SUMMARY OF PRODUCT CHARACTERISTICS

B. Braun Melsungen AG • 34209 Melsungen, Germany 1. NAME OF THE MEDICINAL PRODUCT

Propofol-Lipuro 0.5 % (5 mg/ml)

emulsion for injection or infusion

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml emulsion for injection or infusion contains 5 mg propofol.

1 ampoule with 20 ml contains 100 mg propofol Excipients with known effects:

1 ml of emulsion contains Soya-bean oil refined    50 mg

Sodium    0.03 mg

For the full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM Emulsion for injection or infusion.

White milky oil-in-water emulsion.

4.    CLINICAL PARTICULARS

4.1    Therapeutic indications

Propofol-Lipuro 0.5 % (5 mg/ml) is a short-acting intravenous general anaesthetic indicated for

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

•    induction of sedation for diagnostic and surgical procedures, in adults and children > 1 month

•    short term sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia in adults only.

4.2    Posology and method of administration General instructions

Propofol-Lipuro 0.5 % (5 mg/ml) must only be given in hospitals or adequately equipped day therapy units by physicians trained in anaesthesia or in the care of patients in intensive care. Circulatory and respiratory functions should be constantly monitored (e.g. ECG, pulse-oxymeter) and facilities for maintenance of patient airways, artificial ventilation, and other resuscitation facilities should be immediately available at all times. For sedation during surgical or diagnostic procedures Propofol-Lipuro 0.5 % (5 mg/ ml) should not be given by the same person that carries out the surgical or diagnostic procedure.

Propofol-Lipuro 0.5 % (5 mg/ml) is intended for use in children, adolescents and adults, especially the pain-sensitive ones, because of the lower pain on injec-tion compared to higher strengths.

Supplementary analgesic medicinal products are generally required in addition to Propofol-Lipuro 0.5 % (5 mg/ml).

Posology

Propofol-Lipuro 0.5 % (5 mg/ml) is given intravenously. The dosage is adjusted individually according to the patient's response.

•    General anaesthesia in adults Induction of anaesthesia:

For induction of anaesthesia Propofol-Lipuro 0.5 % (5 mg/ml) should be titrated (20 -40 mg of propofol every 10 seconds) against the patient's response until the clinical signs show the onset of anaesthesia. Most adult patients younger than 55 years are likely to require 1.5 to 2.5 mg of propofol per kg body weight. Repeat bolus injections may be given according to clinical requirements.

In patients over this age and in patients of ASA grades III and IV, especially those with impaired cardiac function, the dosage requirements will be less and the total propofol dose may be reduced to a minimum of 1 mg/kg body weight. In these patients lower rates of administration should be applied (approximately 4 ml of Propofol-Lipuro 0.5 % (5 mg/ml), corresponding to 20 mg of propofol every 10 seconds).

•    Induction of general anaesthesia in children over 1 month of age

For induction of anaesthesia Propofol-Lipuro 0.5 % (5 mg/ml) should be slowly titrated against the patient's response until the clinical signs show the onset of anaesthesia. The dosage should be adjusted according to age and/or body weight. Most patients over 8 years of age require approximately 2.5 mg of propofol per kg body weight for induction of anaesthesia. In younger children, especially between the age of 1 month and

3    years, dose requirement may be higher (2.5 - 4 mg of propofol per kg body weight). Propofol-Lipuro 0.5 % (5 mg/ml) is contraindicated to be used for maintenance of anaesthesia (see also section 4.3)

For ASA III and IV patients lower doses are recommended (see also section 4.4).

•    Sedation for diagnostic and surgical procedures in adult patients

To provide sedation during surgical and diagnostic procedures, doses and administration rates should be adjusted according to the clinical response. Most patients will require 0.5 - 1 mg of propofol per kg body weight over 1 to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating Propofol-Lipuro 0.5 % (5 mg/ml) to the desired level, using e.g. a syringe pump. Most patients will require 1.5 - 4.5 mg of propofol per kg body weight per hour. Additional boluses of 10 - 20 mg of propofol (2 - 4 ml of Propofol-Lipuro 0.5 % (5 mg/ml)) may be given if a rapid increase of the depth of sedation is required.

