DIPRIVAN 2% PFS

Active substance: PROPOFOL

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You may need several different medicines to keep you
asleep or sleepy, free from pain, breathing in a healthy
way and to keep your blood pressure steady. The doctor
will decide which medicines you need and when you
need them.
4. Possible side effects
Like all medicines, Diprivan may cause side effects
although not everybody gets them.
Side effects that can happen during anaesthesia
The following side effects can happen during anaesthesia
(while the injection is being given to you or when you
are sleepy or asleep). Your doctor will be looking out
for these. If they happen, your doctor will give you
appropriate treatment.
Very common (affects more than 1 in 10 people)
• A feeling of pain at the site of the injection (while the
injection is being given, before you fall asleep).
Common (affects less than 1 in 10 people)
• Low blood pressure.
• Changes in your breathing pattern.
• Slow heart beat.
Rare (affects less than 1 in 1,000 people)
• Twitching and shaking of your body, or a fit (may also
happen when you wake up).
• Unusual colour of urine (may also happen when you
wake up).
Very rare (affects less than 1 in 10,000 people)
• Allergic reactions.
• Stopping of your heart beat.
• Build up of fluid in the lungs which can make you very
breathless (may also happen when you wake up).
Side effects that can happen after anaesthesia
The following side effects can happen after anaesthesia
(when you are waking up or after you have woken up).
Common (affects less than 1 in 10 people)
• Feeling sick (nausea).
• Being sick (vomiting).
• Headache.
Uncommon (affects less than 1 in 100 people)
• Swelling and redness along a vein or blood clots.
Very rare (affects less than 1 in 10,000 people)
• Feeling sexually aroused.
• High temperature (fever).
• Redness or soreness where the injection was given.
• Being unconscious after the operation. (When this
has happened, the patients have recovered without
problems.)
Other possible side effects
The following side effects have been seen when Diprivan is
used in intensive care at higher doses than recommended.
Very rare (affects less than 1 in 10,000 people)
• Heart failure.
• Inflamed pancreas (pancreatitis) which causes severe
stomach pain.
• Too much acid in your blood. This may make you
breathe more quickly.
• Increased amount of potassium in your blood.
• High blood level of a type of fat called lipids.
• Abnormal heart beat.
• Enlargement of the liver.
• Kidney failure.

P032396-4 Leaflet.indd 1

The following side effects have been seen in children in
intensive care when Diprivan has been stopped suddenly.
Common (affects less than 1 in 10 people)
• ‘Withdrawal symptoms’. These include unusual
behaviour, sweating, shaking and feeling anxious.
• Flushing of the skin.
Do not be concerned by this list of possible side effects.
You may not get any of them.

4.9

Overdose
Accidental overdosage is likely to cause cardiorespiratory depression.
Respiratory depression should be treated by artificial ventilation with
oxygen. Cardiovascular depression would require lowering of the patient’s
head and, if severe, use of plasma expanders and pressor agents.

5.
5.1

Pharmacological Properties
Pharmacodynamic properties
Propofol (2, 6-diisopropylphenol) is a short-acting general anaesthetic
agent with a rapid onset of action of approximately 30 seconds. Recovery
from anaesthesia is usually rapid. The mechanism of action, like all
general anaesthetics, is poorly understood. However, propofol is thought
to produce its sedative/anaesthetic effects by the positive modulation of
the inhibitory function of the neurotransmitter GABA through the ligandgated GABAA receptors.

Side effects of unknown frequency may include
• Euphoric mood.
• Involuntary movements.
• Drug abuse, mostly by healthcare professionals.
• Abnormal ECG.
• Breakdown of muscle cells (rhabdomyolysis).
If you think you have a side effect or if you notice any
side effects not listed in this leaflet, please tell your
doctor or nurse.

