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PROPOFOL 2% FRESENIUS EMULSION FOR INJECTION OR INFUSION

Active substance(s): PROPOFOL

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SUMMARY OF PRODUCT CHARACTERISTICS
1.

NAME OF THE MEDICINAL PRODUCT
Propofol 2 % (20 mg/1 ml) Fresenius emulsion for injection or infusion

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml emulsion contains 20 mg propofol.
Each 20 ml ampoule contains 400 mg propofol.
Each 50 ml vial contains 1000 mg propofol.
Each 100 ml vial contains 2000 mg propofol.
Excipients with known effect:
1 ml emulsion contains:
soya-bean oil, refined
100 mg
sodium
max. 0.06 mg
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Emulsion for injection or infusion
White oil-in-water emulsion

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications
Propofol 2 % (20 mg/1 ml) Fresenius is a short-acting intravenous general anaesthetic for
- induction and maintenance of general anaesthesia in adults and children > 3 years
- sedation for diagnostic and surgical procedures, alone or in combination with local or
regional anaesthesia in adults and children > 3 years
- sedation of ventilated patients >16 years of age in the intensive care unit

4.2

Posology and method of administration
Propofol Fresenius 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
oxymetry) and facilities for maintenance of patient airways, artificial ventilation, and other
resuscitation facilities should be immediately available at all times.
For sedation during surgical and diagnostic procedures Propofol Fresenius should not be
administered by the same person conducting the surgical or diagnostic procedure.

The dose of Propofol Fresenius emulsion should be individualised based on the response of
the patient and premedications used.
Supplementary analgesic agents are generally required in addition to Propofol Fresenius.
Posology
General anaesthesia in adults
Induction of anaesthesia:
For induction of anaesthesia Propofol Fresenius should be titrated (approximately 20 - 40 mg
propofol every 10 seconds) against the response of the patient until clinical signs show the
onset of anaesthesia.
Most adult patients aged less than 55 years are likely to require 1.5 to 2.5 mg propofol/kg
bodyweight.
In patients over this age and in patients of ASA grades III and IV, especially those with
impaired cardiac function, the requirements will generally be less and the total dose of
Propofol Fresenius may be reduced to a minimum of 1 mg propofol/kg bodyweight. Lower
rates of administration of Propofol 2 % (20 mg/1 ml) Fresenius should be used (approximately
1 ml (20 mg propofol) every 10 seconds).
Maintenance of anaesthesia:
Anaesthesia can be maintained by administering Propofol 2 % (20 mg/1 ml) Fresenius by
continuous infusion.
For maintenance of anaesthesia generally doses of 4 to 12 mg propofol/kg bodyweight/h
should be given. A reduced maintenance dose of approximately 4 mg propofol/kg
bodyweight/h may be sufficient during less stressful surgical procedures such as minimal
invasive surgery.
In elderly patients, patients in unstable general conditions, patients with impaired cardiac
function or hypovolaemic patients and patients of ASA grades III and IV the dosage of
Propofol Fresenius may be reduced further depending on the severity of the patient’s condition
and on the performed anaesthetic technique.
General anaesthesia in children over 3 years of age
Induction of anaesthesia:
For induction of anaesthesia Propofol Fresenius should be titrated slowly until clinical signs
show the onset of anaesthesia. The dose should be adjusted according to age and/or
bodyweight. Most patients over 8 years of age require approximately 2.5 mg/kg bodyweight
Propofol Fresenius for induction of anaesthesia. In younger children, dose requirements may
be higher (2.5 - 4 mg/kg bodyweight).
Maintenance of general anaesthesia:
Anaesthesia can be maintained by administering Propofol Fresenius 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, dose requirements may be higher.
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
propofol/kg bodyweight over 1 to 5 minutes for onset of sedation. Maintenance of sedation
may be accomplished by titrating Propofol Fresenius infusion to the desired level of sedation.
Most patients will require 1.5 - 4.5 mg propofol/kg bodyweight/h. The infusion may be
supplemented by bolus administration of 10 - 20 mg propofol (0.5 - 1 ml Propofol 2 % (20
mg/1 ml) Fresenius) if a rapid increase of the depth of sedation is required.
In patients older than 55 years and in patients of ASA grades III and IV lower doses of
Propofol Fresenius may be required and the rate of administration may need to be reduced.
Sedation for diagnostic and surgical procedures in children over 3 years 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 bodyweight propofol
for onset of sedation. Maintenance of sedation may be accomplished by titrating Propofol
Fresenius infusion to the desired level of sedation. Most patients require 1.5 - 9 mg/kg/h
propofol.
In ASA III and IV patients lower doses may be required.
Sedation in patients over 16 years of age in the intensive care unit
When used to provide sedation for ventilated patients under intensive care conditions, it is
recommended that Propofol Fresenius should be given by continuous infusion. The dose
should be adjusted according to the depth of sedation required. Usually satisfactory sedation is
achieved with administration rates in the range of 0.3 to 4.0 mg propofol/kg bodyweight/h.
Rates of infusion greater than 4.0 mg propofol/kg bodyweight/h are not recommended (see
section 4.4).
Administration of propofol by a target controlled infusion (TCI) system is not advised for
sedation in the intensive care unit (ICU).
Method of administration
For intravenous use.
Propofol 2 % (20 mg/1 ml) Fresenius is administered undiluted intravenously by continuous
infusion. Propofol 2 % (20 mg/1 ml) Fresenius should not be given by repeat bolus injection
for maintenance of anaesthesia.
When Propofol 2 % (20 mg/1 ml) Fresenius is infused, it is recommended that equipment such
as burettes, drop counter, syringe pumps or volumetric infusion pumps should always be used
to control infusion rates.
Containers should be shaken before use.
Use only homogeneous preparations and undamaged containers.
Prior to use, the ampoule neck or rubber membrane should be cleaned using an alcohol spray
or a swab dipped in alcohol. After use, tapped containers must be discarded.
Propofol Fresenius is a lipid containing emulsion without antimicrobial preservatives and may
support rapid growth of micro-organisms.