In patients older than 55 years and in patients of ASA grade III and IV lower doses of Propofol-Lipuro 0.5 % (5 mg/ml) may be required and the rate of ad-ministration may need to be reduced.

•    Induction of 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 propofol for onset of sedation.

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

Method and duration of administration

•    Method of administration Intravenous use

Propofol-Lipuro 0.5 % (5 mg/ml) is administered intravenously undiluted by injection either or by continuous infusion after dilution with glucose 50 mg/ml (5 % w/v) solution, sodium chloride 9 mg/ml (0.9 % w/v) solution.

Containers should be shaken before use.

Before use, the neck of the ampoule should be cleaned with medicinal alcohol (spray or swabs). After use, tapped containers must be discarded.

Propofol-Lipuro 0.5 % (5 mg/ml) contains no antimicrobial preservatives and supports growth of microorganisms. Therefore, Propofol-Lipuro 0.5 % (5 mg/ml) is to be drawn up aseptically into a sterile syringe immediately after opening the ampoule. Administration must commence without delay. Asepsis must be maintained for both Propofol-Lipuro 0.5 % (5 mg/ml) and administration equipment throughout the entire period of administration.

The contents of one ampoule of Propofol-Lipuro 0.5 % (5 mg/ml) and any syringe containing Propofol-Lipuro 0.5 % (5 mg/ml) are for single use in one patient.

If infusion sets with filters are to be used, these must be lipid-permeable. Administration of undiluted Propofol-Lipuro 0.5 % (5 mg/ml)

When administering Propofol-Lipuro 0.5 % (5 mg/ml) continuously, administration rates should always be controlled by appropriate apparatus, e.g a syringe pump. Any portion of Propofol-Lipuro 0.5 % (5 mg/ml) remaining after the end of administration must be discarded.

Infusion of diluted Propofol-Lipuro 0.5 % (5 mg/ml)

For infusion of diluted Propofol-Lipuro 0.5 % (5 mg/ml), burettes, drop counters, syringe pumps, or volumetric infusion pumps should always be used to control infusion rates and to avoid the risk of accidentally uncontrolled infusion of large volumes of diluted Propofol-Lipuro 0.5 % (5 mg/ml).

The maximum dilution must not exceed 1 part of Propofol-Lipuro 0.5 % (5 mg/ml) with

4    parts of glucose 50 mg/ml (5 % w/v) solution or sodium chloride 9 mg/ml (0.9 % w/v) solution (minimum concentration 1 mg propofol/ml).

For suitable diluents please refer to section 6.6.

The pain on initial injection may be reduced by adding lidocaine to Propofol-Lipuro 0.5 % (5 mg/ml): One part of preservative-free lidocaine injection 10 mg/ml (1 %) may be added to 40 parts of Propofol-Lipuro 0.5 % (5 mg/ml).

Before giving the muscle relaxants atracurium or mivacurium subsequent to Propofol-Lipuro 0.5 % (5 mg/ml) through the same intravenous line, it is recom-mended that the line be rinsed prior to administration.

•    Duration ofadministration

Propofol-Lipuro 0.5 % (5 mg/ml) can be administered for a maximum period of 1 hour.

4.3    Contraindications

Propofol-Lipuro 0.5 % (5 mg/ml) is contraindicated in patients with a known hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to peanut or soya.

Propofol-Lipuro 0.5 % (5 mg/ml) is contraindicated:

•    for maintenance of general anaesthesia

•    for maintenance of sedation for diagnostic and surgical procedures in children

•    for sedation for intensive care

Safety and efficacy for these age groups have not been demonstrated (see section 4.4).

4.4    Special warnings and precautions for use

Propofol should be given by those trained in anaesthesia (or, where appropriate, doctors trained in the care of patients in Intensive Care).

Patients should be constantly monitored and facilities for maintenance of a patient airway, artificial ventilation, oxygen enrichment and other resuscitative facilities should be readily available at all times. Propofol should not be administered by the person conducting the diagnostic or surgical procedure.