In general, falls in mean arterial blood pressure and slight changes in
heart rate are observed when Diprivan 2% is administered for induction
and maintenance of anaesthesia. However, the haemodynamic parameters
normally remain relatively stable during maintenance and the incidence of
untoward haemodynamic changes is low.
Although ventilatory depression can occur following administration of
Diprivan 2%, any effects are qualitatively similar to those of other
intravenous anaesthetic agents and are readily manageable in clinical
practice.
Diprivan 2% reduces cerebral blood flow, intracranial pressure and
cerebral metabolism. The reduction in intracranial pressure is greater in
patients with an elevated baseline intracranial pressure.

5. How to store Diprivan
• The doctor and hospital pharmacist are responsible
for storing, using and disposing of Diprivan correctly.
• Store Diprivan between 2°C and 25°C. Do not freeze.
• Do not use Diprivan after the expiry date which is
stated on the carton.

Recovery from anaesthesia is usually rapid and clear-headed with a low
incidence of headache and postoperative nausea and vomiting.
In general, there is less postoperative nausea and vomiting following
anaesthesia with Diprivan 2% than following anaesthesia with inhalational
agents. There is evidence that this may be related to a reduced emetic
potential of propofol.

6. Further information
What Diprivan 2% contains
The active substance is propofol. There is 20 mg of
propofol in each millilitre.
The other ingredients are glycerol, purified egg phosphatide,
sodium hydroxide, soya bean oil, water for injections,
nitrogen and disodium edetate.

Diprivan 2%, at the concentrations likely to occur clinically, does not
inhibit the synthesis of adrenocortical hormones.
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

What Diprivan 2% looks like and contents of the pack
Diprivan 2% is a milky, white liquid. It comes in glass vials
of 50 ml or pre-filled syringes of 50 ml.

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.

Marketing Authorisation Holder and Manufacturer
The Marketing Authorisations for Diprivan 2% are held
by AstraZeneca UK Ltd, 600 Capability Green, Luton,
LU1 3LU, UK.
Diprivan 2% is manufactured by AstraZeneca UK Ltd,
Silk Road Business Park, Macclesfield, Cheshire,
SK10 2NA, UK.

To listen to or request a copy of this leaflet in
Braille, large print or audio please call, free of
charge:
0800 198 5000 (UK only)
Please be ready to give the following information:
Product name
Diprivan 2%
Reference number
1
 7901/0008 or
17901/0009
This is a service provided by the Royal National
Institute of the Blind.

When Diprivan 2% is used to maintain anaesthesia, blood concentrations
asymptotically approach the steady-state value for the given administration
rate. The pharmacokinetics are linear over the recommended range of
infusion rates of Diprivan 2%.
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
Propofol is a drug on which extensive clinical experience has been
obtained. All relevant information for the prescriber is provided elsewhere
in this document.

6.
6.1

Pharmaceutical Particulars
List of excipients
Glycerol Ph. Eur.
Purified Egg Phosphatide
Sodium Hydroxide Ph. Eur.
Soya Bean Oil, Refined Ph. Eur.
Water for Injections Ph. Eur.
Nitrogen Ph. Eur.
Disodium Edetate Ph. Eur.

6.2

Incompatibilities
Diprivan 2% should not be mixed prior to administration with injections or
infusion fluids. However, Diprivan 2% may be co-administered via a Y-piece
connector close to the injection site into infusions of the following:
• Dextrose 5% Intravenous Infusion B.P.
• Sodium Chloride 0.9% Intravenous Infusion B.P.
• Dextrose 4% with Sodium Chloride 0.18% Intravenous Infusion B.P.

Leaflet prepared: January 2012
Diprivan is a trade mark of the
AstraZeneca group of companies.
© AstraZeneca 2012

UK PAI 11 0054b

Pharmacokinetic properties
The decline in propofol concentrations following a bolus dose or following
the termination of an infusion can be described by a three-compartment
open model with very rapid distribution (half-life 2–4 minutes), rapid
elimination (half-life 30–60 minutes), and a slower final phase,
representative of redistribution of propofol from poorly perfused tissue.

The neuromuscular blocking agents, atracurium and mivacurium should
not be given through the same intravenous line as Diprivan 2% without
prior flushing.

