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DIPRIVAN 20 MG/ML (2%) EMULSION FOR INJECTION OR INFUSION

Active substance(s): PROPOFOL

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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
Read all of this leaflet carefully before you start having this medicine because it contains
important information for you.
x Keep this leaflet. You may need to read it again.
x If you have any further questions, ask your doctor or nurse.
x If you get any side effects, talk to your doctor or nurse. This includes any possible side
effects not listed in this leaflet. See section 4.
What is in this leaflet
1. What Diprivan is and what it is used for
2. What you need to know before you use Diprivan
3. How to use Diprivan
4. Possible side effects
5. How to store Diprivan
6. Contents of the pack and other 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:
x Help put you to sleep before an operation or other procedure.
x Keep you asleep during an operation or other procedure.
x 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:
x Sedate you when receiving artificial respiration in an Intensive Care Unit (ICU).

2. What you need to know before you use Diprivan
Do not use Diprivan :
x If you are allergic to propofol or any of the other ingredients of this medicine (listed in
Section 6).
x If you are allergic to peanut or soya. This is because Diprivan contains soya oil.
x If you are pregnant (see the section called ‘Pregnancy and breast-feeding’).
x If 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.

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Warnings and precautions
Diprivan is not recommended in children aged less than 3 years.
Talk to your doctor, anaesthetist or nurse before using Diprivan:
x If you have ever had a fit or convulsion.
x If you have ever been told that you have very high levels of fat in your blood.
x If you have ever been told that your body has problems using fat.
x If your body has lost lots of water (you are dehydrated).
x If you have any other health problems, such as problems with your heart, breathing,
kidneys or liver.
x If you have been generally unwell for some time.
x If you have mitochondrial disease.
If you are not sure if any of the above apply to you, talk to your doctor or nurse before having
Diprivan.
Other medicines and Diprivan
Tell your doctor if you are taking, have recently taken or might take any other medicines.
This includes medicines that you buy without a prescription and herbal medicines.
In particular, tell your doctor, anaesthetist or nurse if you are taking any of the following
medicines:
x Rifampicin (for tuberculosis – TB).
Pregnancy, breast-feeding and fertility
x Do not have Diprivan if you are pregnant.
x If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a
baby, ask your doctor for advice before taking 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.
x If you are able to go home shortly after having Diprivan, do not drive a car or use any
tools or machines.
x Ask your doctor when you can start doing these activities again and when you can go
back to work.
Diprivan contains sodium, soya oil and disodium edetate.
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 medicinal
product.
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 use 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.
x The doctor will give you the injection through a fine plastic tube called a ‘cannula’.

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x

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.).
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, this medicine can 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 (may affect more than 1 in 10 people)
x A feeling of pain at the site of the injection (while the injection is being given,
before you fall asleep).
Common (may affect up to 1 in 10 people)
x Low blood pressure.
x Changes in your breathing pattern.
x Slow heart beat.
Rare (may affect up to 1 in 1,000 people)
x Twitching and shaking of your body, or a fit (may also happen when you wake
up).
x Unusual colour of urine (may also happen when you wake up).
Very rare (may affect up to 1 in 10,000 people)
x Allergic reactions.
x Stopping of your heart beat.
x Build up of fluid in the lungs which can make you very breathless (may also
happen when you wake up).
Not known: frequency cannot be estimated from the available data:
x

Shallow breathing.

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 (may affect up to 1 in 10 people)
x Feeling sick (nausea).
x Being sick (vomiting).
x Headache.

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Uncommon (may affect up to 1 in 100 people)
x Swelling and redness along a vein or blood clots.
Very rare (may affect up to 1 in 10,000 people)
x Feeling sexually aroused.
x High temperature (fever).
x Redness or soreness where the injection was given.
x Being unconscious after the operation. (When this has happened, the patients have
recovered without problems.)
x Tissue damage.
Not known: frequency cannot be estimated from the available data
x A feeling of pain at the site of the injection.
x Swelling at the site of injection.
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 (may affect up to 1 in 10,000 people)
x Heart failure.
x Inflamed pancreas (pancreatitis) which causes severe stomach pain.
x Too much acid in your blood. This may make you breathe more quickly.
x Increased amount of potassium in your blood.
x High blood level of a type of fat called lipids.
x Abnormal heart beat.
x Enlargement of the liver.
x Kidney failure.
The following side effects have been seen in children in intensive care when Diprivan has
been stopped suddenly.
Common (may affect up to 1 in 10 people)
x ‘Withdrawal symptoms’. These include unusual behaviour, sweating, shaking and
feeling anxious.
x Flushing of the skin.
Do not be concerned by this list of possible side effects. You may not get any of them.
Not known: frequency cannot be estimated from the available data
x Euphoric mood.
x Involuntary movements.
x Drug abuse and dependence on Diprivan, mostly by healthcare professionals.
x Abnormal ECG.
x 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.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any
possible side effects not listed in this leaflet. You can also report side effects directly via the

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Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard. By reporting side effects you
can help provide more information on the safety of this medicine.

5. How to store Diprivan
x
x
x
x

Keep this medicine out of the sight and reach of children.
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 after EXP.

6. Contents of the pack and other information
What Diprivan 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.
What Diprivan 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.
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
Reference number

Diprivan 2%
17901/0008 or 17901/0009

This is a service provided by the Royal National Institute of the Blind.

This leaflet was last revised inNovember 2014.
Diprivan is a trade mark of the AstraZeneca group of companies.
© AstraZeneca 2014

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UK PAI 14 0024

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Medical Information Leaflet

Diprivan 2%
(Issued to the Medical Professions Only)
1.

Tradename of the Medicinal Product
Diprivan 20 mg/ml (2%) emulsion for injection or infusion

2.

Qualitative and Quantitative Composition
Propofol 20 mg/ml
Excipient(s) with known effect:
Soya-bean Oil, Refined Ph Eur
For the full list of excipients, see section 6.1.

3.

Pharmaceutical Form
Emulsion for injection or infusion
White aqueous isotonic oil-in-water emulsion

4.

Clinical Particulars

4.1

Therapeutic indications
Diprivan 2% is a short-acting intravenous general anaesthetic for:

4.2

x

Induction and maintenance of general anaesthesia in adults and children >3 years.

x

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

x

Sedation of ventilated patients >16 years of age in the intensive care unit.

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
Posology
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

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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).
Older people
In older people 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.
Paediatric population
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.
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.
Older people
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 older people as this may lead to cardiorespiratory
depression.
Paediatric population
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).

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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.
Older people
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 older
people as this may lead to cardiorespiratory depression.
Paediatric population
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.
Older people
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

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in dose and dose rate. Rapid bolus administration (single or repeated) should not be
used in older people as this may lead to cardiorespiratory depression.
Paediatric population
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%.
In ASA 3 and 4 patients lower doses may be required.

4.2.5 Administration
Method of 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. Profound hypotension has been reported following
anaesthetic induction with propofol in patients treated with rifampicin.
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:
x
x
x

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.

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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 Diprifusor allow the anaesthetist to achieve and control a desired speed of
induction and depth of anaesthesia by setting and adjusting target (predicted) blood
concentrations of propofol. An alternative mode of administration may be accessible
on some Diprifusors but is not recommended for use in the UK.
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.
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.

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4.3

Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section
6.1.
Diprivan 2% contains soya oil and should not be used in patients who are
hypersensitive to peanut or soya.
Diprivan 2% must not be used in patients of 16 years of age or younger for sedation in
intensive care (see section 4.4).

4.4

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.
Abuse of and dependence on Diprivan 2%, predominantly by health care
professionals, have 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:
x
The advisability of being accompanied on leaving the place of administration
x
The timing of recommencement of skilled or hazardous tasks such as driving
x
The use of other agents that may sedate (Eg, benzodiazepines, opiates, alcohol.)

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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).
Use is not recommended with electroconvulsive treatment.
As with other anaesthetics sexual disinhibition may occur during recovery.
Paediatric population
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.
Diprivan 2% is not recommended for use in children < 3 years of age due to difficulty
in titrating small volumes.
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

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dosages of one or more of the following pharmacological agents - vasoconstrictors,
steroids, inotropes and/or Diprivan 2% (usually at dose rates greater than 4mg/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 Diprivan 2% dosage when the above
signs develop. All sedative and therapeutic agents used in the intensive care unit
(ICU), should be titrated to maintain optimal oxygen delivery and haemodynamic
parameters. Patients with raised intra-cranial pressure (ICP) should be given
appropriate treatment to support the cerebral perfusion pressure during these treatment
modifications.
Treating physicians are reminded if possible not to exceed the dosage of 4 mg/kg/h.
Appropriate care should be applied in patients with disorders of fat metabolism and in
other conditions where lipid emulsions must be used cautiously.
It is recommended that blood lipid levels should be monitored if propofol is
administered to patients thought to be at particular risk of fat overload. Administration
of propofol should be adjusted appropriately if the monitoring indicates that fat is
being inadequately cleared from the body. If the patient is receiving other intravenous
lipid concurrently, a reduction in quantity should be made in order to take account of
the amount of lipid infused as part of the propofol formulation; 1.0 mL of Diprivan
contains approximately 0.1 g of fat.

Diprivan 2% contains 0.0018 mmol sodium per ml. To be taken into consideration by
patients on a controlled sodium diet.
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.
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.
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

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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.
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.

4.5

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

4.6

Fertility, 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.
Breast-feeding
Studies of breastfeeding mothers showed that small quantities of Diprivan 2% are
excreted in human milk. Women should therefore not breast-feed 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
Diprivan 2% has moderate influence on the 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).

4.8

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

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The following definitions of frequencies are used:
 
   
    
 
    
       



 


estimated from the available data).

Table of Adverse Drug Reactions
System Organ Class

Frequency

Undesirable Effects

Immune system disorders

Very rare

Anaphylaxis – may include
angioedema, bronchospasm,
erythema and hypotension

Metabolism and nutrition
disorders

Not known (9)

Metabolic acidosis (5),
hyperkalaemia (5),
hyperlipidaemia (5)

Psychiatric disorders

Not known (9)

Euphoric mood. Drug abuse
and drug dependence (8)

Nervous system disorders

Common

Headache during recovery
phase

Rare

Epileptiform movements,
including convulsions and
opisthotonus during induction,
maintenance and recovery

Very rare

Postoperative unconsciousness

Not known (9)

Involuntary movements

Common

Bradycardia (1)

Very rare

Pulmonary oedema

Not known (9)

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

Common

Hypotension (2)

Uncommon

Thrombosis and phlebitis

Common

Transient apnoea during
induction

Not known

Respiratory depression (dose
dependent)

Cardiac disorders

Vascular disorders

Respiratory, thoracic and
mediastinal disorders

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Gastrointestinal disorders

Common

Nausea and vomiting during
recovery phase

Very rare

Pancreatitis

Hepatobiliary disorders

Not known (9)

Hepatomegaly (5)

Musculoskeletal and
connective tissue disorders

Not known (9)

Rhabdomyolysis (3), (5)

Renal and urinary disorders

Very rare

Discolouration of urine
following prolonged
administration

Not known (9)

Renal failure(5)

Reproductive system and
breast disorders

Very rare

Sexual disinhibition

General disorders and
administration site
conditions

Very common

Local pain on induction (4)

Very rare

Tissue necrosis (10) following
accidental extravascular
administration

Not known

Local pain, swelling, following
accidental extravascular
administration

Investigations

Not known (9)

Brugada type ECG (5), (6)

Injury, poisoning and
procedural complications

Very rare

Postoperative fever

(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 Diprivan.
Very rare reports of rhabdomyolysis have been received where Diprivan 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 Diprivan
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.

Dystonia/dyskinesia have been reported.

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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.
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 Yellow Card Scheme. Website: 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 would 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 general anaesthetics
ATC code: N01AX10
Mechanism of action
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 ligand-gated GABAA receptors.
Pharmacodynamic effects
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.
Clinical efficacy and safety
Recovery from anaesthesia is usually rapid and clear-headed with a low incidence of
headache and postoperative nausea and vomiting.

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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.
Diprivan 2%, at the concentrations likely to occur clinically, does not inhibit the
synthesis of adrenocortical hormones.
Paediatric population
Limited studies on the duration of propofol based anaesthesia in children indicate
safety and efficacy is unchanged up to duration of 4 hours. Literature evidence of use
in children documents use for prolonged procedures without changes in safety or
efficacy.

5.2

Pharmacokinetic properties
Absorption
When Diprivan 2% is used to maintain anaesthesia, blood concentrations
asymptotically approach the steady-state value for the given administration rate.
Distribution
Propofol is extensively distributed and rapidly cleared from the body (total body
clearance 1.5–2 litres/minute).
Elimination
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.
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).
Linearity
The pharmacokinetics are linear over the recommended range of infusion rates of
Diprivan 2%.

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.

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6.

Pharmaceutical Particulars

6.1

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:
x
x
x

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 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

Special precautions for disposal and other 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:
x
x
x

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.

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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.
This leaflet was last revised in November 2014.
© AstraZeneca 2014
Diprivan is a trade mark of the AstraZeneca group of companies.
PAI 14 0024

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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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