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PROPOFOL--LIPURO 2% (20MG/ML).

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599/12608212/1011

SUMMARY OF PRODUCT CHARACTERISTICS
B. Braun Melsungen AG · 34209 Melsungen, Germany

1  Name of the Medicinal Product

Propofol-Lipuro 2 %
(20 mg/ml)
emulsion for injection or infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml emulsion for injection or infusion contains
Propofol
20 mg
One vial of 50 ml contains
1000 mg Propofol
Excipients with known effect:
1 ml emulsion for injection or infusion 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 2 % (20 mg/ml) is a short-acting intravenous general
anaesthetic for
• nduction and maintenance of general anaesthesia in adults and chili
dren > 3 years
•  edation of ventilated patients >16 years of age in the intensive care
s
unit
•  edation for diagnostic and surgical procedures, alone or in combinas
tion with local or regional anaesthesia in adults and children > 3 years.
4.2 Posology and method of administration
General instructions
Propofol-Lipuro 2 % (20 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 patent airways, artificial ventilation, and
other resuscitation facilities should be immediately available at all times.
For sedation during surgical or diagnostic procedures Propofol-Lipuro
2 % (20 mg/ml) should not be given by the same person that carries out
the surgical or diagnostic procedure.
Supplementary analgesic medicinal products are generally required in
addition to Propofol-Lipuro 2 % (20 mg/ml).
Posology
Propofol-Lipuro 2 % (20 mg/ml) is given intravenously. The dosage is
adjusted individually according to the patient’s response.
•  eneral anaesthesia in adults
G
Induction of anaesthesia:
For induction of anaesthesia Propofol-Lipuro 2 % (20 mg/ml) should be
titrated (20 – 40 mg 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/
kg body weight.
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 dose of Propofol-Lipuro 2 % (20 mg/ml) may be
reduced to 1 mg/kg body weight or less. In these patients lower rates of
administration should be applied (approximately 1 ml corresponding to
20 mg every 10 seconds).
Maintenance of anaesthesia:
Anaesthesia is maintained by administering Propofol-Lipuro 2 % (20 mg/
ml) by continuous infusion. The dosage requirements usually are in the
range of 4 – 12 mg/kg body weight/h.
In elderly patients, in patients of poor general condition, in patients of
ASA grade III and IV and in hypovolaemic patients the dosage may have
to be reduced further depending on the severity of the patient´s condition and on the performed anaesthetic technique.
•  eneral anaesthesia in children over 3 years of age
G
Induction of anaesthesia:
For induction of anaesthesia Propofol-Lipuro 2 % (20 mg/ml) should be
slowly titrated 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/kg body
weight of propofol for induction of anaesthesia. In younger children, especially between the age of 1 month and 3 years, the dose requirements
may be higher (2.5 – 4 mg/kg body weight).
Maintenance of general anaesthesia:
Anaesthesia can be maintained by administering Propofol Lipuro 20 mg/
ml by infusion to maintain the depth of anaesthesia required. The required rate of administration varies considerably between patients but
rates in the region of 9 – 15 mg/kg/h usually achieve satisfactory anaesthesia. In younger children, especially between the age of 1 month and 3
years, dose requirements may be higher.
For ASA III and IV patients lower doses are recommended (see also section 4.4)
•  edation of ventilated patients in the intensive care unit
S
For sedation during intensive care, it is advised that Propofol-Lipuro 2 %
(20 mg/ml) should be administered by continuous infusion. The infusion
rate should be determined by the desired depth of sedation. In most patients sufficient sedation can be obtained with a dosage of 0.3 – 4.0 mg
of propofol per kg body weight per hour (see section 4.4).
Propofol is not indicated for sedation of patients of 16 years or younger
in intensive care (see section 4.3). Administration of propofol by Target
Controlled Infusion (TCI) system is not advised for sedation in the intensive care unit.
•  edation for diagnostic and surgical procedures in adults
S
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/kg body weight over 1
to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating Propofol-Lipuro 2 % (20 mg/ml) infusion to the
desired level of sedation. Most patients will require 1.5 – 4.5 mg/kg body
weight/h.
In patients older than 55 years and in patients of ASA grade III and IV
lower doses of Propofol-Lipuro 2 % (20 mg/ml) may be required and the
rate of administration may need to be reduced.
According to required dose, alternatively Propofol 1 % (10 mg/ml) may
be used.
•  edation for diagnostic and surgical procedures in children over 3 years
S
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.
Maintenance of sedation may be accomplished by titrating of propofol
infusion to the desired level of sedation. Most patients require 1.5 – 9
mg/kg/h of propofol.
In ASA III and IV patients lower doses may be required.
Method and duration of administration
M
•  ethod of administration
Intravenous use
Propofol-Lipuro 2 % (20 mg/ml) is administered undiluted intravenously.
Containers should be shaken before use.
Before use, the surface of the rubber stopper of the vial should be
cleaned with medicinal alcohol (spray or swabs). After use, tapped containers must be discarded.
Propofol-Lipuro 2 % (20 mg/ml) contains no antimicrobial preservatives
and supports growth of microorganisms. Therefore, Propofol-Lipuro 2 %
(20 mg/ml) is to be drawn up aseptically into a sterile syringe or an infusion set immediately after breaking the vial seal. Administration must
commence without delay. Asepsis must be maintained for both PropofolLipuro 2 % (20 mg/ml) and the infusion equipment throughout the infusion period.
Any medicinal products or fluids added to a running Propofol-Lipuro
2 % (20 mg/ml) infusion must be administered close to the cannula site.
Propofol-Lipuro 2 % (20 mg/ml) must not be administered via infusion
sets with microbiological filters.

The contents of one vial of Propofol-Lipuro 2 % (20 mg/ml) and any
syringe containing Propofol-Lipuro 2 % (20 mg/ml) are for single use
in one patient. Any portion of the contents remaining after use must be
discarded.
For administration of Propofol-Lipuro 2 % (20 mg/ml) by continuous infusion, it is recommended that burettes, drop counters, syringe pumps or
volumetric infusion pumps should always be used to control the infusion
rates. As established for the parenteral administration of all kinds of fat
emulsions, the duration of continuous infusion of Propofol-Lipuro 2 %
(20 mg/ml) from one infusion system must not exceed 12 hours. The
infusion line and the reservoir of Propofol-Lipuro 2 % (20 mg/ml) must
be discarded and replaced after 12 hours at the latest. Any portion of
Propofol-Lipuro 2 % (20 mg/ml) remaining after the end of infusion or
after replacement of the infusion system must be discarded.
This medicinal product must not be mixed with other medicinal products
except those mentioned in section 6.6.
In order to reduce pain on initial injection of Propofol-Lipuro 2 % (20
mg/ml) for induction of general anaesthesia, lidocaine may be injected
immediately prior to the injection of Propofol-Lipuro 2 % (20 mg/ml).
Before giving the muscle relaxants atracurium or mivacurium subsequent to Propofol-Lipuro 2 % (20 mg/ml) through the same intravenous
line, the line should be rinsed prior to administration.
Propofol may also be used by Target Controlled Infusion. Due to the different algorithms available on the market for dosage recommendations
please refer to the instructions for use leaflet of the device manufacturer.
•  uration of administration
D
Propofol-Lipuro 2 % (20 mg/ml) can be administered for a maximum
period of 7 days.
4.3 Contraindications
Propofol-Lipuro 2 % (20 mg/ml) is contraindicated in patients with a
known hypersensitivity to propofol or any of the excipients.
Propofol-Lipuro 2 % (20 mg/ml) contains soya-bean oil and should not
be used in patients who are hypersensitive to peanut or soya.
Propofol-Lipuro 2 % (20 mg/ml) must not be used in patients of 16 years
of age or younger for sedation for intensive care.
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 patent 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 propofol, predominantly by health care professionals, has
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.
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:
•  he advisability of being accompanied on leaving the place of adminT
istration
T
•  he timing of recommencement of skilled or hazardous tasks such as
driving
•  he use of other agents that may sedate (e.g. benzodiazepines, opiates,
T
alcohol.)
As with other intravenous anaesthetic 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
administration of an anticholinergic agent before induction or during
maintenance 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.
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 2 % (20 mg/ml) contains 0.1 g of fat.
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-Lipuro 2 % (20 mg/ml) is not recommended for use in children
< 3 years of age due to difficulty in titrating small volumes.
Advisory statements concerning Intensive Care Unit management
The safety and efficacy of propofol for (background) sedation in children
younger than 16 years of age have not been demonstrated. Although no
causal relationship has been established, serious undesirable effects with
(background) sedation in patients younger than 16 years of age (including cases with fatal outcome) have been reported during unlicensed use.
In particular these effects concerned occurrence of metabolic acidosis,
hyperlipidemia, rhabdomyolysis and/ or cardiac failure. These effects
were most frequently seen in children with respiratory tract infections
who received dosages in excess of those advised in adults for sedation
in intensive care unit.
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 (in some cases
with fatal outcome) in adults. Combinations of these events have been
referred to as the Propofol infusion syndrome.
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 following extended dosing at dose rates greater than 4 mg/kg/h).
Prescribers should be alert to these events and consider decreasing the
propofol dosage or switching to an alternative sedative at the first sign
of occurrence of symptoms. All sedative and therapeutic agents used
in the intensive care unit (ICU), including propofol, should be titrated
to maintain optimal oxygen delivery and haemodynamic parameters.
P
­ atients 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.

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Propofol-Lipuro 2 % (20 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

What is in this leaflet

Propofol-Lipuro 2 % (20 mg/ml) and alcohol

1. What Propofol-Lipuro 2 % (20 mg/ml) is and what it is used for
2.  hat you need to know before you use Propofol-Lipuro 2 % (20 mg/ml)
W
3. How to use Propofol-Lipuro 2 % (20 mg/ml)
4. Possible side effects
5. How to store Propofol-Lipuro 2 % (20 mg/ml)
6. Contents of the pack and other information

Your doctor will advise you on the consumption of alcohol before and
after the use of Propofol-Lipuro 2 % (20 mg/ml).

1. What Propofol-Lipuro 2 % (20 mg/ml) is and
what it is used for
Propofol-Lipuro 2 % (20 mg/ml) 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-Lipuro 2 % (20 mg/ml) is used to:
• nduce and maintain general anaesthesia in adults and children > 3
i
years
•  edate patients > 16 years of age receiving artificial respiration in ins
tensive care
•  edate adults and children > 3 years during diagnostic and surgical
s
procedures, alone or in combination with local or regional anaesthesia.

2. What you need to know before you use PropofolLipuro 2 % (20 mg/ml)
Do not use Propofol-Lipuro 2 % (20 mg/ml):
• f you are allergic (hypersensitive) to propofol, soya peanut or any of
i
the other ingredients of this medicine (listed in section 6).
It must not be used in patients of 16 years of age or younger for sedation
during intensive care.

Warnings and precautions
Special care has to be taken
• 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
i
use of fat emulsions,
• 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
i
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
the dosage of propofol or will switch to an alternative drug.
Please see also section ‘Driving and using machines’ for precautions to be
taken after the use of propfol.
The use of Propofol-Lipuro is not recommended in children < 3 years of age.

Other medicines and Propofol-Lipuro 2 % (20 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
•  rugs you receive before surgery
d
•  ther medicines like muscle relaxing drugs
o
•  naesthetic drugs that can be inhaled
a
•  ain killers.
p
However your physician may give you lower doses of propofol if general
anaesthesia or sedation is needed as a supplement to regional anaesthesia techniques.

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 2 % (20 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 2 %
(20 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 had
an injection or infusion of Propofol-Lipuro 2 % (20 mg/ml).
Your doctor will advise you
• f you should be accompanied when you are leaving.
i
•  hen you can drive and use machinery again.
w
•  n the use of other tranquillizing drugs (e.g. tranquillizers, strong pain
o
killers, alcohol).

Propofol-Lipuro 2 % (20 mg/ml) contains sodium and soya-bean
oil
This medicinal product contains less than 1 mmol (23 mg) sodium in 100
ml, that is, it is essentially ‘sodium free’.
Propofol-Lipuro 2 % (20 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 2 % (20 mg/ml)
Propofol-Lipuro 2 % (20 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 and
to sustain anaesthesia or to achieve the required level of sedation, by
carefully watching your responses and vital signs (pulse, blood pressure,
breathing, etc).
The doctor will also observe limits of the time of application, if necessary.
Propofol-Lipuro 2 % (20 mg/ml) will usually be given by injection when
used to induce general anaesthesia and by continuous infusion (a slower,
longer injection) when used to maintain general anaesthesia. When used
as a sedative it will usually be given by infusion.
Propofol-Lipuro 2 % (20 mg/ml) will only be given for a maximum of
7 days.

Method of administration
You will receive Propofol-Lipuro 2 % (20 mg/ml) by intravenous injection
or infusion, that is, through a needle or small tube placed in one of your
veins.
Because Propofol-Lipuro 2 % (20 mg/ml) does not contain preservatives,
an infusion from one vial of Propofol-Lipuro will not last longer than
12 hours.
Your circulation and breathing will be constantly monitored while you are
being given the injection or infusion.

If you received more Propofol-Lipuro 2 % (20 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.



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Additional precautions
Propofol-Lipuro 2 % (20 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 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. Propofol must not be administered via a microbiological filter.
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 100
ml, i.e. essentially ‘sodium free’.
4.5 nteraction with other medicinal products and other forms of
I
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
i
­ncompatibility has been encountered. Lower doses of propofol may be
required where general anaesthesia or sedation is used as an adjunct to
regional anaesthetic techniques.
4.6 Pregnancy and lactation
Pregnancy
The safety of propofol during pregnancy has not been established. Propofol should not be given to pregnant women except when absolutely
necessary. Propofol crosses the placenta and can cause neonatal depression. Propofol can, however, be used during an induced abortion.
Breast-feeding
Studies of breast-feeding mothers showed that small quantities of propofol are excreted in human milk. Woman should therefore not breastfeed for 24 hours after administration of propofol. Milk produced during
this period should be discarded.
4.7 Effects on the ability to drive and to 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 ADRs 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 Frequency

Undesirable Effects

Immune system
disorders:

Very rare
(<1/10 000)

Anaphylaxis – may
include angioedema,
bronchospasm,
erythema and hypotension

Metabolism and
Nutritional disorder:

Frequency not known (9) Metabolic acidosis (5),
hyperkalaemia (5),
hyperlipidaemia (5)

Psychiatric disorders: Frequency not known (9) Euphoric mood, drug
abuse (8)
Nervous system
disorders:

Common
(>1/100, <1/10)

Headache during
recovery phase

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

Epileptiform movements, including
c
­ onvulsions and
opisthotonus during
induction, maintenance and recovery

Very rare
(<1/10 000)

Postoperative
unconsciousness

Frequency not known (9) Involuntary movements

4.9  Overdose
Accidental overdosage 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 2 % (20 mg/ml), onset of
the hypnotic effect is rapid. 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, clinically relevant accumulation of propofol after repeated bolus injection or after infusion has not
been observed.
Patients recover consciousness rapidly.
Bradycardia and hypotension occasionally occur during induction of anaesthesia probably due to the lack of vagolytic activity. The cardio-circulatory situation usually normalises during maintenance of 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
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
(α-phase). The distribution half-life has is 2 – 4 minutes.
During elimination the decline of blood levels is slower. The elimination
half-life during the β-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 the 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.

Common
(>1/100, <1/10)

Bradycardia (1)

Very rare
(<1/10 000)

Pulmonary oedema

Frequency not
known (9)

Cardiac arrhythmia
(5), cardiac failure
(5), (7)

6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products
except those mentioned in section 6.6.

Common
(>1/100, <1/10)

Hypotension (2)

Uncommon
(>1/1000, <1/100)

Thrombosis and
phlebitis

6.3 Shelf life
2 years.
After first opening: to be used immediately.

Respiratory, thoracic
and mediastinal
disorders:

Common
(>1/100, <1/10)

Transient apnoea during induction

Gastrointestinal
disorders:

Common
(>1/100, <1/10)

Nausea and vomiting
during recovery phase

Very rare
(<1/10 000)

Pancreatitis

Cardiac disorders:

Vascular disorders:

Hepatobiliary disorders

Frequency not known (9) Hepatomegaly (5)

Musculoskeletal and
connective tissue
disorders:

Frequency not known (9) Rhabdomyolysis (3), (5)

Renal and urinary
disorders

Very rare
(<1/10 000)

Discolouration of
urine following prolonged administration

Frequency not known (9) Renal failure (5)
Reproductive system
and breast

Very rare
(<1/10 000)

General disorders and Very common
administration site
(>1/10)
conditions:
Investigations

Sexual disinhibition
Local pain on induction (4)

Frequency not known (9) Brugada type ECG
(5), (6)

Injury, poisoning and Very rare
procedural complica- (<1/10 000)
tions:

Postoperative fever

(1)

S
 erious bradycardias are rare. There have been isolated reports of
progression to asystole.
(2)  ccasionally, hypotension may require use of intravenous fluids and
O
reduction of the administration rate of propofol.
(3)  ery rare reports of rhabdomyolysis have been received where propoV
fol has been given at doses greater than 4 mg/kg/hr for ICU sedation.
(4)  ay be minimised by using the larger veins of the forearm and anM
tecubital fossa. With Propofol-Lipuro 2 % (20 mg/ml) local pain can
also be minimised by the co-administration of lidocaine.
(5)  ombinations of these events, reported as “Propofol infusion synC
drome”, may be seen in seriously ill patients who often have multiple
risk factors for the development of the events, see section 4.4.
(6)  rugada-type ECG - elevated ST-segment and coved T-wave in ECG.
B
(7)  apidly progressive cardiac failure (in some cases with fatal outcome)
R
in adults. The cardiac failure in such cases was usually unresponsive
to inotropic supportive treatment.
(8)  rug abuse, predominantly by health care professionals.
D
(9) Not known as it cannot be estimated from the available clinical trial data.


6.4 Special precautions for storage
Do not store above 25 °C.
Do not freeze.
Keep the vials in the outer carton in order to protect from light.
6.5 Nature and contents of container
The product is supplied in
•  ials of colourless glass (type II Ph. Eur.) sealed with bromobutyl rubber
v
closure and aluminium caps, containing 50 ml of emulsion. It is available in packs of 1 x 50 ml, 10 x 50 ml
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handlings
Any unused product or waste material should be disposed of in accordance with local requirements.
Containers should be shaken before use.
For single use only. Any portion of contents remaining after use must be
discarded, see section 4.2 and 4.4.
If two layers can be seen after shaking the medicinal product should no
be used.
Propofol-Lipuro 2 % (20 mg/ml) must not be mixed with other solutions
for injection or infusion. However, co-administration of Propofol-Lipuro
2 % (20 mg/ml) together with glucose 50 mg/ml (5 % w/v) solution or sodium chloride 9 mg/ml (0.9 % w/v) solution, or sodium chloride 1.8 mg/ml
(0.18 % w/v ) and glucose 40 mg/ml (4 % 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
34212 Melsungen, Germany
Postal address:
34209 Melsungen
Phone: +49/5661/71-0
Fax: +49/5661/71-4567
8 MARKETING AUTHORISATION NUMBER(S)
PA 736/18/3 (Ireland)
PL 03551/0066 (United Kingdom)
9 DATE OF FIRST AUTHORISATION / RENEWAL OF THE
AUTHORISATION
Date of first authorisation:  5 March 2004 (Ireland)
0
06 November 2002 (United Kingdom)
Date of last renewal: 23 November 2010
10 DATE OF REVISION OF THE TEXT
10/2011

B|BRAUN

B. Braun Melsungen AG
34209 Melsungen, Germany

✁----------✁----------✁----------✁----------✁----------✁----------✁----------✁----------✁--------

4. Possible side effects

6. Contents of the pack and other information

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

What Propofol-Lipuro 2 % (20 mg/ml) contains

A doctor must be called immediately if the following happen
Common (may affect up to 1 in 10 people):
•  ow blood pressure that might occasionally need infusion of fluids and
L
reduction of the speed of administration of propofol.
•  oo low heartbeat that might be serious in rare cases.
T
Rare (may affect up to 1 in 1,000 people):
•  onvulsions like in epilepsy
C
Very rare (may affect up to 1 in 10,000 people):
•  llergic reactions including swelling of the face, tongue or throat,
A
wheezing breath, skin redness and low blood pressure
•  here have been cases of unconsciousness occurring after operations.
T
You will therefore be carefully observed during the waking-up time.
•  ater on lungs (lung oedema) after administration of propofol
W
• nflammation of the pancreas.
I
Not known (frequency cannot be estimated from the available data):
•  here have been reports of isolated cases of severe adverse reactions
T
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):
•  ain at the injection site occurring during the first injection. The pain
P
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):
•  hort interruption of breathing
S
•  eadache during the time of recovery
H
•  ickness or vomiting during the time of recovery
S

•  he active substance is propofol.
T
 ach millilitre of Propofol-Lipuro 2 % (20 mg/ml) contains 20 mg of
E
propofol.
1 vial with 50 ml contains 1000 mg propofol.
•  he other ingredients are:
T
Soya-bean oil refined,
Medium-chain triglycerides,
Egg lecithin,
Glycerol,
Sodium oleate,
Water for injections.

What Propofol-Lipuro 2 % (20 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 vials of 50 millilitres, available in packs of one or 10
vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
B. Braun Melsungen AG

Carl-Braun-Straße 1

34212 Melsungen, Germany





Postal address:
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 2 % (20 mg/ml):  zech Republic, Ireland, Latvia,
C
Portugal, Spain, United Kingdom,
Poland, Slovakia
Propofol “B. Braun” 20 mg/ml:
Denmark
Propofol B. Braun 2 % (20 mg/ml): Italy
Propofol-Lipuro 20 mg/ml:
A
 ustria, Estonia, Finland, France,
Germany, Hungary, Lithuania,
Luxembourg, Netherlands, Norway,
Slovenia, Sweden
Propofol-Lipuro 2 %:
Greece

This leaflet was last revised in 10/2011.

Uncommon (may affect up to 1 in 100 people):
•  lood clots in veins or inflammation of veins
B
Very rare (may affect up to 1 in 10,000 people):
•  oss of sexual control during the time of recovery
L
•  bnormal colour of urine after longer lasting administration of propoA
fol
•  ases of fever after an operation
C

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.

Not known (frequency cannot be estimated from the available data):
• nvoluntary movements
I
•  bnormally good mood
A
•  rug abuse
D
•  ailure of the heart
F
•  reakdown of muscle tissue has been reported very rarely in cases
B
where propofol has been given at greater doses than recommanded for
sedation in intensive care units
If you get any side effects, talk to your doctor, pharmacist or nurse. This
includes any possible side effects not listed in this leaflet.

5. How to store Propofol-Lipuro 2 % (20 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.
Keep the vials in the outer carton in order to protect from light. Do not
store above 25°C. Do not freeze.
Propofol-Lipuro 2 % (20 mg/ml) must be used immediately after opening
the vial.
Do not use Propofol-Lipuro 2 % (20 mg/ml) if two separate layers can be
seen after shaking the product.
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.

B|BRAUN
12608212_Propofol2_GIF210x980__GB-IE_599.indd 2

B. Braun Melsungen AG
34209 Melsungen, Germany

26.10.11 13:19

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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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