6.3 Shelf life
6.3.1 Shelf life of the product as packaged for sale
2 years.
6.3.2 Shelf life after dilution
Diprivan 2% should not be diluted.
6.4 Special precautions for storage
Store between 2°C and 25°C.
Do not freeze.
6.5 Nature and contents of container
a) 10 ml pre-filled syringe containing propofol 20 mg/ml.
b) 50 ml pre-filled syringe containing propofol 20 mg/ml.
c) 50 ml vial containing propofol 20 mg/ml.
6.6 Instructions for use/handling
In-use precautions
Containers should be shaken before use. Any portion of the contents
remaining after use should be discarded.
Diprivan 2% should not be mixed prior to administration with injections
or infusion fluids. However, Diprivan 2% may be co-administered via a
Y-piece connector close to the injection site into infusions of the following:
• Dextrose 5% Intravenous Infusion B.P.
• Sodium Chloride 0.9% Intravenous Infusion B.P.
• Dextrose 4% with Sodium Chloride 0.18% Intravenous Infusion B.P.
When the pre-filled syringe presentation is used in a syringe pump,
appropriate compatibility should be ensured. In particular, the pump
should be designed to prevent syphoning and should have an occlusion
alarm set no greater than 1000 mm Hg. If using a programmable or
equivalent pump that offers options for use of different syringes then
choose only the B-D 50/60 ml PLASTIPAK setting when using the
Diprivan pre-filled syringe.

Additional precautions
Diprivan 2% contains no antimicrobial preservatives and supports growth
of micro-organisms. Asepsis must be maintained for both Diprivan 2%
and infusion equipment throughout the infusion period. Any drugs or fluids
added to the Diprivan 2% infusion line must be administered close to the
cannula site. Diprivan 2% must not be administered via a microbiological
filter.
Diprivan 2% and any syringe containing Diprivan 2% are for single use
in an individual patient. For use in long-term maintenance of anaesthesia
or sedation in intensive care it is recommended that the infusion line and
reservoir of Diprivan 2% be discarded and replaced at regular intervals.
7.
Marketing Authorisation Holder
AstraZeneca UK Limited,
600 Capability Green,
Luton, LU1 3LU, UK.
Leaflet updated: January 2012
© AstraZeneca 2012
Diprivan is a trade mark of the AstraZeneca group of companies.

PAI 11 0054b

P032396

Medical Information Leaflet

Diprivan 2%

(Issued to the Medical Professions Only)
Tradename of the Medicinal Product
Diprivan 20 mg/ml (2%) emulsion for injection or infusion
Qualitative and Quantitative Composition
Propofol 20 mg/ml
Pharmaceutical Form
Emulsion for injection or infusion
White aqueous isotonic oil-in-water emulsion
Clinical Particulars
Therapeutic indications
Diprivan 2% is a short-acting intravenous general anaesthetic for:
• nduction and maintenance of general anaesthesia in adults and
I
children >3 years.

•  edation for diagnostic and surgical procedures, alone or in
S
combination with local or regional anaesthesia in adults and
children >3 years.

•  edation of ventilated patients >16 years of age in the intensive care
S
unit.
4.2 Posology and method of administration

For specific guidance relating to the administration of Diprivan 2% with a
target controlled infusion (TCI) device, which incorporates Diprifusor TCI
software, (see Section 4.2.5). Such use is restricted to induction and
maintenance of anaesthesia in adults. The Diprifusor TCI system is not
recommended for use in ICU sedation or in children.
4.2.1 
Induction of general anaesthesia

Adults

Diprivan 2% may be used to induce anaesthesia by infusion.
Administration of Diprivan 2% by bolus injection is not recommended.

Diprivan 2% may be used to induce anaesthesia by infusion but only
in those patients who will receive Diprivan 2% for maintenance of
anaesthesia.

In unpremedicated and premedicated patients, it is recommended that
Diprivan 2% should be titrated (approximately 2 ml [40 mg] every
10 seconds in an average healthy adult by infusion) against the response
of the patient until the clinical signs show the onset of anaesthesia. Most
adult patients aged less than 55 years are likely to require 1.5–2.5 mg/kg
of Diprivan 2%. The total dose required can be reduced by lower rates
of administration (1–2.5 ml/min [20–50 mg/min]). Over this age, the
requirement will generally be less. In patients of ASA Grades 3 and 4,
lower rates of administration should be used (approximately 1 ml [20 mg]
every 10 seconds).

