Health Products Regulatory Authority

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Propofol 2% (20 mg/ml) emulsion for injection/infusion in pre-filled syringe

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml emulsion contains 20 mg propofol.

Each 50 ml pre-filled syringe contains 1000 mg propofol.

Excipients with known effect:

Each ml emulsion contains:
soya-bean oil, refined 50 mg
sodium max. 0.06 mg

For the full list of excipients, see section 6.1. n

3 PHARMACEUTICAL FORM

Emulsion for injection/infusion in pre-filled syringe

White oil-in-water emulsion

pH of emulsion: 7.5 – 8.5

Osmolality of emulsion: 270 - 330 mosmol/kg

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Propofol 2% is a short-acting intravenous general anaesthetic for

 induction and maintenance of general anaesthesia in adults, adolescents and children > 3 years.
 sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia in
adults, adolescents 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 2% 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 2% should not be administered by the same person
conducting the surgical or diagnostic procedure.

The dose of Propofol 2% should be individualised based on the response of the patient and premedications used.
Supplementary analgesic agents are generally required in addition to Propofol 2%.

Posology

General anaesthesia in adults

Induction of anaesthesia:

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For induction of anaesthesia Propofol 2% 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 2% may be reduced to a minimum of 1 mg propofol/kg
bodyweight. Lower rates of administration of Propofol 2% should be used (approximately 1 ml of the 20 mg/ml emulsion
(20 mg propofol) every 10 seconds).

Maintenance of anaesthesia:

Anaesthesia can be maintained by administering Propofol 2% 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 2% 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 2% 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 2% 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 2% 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 2% 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%) 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 2% 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 2% 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

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When used to provide sedation for ventilated patients under intensive care conditions, it is recommended that Propofol 2%
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).

Duration of administration
The duration of administration must not exceed 7 days.

Method of administration

For intravenous use.

For single use only. Any unused emulsion must be discarded.

Pre-filled syringes 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 pre-filled syringes.

Propofol 2% is administered undiluted intravenously by continuous infusion. Propofol 2% should not be given by repeat bolus
injection for maintenance of anaesthesia.

When Propofol 2% is infused, it is recommended that equipment such as burettes, drop counter, syringe pumps (including TCI
systems) or volumetric infusion pumps should always be used to control infusion rates.

Propofol 2% is a lipid containing emulsion without antimicrobial preservatives and may support rapid growth of
micro-organisms.

The emulsion must be drawn aseptically into a giving set immediately after opening the syringe. Administration must
commence without delay.

Asepsis must be maintained for both Propofol 2% and infusion equipment throughout the infusion period. Co-administration
of other medicinal products or fluids added to the Propofol 2% infusion line must occur close to the cannula site using a
Y-piece connector or a three-way valve. For instructions on co-administration of the medicinal product, see section 6.6.

Propofol 2% must not be administered via a microbiological filter.

Propofol 2% and any infusion equipment containing Propofol 2% are for single administration in an individual patient. After
use remaining solution of Propofol 2% has to be discarded.

As usual for fat emulsions, the infusion of undiluted Propofol 2% via one infusion system must not exceed 12 hours. After 12
hours, the infusion system and reservoir of Propofol 2% must be discarded or replaced if necessary

To reduce pain on the injection site, lidocaine may be injected immediately before the use of Propofol 2% (see section 4.4).

Muscle relaxants like atracurium and mivacurium should only be administered after flush of the same infusion site used for
Propofol 2%.

If Propofol 2% is injected into a vein by electric pumps, appropriate compatibility should be ensured.

Application of pre-filled syringes:

Sterility has to be ensured. The outer surface of the syringe and the plunger rod are not sterile.

1) Take out the syringe from the packaging and shake it.
2) Insert the plunger rod by screwing it clock-wise into the syringe.
3) Remove the tip cap from the syringe and connect the infusion line, needle or cannula to the syringe. Get rid of the air
bubble (a small bubble can remain) and the ready-to-use syringe will be installed in the pump or administered manually.

