PACKAGE LEAFLET: INFORMATION FOR THE USER

Fresenius Propoven 1%

Emulsion for Injection or Infusion Propofol

In this leaflet:

1.    What Fresenius Propoven 1% is and what it is used for

2.    Before you use Fresenius Propoven 1%

3.    How to use Fresenius Propoven 1%

4.    Possible side effects

5.    How to store Fresenius Propoven 1%

6.    Further information

1.    WHAT FRESENIUS PROPOVEN 1% IS AND WHAT IT IS USED FOR

Fresenius Propoven 1% belongs to a group of medicines called general anaesthetics. General anaesthetics are used to cause unconsciousness (sleep) so that surgical operations or other procedures can be performed. They can also be used to sedate you (so that you are sleepy but not completely asleep).

Propofol is used to:

•    induce and maintain general anaesthesia in adults and children > 1 month.

•    sedate patients > 16 years of age receiving artificial respiration in intensive care.

•    sedate adults and children > 1 month during diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia

2.    BEFORE YOU USE FRESENIUS PROPOVEN 1% DO NOT use Fresenius Propoven 1%

-    if you are hypersensitive (allergic) to propofol or to any of the other ingredients of this medicine (see section 6 “Further information” at the end of this leaflet).

-    if you are hypersensitive (allergic) to soya or peanut (see “Important information about

some of the ingredients of Fresenius Propoven 1% at the end of section 2).

-    in patients of 16 years of age or younger for sedation in intensive care.

Take special care with Fresenius Propoven 1%

You should not receive Fresenius Propoven 1%, or only under extreme caution and intensive monitoring, if you:

-    have advanced heart failure

-    have any other serious disease of the heart

-    are receiving electroconvulsive therapy (ECT, a treatment for psychiatric problems)

The use of Fresenius Propoven 1% is not recommended in newborn infants. Special care should also be observed when administering Fresenius Propoven 1% to children less than 3 years of age. However, evidence now available does not suggest that this is any less safe than in older children. The safety of propofol for sedation in chidren and adolescents 16 years of age and younger in the intensive care unit has not been demonstrated.

In general, Fresenius Propoven 1% should be given with caution to elderly or weak patients.

Before receiving Fresenius Propoven 1%, tell your anaesthetist or intensive care doctor if you have:

-    heart disease

-    lung disease

-    kidney disease

-    liver disease

-    seizures (epilepsy)

-    a raised pressure inside the skull (raised intracranial pressure). In combination with low blood pressure the amount of blood reaching the brain may be decreased.

-    altered levels of fat in the blood. If you are receiving total parenteral nutrition (feeding through a vein), the levels of fat in your blood must be monitored.

If you have any of the following conditions, they must be treated before you receive Fresenius Propoven 1%:

-    heart failure

-    when there is insufficient blood reaching the tissues (circulatory failure)

-    severe breathing problems (respiratory failure)

-    dehydration (hypovolaemia)

-    seizures (epilepsy)

Fresenius Propoven 1% may increase the risk of

-    epileptic seizures

-    a nervous reflex that slows the heart rate (vagotonia, bradycardia)

-    changes in the blood flow to the organs of the body (haemodynamic effects on the cardiovascular system) if you are overweight and receive high doses of Fresenius Propoven 1%.

Involuntary movements can occur during sedation with Fresenius Propoven 1%. The doctors will

take into account how this might affect surgical procedures being performed under sedation and will take the necessary precautions.

Very occasionally, after anaesthesia, there may be a period of unconsciousness associated with stiffness of the muscles. This requires observation by the medical staff but no other treatment. It will resolve spontaneously.

The injection of Fresenius Propoven 1% can be painful. A local anaesthetic can be used to reduce this pain but can have its own side effects.

You will not be allowed to leave the hospital until you are fully awake.

Using other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

You must take special care if you are also taking any of the following medicines:

-    premedications (your anaesthetist will know which medicines may interact with Fresenius Propoven 1%)

-    other anaesthetics, including general, regional, local and inhalational anaesthetics (lower doses of Fresenius Propoven 1% may be required. Your anaesthetist will know this)

-    analgesics (painkillers)

-    drugs that relax muscles, e.g. suxamethonium

-    benzodiazepines (drugs for anxiety)

-    drugs that affect many of the internal body functions such as the heart rate, e.g. atropine

-    strong painkillers, e.g. fentanyl

-    alcohol

-    neostigmine (a treatment for muscle weakness)

-    cyclosporin (used to prevent transplant rejections)

Using Fresenius Propoven 1% with food and drink

After you have been given Fresenius Propoven 1%, you should not drink alcohol until fully recovered.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.

Fresenius Propoven 1% should not be given to pregnant women unless necessary. Mothers should stop breast-feeding and discard any breast milk for 24 hours after receiving Fresenius Propoven 1%.

Driving and using machines

After you have been given Fresenius Propoven 1%, you must not drive, operate machinery, or work in dangerous situations. You should not go home alone.

Important information about some of the ingredients of Fresenius Propoven 1%

Fresenius Propoven 1% contains soya-bean oil.

This can rarely cause severe hypersensitivity (allergic) reactions (see “Do not use Fresenius Propoven 1%”). Tell your doctor if you know that you have allergic reactions to soya-bean oil.

This medicinal product contains less than 1 mmol (23 mg) sodium per 100 ml, i.e. essentially 'sodium-free'.

3. HOW TO USE FRESENIUS PROPOVEN 1%

Fresenius Propoven 1% will only be given to you in hospitals or suitable therapy units by your anaesthetist or by an intensive care doctor.

The dose you are given will vary depending on your age, body weight and physical condition. The doctor will give the correct dose to start and to sustain anaesthesia or to achieve the required level of sedation, by carefully watching your responses and vital signs (pulse, blood pressure, breathing etc.). It can also be affected by other medicines you may be taking. Most people need 1.5 to 2.5 mg propofol per kg body weight to make them go to sleep (induction of anaesthesia), and then 4 to 12 mg propofol per kg body weight per hour after this to keep them asleep (maintenance of anaesthesia). For sedation, doses of 0.3 to 4 mg propofol per kg body weight per hour are usually sufficient.

For sedation during surgical and diagnostic procedures in adults, most patients will require 0.5 to1 mg propofol per kg body weight over 1 to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating Fresenius Propoven 1% infusion to the desired level of sedation. Most patients will require 1.5 to 4.5 mg propofol per kg body weight per hour. The infusion may be supplemented by bolus administration of 10 to 20 mg propofol (1 to 2 ml Fresenius Propoven 1% if a rapid increase of the depth of sedation is required.

Fresenius Propoven 1% is for intravenous use, usually on the back of the hand or in the forearm. Your anaesthetist may use a needle or cannula (a fine plastic tube). An electric pump may be used to give the injection for long operations and for use in intensive care.

Elderly and weak patients may require lower doses.

Children usually require slightly higher doses. The dose should be adjusted according to age and/or body weight.

When used for sedation, Fresenius Propoven 1% must not be administered for more than 7 days.

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

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

Fresenius Propoven 1% should not be mixed prior to administration with injection or infusion solutions other than 5% w/v glucose solution or 0.9% w/v sodium chloride intravenous infusion solution or 1% preservative-free lidocaine injection solution. Final propofol concentration must not be below 2 mg/ml.

For single use. Any unused emulsion must be discarded.

Containers should be shaken before use.

If two layers can be seen after shaking the emulsion should not be used.

Use only homogeneous preparations and undamaged containers.

Prior to use, the ampoule neck or rubber membrane should be cleaned using an alcohol spray or a swab dipped in alcohol. After use, tapped containers must be discarded.

Fresenius Propoven 1% must only be given in hospitals or adequately equipped therapy units by physicians trained in anaesthesia or in intensive care. For sedation during surgical and diagnostic procedures Fresenius Propoven 1% should not be administered by the same person conducting the surgical or diagnostic procedure.

Circulatory and respiratory functions should be constantly monitored (e.g. ECG, pulse oxymetry) and facilities for maintenance of patient airways, artificial ventilation, and other resuscitation facilities should be immediately available at all times.

Propofol may be administered undiluted or diluted in 5% w/v glucose or 0.9% w/v sodium chloride intravenous infusion solutions.

5% w/v glucose intravenous infusion solution, 0.9% w/v sodium chloride intravenous solution or 0.18% w/v sodium sodium chloride and 4% w/v glucose intravenous infusion solution may be given through the same infusion set. Fresenius Propoven 1% must not be mixed with any other solutions for infusion or injection.

Co-administration of other medicinal products or fluids added to the Fresenius Propoven 1% infusion line must occur close to the cannula site using a Y-piece connector or a three-way valve.

Fresenius Propoven 1% is a lipid containing emulsion without antimicrobial preservatives and may support rapid growth of microorganisms.

The emulsion must be drawn aseptically into a sterile syringe or giving set immediately after opening the ampoule or breaking the vial seal. Administration must commence without delay.

Asepsis must    be maintained    for both

Fresenius Propoven 1% and the infusion equipment throughout the    infusion period.    Fresenius

Propoven 1% must not be administered through a microbiological filter.

Infusion of undiluted Fresenius Propoven 1%:

The use of a burette, drop counter, syringe pump or volumetric infusion pump to control the infusion rate is recommended when Fresenius Propoven 1% is infused undiluted.

As usual for fat emulsions, the infusion of Fresenius Propoven 1% via one infusion system must not exceed 12 hours. The infusion set for Fresenius Propoven 1% must be changed at least every 12 hours.

Infusion of diluted Fresenius Propoven 1%: Burettes, drop counters or volumetric infusion pumps should always be used to control infusion rates. The maximum dilution must not exceed 1 part of Fresenius Propoven 1% to 4 parts of 5% w/v glucose or 0.9% w/v sodium chloride intravenous infusion solution (minimum oncentration 2 mg propofol per ml). The mixture should be prepared aseptically and administered within 6 hours.

If the same injection system used for the Fresenius Propoven 1% is to be used for the injection of muscle relaxants (e.g. atracurium and mivacurium), the injection system must first be flushed.

Lidocaine may be added to the diluted solution (20 parts of Fresenius Propoven 1% to 1 part of 1% preservative-free lidocaine solution for injection) to reduce pain at the site of injection of Fresenius Propoven 1%. Lidocaine must not be used in patients with hereditary acute porphyria. Muscle relaxants like atracurium and mivacurium should only be adminstered after flush of the same infusion site used for Fresenius Propoven 1%.

4. POSSIBLE SIDE EFFECTS

Like all medicines, Fresenius Propoven 1% can cause side effects, although not everybody gets them.

Evaluation of the side effects is based on the following frequencies:

Very common	affects more than 1 user in 10
Common	affects 1 to 10 users in 100
Uncommon	affects 1 to 10 users in 1,000
Rare	affects 1 to 10 users in 10,000
Very rare	affects less than 1 user in 10,000
Not known	frequency cannot be estimated from the available data

If you think you have any of the below mentioned side effects or any other side effects, please inform a physician as soon as possible.

Very common:

-    local pain during the injection.

Common:

-    increase of levels of fat in the blood (hypertriglyceridemia)

These side effects may occur during the induction of anaesthesia:

-    muscle jerks (myoclonus)

-    muscle twitching (minimal excitation)

-    low blood pressure (hypotension)

-    slow heartbeat (bradycardia)

-    rapid heartbeat (tachycardia)

-    hot flushes

-    increased breathing (hyperventilation)

-    stopping breathing (temporary apnoea)

-    coughing after anaesthesia

-    hiccups (singultus)

Uncommon:

-    severe low blood pressure (hypotension)

-    coughing during anaesthesia

-    slowing of the pulse rate (progressive bradycardia)

-    blood clots (thrombosis)

-    inflammation of the blood vessels (phlebitis)

-    discoloration of urine

-    postoperative fever

These rare side effects may occur during the recovery period (waking up):

-    euphoria (feeling happy) and sexual arousal

-    shivering and feeling cold

-    irregular heartbeat (arrhythmia)

-    coughing

-    feeling sick (nausea) or vomiting Very rare:

-    allergic reactions caused by soya-bean oil

-    delayed epileptiform attacks (involuntary movements similar to epilepsy after waking up)

-    convulsions in epileptic patients

-    unconsciousness after anaesthesia

-    fluid on the lungs (pulmonary oedema)

-    inflammation of the pancreas (pancreatitis)

-    severe tissue responses after accidental injection into tissues

-    rhabdomyolysis (a disorder of muscle)

-    a change in the acidity of the blood (metabolic acidosis)

-    a high level of potassium in the blood (hyperkalaemia)

-    heart failure.

When Fresenius Propoven 1% is administered in combination with lidocaine (a local anaesthetic used to reduce the pain at the site of injection), certain side effects may occur rarely:

-    dizziness

-    vomiting

-    sleepiness

-    fits

-    a slowing of the heart rate (bradycardia)

-    irregular heartbeat (cardiac arrhythmias)

-    shock

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

5. HOW TO STORE FRESENIUS PROPOVEN 1%

Keep out of the reach and sight of children.

Rare:

-    a severe allergic reaction , including:

•    swelling of the skin of the face, mouth and throat (angioedema)

•    narrowing of the airways in the lungs that makes it difficult to breathe (bronchospasm)

•    reddening of the skin (erythema)

•    low blood pressure (hypotension)

-    headache

-    dizziness (vertigo)

-    epileptiform movements (involuntary movements similar to epilepsy), including convulsions and opisthotonus ( a rigid posture with the head arched backwards)

Do not use Fresenius Propoven 1% after the expiry date which is stated on the ampoule/vial and the outer packaging after EXP. The expiry date refers to the last day of that month.

Store at or below 25 °C.

Do not freeze.

After opening the product must be used immediately. Administration systems with undiluted Fresenius Propoven 1% should be replaced 12 hours after opening of the ampoule or vial. Dilutions with 5%

w/v glucose solution or 0.9% w/v sodium chloride intravenous infusion solution or an admixture 1% preservative-free lidocaine injection solution (at least 2 mg propofol per ml) should be prepared aseptically (controlled and validated conditions preserved) immediately before administration and has to be administered within 6 hours after preparation.

Containers should be shaken before use. If two layers can be seen after shaking the emulsion should not be used. Use only homogenous preparations and undamaged containers.

Medicines should not be disposed via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. FURTHER INFORMATION

What Fresenius Propoven 1% contains

- The active substance is propofol.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

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

Manufacturer:

Fresenius Kabi Austria GmbH A-8055 Graz, Hafnerstrasse 36 Austria

Fresenius Kabi AB

S-75174 Uppsala, Rapsgatan 7

Sweden

This leaflet was last approved in 10/2010

This medicinal product is authorised in the Member States of the EEA under the following names:

Country Trade Name