Elderly patients
In elderly patients the dose requirement for induction of anaesthesia
with Diprivan 2% is reduced. The reduction should take into account the
physical status and age of the patient. The reduced dose should be given
at a slower rate and titrated against the response.

Children
Diprivan 2% is not recommended for induction of anaesthesia in children
less than 3 years of age.
For induction of anaesthesia in children over 3 years of age, Diprivan 2%
should be titrated slowly until clinical signs show the onset of anaesthesia.
The dose 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 Diprivan 2% for induction of anaesthesia. In younger children, dose
requirements may be higher (2.5–4 mg/kg body weight).
For ASA 3 and 4 patients lower doses are recommended (see also
Section 4.4)
Administration of Diprivan 2% by a Diprifusor TCI system is not
recommended for induction of general anaesthesia in children.
4.2.2 Maintenance of general anaesthesia
Anaesthesia can be maintained by administering Diprivan 2% by
continuous infusion to prevent the clinical signs of light anaesthesia.
Administration of Diprivan 2% by bolus injection is not recommended.
Recovery from anaesthesia is typically rapid and it is therefore important
to maintain Diprivan 2% administration until the end of the procedure.
1.

2.

3.


4.
4.1





Adults
The required rate of administration varies considerably between patients,
but rates in the region of 4–12 mg/kg/h usually maintain satisfactory
anaesthesia.

Elderly patients
When Diprivan 2% is used for maintenance of anaesthesia the rate of
infusion or ‘target concentration’ should also be reduced. Patients of ASA
grades 3 and 4 will require further reductions in dose and dose rate. Rapid
bolus administration (single or repeated) should not be used in the elderly
as this may lead to cardiorespiratory depression.

Children
Diprivan 2% is not recommended for maintenance of anaesthesia in
children less than 3 years of age.
Anaesthesia can be maintained in children over 3 years of age by
administering Diprivan 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 3 and 4 patients lower doses are recommended (see also
Section 4.4).
Administration of Diprivan 2% by a Diprifusor TCI system is not
recommended for maintenance of general anaesthesia in children.
4.2.3 Sedation during intensive care

Adults
For sedation during intensive care it is advised that Diprivan 2% 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 mg/kg/h of Diprivan 2% (see 4.4 Special
warnings and special precautions for use). Diprivan 2% is not indicated for
sedation in intensive care of patients of 16 years of age or younger (see
4.3 Contraindications). Administration of Diprivan 2% by Diprifusor TCI
system is not advised for sedation in the intensive care unit.
It is recommended that blood lipid levels be monitored should Diprivan 2%
be administered to patients thought to be at particular risk of fat overload.
Administration of Diprivan 2% 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 Diprivan 2% formulation: 1 ml of Diprivan 2%
contains approximately 0.1 g of fat.
If the duration of sedation is in excess of 3 days, lipids should be
monitored in all patients.

Elderly patients
When Diprivan 2% is used for sedation or anaesthesia the rate of infusion
should also be reduced. Patients of ASA grades 3 and 4 will require
further reductions in dose and dose rate. Rapid bolus administration
(single or repeated) should not be used in the elderly as this may lead to
cardiorespiratory depression.

Children
Diprivan 2% is contraindicated for the sedation of ventilated children aged
16 years or younger receiving intensive care.
4.2.4 Sedation for Surgical and Diagnostic Procedures

Adults
To provide sedation for surgical and diagnostic procedures, rates of
administration should be individualised and titrated to clinical response.
Most patients will require 0.5-1 mg/kg over 1-5 minutes for onset of
sedation.
Maintenance of sedation may be accomplished by titrating Diprivan 2%
infusion to the desired level of sedation - most patients will require
1.5-4.5 mg/kg/h. In addition to the infusion, bolus administration of
10-20 mg may be used if a rapid increase in the depth of sedation is
required. In patients of ASA Grades 3 and 4 the rate of administration and
dosage may need to be reduced.
Administration of Diprivan 2% by a ‘Diprifusor’ TCI system is not
recommended for sedation for surgical and diagnostic procedures.

10/01/2012 12:20





Elderly Patients
When Diprivan 2% is used for sedation the rate of infusion or ‘target
concentration’ should also be reduced. Patients of ASA grades 3 and 4 will
require further reductions in dose and dose rate. Rapid bolus administration
(single or repeated) should not be used in the elderly as this may lead to
cardiorespiratory depression.
Children
Diprivan 2% is not recommended for surgical and diagnostic procedures in
children aged less than 3 years.
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 body weight of
Diprivan 2% for onset of sedation. Maintenance of sedation may be
accomplished by titrating Diprivan 2% infusion to the desired level of
sedation. Most patients require 1.5–9 mg/kg/h Diprivan 2%.



4.3

In ASA 3 and 4 patients lower doses may be required.
4.2.5 Administration
Diprivan 2% has no analgesic properties and therefore supplementary
analgesic agents are generally required in addition to Diprivan 2%.
Diprivan 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
Diprivan 2% may be required where general anaesthesia is used as an
adjunct to regional anaesthetic techniques.
Diprivan 2% should not be diluted. Diprivan 2% can be used for infusion
undiluted from glass containers, plastic syringes or Diprivan 2% pre-filled
syringes.
When Diprivan 2% is used to maintain anaesthesia, it is recommended that
equipment such as syringe pumps or volumetric infusion pumps should
always be used to control infusion rates.
Diprivan 2% should not be mixed prior to administration with injections or
infusion fluids. However, Diprivan 2% may be co-administered via a
Y-piece connector close to the injection site into infusions of the following:
• Dextrose 5% Intravenous Infusion B.P.
• Sodium Chloride 0.9% Intravenous Infusion B.P.
• Dextrose 4% with Sodium Chloride 0.18% Intravenous Infusion B.P.
The glass pre-filled syringe (PFS) has a lower frictional resistance than
plastic disposable syringes and operates more easily. Therefore, if
Diprivan 2% is administered using a hand held pre-filled syringe, the line
between the syringe and the patient must not be left open if unattended.
When the pre-filled syringe presentation is used in a syringe pump
appropriate compatibility should be ensured. In particular, the pump
should be designed to prevent syphoning and should have an occlusion
alarm set no greater than 1000 mm Hg. If using a programmable or
equivalent pump that offers options for use of different syringes then
choose only the B-D 50/60 ml PLASTIPAK setting when using the
Diprivan 2% pre-filled syringe.


Target Controlled Infusion – Administration of Diprivan 2% by a
Diprifusor TCI System in adults
Administration of Diprivan 2% by a Diprifusor TCI system is restricted
to induction and maintenance of general anaesthesia in adults. It is not
recommended for use in ICU sedation or in children.
Diprivan may be administered by TCI only with a Diprifusor TCI system
incorporating Diprifusor TCI software.
Such systems will operate only on recognition of electronically tagged
pre-filled syringes containing Diprivan 1% or 2% Injection. The Diprifusor
TCI system will automatically adjust the infusion rate for the concentration
of Diprivan recognised. Users must be familiar with the infusion pump
users manual, and with the administration of Diprivan 2% by TCI and with
the correct use of the syringe identification system.
The systems allow the anaesthetist or intensivist to achieve and control
a desired speed of induction and depth of anaesthesia by setting and
adjusting target (predicted) blood concentrations of propofol.
The Diprifusor TCI system assumes 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 Diprifusor TCI. Similarly, the immediate
recommencement of Diprifusor TCI 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.
In adult patients under 55 years of age anaesthesia can usually be induced
with target propofol concentrations in the region of 4–8 micrograms/ml.
An initial target of 4 micrograms/ml is recommended in premedicated
patients and in unpremedicated patients an initial target of
6 micrograms/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 microgram/ml at
intervals of 1 minute to achieve a gradual induction of anaesthesia.

P032396-4 Leaflet.indd 2

4.4

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 micrograms/ml usually maintain satisfactory anaesthesia.
The predicted propofol concentration on waking is generally in the region
of 1–2 microgram/ml and will be influenced by the amount of analgesia
given during maintenance.
Sedation during intensive care
Target blood propofol concentration settings in the range of
0.2–2 micrograms/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.
Contraindications
Diprivan is contraindicated in patients with a known hypersensitivity to
propofol or any of the excipients.
Diprivan 2% must not be used in patients of 16 years of age or younger
for sedation in intensive care (see 4.4 Special warnings and precautions
for use).
Diprivan 2% contains soya oil and should not be used in patients who are
hypersensitive to peanut or soya.
Special warnings and precautions for use
Diprivan 2% should be given by those trained in anaesthesia (or, where
appropriate, doctors trained in the care of patients in Intensive Care).
Patients should be constantly monitored and facilities for maintenance
of a patient airway, artificial ventilation and oxygen enrichment and other
resuscitative facilities should be readily available at all times. Diprivan 2%
should not be administered by the person conducting the diagnostic or
surgical procedure.
The abuse of Diprivan 2%, predominantly by health care professionals, has
been reported. As with other general anaesthetics, the administration of
Diprivan 2% without airway care may result in fatal respiratory complications.
When Diprivan 2% 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.
During induction of anaesthesia, hypotension and transient apnoea may
occur depending on the dose and use of premedicants and other agents.
Occasionally, hypotension may require use of intravenous fluids and
reduction of the rate of administration of Diprivan 2% during the period of
anaesthetic maintenance.
As with other sedative agents, when Diprivan 2% 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 Diprivan 2%. Very rarely the use of Diprivan 2%
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.
Diprivan 2% induced impairment is not generally detectable beyond
12 hours. The effects of Diprivan 2%, 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
T
administration
•  he timing of recommencement of skilled or hazardous tasks such as
T
driving
•  he use of other agents that may sedate (Eg, benzodiazepines,
T
opiates, 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. Diprivan 2% clearance is blood
flow dependent, therefore, concomitant medication that reduces cardiac
output will also reduce Diprivan 2% clearance.
Diprivan 2% 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 Diprivan 2%
is used in conjunction with other agents likely to cause a bradycardia.
When Diprivan 2% 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 (see section 4.2).
It is recommended that blood lipid levels should be monitored if
Diprivan 2% is administered to patients thought to be at particular risk
of fat overload. Administration of Diprivan 2% 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 Diprivan 2%
formulation; 1.0 mL of Diprivan contains approximately 0.1 g of fat.
Use is not recommended with electroconvulsive treatment.
As with other anaesthetics sexual disinhibition may occur during recovery.

The use of Diprivan 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.

4.8

Side effects during induction, maintenance and recovery occur uncommonly.
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 Diprivan 2% may be related to the condition of the recipients
and the operative or therapeutic procedures being undertaken.

Diprivan 2% 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 Diprivan 2% 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 the intensive care unit.



System Organ Class
Immune system
disorders:
Metabolism and
Nutritional disorder:
Psychiatric disorders:
Nervous system
disorders:

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
Diprivan 2% (usually following extended dosing at dose rates greater than
4mg/kg/h).

Cardiac disorders:

Prescribers should be alert to these events and consider decreasing the
Diprivan 2% 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 Diprivan 2%, 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.

Vascular disorders:

Respiratory, thoracic
and mediastinal
disorders:
Gastrointestinal
disorders:

Diprivan 2% contains 0.0018 mmol sodium per ml.
Additional Precautions
Diprivan 2% contains no antimicrobial preservatives and supports growth
of micro-organisms.
EDTA chelates metal ions, including zinc, and reduces microbial growth
rates. The need for supplemental zinc should be considered during
prolonged administration of Diprivan 2%, particularly in patients who are
predisposed to zinc deficiency, such as those with burns, diarrhoea and/or
major sepsis.

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

When Diprivan 2% 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 Diprivan 2% and infusion equipment
throughout the infusion period. Any infusion fluids added to the Diprivan 2%
line must be administered close to the cannula site. Diprivan 2% must not
be administered via a microbiological filter.

4.5




Interaction with other medicaments and other forms of interaction
See section 4.2.5 Administration.

4.6

Pregnancy and lactation
Pregnancy Teratology studies in rats and rabbits showed no teratogenic
effects.
The safety of Diprivan 2% during pregnancy has not been established.
Diprivan 2% should not be given to pregnant women except when
absolutely necessary. Diprivan 2% can, however, be used during an
induced abortion.









Obstetrics Diprivan 2% crosses the placenta and can cause neonatal
depression. It should not be used for obstetric anaesthesia.
Lactation Studies of breastfeeding mothers showed that small quantities
of Diprivan 2% are excreted in human milk. Women should therefore
not breastfeed for 24 hours after administration of Diprivan 2%. 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
general anaesthesia.
Diprivan 2% induced impairment is not generally detectable beyond
12 hours (please see section 4.4).

Frequency
Very rare
(<1/10 000)

Undesirable Effects
Anaphylaxis – may
include angioedema,
bronchospasm, erythema
and hypotension
Frequency not known (9) Metabolic acidosis (5),
hyperkalaemia (5),
hyperlipidaemia (5)
Frequency not known (9) Euphoric mood, drug
abuse(8)
Common
Headache during
(>1/100, <1/10)
recovery phase
Rare
Epileptiform movements,
(>1/10 000, <1/1000)
including convulsions
and opisthotonus during
induction, maintenance
and recovery
Very rare
Postoperative
(<1/10 000)
unconsciousness
Frequency not known (9) Involuntary movements
Common
Bradycardia (1)
(>1/100, <1/10)
Very rare
Pulmonary oedema
(<1/10 000)
Frequency not known (9) Cardiac arrhythmia (5),
cardiac failure (5), (7)
Common
Hypotension (2)
(>1/100, <1/10)
Uncommon
Thrombosis and
(>1/1000, <1/100)
phlebitis
Common
Transient apnoea during
(>1/100, <1/10)
induction
Common
(>1/100, <1/10)
Very rare
(<1/10 000)
Frequency not known (9)
Frequency not known (9)

Nausea and vomiting
during recovery phase
Pancreatitis
Hepatomegaly (5)
Rhabdomyolysis (3), (5)

Very rare
(<1/10 000)

Discolouration of urine
following prolonged
administration
Frequency not known (9) Renal failure(5)
Very rare
Sexual disinhibition
(<1/10 000)
Very common
Local pain on induction (4)
(>1/10)

Reproductive system
and breast
General disorders and
administration site
conditions:
Frequency not known (9) Brugada type ECG (5), (6)
Investigations
Very rare
Postoperative fever
Injury, poisoning and
procedural complications: (<1/10 000)

Diprivan 2% and any syringe containing Diprivan 2% are for single use
in an individual patient. In accordance with established guidelines for
other lipid emulsions, a single infusion of Diprivan 2% must not exceed
12 hours. At the end of the procedure or at 12 hours, whichever is the
sooner, both the reservoir of Diprivan 2% and the infusion line must be
discarded and replaced as appropriate.




 erious bradycardias are rare. There have been isolated reports of
S
progression to asystole.
(2)
 ccasionally, hypotension may require use of intravenous fluids and
O
reduction of the administration rate of Diprivan.
(3)
 ery rare reports of rhabdomyolysis have been received where Diprivan
V
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 antecubital
M
fossa. With Diprivan 1% local pain can also be minimised by the coadministration of lidocaine.
(5)
 ombinations of these events, reported as “Propofol Infusion Syndrome”,
C
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)
 ot known as it cannot be estimated from the available clinical trial data.
N
(1)

Dystonia/dyskinesia have been reported.


For further copies of this leaflet, visit emc.medicines.org.uk or call AstraZeneca on 01582 836836.

PACKAGE LEAFLET: INFORMATION FOR THE USER

Diprivan 20 mg/ml (2%)
Emulsion for Injection or Infusion
propofol

Table of Adverse Drug Reactions

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.



Undesirable effects
General
Induction and maintenance of anaesthesia or sedation is generally smooth
with minimal evidence of excitation.

Local
The local pain which may occur during the induction phase can be
minimised by the use of the larger veins of the forearm and antecubital
fossa. Thrombosis and phlebitis are rare. Accidental clinical extravasation
and animal studies showed minimal tissue reaction. Intra-arterial injection
in animals did not induce local tissue effects.

Read all of this leaflet carefully before you start
having this medicine.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or
nurse.
• If you think you have a side effect, or if you notice
any side effects not listed in this leaflet, please tell
your doctor or nurse.
In this leaflet:
1. What Diprivan is and what it is used for
2. Before you have Diprivan
3. How to have Diprivan
4. Possible side effects
5. How to store Diprivan
6. Further information
1. What Diprivan is and what it is used for
Diprivan contains a medicine called propofol. This
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).
Diprivan will be given to you as an injection by a doctor.
In adults and children over 3 years of age it is used to:
• Help put you to sleep before an operation or other
procedure.
• Keep you asleep during an operation or other procedure.
• Sedate you during diagnostic and surgical procedures,
alone or in combination with local or regional
anaesthesia.
In people over 16 years of age it is also used to:
• Sedate you when receiving artificial respiration in an
Intensive Care Unit (ICU).
2. Before you have Diprivan
Do not have Diprivan if:
• You are allergic (hypersensitive) to propofol or any of
the other ingredients of Diprivan (listed in Section 6:
Further information).
• You are allergic to peanut or soya. This is because
Diprivan contains soya oil.
• You are pregnant (see the section called ‘Pregnancy
and breast-feeding’).
• You are 16 years of age or younger for sedation in
intensive care.
If any of the above apply to you, do not have Diprivan
and tell your doctor, anaesthetist or nurse. If you are not
sure, talk to one of these people before having Diprivan.
Take special care with Diprivan
Diprivan is not recommended in children aged less than
3 years.

Before you have this medicine, tell your doctor,
anaesthetist or nurse if:
• You have ever had a fit or convulsion.
• You have ever been told that you have very high levels
of fat in your blood.
• You have ever been told that your body has problems
using fat.
• Your body has lost lots of water (you are dehydrated).
• You have any other health problems, such as problems
with your heart, breathing, kidneys or liver.
• You have been generally unwell for some time.
If you are not sure if any of the above apply to you, talk
to your doctor or nurse before having Diprivan.
Taking other medicines
Tell your doctor if you are taking or have recently taken
any other medicines. This includes medicines that you
buy without a prescription and herbal medicines.
Pregnancy and breast-feeding
• Do not have Diprivan if you are pregnant.
• If you are trying to get pregnant or if you are breastfeeding, talk to your doctor or nurse before having
this medicine.
Driving and using machines
After having Diprivan, you may still feel sleepy for some
time. Do not drive or use any tools or machines until
you are sure the effects have worn off.
• If you are able to go home shortly after having Diprivan,
do not drive a car or use any tools or machines.
• Ask your doctor when you can start doing these
activities again and when you can go back to work.
Important information about some of the ingredients
of Diprivan
Diprivan contains sodium. If you are on a sodium
controlled diet, you will need to take this into account.
Diprivan contains soya oil. If you are allergic to peanut
or soya, do not use this medicine.
Diprivan contains disodium edetate. During prolonged
use of Diprivan for intensive care, you may need to be
given a zinc (a mineral) supplement.
3. How to have Diprivan
You will be given Diprivan by a doctor. It will be given
to you as an injection into a vein. This is usually in the
back of your hand or in your forearm.
• The doctor will give you the injection through a fine
plastic tube called a ‘cannula’.
• The doctor can also use an electric pump to control
how fast the injection is given. This may be done if
you are having a long operation or if you are in an
Intensive Care Unit.
The dose of Diprivan varies from one patient to another.
The amount of Diprivan that you need depends on your
age, size, physical fitness and the level of sleepiness or
sleep that you need. The doctor will give you 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.).
P032396

10/01/2012 12:20

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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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