Akynzeo 235 mg/0.25 mg powder for concentrate for solution for infusion – patient leaflet, side effects, dosage

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 adults with cancer feeling sick (nausea) or being sick (vomiting) while having cancer treatment called ‘chemotherapy’.

How Akynzeo works

Chemotherapy medicines can cause the body to release substances called serotonin and substance P. This stimulates the vomiting centre in the brain, making you feel or be sick. The medicines in Akynzeo attach to the receptors in the nervous system through which serotonin and substance P work: fosnetupitant which is converted to netupitant (an NK₁ receptor antagonist) in your body blocks the receptors for substance P, and palonosetron (a 5-HT₃ receptor antagonist) blocks certain receptors for serotonin. By blocking the actions of substance P and serotonin in this way, the medicines help prevent the stimulation of the vomiting centre and the resulting sickness.

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

You should not be given Akynzeo 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, talk to your doctor, pharmacist or nurse before you are given this medicine.
• you are pregnant.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before being given Akynzeo if:

• you have liver problems
• you have a blockage in your gut or you have had constipation in the past
• you or one of your close relatives has ever had a heart problem called ‘QT interval prolongation’
• you have any other heart problems
• you have been told you have an imbalance of minerals in your blood such as potassium and magnesium that has not been corrected.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being given Akynzeo.

Children and adolescents

Akynzeo should 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 re-uptake inhibitors) - such as fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram or escitalopram
• medicines for depression or anxiety called SNRIs (serotonin noradrenaline re-uptake inhibitors) - such as venlafaxine or 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 other medicines:

• medicines that might cause abnormal heartbeat such as amiodarone, nicardipine, quinidine, moxifloxacin, haloperidol, chlorpromazine, quetiapine, thioridazine or domperidone
• medicines with a narrow therapeutic range that are primarily metabolized by CYP3A4, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, diergotamine, 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 - can be used to treat feeling and being sick
• ketoconazole - to treat Cushing's syndrome
• rifampicin - to treat tuberculosis (TB) and other infections.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or nurse before being 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 being given this medicine.

You should not be given Akynzeo if you are pregnant or if you are a woman of childbearing potential not using contraception.

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

This medicine contains 24.8 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 1.24% of the recommended maximum daily dietary intake of sodium for an adult.

If reconstituted and diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, the final solution contains approximately 202 mg of sodium per dose. This is equivalent to 10.1% of the recommended maximum daily dietary 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 your chemotherapy.

• The powder is reconstituted and diluted before use.
• Akynzeo is given to you by a doctor or nurse
• Akynzeo is given as a drip into a vein (intravenous infusion) about 30 minutes before you start your chemotherapy treatment.

Your doctor will ask you to take other medicines including a corticosteroid (such as dexamethasone) to prevent you feeling and being sick. Check with your doctor or nurse if you are not sure.

If you stop being given Akynzeo

Akynzeo is given to help prevent you feeling and being sick when you are having chemotherapy. If you do not want to be given Akynzeo, discuss this with your doctor. If you decide not to be given Akynzeo (or another similar medicine), your chemotherapy is likely to make you feel and be sick.

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 being given Akynzeo and tell your doctor straight away 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, swollen 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
• raised, itchy rash on the skin (hives)
• problems with the muscles in your heart (cardiomyopathy)
• spinning sensation (vertigo), feeling dizzy or trouble sleeping (insomnia)
• stomach problems including stomach discomfort, feeling bloated, nausea, pain, indigestion, hiccups, wind or diarrhoea
• high levels of certain enzymes, including blood alkaline phosphatase and liver transaminases (shown in blood tests)
• high levels of creatinine - which measures kidney function (shown in blood tests)
• ECG (electrocardiogram) problems (called ‘QT and PR interval prolongation’, ‘conduction disorder’, ‘tachycardia’ and ‘atrioventricular block first degree’)
• low levels of ‘neutrophils’ - a kind of white blood cell which fight infections (shown in blood tests)
• high level of white blood cells (shown in blood tests).

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

• back pain, joint pain
• feeling hot, reddening of the face or other areas of the skin (feeling flushed)
• itchy skin rash
• feeling drowsy
• sleep problems
• ring in the ear
• vomiting
• low blood pressure
• chest pain (not related to the heart)
• numbness, blurred vision
• sudden nervous breakdown, change in mood
• infection and inflammation in the bladder (cystitis)
• haemorrhoids
• conjunctivitis (a type of eye inflammation)
• low level of potassium (shown in blood tests)
• modifications (or disturbances) in heart rhythm
• heart valve disorder (mitral valve incompetence)
• coating of the tongue, difficulty swallowing, dry mouth, belching, abnormal taste after medicine intake
• decreased blood flow to the heart muscle (myocardial ischemia)
• high levels of creatine phosphokinase//creatine phosphokinase MB - which indicates sudden decreased blood flow to the heart muscle (shown in blood tests)
• high levels of troponin - which indicates heart muscle dysfunction (shown in blood tests)
• high levels of the pigment bilirubin - which indicates liver dysfunction (shown in blood tests)
• high levels of myoglobin – which indicates muscle injury (shown in blood tests)
• high levels of blood urea – which indicates kidney dysfunction (shown in blood tests)
• high level of ‘lymphocytes’– type of white blood cell which help the body fight disease (shown in blood tests)

• low level of white blood cells (shown in blood tests)

  • ECG (electrocardiogram) problems (called ‘ST segment depression’, ‘ST-T segment abnormal’ ‘bundle branch block right/left’, and ‘atrioventricular block second degree’)

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. 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 refers to the last day of that month.
• Store in a refrigerator (2°C – 8°C).
• Keep the vial in the outer carton in order to protect from light.
• The total time from reconstitution to the start of the infusion should not exceed 24 hours. Store the reconstituted solution and the final diluted solution below 25°C.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures 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 ingredients are mannitol, disodium edetate (E386), sodium hydroxide (E524), hydrochloric acid diluted (E507) (for pH adjustment).

What Akynzeo looks like and contents of the pack

Akynzeo powder for concentrate for solution for infusion is a sterile, white to off-white lyophilized powder and is supplied in a pack of one Type I glass vial with chlorobutyl siliconised rubber stopper and aluminium cap. Each vial contains one dose.

Pack of 1 vial.

Marketing Authorisation Holder and Manufacturer:

Helsinn Birex Pharmaceuticals Ltd.

Damastown

Mulhuddart

Dublin 15

Ireland

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

This leaflet was last revised in

Other sources of information

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

The following information is intended for medical or healthcare professionals only:

Instructions of how to reconstitute and dilute AKYNZEO 235 mg/0.25 mg

Preparation of Akynzeo

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

Parenteral medicines should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

The appearance of the reconstituted solution is the same as the appearance of the diluent.

Discard any remaining solution and waste material. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

The medicinal product must not be reconstituted or mixed with solutions for which physical and chemical compatibility has not been established (see Summary of Product Characteristic (SmPC), section 6.2).