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PROPOFOL-LIPURO 0.5% (5MG/ML) EMULSION FOR INJECTION OR INFUSION

Active substance(s): PROPOFOL

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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 PropofolLipuro 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 PropofolLipuro 0.5 % (5 mg/ml) through the same intravenous line, it is recom-mended that the
line be rinsed prior to administration.
• Duration of administration
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 PropofolLipuro 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 Interaction 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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Production site: Berlin

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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.
2.
3.
4.
5.
6.

What Propofol-Lipuro 0.5 % (5 mg/ml) is and what it is used for
What you need to know before you use Propofol-Lipuro 0.5 % (5 mg/ml)
How to use Propofol-Lipuro 0.5 % (5 mg/ml)
Possible side effects
How to store Propofol-Lipuro 0.5 % (5 mg/ml)
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
• induce general anaesthesia in adults and children > 1 month
• induce 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-Lipuro 0.5 % (5 mg/ml)
Do not use Propofol-Lipuro 0.5 % (5 mg/ml)
• if 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
• if you have serious head injuries,
• if you have a mitochondrial disease,
• if you have a disorder in which your body does not handle fat properly,
• if you have any other health problems which require much caution in the use
of fat emulsions,
• if your blood volume is too low (hypovolaemia),
• if you are very weak (debilitated) or have heart, kidney or liver problems,
• if you have high pressure within in the skull,
• if you have problems with your breathing,
• if you have epilepsy,
• if 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 wakingup 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.

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
• if 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

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).

12610266_Propofol0,5_GIF-L06__GB-IE.indd 1

B|BRAUN
B. Braun Melsungen AG
34209 Melsungen
Germany

29.02.16 15:02

4.6 Fertility, pregnancy and lactation
Pregnancy
The safety of propofol during pregnancy has not been established. Propofol should not
be given to pregnant woman except when absolutely necessary. Propofol crosses the
placenta and can cause neonatal depression. Propofol can however be used during
induced abortion.
Breast-feeding
Studies of breast-feeding mothers showed that small quantities of propofol are excreted in human milk. Women should therefore not breastfeed for 24 hours after administration of propofol. Milk produced during this period should be discarded.
4.7 Effects on ability to drive and use machines
Patients should be advised that performance at skilled tasks, such as driving and operating machinery, may be impaired for some time after use of propofol.
Propofol induced impairment is not generally detectable beyond 12 hours (please see
section 4.4).
4.8 Undesirable effects
Induction and maintenance of anaesthesia or sedation with propofol is generally
smooth with minimal evidence of excitation. The most commonly reported ADR are
pharmacologically predictable side effects of an anaesthetic/sedative agent, such as
hypotension. The nature, severity and incidence of adverse events observed in patients
receiving propofol may be related to the condition of the recipients and the operative
or therapeutic procedures being undertaken.
Table of Adverse Drug Reactions
System Organ Class
Immune system
disorders:

Frequency
Very rare
(<1/10 000)

Metabolism and
Nutritional disorder:

Frequency not known (9)

Psychiatric disorders:

Frequency not known (9)

Nervous system disorders:

Common
(>1/100, <1/10)
Rare
(>1/10 000, <1/1000)

Cardiac disorders:

Vascular disorders:

Respiratory, thoracic
and mediastinal
disorders:
Gastrointestinal
disorders:

Hepatobiliary disorders
Musculoskeletal and
connective tissue
disorders:
Renal and urinary
disorders

Very rare
(<1/10 000)
Frequency not known (9)
Common
(>1/100, <1/10)
Very rare
(<1/10 000)
Frequency not
known (9)
Common
(>1/100, <1/10)
Uncommon
(>1/1000, <1/100)
Common
(>1/100, <1/10)
Frequency not
known (9)
Common
(>1/100, <1/10)
Very rare
(<1/10 000)

Undesirable Effects
Anaphylaxis – may include
angioedema, bronchospasm,
erythema and hypotension
Metabolic acidosis (5),
hyperkalaemia (5),
hyperlipidaemia (5)
Euphoric mood, drug abuse
and drug dependence(8)
Headache during
recovery phase
Epileptiform movements,
including convulsions and
opisthotonus during induction, maintenance and
recovery
Postoperative
unconsciousness
Involuntary movements
Bradycardia (1)
Pulmonary oedema
Cardiac arrhythmia (5),
cardiac failure (5), (7)
Hypotension (2)
Injection site thrombosis
and phlebitis
Transient apnoea during
induction
Respiratory depression
(dose-dependent)
Nausea and vomiting during recovery phase
Pancreatitis

Frequency not known (9)
Frequency not known (9)

Hepatomegaly (5)
Rhabdomyolysis (3), (5)