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Target Controlled Infusion – Administration of Propofol 2% by pumps:
Administration of Propofol 2% by a Target Controlled Infusion system is restricted to induction and maintenance of general
anaesthesia in adults. It is not recommended for use in ICU sedation or sedation for surgical and diagnostic procedures.

Propofol 2% may be administered by a Target Controlled Infusion system incorporating appropriate Target Controlled Infusion
software. Users must be familiar with the infusion pump users' manual, and with the administration of Propofol 2% by Target
Controlled Infusion.

The system allows the anaesthetist or intensivist to achieve and control a desired speed of induction and depth of anaesthesia
by setting and adjusting target (predicted) plasma and/or effect-side concentrations of propofol.

Different modalities of the various pump systems should be considered i.e. the Target Controlled Infusion system might
assume that the initial blood propofol concentration in the patient is zero. Therefore, in patients who have received prior
propofol, there may be a need to select a lower initial target concentration when commencing Target Controlled Infusion.
Similarly, the immediate recommencement of Target Controlled Infusion is not recommended if the pump has been switched
off.

Guidance on propofol target concentrations is given below. In view of interpatient variability in propofol pharmacokinetics and
pharmacodynamics, in both premedicated and unpremedicated patients the target propofol concentration should be titrated
against the response of the patient in order to achieve the depth of anaesthesia required.

Induction and Maintenance of General Anaesthesia during target controlled infusion

In adult patients under 55 years of age anaesthesia can usually be induced with target propofol concentrations in the region of
4 – 8 microgram/ml. An initial target of 4 microgram/ml is recommended in premedicated patients and in unpremedicated
patients an initial target of 6 microgram/ml is advised. Induction time with these targets is generally within the range of 60–120
seconds. Higher targets will allow more rapid induction of anaesthesia but may be associated with more pronounced
haemodynamic and respiratory depression.

A lower initial target concentration should be used in patients over the age of about 55 years and in patients of ASA grades 3
and 4. The target concentration can then be increased in steps of 0.5 – 1.0 microgram/ml at intervals of 1 minute to achieve a
gradual induction of anaesthesia.

Supplementary analgesia will generally be required and the extent to which target concentrations for maintenance of
anaesthesia can be reduced will be influenced by the amount of concomitant analgesia administered. Target propofol
concentrations in the region of 3–6 microgram/ml usually maintain satisfactory anaesthesia.

The predicted propofol concentration on waking is generally in the region of 1.0 – 2.0 microgram/ml and will be influenced by
the amount of analgesia given during maintenance.

Sedation during intensive care (target controlled infusion not advised)

Target blood propofol concentration settings in the range of 0.2 – 2.0 microgram/ml will generally be required. Administration
should begin at low target setting which should be titrated against the response of the patient to achieve the depth of
sedation desired.

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 2% 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).

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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.

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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% is not recommended in children < 3 years of age since the 20 mg/ml strength is difficult to be adequately titrated
in small children due to the extremely small volumes needed. The use of Propofol 2% 10 mg/ml 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, 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 immediately discontinue the propofol
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 2% 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 2% contains no antimicrobial preservatives and supports growth of micro-organisms.

When propofol is to be aspirated, it must be drawn aseptically into a giving set immediately after opening the syringe.
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.

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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 2%, lidocaine can be injected prior to the
propofol emulsion (see section 4.2).
Intravenous lidocaine must not be used in patients with hereditary acute porphyria.

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.

A need for lower propofol doses has been observed in patients taking midazolam. The co-administration of propofol with
midazolam is likely to result in enhanced sedation and respiratory depression. When used concomitantly, a dose reduction of
propofol should to be considered.

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 2% 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 2% in patients receiving
cyclosporine.

A need for lower propofol doses has been observed in patients taking valproate. When used concomitantly, a dose reduction
of propofol may be considered.

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.

