AKYNZEO 235 mg/0.25 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

2. What you need to know before you are given Akynzeo

Akynzeo must not be given to you:

• if you are allergic to fosnetupitant, 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 you are given this medicine;
• if you are pregnant.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you are given Akynzeo:

• if you have liver problems;

• if you have a blockage in your intestines or a history of constipation;
• if you or a close family member have ever had a heart problem called “prolonged QT interval”;
• 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), talk to your doctor, pharmacist, or nurse before you are given Akynzeo.

Children and adolescents

Akynzeo must not be given to children and adolescents under 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 and noradrenaline reuptake inhibitors), such as venlafaxine and duloxetine.

Talk to your doctor, pharmacist, or nurse if you are taking any of the following medicines, because 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 index that are mainly metabolized by CYP3A4, such as cyclosporin, tacrolimus, sirolimus, everolimus, alfentanil, dihydroergotamine, ergotamine, fentanyl, or quinidine;
• certain chemotherapy medicines, such as docetaxel or etoposide;
• erythromycin, to treat bacterial infections;
• midazolam, a sedative used to treat anxiety;
• dexamethasone, which may 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 applies to you (or if you are not sure), talk to your doctor, pharmacist, or nurse before you are given Akynzeo.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before you are given this medicine.

Akynzeo must not be given to you if you are pregnant or if you are a woman of childbearing age and not using contraceptive methods.

Do not breast-feed if you are given 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 you are given Akynzeo. If this happens, do not drive or use tools or machines.

This medicine contains 24.8 mg of sodium (the main component of common/table salt) in each vial. This is equivalent to 1.24% of the maximum recommended daily intake of sodium for an adult. If it is reconstituted and diluted with sodium chloride 9 mg/ml (0.9%) injection solution, the final solution contains approximately 202 mg of sodium per dose. This is equivalent to 10.1% of the maximum recommended daily intake of sodium for an adult.

3. How Akynzeo is given

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.
• A doctor or nurse will give you Akynzeo.
• Akynzeo is given as an infusion into a vein (intravenous infusion) about 30 minutes before your chemotherapy treatment starts.

Your doctor will ask you to take other medicines, including a corticosteroid (such as dexamethasone), to prevent nausea and vomiting. If you are not sure, ask your doctor or nurse again.

If you stop being given Akynzeo

Akynzeo is given to help prevent nausea and vomiting when you are receiving chemotherapy. If you do not want to be given Akynzeo, talk to your doctor. If you decide not to be given Akynzeo (or a similar medicine), it is likely that the chemotherapy will make you feel sick or vomit.

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 receiving 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: the 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 patches (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 blood transaminases (detected in blood tests);
• high levels of creatinine, which measures kidney function (detected in blood tests);
• abnormalities on the ECG (electrocardiogram) (“prolonged 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 (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, flushing of the face or other areas of the skin (hot flushes);
• skin rash with itching;
• 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 (detected in blood tests);
• heart rhythm disorders;
• heart valve problems (mitral valve 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 (detected in blood tests);
• high levels of troponin, indicating heart muscle failure (detected in blood tests);
• high levels of the pigment bilirubin, indicating liver failure (detected in blood tests);
• high levels of myoglobin, indicating muscle damage (detected in blood tests);
• high levels of urea in the blood, indicating kidney failure (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 levels of white blood cells (detected in blood tests);
• abnormalities on the ECG (electrocardiogram) (“ST segment depression”, “ST-T segment abnormality”, “right/left bundle branch block”, and “second-degree atrioventricular block”).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are 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. 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 carton and vial after EXP. The expiry date is the last day of the month stated.
• Store in a refrigerator (between 2°C and 8°C).
• Keep the vial in the outer packaging to protect it from light.
• The total time from reconstitution to the start of infusion must not exceed 24 hours. Store the reconstituted solution and the final diluted solution below 25°C.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container contents and additional information

Akynzeo composition

• The active ingredients are fosnetupitant and palonosetron. Each vial contains 235 mg of fosnetupitant and 0.25 mg of palonosetron.
• The other components are mannitol, disodium edetate (E386), sodium hydroxide (E524), and diluted hydrochloric acid (E507) (for pH adjustment).

Product appearance and container contents

Akynzeo powder for concentrate for solution for infusion is a sterile, lyophilized powder, white to off-white in color, and is supplied in a Type I glass vial with a siliconized chlorobutyl rubber stopper and an aluminum seal cap. Each vial contains one dose.

Packs of 1 vial.

Marketing authorization holder and manufacturer

Helsinn Birex Pharmaceuticals Ltd.

Damastown

Mulhuddart

Dublin 15

Ireland

Further information about this medicinal product can be obtained from the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Other sources of information

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

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This information is intended for healthcare professionals only:

Instructions for the reconstitution and dilution of AKYNZEO 235 mg/0.25 mg Preparation of Akynzeo

The reconstituted and diluted solution is stable for 24 hours at 25°C.

Before administration, whenever the solution and container permit, parenteral drugs should be inspected visually for particles or color change.

The reconstituted solution has the same appearance as the diluent.

Discard any remaining solution and materials that have come into contact with it. The disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.

This medicinal product should not be reconstituted or mixed with other solutions with which physical and chemical compatibility has not been established (see Summary of Product Characteristics or package leaflet, section 6.2).