Very rare
(<1/10 000)

Discolouration of urine
following prolonged administration
Renal failure (5)
Sexual disinhibition

Frequency not known (9)
Reproductive system and Very rare
breast
(<1/10 000)
General disorders and
Very common
administration site
(>1/10)
conditions:
Very rare
(<1/10 000)
Frequency not known (9)

Local pain on induction (4)
Tissue necrosis(10) following
accidental extravascular
administration
Local pain, swelling, following accidental extravascular administration
Brugada type ECG (5), (6)
Postoperative fever

Investigations
Frequency not known (9)
Injury, poisoning and
Very rare
procedural complica(<1/10 000)
tions:
(1)
Serious bradycardias are rare. There have been isolated reports of progression to
asystole.
(2)
Occasionally, hypotension may require use of intravenous fluids and reduction of
the administration rate of propofol.
(3)
Very rare reports of rhabdomyolysis have been received where propofol has been
given at doses greater than 4 mg/kg/hr for ICU sedation.
(4)
May be minimised by using the larger veins of the forearm and antecubital fossa.
With Propofol-Lipuro 0.5 % (5 mg/ml) local pain can also be minimised by the
co-administration of lidocaine.
(5)
Combinations of these events, reported as “Propofol infusion syndrome”, may be
seen in seriously ill patients who often have multiple risk factors for the development of the events, see section 4.4.
(6)
Brugada-type ECG - elevated ST-segment and coved T-wave in ECG.
(7)
Rapidly progressive cardiac failure (in some cases with fatal outcome) in adults.
The cardiac failure in such cases was usually unresponsive to inotropic supportive
treatment.
(8)
Abuse of and drug dependence on propofol, predominantly by health care professionals.
(9)
Not known as it cannot be estimated from the available clinical trial data.
(10)
Necrosis has been reported where tissue viability has been impaired.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the following:
United Kingdom
- Yellow card scheme:
www.mhra.gov.uk/yellowcard
Ireland
HPRA Pharmacovigilance
Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Website: www.hpra.ie
e-mail: medsafety@hpra.ie
4.9 Overdose
Accidental overdose is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression
may require lowering the patient’s head and, if severe, use of plasma expanders and
pressor agents.

5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmaco-therapeutic group: other general anaesthetics, ATC-code N01AX10.
Mechanism of action, pharmacodynamic effect
After intravenous injection of Propofol-Lipuro 0.5 % (5 mg/ml), onset of the hypnotic
effect occurs rapidly. Depending on the rate of injection, the time to induction of anaesthesia is between 30 and 40 seconds. The duration of action after a single bolus
administration is short due to the rapid metabolism and excretion (4 – 6 minutes).
With the recommended dosage schedule, a clinically relevant accumulation of propofol
after repeated bolus injection has not been observed.
Patients recover consciousness rapidly.
Bradycardia and hypotension occasionally occur during induction of anaesthesia probably due to a lack of vagolytic activity. The cardio-circulatory situation usually normalises during maintenance of anaesthesia.
The rationale for development of propofol-Lipuro 0.5% (5 mg/ml) was the the reduction of pain at the injection site; this was clearly demonstrated in a clinical study in
children.
The reduction of pain, in adults, was demonstrated in a clinical study and was only
extrapolated from the data in children.
The formulation of propofol in a mixed medium- and long-chain triglyceride emulsion leads to lower concentrations of free propofol in the aqueous phase compared to
pure long-chain triglyceride emulsions. This difference may explain the reduced pain
frequency and intensity observed with Propofol-Lipuro formulations in comparative
clinical studies, especially with Propofol-Lipuro 0.5 % (5 mg/ml) due to the very low
concentration of free propofol.
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
Distribution
After intravenous administration about 98 % of propofol is bound to plasma protein.
After intravenous bolus administration the initial blood level of propofol declines rapidly due to rapid distribution into different compartments (a-phase). The distribution
half-life has been calculated as 2 – 4 minutes.
During elimination the decline of blood levels is slower. The elimination half-life during the b-phase is in the range of 30 to 60 minutes. Subsequently a third deep compartment becomes apparent, representing the re-distribution of propofol from weakly
perfused tissue.
The central volume of distribution is in the range of 0.2 – 0.79 l/kg body weight, the
steady-state volume of distribution in the range of 1.8 – 5.3 l/kg body weight.
Biotransformation
Propofol is mainly metabolized in the liver to form glucuronides of propofol and glucuronides and sulphate conjugates of its corresponding quinol. All metabolites are
inactive.
Elimination
Propofol is rapidly cleared from the body (total clearance approx. 2 l/min). Clearance
occurs by metabolism, mainly in the liver, where it is blood flow dependent. Clearance
is higher in children compared with adults. About 88 % of an administered dose is
excreted in the form of metabolites in urine. Only 0.3 % is excreted unchanged in urine.
Paediatric population
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.
Median propofol clearance in older aged children after a single 3 mg/kg bolus was
37.5 ml/min/kg (4 – 24 months) (n=8), 38.7 ml/min/kg (11 – 43 months) (n=6), 48 ml/
min/kg (1 – 3 years)(n = 12), 28.2 ml/min/kg (4 – 7 years)(n = 10) as compared with
23.6 ml/min/kg in adults (n=6).
5.3 Preclinical safety data
Preclinical data reveal no specific hazard for humans based on conventional studies on repeated dose toxicity or genotoxicity. Carcinogenicity studies have not been
conducted.
Reproductive toxicity studies have shown effects related to pharmacodynamic properties of propofol only at high doses. Teratogenic effects have not been observed.
In local tolerance studies, intramuscular injection resulted in tissue damage around
the injection site.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Soya-bean oil refined,
medium-chain triglycerides,
glycerol,
egg lecithin,
sodium oleate,
water for injections.
6.2 Incompatibilities
This medicinal product must not be mixed with other products except those mentioned
in section section 6.6.
6.3 Shelf life
2 years.
After first opening: to be used immediately.
After dilution according to directions: administration of dilutions must commence
immediately after preparation.
6.4 Special Precautions for Storage
Do not store above 25 °C.
Do not freeze.
6.5 Nature and contents of container
This medicinal product is supplied in glass ampoules of 20 ml
Glass ampoules are made of colourless glass (type I) according to Pharm. Eur.
Pack sizes:
Glass ampoules: 5 x 20 ml
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Any unused product or waste material should be disposed of in accordance with local
requirements.
Containers should be shaken before use.
For single use in one patient only. Any portion of contents remaining after use must
be discarded.
If two layers can be seen after shaking the product should not be used.
Propofol-Lipuro 0.5 % (5 mg/ml) should only be mixed with the following products:
glucose 50 mg/ml (5 % w/v)solution, sodium chloride 9 mg/ml (0.9 % w/v) solution and
preservative-free lidocaine injection 10 mg/ml (1 %) (refer to section 4.2, subsection
“Infusion of diluted Propofol-Lipuro 0.5 % (5 mg/ml)”)
Co-administration of Propofol-Lipuro 0.5 % (5 mg/ml) together with glucose 50 mg/ml
(5% w/v) solution or sodium chloride 9 mg/ml (0.9 % w/v) solution via a Y-connector
close to the injection site is possible.
7. MARKETING AUTHORISATION HOLDER
B. Braun Melsungen AG
Carl-Braun-Strasse 1
Postal address:
34212 Melsungen, Germany
34209 Melsungen, Germany
Phone: +49/5661/71-0
Fax: +49/5661/71-4567
8. MARKETING AUTHORISATION NUMBER
PA0736/018/004 (Ireland)
PL03551/0113 (United Kingdom)
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation:
21st July 2008 (Ireland)
20th August 2008 (United Kingdom)
Date of latest Renewal:
5th June 2013
10. DATE OF REVISION OF THE TEXT
February 2016

--✁----------✁----------✁----------✁----------✁----------✁--------✁----------✁----------✁----------✁----------✁----------✁----------✁----------✁-----Method of administration
You will receive Propofol-Lipuro 0.5 % (5 mg/ml) by intravenous injection or infusion, that is, through a needle or small tube placed in one of your veins.
Your circulation and breathing will be constantly monitored while you are being
given the injection or the infusion.

If you received more Propofol-Lipuro 0.5 % (5 mg/ml) than you should
It is unlikely that this occurs because the doses you receive are very carefully
controlled.
Yet if you accidentally got an overdose, this could lead to depression of heart
function and breathing. In this case your doctor will employ any necessary treatment immediately.
If you have any further questions on the use of this product, ask your doctor or
pharmacist.

4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody
gets them.

A doctor must be called immediately if the following happen
Common (may affect up to 1 in 10 people):
• Low blood pressure that might occasionally need infusion of fluids and reduction of the speed of administration of propofol.
• Too low heartbeat that might be serious in rare cases.
Rare (may affect up to 1 in 1,000 people):
• Convulsions like in epilepsy
Very rare: (may affect up to 1 in 10,000 people)
• Allergic reactions including swelling of the face, tongue or throat, wheezing
breath, skin redness and low blood pressure
• There have been cases of unconsciousness occurring after operations. You will
therefore be carefully observed during the waking-up time.
• Water on the lungs (lung oedema) after administration of propofol
• Inflammation of the pancreas
Not known (frequency cannot be estimated from the available data):
• There have been reports of isolated cases of severe adverse reactions presenting as
a combination of the following symptoms: breakdown of muscle tissue, accumulation of acidic (sour) substances in the blood, abnormally high blood potassium
level, high blood fat levels, abnormalities in the electrocardiogram (Brugada-type
ECG), liver enlargement, irregular heart-beat, kidney failure and heart failure. This
has been called the “propofol infusion syndrome”. Some of the affected patients
eventually died. These effects have only been seen in patients in intensive care with
doses higher than 4 mg of propofol per kg body weight per hour. See also section 2,
‘Warnings and precautions’.

Other side effects are:
Very common (affects more than 1 treated patient of 10):
• Pain at the injection site occurring during the first injection. The pain may be
reduced by injecting propofol into larger veins of the forearm. Injection of lidocaine (a local anaesthetic) and propofol at the same time also helps to reduce
the pain at the injection site.
Common (may affect up to 1 in 10 people):
• Short interruption of breathing
• Headache during the time of recovery
• Sickness or vomiting during the time of recovery
Uncommon (may affect up to 1 in 100 people):
• Blood clots in veins or inflammation of veins at the injection site
Very rare (may affect up to 1 in 10,000 people)
• Loss of sexual control during the time of recovery
• Abnormal colour of urine after longer lasting administration of propofol
• Cases of fever after an operation
• Tissue damage after the medicine was accidentally injected outside of a vein

Not known (frequency cannot be estimated from the available data):
• Involuntary movements
• Abnormally good mood
• Drug abuse and drug dependence
• Failure of the heart
• Shallow breathing
• Pain and/or swelling at the injection site after the medicine was accidentally
injected outside of a vein
• Breakdown of muscle tissue has been reported very rarely in cases where
propofol has been given at greater doses than recommended for sedation in
intensive care units
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any
possible side effects not listed in this leaflet. You can also report side effects
directly (see details below). By reporting side effects you can help provide more
information on the safety of this medicine.
United Kingdom:
- to the Medicines and Healthcare Products Regulatory Agency via the yellow
card scheme:
www.mhra.gov.uk/yellowcard
Ireland:
HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2;
Tel: +353 1 6764971; Fax: +353 1 6762517.
Website: www.hpra.ie; e-mail: medsafety@hpra.ie

5. How to store Propofol-Lipuro 0.5 % (5 mg/ml)
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 label and the
carton after EXP. The expiry date refers to the last day of that month.
Do not store above 25°C. Do not freeze.
Propofol-Lipuro 0.5 % (5 mg/ml) must be used immediately after opening/dilution.
Do not use Propofol-Lipuro 0.5 % (5 mg/ml) if two separate layers can be seen
after shaking the ampoule.
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 Propofol-Lipuro 0.5 % (5 mg/ml) contains
• The active substance is propofol.
Each millilitre of Propofol-Lipuro 0.5 % (5 mg/ml) contains 5 mg of propofol.
1 ampoule of 20 ml contains 100 mg propofol.
• The other ingredients are:
Soya-bean oil, refined,
Medium-chain triglycerides,
Egg lecithin,
Glycerol,
Sodium oleate,
Water for injections.

What Propofol-Lipuro 0.5 % (5 mg/ml) looks like and contents of
the pack
It is an emulsion for injection or infusion.
It is a milky-white oil-in water emulsion.
It comes in glass ampoules of 20 millilitres, available in packs of 5 ampoules.

Marketing Authorisation Holder and Manufacturer
B. Braun Melsungen AG
Carl-Braun-Straße 1
Postal address:
34212 Melsungen, Germany
34209 Melsungen, Germany
Phone: +49/5661/71-0, Fax: +49/5661/71-4567

This medicinal product is authorised in the Member States of the EEA
under the following names:
Propofol-Lipuro 0.5 % (5 mg/ml):
Propofol-Lipuro 5 mg/ml:
Propofol “B. Braun” 5 mg/ml:
Propofol-Lipuro 5 mg/ml:

Czech Republic, Spain, Ireland,
Portugal, Slovakia, United Kingdom
Italy
Denmark
Finland, France, Hungary, Norway,
Poland, Sweden

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

Austria, Germany, Luxembourg.

This leaflet was last revised in February 2016.
The following information is intended for healthcare professionals only:
The containers are for single use in one patient only.
Any unused emulsion must be thrown away at the end of administration.
The containers must be shaken before use.
For complete information on this medicinal product please refer to the summary
of product characteristics.

12610266_Propofol0,5_GIF-L06__GB-IE.indd 2

29.02.16 15:02

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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