorbitan, titanium dioxide (E171), lacquer (partially esterified), yellow, red, and black iron oxide (E172), propylene glycol (E1520).

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

Appearance and packaging

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 aluminum blister or 4 x 1 hard capsules in unit-dose blisters. 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:

Date of last revision of this leaflet:

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