The abuse of and dependence on propofol, predominantly by health care professionals, have been reported. As with other general anaesthetics, the administration of propofol without airway care may result in fatal respiratory complications.

When propofol is administered for conscious sedation, for surgical and diagnostic procedures, patients should be continually monitored for early signs of hypotension, airway obstruction and oxygen desaturation.

In case of repeated boli for induction of anaesthesia the maximum fat administration should not exceed 150 mg fat/kg/h which corresponds to 1.5 ml/kg/h of Propofol-Lipuro 0.5 % (5 mg/ml).

As with other sedative agents, when propofol is used for sedation during operative procedures, involuntary patient movements may occur. During procedures requiring immobility these movements may be hazardous to the operative site.

An adequate period is needed prior to discharge of the patient to ensure full recovery after use of propofol. Very rarely the use of propofol may be associated with the development of a period of post-operative unconsciousness, which may be accompanied by an increase in muscle tone. This may or may not be preceded by a period of wakefulness. Although recovery is spontaneous, appropriate care of an unconscious patient should be administered.

Propofol induced impairment is not generally detectable beyond 12 hours. The effects of propofol, the procedure, concomitant medications, the age and the condition of the patient should be considered when advising patients on:

•    The advisability of being accompanied on leaving the place of administration

•    The timing of recommencement of skilled or hazardous tasks such as driving

•    The use of other agents that may sedate (e.g. benzodiazepines, opiates, alcohol.)

As with other intravenous agents, caution should be applied in patients with cardiac, respiratory, renal or hepatic impairment or in hypovolaemic or debilitated patients. Propofol clearance is blood flow dependent, therefore, concomitant medication that reduces cardiac output will also reduce propofol clearance.

Propofol lacks vagolytic activity and has been associated with reports of bradycardia (occasionally profound) and also asystole. The intravenous administra-tion of an anticholinergic agent before induction of anaesthesia should be considered, especially in situations where vagal tone is likely to predominate or when propofol is used in conjunction with other agents likely to cause bradycardia.

When propofol is administered to an epileptic patient, there may be a risk of convulsion.

Appropriate care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsions must be used cautiously.

Paediatric population

The use of propofol is not recommended in newborn infants as this patient population has not been fully investigated. Pharmacokinetic data (see section 5.2) indicate that clearance is considerably reduced in neonates and has a very high inter-individual variability. Relative overdose could occur on administering doses recommended for older children and result in severe cardiovascular depression.

Propofol must not be used in patients of 16 years of age or younger for sedation for intensive care as the safety and efficacy of propofol for sedation in this age group have not been demonstrated (see section 4.3).

Advisory statements concerning Intensive Care Unit management

Use of propofol for ICU sedation has been associated with a constellation of metabolic disturbances and organ system failures that may result in death.

Reports have been received of combinations of the following: Metabolic acidosis, Rhabdomyolysis, Hyperkalaemia, Hepatomegaly, Renal failure, Hyperlipidaemia, Cardiac arrhythmia, Brugada-type ECG (elevated ST-segment and coved T-wave) and rapidly progressive Cardiac failure usually unresponsive to inotropic supportive treatment. Combinations of these events have been referred to as the Propofol infusion syndrome.

These events were mostly seen in patients with serious head injuries and children with respiratory tract infections who received dosages in excess of those advised in adults for sedation in the intensive care unit. The following appear to be the major risk factors for the development of these events: decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; high dosages of one or more of the following pharmacological agents - vasoconstrictors, steroids, inotropes and/or propofol (usually at dose rates greater than 4 mg/kg/h for more than 48 hours).

Prescribers should be alert to these events in patients with the above risk factors and promptly consider decreasing or stopping the propofol dosage when the above signs develop. All sedative and therapeutic agents used in the intensive care unit (ICU), should be titrated to maintain optimal oxygen delivery and haemodynamic parameters. Patients with raised intra-cranial pressure (ICP) should be given appropriate treatment to support the cerebral perfusion pressure during these treatment modifications. Treating physicians are reminded if possible not to exceed the dosage of 4 mg/kg/h. Appropriate care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsions must be used cautiously.

