SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Curtega 10 mg/ml Emulsion for injection/infusion.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of emulsion for injection/infusion contains 10 mg of propofol.

Each 10 ml vial contains 100 mg of propofol.

Each 20 ml vial contains 200 mg of propofol.

Each 50 ml vial contains 500 mg of propofol.

Each 100 ml vial contains 1000 mg of propofol.

Excipient:

Each ml of emulsion for injection/infusion contains: Soyabean oil refined 100 mg, Sodium 0.03 mg.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Emulsion for injection/infusion.

White oil-in-water emulsion.

Osmolality: 250 to 350 mOsm/Kg.

pH between 7.00 and 8.50.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Curtega is a short-acting intravenous general anaesthetic for

•    induction and maintenance of general anaesthesia in adults and children > 1 month

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

•    sedation of ventilated patients > 16 years of age in the intensive care unit.

4.2 Posology and method of administration

Curtega 10 mg/ml can only be administered in hospitals or well equipped units by doctors who are trained in anaesthesia or the treatment of intensive care patients.

Continuous surveillance of circulation and breathing (e.g. ECG, pulse oxymeter) is necessary. Facilities for maintenance of patient airways, artificial ventilation and other resuscitation facilities should be available immediately and at all times.

During surgical or diagnostic procedures Curtega 10 mg/ml should not be administered for sedation by the same person who executes the surgical or diagnostic intervention.

Curtega 10 mg/ml has no analgesic properties and therefore supplementary analgesic agents are generally required in addition to Curtega 10 mg/ml.

Posology

Curtega 10 mg/ml is administered intravenously. The dosage is individually adapted according to the patient's response.

Adults

General anaesthesia for adults Induction of anaesthesia:

For induction of anaesthesia Curtega 10 mg/ml must be titrated (20 - 40 mg propofol every 10 seconds), and the reaction of the patient must be constantly monitored for clinical signals showing the onset of anaesthesia.

Usually an adult patient, below 55 years old, will need 1.5 - 2.5 mg of propofol per kg body weight. In older patients and in patients with ASA (American Society of Anaesthesiologists) classification III or IV, in particular those with impaired heart function, the need will be less and the total dose of Curtega 10 mg/ml can be reduced to 1 mg of propofol per kg body weight.

These patients also need a slower rate of administration (approximately 2 ml, which corresponds to 20 mg per 10 seconds).

Maintenance of anaesthesia:

Anaesthesia can be maintained by administering Curtega 10 mg/ml as a continuous infusion or a repeated bolus injection. When using the latter method, dosages of 25 mg (2.5 ml Curtega 10 mg/ml) up to 50 mg (5 ml Curtega 10 mg/ml) must be administered depending on the clinical requirements. When using a continuous infusion for the maintenance of anaesthesia the dosage will normally be 4 - 12 mg / kg body weight / hour. For older patients, patients with a poor condition, patients with an ASA classification III or IV and patients with hypovolemia, the dosage can be further reduced, depending on the condition of the patient and the applied method of anaesthesia.

Sedation of mechanically ventilated patients in intensive care

To sedate mechanically ventilated patients in intensive care conditions, the administration of Curtega 10 mg/ml as a continuous infusion is recommended.

The rate of administration has to be adapted to the necessary level of sedation. A satisfactory level of anaesthesia can generally be attained with a dose of 0.3 - 4.0 mg / kg body weight / hour, (see section 4.4).

Curtega 10 mg/ml should not be used for sedation in intensive care conditions for children and adolescent under 16 years (see section 4.3).

Administering Curtega through a TCI-system for sedation in intensive care is not recommended.

It is recommended that blood lipid levels be monitored should Curtega 10 mg/ml be administered to patients thought to be at particular risk of fat overload. Administration of Curtega 10 mg/ml should be adjusted appropriately if the monitoring indicates that fat is being inadequately cleared from the body. If the patient is receiving other intravenous lipid concurrently, a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the Curtega 10 mg/ml formulation; 1.0 ml of Curtega 10 mg/ml contains approximately 0.1g of fat.

If the duration of sedation is in excess of 3 days, lipids should be monitored in all patients.

Sedation for diagnostic and surgical interventions in adults

For sedation for diagnostic and surgical interventions the dose and rate of administration need to be adapted to the clinical response.

As induction most patients need 0.5 - 1 mg/kg body weight for 1 - 5 minutes.

For maintaining sedation the Curtega 10 mg/ml infusion should be titrated until the desired level of sedation is reached. Generally 1.5 - 4.5 mg / kg body weight / hour will be necessary.

The infusion can be supplemented with bolus injections of 10 - 20 mg (1 - 2 ml Curtega 10 mg/ml), when reaching a deeper level of sedation quickly is required. In patients older than 55 years and in patients with ASA-classification III and IV it might be necessary to lower the dosage and rate of administration.

Paediatric population

General anaesthesia in children over 1 month of age

Curtega 10 mg/ml is not recommended for maintenance of anaesthesia in children less than 1 month old.

Induction of anaesthesia:

For induction of anaesthesia Curtega 10 mg/ml should be titrated slowly and the reaction of the patient must be constantly monitored for clinical signs showing the onset of anaesthesia. The dose should be adjusted according to age and/or body weight. Most patients over 8 years of age require approximately 2.5 mg/kg body weight Curtega for induction of anaesthesia.

In younger children, especially between the age of 1 month and 3 years, dose requirements may be higher (2.5 - 4 mg/kg body weight).

Maintenance of anaesthesia:

A satisfactory level of anaesthesia can generally be attained with a continuous infusion or by repeated bolus injection, using a dosage of 9 - 15 mg / kg body weight / hour.

The dose needs to be individually adapted and special attention needs to be given to obtain adequate analgesia. In younger children, especially between the age of 1 month and 3 years might need a higher dose, within the recommended dosage limits. For ASA III and IV patients lower doses are recommended (see also section 4.4).

Sedation for diagnostic and surgical procedures in children over 1 month of age

Doses and administration rates should be adjusted according to the required depth of sedation and the clinical response. Most paediatric patients require 1 -2 mg/kg body weight of Curtega 10 mg/ml for onset of sedation. Maintenance of sedation may be accomplished by titrating Curtega 10 mg/ml infusion to the desired level of sedation. Most patients require 1.5 - 9 mg/kg/h Curtega 10 mg/ml. The infusion may be supplemented by bolus administration of up to 1 mg/kg b.w. if a rapid increase of depth of sedation is required.

In ASA III and IV patients lower doses may be required.

Curtega is contraindicated in children of 16 years of age or younger in the indication for sedation in intensive care (see section 4.3 Contraindications).

Method of administration

Containers should be shaken before use. If two layers can be seen after shaking, the emulsion should not be used.

Curtega 10 mg/ml is administered intravenously as an injection or as a continuous infusion, undiluted or diluted with a solution of 5% glucose, 0.9% sodium chloride or combinations of 4% glucose with 0.18% sodium chloride solutions (see also section 6.6).

Before using, the rubber stopper of the infusion vial must be disinfected with medicinal alcohol (spray or tissues). After use anything remaining should be discarded.

Curtega 10 mg/ml does not contain preservatives and is capable of supporting the growth of micro-organisms. The emulsion should immediately be drawn, aseptically, in a sterile syringe or the infusion system, after spiking the vial.

Administration should commence immediately afterwards. During the infusion the sterility of Curtega 10 mg/ml as well as the infusion system needs to be maintained.

Medicines or liquids that are added to a running Curtega 10 mg/ml infusion should be added close to the cannula. Curtega 10 mg/ml should not be administered via infusion systems that are provided with microbial filters.

The contents of one vial with Curtega 10 mg/ml and every syringe of Curtega 10 mg/ml is intended for single use for one patient.

The remainder must be discarded immediately after use.

Infusion of undiluted Curtega 10 mg/ml

When Curtega 10 mg/ml is administered through a continuous infusion, checking the rate of infusion through a burette, dropper, syringe pump or volumetric infusion pump is recommended. As applies to parenteral administration of all kinds of fat emulsions, the duration of use for one infusion system for a continuous infusion of Curtega 10mg/ml should be limited to maximum 12 hours. The infusion system and the container should be removed and changed after maximum 12 hours.

The simultaneous administration of Curtega 10 mg/ml together with an infusion of 5% glucose, 0.9% sodium chloride or combinations of 4% glucose with 0.18% sodium chloride solutions close to the Y-connector near the place of injection, is possible.

Any Curtega 10 mg/ml remaining at the end of the infusion period or after changing the system needs to be discarded and destroyed.

Infusion of diluted Curtega 10 mg/ml

When Curtega 10 mg/ml is administered diluted through a continuous infusion, the checking of the rate of administration by means of a burette, dropper, syringe pump or volumetric infusion pump is recommended, to prevent the accidental administration of too high doses of diluted Curtega 10 mg/ml.

Curtega 10 mg/ml must not be mixed with other injection or infusion liquids other than the ones mentioned in section 6.6.

To lessen the pain at the start of the injection, Curtega 10 mg/ml can be mixed with a lidocaine 1% solution for injection without preservatives (see also section 6.6). For the specific risks of lidocaine see sections 4.4 and 4.8.

The infusion system should be rinsed before administration of muscle relaxants like atracurium or mivacurium when using the same infusion system for Curtega 10 mg/ml.

Duration of Administration

Curtega 10 mg/ml can be administered for a maximum of 7 days.

4.3 Contraindications

Curtega must not be used:

•    in patients with a known hypersensitivity to propofol or one of its additives or fat emulsions (see also section 4.4).

•    in patients, allergic to soya or peanuts.

•    in patients of 16 years of age or younger for sedation in intensive care (see also section 4.4).

4.4 Special warnings and precautions for use

Caution must be taken in patients with cardiac, respiratory, renal or hepatic problems or in patients suffering from hypovolemia, patients that are weakened or suffer from epileptic fits, to whom Curtega needs to be administered at a slower rate of administration (see section 4.2).

Propofol clearance is blood flow dependent, therefore, concomitant medication which reduces cardiac output will also reduce propofol clearance.

If possible hypovolemia, cardiac insufficiency, diminished blood circulation or diminished breathing must be compensated before Curtega is administered.

To anaesthetise an epileptic patient, one needs to check if the patient is receiving antiepileptic treatment. Although different studies show the effectiveness in the treatment of status epilepticus, administering propofol to epileptic patients can heighten the risk of an attack.

As with other intravenous anaesthetic and sedative agents, patients should be instructed to avoid alcohol before and for at least 8 hours after administration of Curtega.

Curtega must be administered with caution to patients, who have to undergo interventions where unexpected movements are undesirable e.g. in ophthalmology. The use of Curtega in electroconvulsive therapy is not recommended.

In patients with a seriously worsened heart function it is recommended to administer Curtega with the utmost care and under intense supervision.

During induction of anaesthesia, hypotension and transient apnoea may occur depending on the dose and use of premedicants and other agents.

The risk of relative vagotonia can be heightened because Curtega has no vagolytic activity. The intravenous administration of an anticholinergic preceding induction or during the maintenance of sedation, especially in situations where increases in the vagal tone are anticipated or when propofol is used in combination with other medicines, are likely to cause bradycardia.

Administration of Curtega for anaesthesia in infants and children up to the age of 3 needs extra attention, although recent data shows that there are no clear safety differences in comparison to children older than 3 years.

The safety and efficiency of Curtega for (background) sedation in children and adolescent under 16 years has not been proven.

The use of Curtega for general anaesthesia in children younger than 1 month is not recommended as this patient population has not been fully investigated. Pharmacokinetic data (see section 5.2) indicate that clearance is considerably reduced in neonates with a very high inter-individual variability. Relative overdose could occur administering doses recommended for older children resulting in severe cardiovascular depression.

Although a causal link has not been established, serious undesirable effects (including cases with a fatal ending) during (background) sedation of children and adolescent under 16 years have been reported during unlicensed use. These were mostly cases of metabolic acidosis, hyperlipidemia, rhabdomyolysis and /or cardiac failure. These effects were often noticed in children with infections of the airways, who received larger doses than advised for adults for sedation in intensive care.

Similarly rare reports have been received on the occurrence of metabolic acidosis, rhabdomyolysis, hyperkalemia and /or fast progressively cardiac failure (in some cases fatal) in adults, who were treated for more than 58 hours with doses larger than 5 mg/kg body weight per hour. This exceeds the maximum dosage of 4 mg/kg body weight per hour, which is now recommended for sedation in intensive care. The affected patients were mostly (but not exclusively) seriously wounded to the head and had increased intracranial pressure. In such cases cardiac failure generally did not react to inotropic stimulation.

Prescribers are reminded not to exceed a dose of 4 mg/kg body weight per hour.

Prescribers should stay alert to these possible undesired effects and to consider reducing the dose, or to change to another sedative at the first sign of such undesired side effects appearing. The blood flow of the brain of patients with increased intercranial pressure needs to be supported in the right manner during the adaptation of this treatment.

Extra attention is needed in patients with an increased intracranial pressure and lowered arterial pressure, because a risk exists for a significant decrease of intracerebral perfusion pressure.

Caution should be exercised in cases of abnormalities in the fat metabolism and/ or illnesses, which require that the use of fat emulsions be handled very carefully.

In patients receiving parenteral nutrition, it is necessary to take into account the amount of lipids in Curtega 10 mg/ml: 1.0 ml Curtega 10 mg/ml contains 0.1 gram of fat.

The plasma lipid levels must be checked after 3 days during treatment in the intensive care unit.

As a result of the higher doses than normally have to be administered to seriously overweight patients, a heightened risk of undesired hemodynamic side effects should be taken into account.

Dilutions with a lidocaine solution should not be administered to patients with a hereditary predisposition to acute porphyria.

In rare cases a period of post-operative unconsciousness, accompanied by an increase in muscle tone, might occur. This is not linked to the fact of the patient being awake or not. Although consciousness returns spontaneously, unconscious patients should be observed carefully.

Before discharge the patient should be checked to see if there is complete recovery from the general anaesthesia.

For use during breast feeding, see section 4.6.

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

4.5 Interaction with other medicinal products and other forms of interaction

Curtega can be administered in combination with other medicines for anaesthesia (pre-medication, inhalation-anaesthesia, analgesics, muscle relaxants, local anaesthesia). Until now no serious interactions with these medicines have been reported. Some of these centrally acting medicines can cause circulatory or respiratory depression. In combination with propofol, the effect can be reinforced. Continuation of the anaesthesia and a decrease of the breathing frequency have been reported after simultaneous use with benzodiazepines, parasympathicolytics or inhalation anaesthesia.

After additional pre-medication with opioids a higher incidence and longer duration of apnoea can occur.

Bradycardia and cardiac arrest can occur after treatment with suxamethonium or neostigmine.

It should be taken into consideration that the simultaneous use of propofol and medicines for pre-medication, inhalation anaesthesia or analgesics can reinforce the anaesthesia and cardio-vascular side-effects. The simultaneous use with compounds that can lead to depression of the central nervous system, like alcohol, general anaesthesia or narcotic analgesics, will result in an increase in their sedative effects.

After administration of fentanyl the level of propofol in the blood can be temporarily increased with an increase in the degree of apnoea.

Leukoencephalopathy has been reported after the administration of fat emulsions, like propofol, to patients, who also had ciclosporin administered.

When used as supplementation to local anaesthesia it may be necessary to decrease the dose of Curtega 10 mg/ml.

4.6 Pregnancy and lactation

Pregnancy

The safety of Curtega during pregnancy has not been established. Therefore Curtega should not be used in pregnancy unless clearly necessary. Curtega crosses the placenta and can cause neonatal depression (see also section 5.3). High dosages (more than 2.5 mg/kg body weight for induction and 6 mg/kg body weight per hour for maintenance of the anaesthesia) should be avoided.

Breast Feeding

Studies in breastfeeding mothers showed that small quantities of Curtega are excreted in human milk. Women should therefore not breastfeed for 24 hours after administration of Curtega and the human milk produced during this time should be discarded.

4.7 Effects on ability to drive and use machines

After administration of Curtega the patient should be observed long enough to ensure full recovery.

The patient must be instructed not to drive, operate machinery or work in potentially dangerous situations. When returning home, patients should be accompanied and should be instructed not to drink alcohol.

4.8 Undesirable effects

Hypotension and breathing depression are the most common side-effects of propofol. The effects depend not only on the quantity of administered propofol but also on the kind of pre-medication and other simultaneously administered medication. The following side-effects have been explicitly reported:

In this section undesirable effects are defined as follows:

Very common	(>1/10)
Common	(>1/100 to <1/10)
Uncommon	(>1/1,000 to <1/100)
Rare	(>1/10,000 to <1/1,000)
Very rare	(<1/10,000), not known (cannot be estimated from the available data)>

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Immune system disorders

Rare:

Serious hypersensitivity reactions (anaphylactic), including Quincke's oedema, bronchospasms, erythema and hypotension.

Psychiatric disorders

Rare:

Euphoria and sexual disinhibition during recovery.

Nervous system disorders

Common: During induction of anaesthesia spontaneous movements and myoclonic movements.

Rare: During the recovery period headaches, dizziness, shivers and sensations of cold, as well as epileptiform convulsions including opisthotonos.

Very Rare: Delayed epileptic fits with a delay that can vary from a few hours to several days. Occasionally convulsions after the administration of Curtega to epileptic patients.

Cases of post operative unconsciousness (see section 4.4).

Cardiac disorders, vascular disorders

Common: Mild or moderate hypotension Uncommon: Marked hypotension.

This can necessitate the use of intravenous liquids, if necessary vasoconstrictives, as well as a slower rate of administration of Curtega.

The possibility of a serious decrease in blood pressure in patients with a diminished coronary or cerebral perfusion or with hypervolemia, must be taken into account.

Rare: Cardiac arrhythmia during recovery.

During general anaesthesia incidental progressive (asystole) bradycardia may occur. Consider the intravenous administration of an anticholinergic preceding induction or during maintenance (see also section 4.4).

Respiratory, thoracic and mediastinal disorders

Common: During induction of anaesthesia hyperventilation, temporary apnoea and coughing.

Uncommon: Coughing during maintenance.

Rare: Coughing during recovery.

Very Rare: Isolated cases of pulmonary oedema after administration. Gastrointestinal disorders

Common: Hiccupping during induction of anaesthesia.

Rare: Nausea and vomiting during recovery.

Very Rare: Pancreatitis has been reported after the administration of Curtega. A causal link could not be established.

Renal and urinary disorders

Rare: Cases of discolouration of the urine after an extended treatment of Curtega 10 mg/ml.

General disorders and administration site conditions

Very Common: Local pain during the first injection. Prophylaxis or treatments see below.

Common: Warm flush during induction of anaesthesia.

Rare: Fever after the intervention. Thrombosis and phlebitis.

Very Rare: In rare cases rhabdomyolysis, metabolic acidosis, hyperkalemia or cardiac failure, in some cases fatal, after administration of Curtega in doses higher than 4mg/kg body weight per hour for sedation in intensive care were reported(see also section 4.4).

Incidental cases of serious reactions to the tissue after accidental extravasation.

Local pain, which can occur during the first injection of Curtega, can be lessened by the simultaneous administration of lidocaine (see also section 4.2) as well as by the use of larger veins in the forearm and elbow crease. After simultaneous administration of lidocaine the following side-effects may occur: Giddiness, vomiting, grogginess, convulsions, bradycardia, cardiac arrhythmia and shock.

4.9 Overdose

Accidental overdose is likely to cause cardio-respiratory depression. The respiratory depression must be treated by artificial ventilation with oxygen. Cardiovascular depression may require lowering the patient’s head and administering plasma expanders and pressor agents

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharma-cotherapeutic group: Anaesthetics, general; other general anaesthetics: ATC-code: NO1AX10.

The hypnotic effect occurs quickly after the intravenous administration of Curtega. Depending on the injection speed the time for induction of the anaesthesia is between 30 and 40 seconds. The duration of action after a single bolus administration is short due to rapid metabolism and excretion (4-6 minutes).

With the recommended dosage schedule, a clinically relevant accumulation of propofol after repeated administration of bolus injections has not been reported. The patients regain consciousness quickly.

Bradycardia and hypotension can occur occasionally during the induction of anaesthesia, probably due to a lack of vagolytic activity. The cardiac and

circulatory situation usually normalises during the maintenance of the anaesthesia.

Paediatric population

Limited studies on the duration of propofol based anaesthesia in children indicate safety and efficacy is unchanged up to duration of 4 hours. Literature evidence of use in children documents use for prolonged procedures without changes in safety or efficacy.

5.2 Pharmacokinetic properties

After intravenous administration about 98% of propofol is bound to plasma protein.

After an intravenous bolus injection the initial concentration of propofol diminishes quickly because of a fast distribution over different compartments (a-phase).

The distribution half-life is 2 - 4 minutes.

During the elimination phase the concentration diminishes slowly. The elimination half-life during the P-phase is 30 - 60 minutes. After that a third compartment occurs, that reflects the redistribution of propofol from tissue with a slight perfusion.

After a single dose of 3 mg/kg intravenously, propofol clearance/kg body weight increased with age as follows: Median clearance was considerably lower in neonates < 1 month old (n=25) (20 mL/kg/min) compared to older children (n=36, age range 4 months - 7 years). Additionally inter-individual variability was considerable in neonates (range 3.7-78 mL/kg/min). Due to this limited trial data that indicates a large variability, no dose recommendations can be given for this age group.

Clearance in children is higher than in adults.

The central distribution volume varies from 0.2 to 0.79 L/kg body weight; the steady-state volume is 1.8 - 5.3 L/kg body weight. Propofol is eliminated quickly from the body (total clearance around 2 L/minute).

Clearance takes place through metabolism, mainly in the liver, where it is blood flow dependent to form glucoronides of propofol as well as glucoronides and sulphate compounds of the metabolite quinol. All metabolites are inactive. Around 88% of the administered dose is excreted through urine in the form of metabolites. Only 0.3% is excreted unchanged in the urine.

5.3 Preclinical safety data

Pre-clinical data, based on conventional research, on the toxicity after repeated administration, or gentoxicity showed no specific risks for humans.

Research for carcinogenic effects have not been conducted.

Research on toxicity in reproduction showed effects which are related to the pharmacodynamic properties of propofol in high dosages. No teratogenic effects have been reported.

During research in local effects, intramuscular injection caused tissue damage around the place of injection.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Soya-bean oil, refined

Glycerol

Egg lecithin

Sodium oleate

Water for injections

Sodium hydroxide (for pH adjustment)

6.2 Incompatibilities

Before administration Curtega 10 mg/ml should not be mixed with injection and infusion liquids other than the ones listed in section 6.6. Curtega 10 mg/ml should not be administered together with blood or blood plasma through the same IV tube; although the clinical significance of this is not known. In vitro studies have shown that the fat globules from the emulsion base formed aggregates, when they come in contact with human plasma.

The neuromuscular blocking agents, atracurium and mivacurium should not be given through the same intravenous line as Curtega 10 mg/ml without prior flushing.

6.3 Shelf life

3 years

After first opening and/or dilution: to be used immediately.

Chemical and physical in-use stability has been demonstrated for 30 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 / dilution (etc) has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

Do not store above 25° C. Do not freeze.

Store in the original carton in order to protect from light.

For storage conditions of the diluted medicinal product, see section 6.3.

6.5 Nature and contents of container

Package with one glass vial (type II) with bromobutyl rubber stopper and plastic cap containing 10 ml, 20 ml, 50 ml or 100 ml emulsion for injection/infusion.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Shake before use. If two layers can be seen after shaking, the emulsion should not be used.

Curtega can be diluted with solutions of glucose 5%, sodium chloride 0.9 % or combinations of 4% glucose and 0.18% sodium chloride (see section 4.2 "Method of administration").

The maximum dilution should not exceed 1 part Curtega 10 mg/ml for 4 parts of the solutions mentioned above (minimal concentration 2 mg Propofol/ ml). Furthermore Curtega can be mixed with a lidocaine 1 % solution for injection without preservatives. One part lidocaine solution for injection should then be mixed with 20 parts Curtega 10 mg/ml.

The mixtures should be prepared aseptically immediately before administration.

Solutions in glass bottles or PVC bags can both be used, as long as they are well mixed prior to administration.

The simultaneous administration of Curtega 10 mg/ml together with an infusion of 5% glucose, 0.9% sodium chloride or combinations of 4% glucose with 0.18% sodium chloride solution close to the Y-connector near the place of injection, is also possible.

For single use only. Any unused product or waste material should be disposed of in accordance with local requirements, immediately after use.

7    MARKETING AUTHORISATION HOLDER

Pfizer Limited, Ramsgate Road, Sandwich,

Kent CT13 9NJ

8    MARKETING AUTHORISATION NUMBER(S)

PL 00057/1121

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

28/06/2011

10 DATE OF REVISION OF THE TEXT

28/06/2011