The emulsion must be drawn aseptically into a sterile syringe or giving set immediately after
opening the ampoule or breaking the vial seal. Administration must commence without delay.
Asepsis must be maintained for both Propofol Fresenius and infusion equipment throughout
the infusion period. Co-administration of other medicinal products or fluids added to the
Propofol Fresenius infusion line must occur close to the cannula site using a Y-piece
connector or a three-way valve.
Propofol Fresenius must not be mixed with other solutions for infusion or injection. But 5 %
w/v glucose solution, 0.9 % w/v sodium chloride solution or 0.18 % w/v sodium chloride and
4 % w/v glucose solution may be administered via suitable appendages at the cannula site.
Propofol Fresenius must not be administered via a microbiological filter.
Propofol Fresenius and any infusion equipment containing Propofol Fresenius are for single
administration in an individual patient. After use remaining solution of Propofol Fresenius
has to be discarded.
As usual for fat emulsions, the infusion of Propofol Fresenius via one infusion system must
not exceed 12 hours. After 12 hours, the infusion system and reservoir of Propofol Fresenius
must be discarded or replaced if necessary.
To reduce pain on the injection site, Propofol 2 % (20 mg/1 ml) Fresenius should be
administered in a larger vein or lidocaine injection solution may be administered before
induction of anaesthesia with Propofol 2 % (20 mg/1 ml) Fresenius (see section 4.4).
Muscle relaxants like atracurium and mivacurium should only be administered after flush of
the same infusion site used for Propofol Fresenius.
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.
Duration of administration
The duration of administration must not exceed 7 days.

4.3

Contraindications
Propofol is contraindicated in patients with a known hypersensitivity to propofol or any of the
excipients listed in section 6.1.
Propofol Fresenius contains soya oil and should not be used in patients who are hypersensitive
to peanut or soya.
Propofol must not be used in patients of 16 years of age or younger for sedation for intensive
care (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 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.
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.
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.)
Delayed epileptiform attacks may occur even in non-epileptic patients, the delay period
ranging from a few hours to several days."
Special patient groups
Cardiac, circulatory or pulmonary insufficiency and hypovolaemia
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 which reduces
cardiac output will also reduce propofol clearance.
Cardiac, circulatory or pulmonary insufficiency and hypovolaemia should be compensated
before administration of propofol.
Propofol should not be administered in patients with advanced cardiac failure or other severe
myocardial disease except with extreme caution and intensive monitoring.
Due to a higher dosage in patients with severe overweight the risk of haemodynamic effects
on the cardiovascular system should be taken into consideration.

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 a bradycardia.
Epilepsy
When propofol is administered to an epileptic patient, there may be a risk of convulsion.
In epileptic patients delayed epileptiform attacks may occur, the delay period ranging from a
few hours to several days.
Before anaesthesia of an epileptic patient, it should be checked that the patient has received
the antiepileptic treatment. Although several studies have demonstrated efficacy in treating
status epilepticus, administration of propofol in epileptic patients may also increase the risk of
seizure.
Use of propofol is not recommended with electroconvulsive therapy.
Patients with disorders of fat metabolism
Appropriate care should be applied in patients with disorders of fat metabolism and in other
conditions where lipid emulsions must be used cautiously.
Patients with a high intracranial pressure
Special care should be recognised in patients with a high intracranial pressure and a low mean
arterial pressure as there is a risk of a significant decrease of the intracerebral perfusion
pressure.
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 of the SmPC) 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 2 % (20 mg/1 ml) Fresenius is not recommended in children < 3 years of age since
the 2 % strength is difficult to be adequately titrated in small children due to the extremely
small volumes needed. The use of Propofol 1 % (10 mg/1 ml) Fresenius should be considered
in children between 1 month and 3 years of age if a dose less than e.g. 100 mg/h is expected.
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 emulsion infusions for ICU sedation has been associated with a constellation
of metabolic derangements 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, Brugadatype 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 intracranial 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 Fresenius 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 Fresenius contains no antimicrobial preservatives and supports growth of microorganisms.
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. 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.

Pain on the injection site
To reduce pain on the injection site during induction of anaesthesia with Propofol Fresenius,
lidocaine can be injected prior to the propofol emulsion. Lidocaine must not be used in
patients with hereditary acute porphyria (see section 4.2).

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

4.5

Interaction with other medicinal products and other forms of interaction
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.
Concomitant use of benzodiazepines, parasympatholytic agents or inhalational anaesthetics
has been reported to prolong the anaesthesia and to reduce the respiratory rate.
After additional premedication with opioids, the sedative effects of propofol may be
intensified and prolonged, and there may be a higher incidence and longer duration of apnoea.
It should be taken into consideration that concomitant use of propofol and medicinal products
for premedication, inhalation agents or analgesic agents may potentiate anaesthesia and
cardiovascular side effects.
Concomitant use of central nervous system depressants (e.g. alcohol, general anaesthetics,
narcotic analgesics) will result in intensification of their sedative effects. When Propofol
Fresenius is combined with centrally depressant drugs administered parenterally, severe
respiratory and cardiovascular depression may occur.
After administration of fentanyl, the blood level of propofol may be temporarily increased
with an increase in the rate of apnoea.
Bradycardia and cardiac arrest may occur after treatment with suxamethonium or neostigmine.
Leucoencephalopathy has been reported with administration of lipid emulsions as used for
Propofol Fresenius in patients receiving cyclosporine.

4.6

Fertility, 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.
High doses (more than 2.5 mg propofol/kg bodyweight for induction or 6 mg propofol/kg
bodyweight/h for maintenance of anaesthesia) should be avoided.
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.
After administration of Propofol Fresenius, the patient should be kept under observation for an
appropriate period of time. The patient should be instructed not to drive, operate machinery, or
work in potentially hazardous situations. The patient should not be allowed to go home
unaccompanied, and should be instructed to avoid consumption of alcohol.
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, sexual
disinhibition.
Drug abuse and drug dependence
(8)

Nervous system disorders:

Cardiac disorders:

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

Headache during recovery phase

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

Epileptiform movements,
including convulsions and
opisthotonus during induction,
maintenance and recovery.
Vertigo, shivering and sensation
of cold during recovery

Very rare
(<1/10 000)

Postoperative unconsciousness

Frequency not known (9)

Involuntary movements

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

Bradycardia (1)
and tachycardia during induction

Very rare
(<1/10 000)

Pulmonary oedema

Frequency not known (9)

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

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

Hypotension (2)

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

Thrombosis and phlebitis

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

Transient apnoea, coughing and
singultus during induction

Frequency not known (9)

Respiratory depression (dose
dependant)

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

Nausea and vomiting during
recovery phase

Very rare
(<1/10 000)

Pancreatitis

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)

Very common
(>1/10)

Local pain on induction (4)

Very rare
(<1/10 000)

Tissue necrosis (10) following
accidental extravascular
administration

Frequency not known (9)

Local pain, swelling, following
accidental extravascular
administration

Investigations

Frequency not known (9)

Brugada type ECG (5), (6)

Injury, poisoning and
procedural complications:

Very rare
(<1/10 000)

Postoperative fever

Vascular disorders:

Respiratory, thoracic and
mediastinal disorders:

Gastrointestinal disorders:

General disorders and
administration site conditions:

(1)
(2)
(3)

(4)

(5)

(6)
(7)

(8)
(9)
(10)

Serious bradycardias are rare. There have been isolated reports of progression to asystole.
Occasionally, hypotension may require use of intravenous fluids and reduction of the administration rate of propofol.
Very rare reports of rhabdomyolysis have been received where propofol has been given at doses greater than 4 mg/kg/hr for ICU
sedation.
May be minimised by using the larger veins of the forearm and antecubital fossa. With propofol 1 % local pain can also be minimised
by the co-administration of lidocaine.
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.
Brugada-type ECG - elevated ST-segment and coved T-wave in ECG.
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.
Abuse of and drug dependence on propofol, predominantly by health care professionals.
Not known as it cannot be estimated from the available clinical trial data.
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 national
reporting scheme.
For UK:
You can report adverse reactions directly via the Yellowcard scheme at:
http://www.mhra.gov.uk/yellowcard

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 of the patient's head and, if severe, use of plasma expanders and pressor agents.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Other anaesthetics
ATC-Code: NO1AX10
Propofol (2,6-diisopropylphenol) is a short-acting general anaesthetic agent with a
rapid onset of action. 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 and lasts, depending on the metabolism and elimination, 4 to 6
minutes.
Under the usual maintenance regimen significant accumulation with either repeated
injections or infusions of propofol has not been seen. Patients recover consciousness
rapidly.
Bradycardia and hypotension reported during induction of anaesthesia may be caused
by a cerebral vagotonic effect or inhibition of sympathetic activity. However,
haemodynamics generally revert to normal during maintenance of anaesthesia.
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
Propofol is bound to plasma proteins for 98%. Following intravenous administration the
pharmacokinetics of propofol can be described by a 3-compartment model.
Propofol is extensively distributed and rapidly cleared from the body (total body clearance:
1.5 - 2 litres/minute). Clearance occurs by metabolic processes, mainly in the liver where it is
blood flow dependent, to form inactive conjugates of propofol and its corresponding quinol,
which are excreted in urine.

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 special 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, paravenous and subcutaneous injection induced
histological reactions marked by inflammatory infiltration and focal fibrosis.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Soya-bean oil, refined
Purified egg phosphatides
Glycerol
Oleic acid
Sodium hydroxide
Water for injections

6.2

Incompatibilities
This medicinal product must not be mixed with other medicinal products.

6.3

Shelf life
The shelf life of the product in its original package is 2 years.
Administration systems with undiluted Propofol Fresenius should be replaced after 12 hours.
After opening the product must be used immediately.

6.4

Special precautions for storage
Do not store above 25 °C. Do not freeze.

6.5

Nature and contents of container
Colourless glass ampoule(s) (type I) of 20 ml
Colourless glass vial(s) (type II) of 50 ml with a bromobutyl rubber closure
Colourless glass vial(s) (type II) of 100 ml with a bromobutyl rubber closure
Packs containing 5 glass ampoules with 20 ml emulsion
Packs containing 1 glass vial with 50 or 100 ml emulsion
Packs containing 10 glass vials with 50 or 100 ml emulsion
Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling
For single use. Any unused emulsion must be discarded.
Containers should be shaken before use.
If two layers can be seen after shaking the emulsion should not be used.
Use only homogeneous preparations and undamaged containers.
Prior to use, the ampoule neck or rubber membrane should be cleaned using an alcohol spray
or a swab dipped in alcohol. After use, tapped containers must be discarded.

7

MARKETING AUTHORISATION HOLDER
Fresenius Kabi Limited
Cestrian Court
Eastgate Way
Manor Park
Runcorn
Cheshire
WA7 1NT
United Kingdom

8

MARKETING AUTHORISATION NUMBER
PL 08828/0155

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
25/10/2010

10

DATE OF REVISION OF THE TEXT
17/06/2016

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Source: Medicines and Healthcare Products Regulatory Agency

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