It is recommended that blood lipid levels should be monitored if propofol is administered to patients thought to be at particular risk of fat overload. Administration of propofol 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 propofol formulation; 1.0 ml of Propofol-Lipuro contains approximately 0.1 g of fat.

Additional precautions

Caution should be taken when treating patients with mitochondrial disease. These patients may be susceptible to exacerbations of their disorder when undergoing anaesthesia, surgery and ICU care. Maintenance of normothermia, provision of carbohydrates and good hydration are recommended for such patients. The early presentations of mitochondrial disease exacerbation and of the 'propofol infusion syndrome' may be similar.

Propofol-Lipuro 0.5 % (5 mg/ml) contains no antimicrobial preservatives and supports growth of micro-organisms.

When propofol is to be aspirated, it 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 propofol and infusion equipment throughout the infusion period. Any infusion fluids added to the propofol line must be administered close to the cannula site. If infusion sets with filters are to be used, these must be lipid-permeable.

Propofol and any syringe containing propofol are for single use in an individual patient. In accordance with established guidelines for other lipid emulsions, a single infusion of propofol must not exceed 12 hours. At the end of the procedure or at 12 hours, whichever is the sooner, both the reservoir of propofol and the infusion line must be discarded and replaced as appropriate.

This medicinal product contains less than 1 mmol (23 mg) sodium in 20 ml, i.e. essentially 'sodium free'.

4.5    I nteraction with other medicinal products and other forms of interaction

Propofol has been used in association with spinal and epidural anaesthesia and with commonly used premedicants, neuromuscular blocking drugs, inhalational agents and analgesic agents; no pharmacological incompatibility has been encountered. Lower doses of propofol may be required where general anaesthesia or sedation is used as an adjunct to regional anaesthetic techniques.

Profound hypotension has been reported following anaesthetic induction with propofol in patients treated with rifampicin.

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Format = 210 x 745 mm 2 Seiten

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918/12610266/0216 GIF (L06)

Production site: Berlin

Font size: 9,0 pt.

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Propofol-Lipuro 0.5 % (5 mg/ml)

emulsion for injection or infusion

Propofol

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist.

•    If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

•    See Section 4.

What is in this leaflet

1.    What Propofol-Lipuro 0.5 % (5 mg/ml) is and what it is used for

2.    What you need to know before you use Propofol-Lipuro 0.5 % (5 mg/ml)

3.    How to use Propofol-Lipuro 0.5 % (5 mg/ml)

4.    Possible side effects

5.    How to store Propofol-Lipuro 0.5 % (5 mg/ml)

6.    Contents of the pack and other information

1.    What Propofol-Lipuro 0.5 % (5 mg/ml) is and what it

is used for_

Propofol-Lipuro 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

•    i nduce general anaesthesia in adults and children > 1 month

•    i nduce sedation in adults and children > 1 month during diagnostic and surgical procedures,.

•    sedate adult patients > 16 years of age during diagnostic and surgical procedures for a short time, alone or in combination with local or regional anaesthesia

2.    What you need to know before you use Propofol-Li-

puro 0.5 % (5 mg/ml)_

Do not use Propofol-Lipuro 0.5 % (5 mg/ml)

•    i f you are allergic (hypersensitive) to propofol, soya, peanut or any of the other ingredients of this medicine (listed in section 6).

•    for maintenance of general anaesthesia or of sedation for diagnostic and surgical procedures in children

•    for sedation during intensive care.

Warnings and precautions

Special care has to be taken

•    i f you have serious head injuries,

•    i f you have a mitochondrial disease,

•    i f you have a disorder in which your body does not handle fat properly,

•    i f you have any other health problems which require much caution in the use of fat emulsions,

•    i f your blood volume is too low (hypovolaemia),

•    i f you are very weak (debilitated) or have heart, kidney or liver problems,

•    i f you have high pressure within in the skull,

•    i f you have problems with your breathing,

•    i f you have epilepsy,

•    i f you are undergoing some procedures where spontaneous movements are particularly undesirable.