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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 2%, 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 Reaction

System Organ Class Frequency Undesirable Effects

Anaphylaxis – may include
Immune system disorders:
Very rare (<1/10 000) angioedema, bronchospasm, erythema
and hypotension
Metabolic acidosis (5), hyperkalaemia
Metabolism and Nutritional disorder: Frequency not known (9) (5)
, hyperlipidaemia (5)
Euphoric mood, sexual disinhibition.
Psychiatric disorders: Frequency not known (9)
Drug abuse and drug dependence (8)
Common (>1/100, <1/10) Headache during recovery phase
Epileptiform movements, including
convulsions and opisthotonus during
Rare (>1/10 000, <1/1000) induction, maintenance and recovery.
Nervous system disorders: ​
Vertigo, shivering and sensation of
cold during recovery
Very rare (<1/10 000) Postoperative unconsciousness
Frequency not known (9) Involuntary movements
Bradycardia (1)
Common (>1/100, <1/10)
and tachycardia during induction
Cardiac disorders: ​ Very rare (<1/10 000) Pulmonary oedema
Cardiac arrhythmia (5), cardiac failure (5),
Frequency not known (9) (7)

Common (>1/100, <1/10) Hypotension (2)

Vascular disorders:
Uncommon (>1/1000, <1/100) Thrombosis and phlebitis
Transient apnoea, coughing and
Common (>1/100, <1/10)
singultus during induction
Respiratory, thoracic and mediastinal disorders:
Respiratory depression (dose
Frequency not known (9)
dependant)
Nausea and vomiting during recovery
Common (>1/100, <1/10)
Gastrointestinal disorders: 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)
Reproductive system and breast disorders Not known Priapism
Discolouration of urine following
Renal and urinary disorders ​ Very rare (<1/10 000)
prolonged administration

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Frequency not known (9) Renal failure(5)
Very common (>1/10) Local pain on induction (4)
Tissue necrosis (10) following accidental
Very rare (<1/10 000)
General disorders and administration site conditions: ​ ​ extravascular administration
Local pain, swelling, following
Frequency not known (9)
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

(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 and/or can also be minimised by the
injection of lidocaine immediately before the use of Propofol 2%.
(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 HPRA Pharmacovigilance. Website: www.hpra.ie .

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: Anaesthetics; Other general anaesthetics

ATC-Code: N01AX10

Mechanism of action/Pharmacodynamic effects

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.

Clinical efficacy and safety

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 reverts to normal 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.

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5.2 Pharmacokinetic properties

Absorption
Propofol is bound to plasma proteins for 98%. Following intravenous administration the pharmacokinetics of propofol can be
described by a 3-compartment model.

Distribution/ Biotransformation/Elimination
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. 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.

Published studies in animals (including primates) at doses resulting in light to moderate anaesthesia demonstrate that the use
of anaesthetic agents during the period of rapid brain growth or synaptogenesis results in cell loss in the developing brain that
can be associated with prolonged cognitive deficiencies. The clinical significance of these nonclinical findings in not known.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Soya-bean oil, refined

Medium-chain triglycerides
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

Shelf life of the medicinal product in its original package before opening: 2 years.

Shelf life after first opening: Medicinal product must be used immediately after first opening.
Administration systems with undiluted Propofol 2% should be replaced after 12 hours.

6.4 Special precautions for storage

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

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 Health Products Regulatory Authority
6.5 Nature and contents of container

50ml pre-filled syringe (cyclo-olefine-copolymer) with bromobutyl tip cap, bromobutyl plunger and PP piston rod.

Packs containing 1 syringe with 50 ml emulsion.

6.6 Special precautions for disposal and other handling

Co-administration of a glucose 50 mg/ml (5 %) solution for injection or sodium chloride 9 mg/ml solution for injection or
sodium chloride 1.8 mg/ml (0.18 %) solution for injection and glucose 40 mg/ml (4 %) solution for injection with Propofol 2% is
permitted via a Y-piece connector close to the injection site.

Propofol 2% must not be mixed with other solutions for infusion or injection.

7 MARKETING AUTHORISATION HOLDER

Fresenius Kabi Deutschland GmbH

Else-Kroener Strasse 1
Bad Homburg v.d.H 61352
Germany

8 MARKETING AUTHORISATION NUMBER

PA2059/017/005

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of First Authorisation: 18th April 2013

Date of Last Renewal: 12th March 2018

10 DATE OF REVISION OF THE TEXT

January 2024

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