PACKAGE LEAFLET: INFORMATION FOR THE USER

Remifentanil 1    mg    powder for concentrate for    solution    for    injection    or    infusion

Remifentanil 2    mg    powder for concentrate for    solution    for    injection    or    infusion

Remifentanil 5    mg    powder for concentrate for    solution    for    injection    or    infusion

Remifentanil (as hydrochloride)

In this leaflet:

1.    What Remifentanil is and what it is used for

2.    Before you have Remifentanil

3.    How to use Remifentanil

4.    Possible side effects

5.    How to store Remifentanil

6.    Further information

1. WHAT REMIFENTANIL IS AND WHAT IT IS USED FOR

Remifentanil belongs to a group of medicines called opioids. It differs from other medicines in this group by its very quick onset and very short duration of action.

-    Remifentanil may be used to stop you feeling pain before or while you are having an operation.

-    Remifentanil may be used to relieve pain while you are under controlled mechanical ventilation in an Intensive Care Unit (for patients 18 years of age and over).

2. BEFORE YOU HAVE REMIFENTANIL

You should not be given Remifentanil

-    if you are allergic (hypersensitive) to remifentanil, any ofthe other ingredients (see list of ingredients in Section 6) or fentanyl derivates (such as alfentanil, fentanyl, sufentanil). An allergic reaction may include rash, itching, difficulty of breathing or swelling of the face, lips, throat or tongue. You may know this from earlier experience

-    as injection into the spinal canal

-    as sole medicine to initiate anaesthesia

Take special care with Remifentanil

Before you receive Remifentanil, tell your doctor if you:

-    ever had any adverse reactions during an operation

-    ever had any allergic reactions or if you have been told that you are allergic to:

o any medicines used during an operation o opioid medicines (e.g., morphine, fentanyl, pethidine, codeine), see also section above "You should not be given Remifentanil"

-    suffer from impaired lung and/or liver function (you may be more sensitive for breathing difficulties)

Elderly or weak patients (caused by decreased blood volume and/or low blood pressure) are more sensitive to suffer from cardiac or circulatory disturbances.

Using other medicines

Please tell your doctor or pharmacist if you are taking, or have recently taken, any other medicines, including medicines you can get without a prescription. This is especially important with the following medicines as they may interact with your Remifentanil: o medicines for blood pressure or heart problems (known as beta-blockers or calcium channel blockers). These medicines may increase the effect of Remifentanil on your heart (lowering of your blood pressure and your heart beat). o other sedative medicines, such as benzodiazepines. Your doctor or pharmacist will alter the dose of these medicines when you are being given Remifentanil.

It may still be all right for you to receive Remifetanil and your doctor will be able to decide what is suitable for you.

Children

Remifentanil is not recommended in neonates and infants (children under the age of one year).

There is little experience of use of Remifentanil to treat children in intensive care units.

Elderly

If used for an operation under general anaesthesia, the initial dose of Remifentanil should be appropriately reduced in elderly patients.

Taking Remifentanil with food and drink

After having received Remifentanil you should not drink alcohol until fully recovered.

Pregnancy and breast-feeding

Remifentanil should not be given to pregnant women unless medically justified. Remifentanil is not recommended during labour or a Caesarian section.

It is recommended that you stop breast-feeding for 24 hours after Remifentanil has been given to you. Ask your doctor or pharmacist for advice before taking any medicine. Your doctor will discuss the possible risks and benefits of being given Remifentanil if you are pregnant or breast-feeding.

Driving and using machines

This medicine is only used in hospitalised patients. If you are discharged early, after you have been given Remifentanil, you must not drive, operate machinery, or work in dangerous situations. You should not go home alone.

3. HOW TO USE REMIFENTANIL

Remifentanil must only be given under carefully controlled conditions and emergency equipment has to be available. Remifentanil will be given by or under the supervision of an experienced doctor who is familiar with the use and action of the type of medicine. You will never be expected to give yourself this medication. It will always be given to you by a person who is qualified to do so.

Remifentanil must be given only by injection or infusion directly into a vein.

It should not be given over less than 30 seconds. Remifentanil must not be injected into the spinal canal (intrathecal or epidural).

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

PREPARATION GUIDE for

Remifentanil 1 mg powder for concentrate for

solution for injection or infusion

Remifentanil 2 mg powder for concentrate for

solution for injection or infusion

Remifentanil 5 mg powder for concentrate for

solution for injection or infusion

It is important that you read the entire contents of

this guide prior to the preparation of this medicinal

product.

Remifentanil should not be administered without further dilution after reconstitution of the lyophilised powder.

Reconstitution:

Remifentanil 1 mg / 2 mg /5 mg should be prepared for intravenous use by adding the appropriate volume (as stated in the table below) of one of the below listed diluents to give a reconstituted solution with a concentration of approximately 1 mg/ml.

Shake until completely dissolved. The reconstituted solution should be clear, colourless and free of visible particles.

Further Dilution:

After reconstitution, Remifentanil should not be administered without further dilution to concentrations of 20 to 250 pg/ml (50 pg/ml is the recommended dilution for adults and 20 to 25 pg/ ml for paediatric patients aged 1 year and over) with one of the following IV fluids llisted below.

For target controlled infusion (TCI) the recommended dilution of Remifentanil is 20 to 50 pg/ml.

The dilution is dependent upon the technical capability of the infusion device and the anticipated requirements of the patient.

One of the following solutions should be used for dilution: Water for Injections

Glucose 50 mg/ml (5%) solution for injection Glucose 50 mg/ml (5%) solution for injection and sodium chloride 9 mg/ml (0.9%) solution for injection Sodium chloride 9 mg/ml (0.9%) solution for injection Sodium chloride 4.5 mg/ml (0.45%) solution for injection

The following intravenous fluids may also be used when administered into a running IV catheter: Lactated Ringer's Injection

Lactated Ringer's and glucose 50 mg/ml (5%) solution for injection

Remifentanil is compatible with propofol when administered into a running IV catheter.

No other diluents should be used.

The solution is to be inspected visually for particulate matter prior to administration. The solution should

Dosage

The dosing and the duration of your infusion will be worked out by the doctor and can vary according to factors such as your body weight, age, physical fitness, other medicines you are given and the type of operation you have.

Dosage in adults:

Most patients respond to infusion rates between 0.1 and 2 microgram per kg body weight per minute. Dosage can be reduced or enhanced by your doctor according to your condition and/or response.

Dosage in elderly

If used for an operation under general anaesthesia, the initial dose of Remifentanil should be appropriately reduced in elderly patients.

Dosage in children (1 to 12 years of age):

For most children, infusion rates between 0.05 and 1.3 microgram per kg body weight per minute are sufficient to maintain sleep during an operation. The doses can be altered by the doctor and may be as high as 3 microgram per kg body weight per minute.

There is little experience of use of Remifentanil to treat children in intensive care units.

Remifentanil is not recommended in neonates and infants (children under the age of one year).

Dosage in special patient groups In obese or critically ill patients the initial dose will be appropriately reduced and enhanced due to the response. In patients with impaired liver or kidney function and in patients undergoing neurosurgery a dose reduction will not be necessary.

If you receive more Remifentanil than you should or if you miss a dose of Remifentanil

Since Remifentanil will usually be given to you by a doctor or nurse under carefully controlled conditions, it is unlikely that you will be given too much or that you will miss a dose.

If you have received too much of Remifentanil, or if it is suspected, that you may have received too much, appropriate action will be taken promptly by your healthcare specialist team.

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

4. POSSIBLE SIDE EFFECTS

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

Tell your doctor immediately if you notice any of the following severe allergic reactions;

-    pale, sweaty, raised heart beat or confusion caused by shock or circulatory failure.

-    chest pain or shortness of breath caused by a heart attack.

The following side effects have been reported:

Very common (affects more than 1 user in 10)

-    muscle stiffness

-    feeling sick (nausea)

-    being sick (vomiting)

-    low blood pressure (hypotension)

Common (affects 1 to 10 users in 100)

-    slow heart beat (bradycardia)

-    shallow breathing (respiratory depression)

-    breathing stops (apnoea)

-    itching

-    shivering after the operation

-    high blood pressure (hypertension) after the operation

Uncommon (affects 1 to 10 users in 1 000)

-    constipation

-    pain after the operation

-    oxygen deficiency (hypoxia)

Rare (affects 1 to 10 users in 10 000)

-    slow heart beat followed by heart block in patients receiving remifentanil with one or more anaesthetic medicines

-    sleepiness (during recovering from the operation)

As with other medicines of this class (opioids), longterm use of Remifentanil can lead to dependence. Please ask your doctor for advise.

If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5.    HOW TO STORE REMIFENTANIL

Keep out of the sight and reach of children.

Remifentanil should not be used after the expiry date which is stated on the carton and label after "EXP.". The expiry date refers to the last day of that month.

Unopened vials: Do not store above 25°C. Do not refrigerate or freeze.

Reconstituted/diluted solution: the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

Do not use Remifentanil if you notice the solution is not clear and free of particles or if the container is damaged.

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 to protect the environment.

6.    FURTHER INFORMATION

What Remifentanil contains

The active substance is remifentanil.

Each vial contains either 1 mg, 2 mg or 5 mg of remifentanil (as hydrochloride). After reconstitution as directed each ml contains 1 mg remifentanil.

Other ingredients are glycine and hydrochloric acid.

What Remifentanil looks like and contents of the pack

Remifentanil is a white to off white or yellowish powder for concentrate for solution for injection or infusion. It is supplied in colourless glass vials.

Package size:

Remifentanil 1 mg powder for concentrate for solution for injection or infusion: 1 or 5 vials per pack Remifentanil 2 mg powder for concentrate for solution for injection or infusion: 1 or 5 vials per pack Remifentanil 5 mg powder for concentrate for solution for injection or infusion: 1 or 5 vials per pack

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder Fresenius Kabi Ltd

Cestrian Court, Eastgate Way, Manor Park Runcorn, Cheshire, WA7 1NT United Kingdom

Manufacturer IDT Biologika GmbH

Am Pharmapark, 06861 Dessau-RoBlau,Germany

Important note: In the event of the need to return product, please forward any samples to the following address:

Fresenius Kabi Ltd, Cestrian Court, Eastgate Way, Manor Park, Runcorn, Cheshire, WA7 1NT, UK.

This leaflet was last approved in 10/2011.

only be used if the solution is clear and free from particles.

Ideally, intravenous infusions of Remifentanil should be prepared at the time of administration.

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

The content of the vial is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.

Special precautions for storage

Do not store above 25°C.

Do not refrigerate or freeze.

For storage condition of the reconstituted/diluted medicinal product, see section above under Further dilution.

V001 4-5531001/00 GB/IE