Please tell your doctor if you have one of these diseases or conditions.

If you are receiving other lipids by a drip into your vein at the same time your doctor will pay attention to your total daily fat intake.

Propofol will be administered to you by a physician trained in anaesthesia or intensive care. You will be constantly monitored during anaesthesia and waking-up time.

If you experience signs of the so called 'propofol infusion syndrome' (for a detailed list of the symptoms see section 4 'Possible side effects', a doctor must be called if the following happen') your doctor will decrease or stop the dosage of propofol.

Please see also section 'Driving and using machines' for precautions to be taken after the use of propofol.

Children and adolescents

The use of Propofol-Lipuro 0.5 % (5 mg/ml) is not recommended in newborn infants Other medicines and Propofol-Lipuro 0.5 % (5 mg/ml)

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines.

Propofol has effectively been used with different regional anaesthesia techniques that only numb a part of your body (epidural and spinal anaesthesia).

Additionally, safe use has been demonstrated in combination with

•    drugs you receive before surgery

•    other medicines like muscle relaxing drugs

•    anaesthetic drugs that can be inhaled

•    pain killers.

However your physician may give you lower doses of propofol if general anaesthesia or sedation is needed as a supplement to regional anaesthesia techniques.

Special care will also be taken if you receive in parallel an antibiotic containing rifampicin - you may develop profound low blood pressure.

Propofol-Lipuro 0.5 % (5 mg/ml) and alcohol

Your doctor will advise you on the consumption of alcohol before and after the use of Propofol-Lipuro.

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 or pharmacist for advice before taking this medicine.

Propofol-Lipuro 0.5 % (5 mg/ml) should not be used during pregnancy unless it is definitely needed. It crosses the placenta and may depress the vital functions of the newborn.

However, propofol may be used during an induced abortion.

If you are breast-feeding your child you should stop nursing and discard breast milk for 24 hours after you have received Propofol-Lipuro 0.5 % (5 mg/ml). Studies in breast-feeding women showed that propofol is excreted in small amounts into the milk.

Driving and using machines

You should not drive or operate machinery for a while after you have an injection or infusion of Propofol-Lipuro..

Your doctor will advise you

•    i f you should be accompanied when you are leaving.

•    when you can drive and use machinery again.

•    on the use of other tranquillizing drugs (e.g. tranquillizers, strong pain killers, alcohol).

Propofol-Lipuro 0.5 % (5 mg/ml) contains sodium and soya-bean oil

This medicinal product contains less than 1 mmol (23 mg) sodium in 20 ml, that is, it is essentially 'sodium free'.

Propofol-Lipuro 0.5 % (5 mg/ml) contains soya-bean oil. If you are allergic to peanut or soya, do not use this medicine.

3. How to use Propofol-Lipuro 0.5 % (5 mg/ml)_

Propofol-Lipuro 0.5 % (5 mg/ml) will only be given by anaesthetists or by specially trained doctors in an intensive care unit.

Dosage

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 anaesthesia or to achieve the required level of sedation, by carefully watching your responses and vital signs (pulse, blood pressure, breathing, etc). The doctor will also observe the limits of the time of application, if necessary.

Propofol-Lipuro 0.5 % (5 mg/ml) will usually be given by injection when used to induce general anaesthesia. When used as a sedative it will usually be administered slowly and continuously by infusion using an appropriate apparatus. When given as an infusion it will be diluted in advance.

Propofol-Lipuro 0.5 % (5 mg/ml) will only be given for a maximum of 1 hour.

918/12610266/0216

Propofol-Lipuro 0.5 % (5 mg/ml)

emulsion for injection or infusion

Propofol

BlBRAUN

B. Braun Melsungen AG

34209 Melsungen Germany

Table of Adverse Drug Reactions

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Propofol-Lipuro 0.5 % (5 mg/ml):

Propofol-Lipuro 5 mg/ml:

Propofol "B. Braun" 5 mg/ml: Propofol-Lipuro 5 mg/ml:

Propofol-Lipuro 5 mg/ml Emulsion zur Injektion oder Infusion: