Package leaflet: Information for the patient

DIPRIVAN 10 mg/ml injectable emulsion for intravenous use, 10 mg/ml infusion emulsion, 20 mg/ml infusion emulsion

propofol
Please read this leaflet carefully before this medicine is administered to you because
it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or nurse.
If you get any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Diprivan is and what it is used for
What you need to know before Diprivan is administered to you
How Diprivan will be administered to you
Possible side effects
How to store Diprivan
Contents of the pack and other information

1. What Diprivan is and what it is used for

Diprivan is a medicine for intravenous use, containing the active substance propofol, a medicine belonging to the group of medicines called "general anaesthetics".
Diprivan is used by the anaesthetist (the doctor who administers anaesthesia) to:

induce and maintain general anaesthesia (a state of general body numbness with loss of consciousness) during surgical procedures. Diprivan 10 mg/ml is used in adults, adolescents and children over one month of age. Diprivan 20 mg/ml is used in adults, adolescents and children over 3 years of age.
provide sedation (physical and mental relaxation) during intensive care in adults and adolescents over 16 years of age who are receiving assisted respiration from a machine.

2. What you need to know before you are given Diprivan

You must not be given Diprivan

if you are allergic to propofol or to any of the other ingredients of this medicine (listed in section 6)
if you are allergic to peanuts or soya (see section “Diprivan contains soya oil”)
if the patient is a child or adolescent under 16 years of age and sedation during intensive care treatment is required.

Warnings and precautions
This medicine is available only in hospital. Therefore, this medicine will be administered to you only under close supervision by qualified medical personnel.
In particular, before you are given Diprivan, inform your doctor:

if you have heart disorders (heart failure) or a severe heart disease
if you have lung disorders or breathing difficulties
if you have kidney disorders (renal failure)
if you have liver disorders (hepatic failure)
if you are in a condition with reduced blood volume (hypovolemia)
if you are debilitated (a state of physical and mental weakness)
if you have increased pressure of the blood inside the skull (elevated intracranial pressure)
if you have low blood pressure
if you have epilepsy (a disease characterized by seizures, involuntary contractions of certain muscles), as this may increase the risk of seizures
if you have disorders related to fat metabolism or any other condition requiring caution when lipid emulsions (oily preparations) are administered. In such cases, your doctor will measure the level of fats in your blood and, if necessary, adjust the administration of Diprivan
if you have mitochondrial disorders, as your condition may worsen during anaesthesia, surgery, or intensive care treatments
if you are prone to developing zinc deficiencies.

Children and adolescents

Diprivan must not be administered to children aged 16 years or younger when used for sedation during intensive care.
Diprivan 10 mg/ml is not recommended in neonates (age up to and including one month).
Diprivan 20 mg/ml is not recommended in children aged 3 years or younger.

Animal studies in young animals and preclinical data suggest that repeated or prolonged use of general anaesthetics or sedatives in children under 3 years of age or in pregnant women during the third trimester may have negative effects on the child's brain development. Parents and caregivers should discuss with their doctors the benefits, risks, timing, and duration of surgery or procedures requiring anaesthesia or sedation.
In rare cases, after prolonged administration of propofol, a condition known as Propofol Infusion Syndrome (PIS) may develop. This condition may damage the heart, muscles, and kidneys, cause other serious problems, and may lead to death. However, your doctor will closely monitor you and take necessary measures to prevent this from occurring.
Other medicines and Diprivan
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, as several medicines may interact with propofol.
In particular, inform your doctor if you are taking:

rifampicin (an antibiotic), as cases of severe drop in blood pressure have been reported when used together with Diprivan
dexmedetomidine (used to induce sedation (a very relaxed state of calm, drowsiness, or sleep))
midazolam (used to induce sedation (a very relaxed state of calm, drowsiness, or sleep) and to reduce anxiety and muscle tension).

Diprivan and alcohol
Using Diprivan with alcoholic drinks may increase sedation (physical and mental relaxation).
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before you are given this medicine.
Pregnancy
The safety of Diprivan in pregnant women has not been established; therefore, Diprivan must not be administered during pregnancy. However, your doctor may administer this medicine during pregnancy only if absolutely necessary.
Diprivan passes through the placenta (the barrier separating maternal and fetal blood) and may cause respiratory depression in the newborn.
Your doctor may administer Diprivan during an induced abortion.
Breastfeeding
Studies have shown that small amounts of Diprivan pass into breast milk. Therefore, you must not breastfeed your baby for 24 hours after receiving Diprivan.
Breast milk produced during this time must not be used.
Driving and using machines
After general anaesthesia, your ability to drive or operate machinery may be impaired for some time. This means that until your doctor considers you fully recovered, you must not drive or operate machinery after surgery.
Your doctor will assess whether you need to be accompanied when leaving the hospital.
Diprivan contains sodium
Diprivan 10 mg/ml contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.
Diprivan 20 mg/ml contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.
Diprivan contains soya oil
Diprivan 10 mg/ml contains soya oil. If you are allergic to peanuts or soya, do not use this medicine.
Diprivan 20 mg/ml contains soya oil. If you are allergic to peanuts or soya, do not use this medicine.

3. How Diprivan will be administered to you

This medicine is available only in a hospital setting. Therefore, this medicine will be administered to you only under the close supervision of qualified medical personnel.
Your anaesthetist (the doctor performing the anaesthesia) will determine the most suitable dose for you based on your age, weight, and general health condition. Your doctor will administer the appropriate dose of Diprivan to induce and maintain anaesthesia or to achieve the desired level of sedation, carefully monitoring your response and vital signs (pulse, blood pressure, etc.).

Use in children and adolescents
The dose will be determined by the anaesthetist based on the child's age and weight.
Diprivan is not administered to children aged 16 years or younger when used for sedation during intensive care therapy.
Diprivan 10 mg/ml is not recommended in neonates (age ≤1 month).
Diprivan 20 mg/ml is not recommended in children aged 3 years or younger.

Method of administration
Diprivan 10 mg/ml will be administered to you either by repeated intravenous injections or by continuous intravenous infusion.
Diprivan 20 mg/ml will be administered to you only by continuous intravenous infusion.
For sedation in intensive care, your doctor will administer propofol by intravenous infusion.
Sleep induction occurs within 1–5 minutes after administration.
If you are elderly or debilitated, or have lung, heart, kidney, or liver problems, or are in a condition with reduced blood volume (hypovolemia), your doctor will reduce the infusion rate of propofol.
If you are receiving intensive care treatment in hospital, your doctor will arrange for blood tests after 3 days of propofol administration to assess your blood fat (lipid) levels.
You will be discharged once your doctor has ensured a full recovery of your physical and mental condition.

If you are given more Diprivan than you should
It is highly unlikely that you will be given more Diprivan than required, as your doctor will closely monitor you during treatment.
However, if an excessive dose of Diprivan is administered, your doctor will provide appropriate supportive therapy.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
During administration of Diprivan, the following serious side effects may occur; in such cases, the doctor will immediately initiate appropriate treatment:

allergic reactions, even severe (anaphylaxis), including anaphylactic shock, such as:
- swelling of hands, feet, ankles, face, lips, tongue and/or throat (angioedema)
- narrowing of the bronchi causing severe breathing difficulty due to reduced airflow (bronchospasm)
- skin irritation (erythema)
- low blood pressure (hypotension). Allergic reactions may also occur if you are allergic to soya oil, peanuts, and soya (see sections “Diprivan contains soya oil” and “You will not be given Diprivan”)
reduced heart rate (bradycardia)
severe heart disease (heart failure), which may lead to death.

The side effects are listed below according to the following frequency:
Very common (may affect more than 1 in 10 people)

pain at the injection site

Common (may affect up to 1 in 10 people)
During the recovery phase, the following may occur:

headache (cephalalgia)
nausea, vomiting
During induction of anaesthesia, depending on the dose administered and concomitant use of other medicines, the following may occur:
low blood pressure
brief respiratory arrest

Uncommon (may affect up to 1 in 100 people)

formation of a blood clot inside a blood vessel (thrombosis)
inflammation of a vein (phlebitis)

Rare (may affect up to 1 in 1,000 people)

seizures (involuntary contraction of certain muscles as in epilepsy), even hours or days after propofol administration
severe muscle spasm of head, neck and back (opisthotonus)

Very rare (may affect up to 1 in 10,000 people)

postoperative unconsciousness
tissue death (necrosis) at the site of administration following accidental extravascular injection of Diprivan
fluid accumulation in the lungs (pulmonary edema)
inflammation of the pancreas (pancreatitis)
discoloration of urine following prolonged administration
sexual disinhibition. This effect may occur during induction of anaesthesia and depends on the dose administered and concomitant use of other medicines
postoperative fever

Not known (frequency cannot be estimated from available data)

increased levels of acid in the blood (metabolic acidosis)
increased levels of potassium in the blood (hyperkalemia)
increased levels of fat in the blood (hyperlipidemia)
euphoric mood
drug abuse
drug dependence (mainly among healthcare professionals)
involuntary movements
change in heart rhythm, i.e. number of heartbeats per minute (cardiac arrhythmia)
severe heart disease (heart failure)
respiratory depression (dose-dependent)
enlargement of the liver (hepatomegaly)
muscle damage (rhabdomyolysis)
reduced kidney function (renal failure)
pain at the site of administration
swelling at the site of administration following accidental extravascular injection of Diprivan (edema)
electrocardiogram (ECG) abnormalities (Brugada-type), a test to assess heart function
prolonged and painful erection (priapism)
hepatitis (liver inflammation), acute liver failure whose symptoms may include yellowing of the skin and eyes, itching, dark urine, stomach pain and liver tenderness (pain felt under the front part of the rib cage on the right side), sometimes with loss of appetite.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Diprivan

Keep this medicine out of the sight and reach of children.
The anaesthetist and the hospital pharmacist are responsible for the correct storage, use, and
distribution of the medicine.
Store between +2°C and +25°C. Do not freeze.
Do not use this medicine after the expiry date stated on the carton after "Exp".
The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Diprivan contains
Diprivan 10 mg/ml

The active substance is: propofol (1 ml contains 10 mg of propofol)
The other components are: edetate disodium, sodium hydroxide, refined soya oil, purified egg phosphatide, glycerol, water for injections.

Diprivan 20 mg/ml

The active substance is: propofol (1 ml contains 20 mg of propofol)
The other components are: edetate disodium, sodium hydroxide, refined soya oil, purified egg phosphatide, glycerol, sodium hydroxide, water for injections.

Description of the appearance of Diprivan and contents of the pack
Diprivan 10 mg/ml
Diprivan 10 mg/ml is presented as a white emulsion for intravenous use in the following presentations:
Diprivan 10 mg/ml injectable emulsion:

5 colourless transparent glass vials of 20 ml

Diprivan 10 mg/ml emulsion for infusion:

1 colourless transparent glass vial of 50 ml
1 pre-filled colourless transparent glass syringe of 20 ml with 1 connecting needle
1 pre-filled colourless transparent glass syringe of 50 ml with 1 connecting needle

Diprivan 20 mg/ml
Diprivan 20 mg/ml is presented as a white emulsion for intravenous use in the following presentation:
Diprivan 20 mg/ml emulsion for infusion:

1 colourless transparent glass vial of 50 ml
1 pre-filled colourless transparent glass syringe of 10 ml with 1 connecting needle
1 pre-filled colourless transparent glass syringe of 50 ml with 1 connecting needle.

Not all pack sizes may be marketed.
Marketing Authorization Holder
Aspen Pharma Trading Limited
3016 Lake Drive
Citywest Business Campus
Dublin 24
Ireland
Tel: +39 0687 502 429
Manufacturer
Corden Pharma S.p.A., Viale dell’Industria 3, 20867 Caponago (MB), Italy

The following information is intended exclusively for healthcare professionals:

Administration method:
Diprivan 20 mg/ml must not be diluted with other infusion fluids.
Maintenance of general anesthesia is achieved with:
Diprivan 10 mg/ml via repeated boluses or infusion
Diprivan 20 mg/ml via infusion.
Sedation in intensive care is performed by propofol infusion; it is recommended not to exceed
a dose of 4 mg/kg/h.
Elimination of propofol depends on blood flow; therefore, concomitant administration of
drugs that reduce blood flow may also reduce propofol elimination.

Administration method of Diprivan 20 mg/ml
The dose of Diprivan 20 mg/ml must be individualized by an experienced anesthesiologist based on body
weight, patient sensitivity, and concomitant therapies. Propofol is a short-acting intravenous anesthetic and
has been used in combination with spinal and epidural anesthesia.
It is recommended to titrate the propofol dose according to the patient's response until clinical onset of
anesthesia is evident.
The contents of a vial or bottle of Diprivan 20 mg/ml are intended for single use in one patient only.
For specific instructions regarding administration of Diprivan via the computerized infusion system
“Diprifusor” TCI (Target Controlled Infusion) containing the “Diprifusor” software, see:
“TCI administration method – Administration of Diprivan via the ‘Diprifusor’ TCI system”.
This system is intended exclusively for induction and maintenance of anesthesia in adults. Use of the
“Diprifusor” TCI system is not recommended for intensive care sedation or in children.

Induction of general anesthesia
Adults
For adult patients under 55 years of age, doses between 1.5 and 2.5 mg/kg are required.
In healthy adult patients, a rate of administration of approximately 1–2 ml (20–40 mg) over ten seconds is
required.
In high-risk patients classified as ASA (American Society of Anesthesiologists) classes 3 and 4, the rate of
administration should be 1 ml (20 mg) every 10 seconds.

Children over 3 years of age
Diprivan 20 mg/ml is not recommended for induction of general anesthesia in children under 3 years of age.
It is recommended to administer Diprivan 20 mg/ml slowly until clinical onset of anesthesia is evident.
The dose should be proportionate to age and/or body weight.
Most children over eight years of age require a dose of approximately 2.5 mg/kg for induction of anesthesia.
For younger children, the required dose may be higher (2.5–4 mg/kg). Due to lack of clinical experience, lower
doses are recommended for high-risk children (ASA grade III and IV).
Administration of Diprivan via the “Diprifusor” TCI system is not recommended in children for any indication.

Elderly
In patients over 55 years of age, a lower dose is generally required.

Maintenance
Anesthesia should be maintained by continuous infusion of Diprivan 20 mg/ml to prevent signs of light anesthesia.
 Infusion in adults: 4–12 mg/kg/h.
 Infusion in elderly, debilitated, hypovolemic, and ASA class III and IV patients: 4 mg/kg/h.
 Infusion in children over three years of age: the required rate of administration varies considerably between patients, but rates of 9–15 mg/kg/h usually allow satisfactory anesthesia. In younger children, the required dose may be higher.
Lower doses are recommended in ASA class III and IV patients (see also section 4.4).
Administration of Diprivan 20 mg/ml is not recommended for maintenance of anesthesia in children under 3 years of age.

Sedation in ventilated patients in Intensive Care Units (ICU)
For sedation of patients in intensive care units, Diprivan 20 mg/ml should be administered via continuous infusion. The infusion rate depends on the required depth of sedation; generally, infusion rates between 0.3 and 4.0 mg/kg/h allow satisfactory levels of sedation.
Diprivan 20 mg/ml is not indicated for sedation of patients under 16 years of age in Intensive Care Units.
It is recommended not to exceed a dose of 4 mg/kg/h.
Administration of Diprivan via the “Diprifusor” TCI system is not recommended during intensive care sedation.
There are no data on optimal site-of-action concentration for sedation of ventilated ICU patients (see section TCI – Target Controlled Infusion); therefore, such use is not recommended.

Infusion administration
Diprivan 20 mg/ml must not be administered as a bolus injection but only by infusion.
Diprivan 20 mg/ml can be administered using various infusion techniques. For maintenance of anesthesia, it is recommended to infuse Diprivan 20 mg/ml using a volumetric pump or syringe pump to control the rate of administration.
Diprivan 20 mg/ml must not be diluted.
Diprivan 20 mg/ml must not be mixed before administration with other injectable fluids.
However, Diprivan 20 mg/ml may be administered simultaneously, via a “Y”-site connector close to the injection site, with the following intravenous infusions:

5% Dextrose
0.9% Sodium chloride

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

Additional use information for Diprivan 20 mg/ml
Diprivan may be administered simultaneously via a “Y”-site connector close to the injection site with intravenous infusions of 5% glucose, 0.9% sodium chloride, or 4% glucose with 0.18% sodium chloride.
The pre-filled glass syringe has lower gliding resistance than disposable plastic syringes and functions more easily. Therefore, if Diprivan is administered manually using a pre-filled syringe without a pump, the infusion line between the syringe and the patient must not be left unattended.
When pre-filled syringes are used, it is important to ensure compatibility with syringe pumps. In particular, pumps must be designed to prevent uncontrolled infusions and must have an occlusion alarm system with pressure not exceeding 1000 mm Hg. If a programmable or equivalent pump is used for Diprivan pre-filled syringes, allowing selection among different syringe types, the program B'-D' 50/60 ml "PLASTIPAK" must be selected.

TCI (Target Controlled Infusion) – Administration of Diprivan via the “Diprifusor” TCI system
Diprivan can be administered via TCI using the “Diprifusor” TCI system containing the “Diprifusor” TCI software. This system operates only through electronic recognition of a site on pre-filled syringes containing Diprivan 10 mg/ml or Diprivan 20 mg/ml. The “Diprifusor” TCI system automatically adjusts the infusion rate to achieve the concentration selected by the operator. The user must be familiar with the infusion pump user manual, administration of Diprivan via the TCI system, and correct use of the syringe identification system—all of which are detailed in the “Diprifusor” user manual available from AstraZeneca.
The “Diprifusor” TCI system can provide two modes of optimally controlled infusion: optimal blood concentration and optimal site-of-action concentration (brain). Previous models provide only the optimal blood concentration mode.
Administration of Diprivan via the “Diprifusor” TCI system is indicated only in adults for induction and maintenance of general anesthesia. It is not recommended for intensive care sedation or in children.
To achieve induction and maintenance of anesthesia in adults, Diprivan can be administered via a computerized infusion system (TCI). This system allows control of induction and depth of anesthesia or sedation by selecting and adjusting theoretical optimal blood or site-of-action concentrations of propofol. Use of the site-of-action optimal concentration mode allows faster induction of sedation or anesthesia compared to the optimal blood concentration mode.
If the “Diprifusor” TCI system has been used for anesthesia, it may be continued in the postoperative period to provide intensive care sedation by appropriate selection of the optimal concentration.
Below is a guide to optimal propofol concentrations.
Due to inter-individual variability in propofol pharmacokinetics and pharmacodynamics, both in premedicated and non-premedicated patients, optimal propofol concentrations should be selected based on patient response to achieve the required depth of anesthesia.
In adult patients under 55 years of age, anesthesia can generally be induced with optimal blood concentrations of propofol of 4–8 micrograms/ml or with optimal site-of-action concentrations of 2.5–4 micrograms/ml. In premedicated patients, an initial optimal blood concentration of 4 micrograms/ml or an optimal site-of-action concentration of 2.5 micrograms/ml is recommended; in non-premedicated patients, an initial optimal blood concentration of 6 micrograms/ml or an optimal site-of-action concentration of 4 micrograms/ml is recommended. Induction time with optimal blood concentrations is generally 60–120 seconds. Higher optimal blood concentrations allow faster induction of anesthesia but may cause more pronounced respiratory and hemodynamic depression.
When using optimal site-of-action concentrations, using higher optimal concentrations to achieve faster anesthesia induction is unnecessary and not recommended.
Lower initial concentrations should be used in patients over 55 years of age and in ASA grade 3–4 patients (use of the site-of-action mode in ASA grade 4 patients is not recommended). For the site-of-action mode, an initial optimal concentration of 0.5–1.0 micrograms/ml should be used. For both optimal concentration modes, concentrations may then be increased in successive increments of 0.5–1.0 micrograms/ml at one-minute intervals to achieve gradual induction of anesthesia.
Supplemental analgesia is generally required, and the extent of reduction in optimal concentrations for maintenance of anesthesia is related to the amount of concomitantly administered analgesic. Optimal blood concentrations of propofol of 3–6 micrograms/ml and optimal site-of-action concentrations of 2.5–4 micrograms/ml usually induce and maintain satisfactory anesthesia. In the absence of additional analgesia, higher optimal site-of-action concentrations of 5–6 micrograms/ml may be necessary to facilitate laryngoscopy or suppress responses to painful stimuli.
For both optimal concentration modes, predicted propofol concentrations (blood or site-of-action) at awakening are generally in the range of 1.0–2.0 micrograms/ml and depend on the amount of analgesic administered during maintenance. When optimal concentrations are reduced, the “Diprifusor” temporarily stops the infusion to allow concentrations to decrease and reach a new target more quickly.

Administration method of Diprivan 10 mg/ml
The dose of Diprivan must be individualized by an experienced anesthesiologist based on age and/or body weight, patient sensitivity, and concomitant therapies. Propofol is a short-acting intravenous anesthetic and has been used in combination with spinal and epidural anesthesia.
It is recommended to titrate the propofol dose based on patient response until clinical onset of anesthesia is evident.
The contents of a vial or bottle of Diprivan are intended for single use in one patient only.
For specific instructions regarding administration of Diprivan via the computerized infusion system “Diprifusor” TCI (Target Controlled Infusion) containing the “Diprifusor” software, see: “TCI administration method – Administration of Diprivan via the ‘Diprifusor’ TCI system”. Use of this system is intended exclusively for induction and maintenance of anesthesia in adults. Use of the “Diprifusor” TCI system is not recommended for intensive care sedation or in children.

Induction of general anesthesia
Adults
For adult patients under 55 years of age, doses between 1.5 and 2.5 mg/kg are required. In healthy adult patients, a rate of administration of approximately 2–4 ml (20–40 mg) over ten seconds is required. In high-risk patients classified as ASA (American Society of Anesthesiologists) classes 3 and 4, the rate of administration should be 2 ml (20 mg) over 10 seconds.

Children over 1 month of age
It is recommended to administer Diprivan slowly until clinical onset of anesthesia is evident.
The dose should be proportionate to age and/or body weight.
Most children over eight years of age require a dose of approximately 2.5 mg/kg for induction of anesthesia.
For younger children, particularly those between 1 month and 3 years of age, the required dose may be higher (2.5–4 mg/kg). Due to lack of clinical experience, lower doses are recommended for high-risk children (ASA grade III and IV).
Administration of Diprivan via the “Diprifusor” TCI system is not recommended in children for any indication.

Elderly
In patients over 55 years of age, a lower dose is generally required.

Maintenance
Anesthesia should be maintained by administering Diprivan 10 mg/ml to prevent signs of light anesthesia, either via repeated boluses of 25 mg (2.5 ml) to 50 mg (5.0 ml) or via continuous infusion:
 in adults: 4–12 mg/kg/h.
 in elderly, debilitated, hypovolemic, and ASA class III and IV patients: 4 mg/kg/h.
 in children over 1 month of age: the required rate of administration varies considerably between patients, but rates of 9–15 mg/kg/h generally allow satisfactory anesthesia. In younger children, particularly those between 1 month and 3 years of age, the required dose may be higher.
Lower doses are recommended in ASA class III and IV patients (see also section 4.4).

Sedation in ventilated patients in Intensive Care Units (ICU)
For sedation of patients in intensive care units, Diprivan should be administered via continuous infusion. The infusion rate depends on the required depth of sedation; generally, infusion rates between 0.3 and 4.0 mg/kg/h allow satisfactory levels of sedation.
Propofol is not indicated for sedation of patients under 16 years of age in Intensive Care Units.
It is recommended not to exceed a dose of 4 mg/kg/h.
Administration of Diprivan via the “Diprifusor” TCI system is not recommended during intensive care sedation.
There are no data on optimal site-of-action concentration for sedation of ventilated ICU patients (see section TCI – Target Controlled Infusion); therefore, such use is not recommended.

Infusion administration
Diprivan 10 mg/ml, either undiluted or diluted in 5% dextrose solution, may be administered by intravenous infusion using various infusion control systems.
When used undiluted for maintenance of anesthesia, syringe pumps or volumetric pumps capable of controlling infusion rate must be used.
For diluted emulsion, the infusion line must include at least a burette, drip chamber, or volumetric pump to avoid the risk of accidental and uncontrolled administration of large volumes of Diprivan 10 mg/ml.
The maximum volume of diluted solution to be added to the burette must be calculated considering the risk of uncontrolled infusion.
Diprivan 10 mg/ml may be administered simultaneously via a “Y”-site connector close to the injection site with intravenous infusions of 0.9% sodium chloride or 5% dextrose.
Diprivan 10 mg/ml may be premixed with 5% dextrose intravenous infusion solutions in glass bottles or PVC infusion bags. One part of Diprivan 10 mg/ml should be mixed with up to four parts of 5% dextrose. In the case of PVC bags, it is recommended that the bag be full and that the volume removed from the bag for dilution be replaced with an equal volume of Diprivan 10 mg/ml.
The diluted emulsion should be prepared under appropriate aseptic conditions immediately before administration and used within 6 hours of dilution.
Only in cases of anesthesia induction may Diprivan 10 mg/ml be premixed immediately before administration and aseptically with injectable lidocaine hydrochloride (0.5–1%, without preservatives) in a ratio of 20 parts Diprivan 10 mg/ml to up to 1 part injectable lidocaine hydrochloride (0.5–1%, without preservatives).
Diprivan 10 mg/ml may be premixed with injectable solution of 500 micrograms/ml alfentanil in a ratio from 20:1 to 50:1 v/v. Mixtures must be prepared using sterile technique and used within 6 hours of preparation.

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

Additional use information for Diprivan 10 mg/ml
Diprivan may be administered simultaneously via a “Y”-site connector close to the injection site with intravenous infusions of 5% glucose, 0.9% sodium chloride, or 4% glucose with 0.18% sodium chloride.
The pre-filled glass syringe has lower gliding resistance than disposable plastic syringes and functions more easily. Therefore, if Diprivan is administered manually using a pre-filled syringe without a pump, the infusion line between the syringe and the patient must not be left unattended.
When pre-filled syringes are used, it is important to ensure compatibility with syringe pumps. In particular, pumps must be designed to prevent uncontrolled infusions and must have an occlusion alarm system with pressure not exceeding 1000 mm Hg. If a programmable or equivalent pump is used for Diprivan pre-filled syringes, allowing selection among different syringe types, the program B'-D' 50/60 ml "PLASTIPAK" must be selected.

TCI (Target Controlled Infusion) – Administration of Diprivan via the “Diprifusor” TCI system
Diprivan can be administered via TCI using the “Diprifusor” TCI system containing the “Diprifusor” TCI software. This system operates only through electronic recognition of a site on pre-filled syringes containing Diprivan 10 mg/ml or Diprivan 20 mg/ml. The “Diprifusor” TCI system automatically adjusts the infusion rate to achieve the concentration selected by the operator. The user must be familiar with the infusion pump user manual, administration of Diprivan via the TCI system, and correct use of the syringe identification system—all of which are detailed in the “Diprifusor” user manual available from AstraZeneca.
The “Diprifusor” TCI system can provide two modes of optimally controlled infusion: optimal blood concentration and optimal site-of-action concentration (brain). Previous models provide only the optimal blood concentration mode.
Administration of Diprivan via the “Diprifusor” TCI system is indicated only in adults for induction and maintenance of general anesthesia. It is not recommended for intensive care sedation or in children.
To achieve induction and maintenance of anesthesia in adults, Diprivan can be administered via a computerized infusion system (TCI). This system allows control of induction and depth of anesthesia or sedation through selection and adjustment of theoretical optimal blood or site-of-action concentrations of propofol. Use of the site-of-action optimal concentration mode allows faster induction of sedation or anesthesia compared to the optimal blood concentration mode.
If the “Diprifusor” TCI system has been used for anesthesia, it may be continued in the postoperative period to provide intensive care sedation by appropriate selection of the optimal concentration.
Below is a guide to optimal propofol concentrations.
Due to inter-individual variability in propofol pharmacokinetics and pharmacodynamics, both in premedicated and non-premedicated patients, optimal propofol concentrations should be selected based on patient response to achieve the required depth of anesthesia.
In adult patients under 55 years of age, anesthesia can generally be induced with optimal blood concentrations of propofol of 4–8 micrograms/ml or with optimal site-of-action concentrations of 2.5–4 micrograms/ml. In premedicated patients, an initial optimal blood concentration of 4 micrograms/ml or an optimal site-of-action concentration of 2.5 micrograms/ml is recommended; in non-premedicated patients, an initial optimal blood concentration of 6 micrograms/ml or an optimal site-of-action concentration of 4 micrograms/ml is recommended. Induction time with optimal blood concentrations is generally 60–120 seconds. Higher optimal blood concentrations allow faster induction of anesthesia but may cause more pronounced respiratory and hemodynamic depression.
When using optimal site-of-action concentrations, using higher optimal concentrations to achieve faster anesthesia induction is unnecessary and not recommended.
Lower initial concentrations should be used in patients over 55 years of age and in ASA grade 3–4 patients (use of the site-of-action mode in ASA grade 4 patients is not recommended). For the site-of-action mode, an initial optimal concentration of 0.5–1.0 micrograms/ml should be used. For both optimal concentration modes, concentrations may then be increased in successive increments of 0.5–1.0 micrograms/ml at one-minute intervals to achieve gradual induction of anesthesia.
Supplemental analgesia is generally required, and the extent of reduction in optimal concentrations for maintenance of anesthesia is related to the amount of concomitantly administered analgesic. Optimal blood concentrations of propofol of 3–6 micrograms/ml and optimal site-of-action concentrations of 2.5–4 micrograms/ml usually induce and maintain satisfactory anesthesia. In the absence of additional analgesia, higher optimal site-of-action concentrations of 5–6 micrograms/ml may be necessary to facilitate laryngoscopy or suppress responses to painful stimuli.
For both optimal concentration modes, predicted propofol concentrations (blood or site-of-action) at awakening are generally in the range of 1.0–2.0 micrograms/ml and depend on the amount of analgesic administered during maintenance. When optimal concentrations are reduced, the “Diprifusor” temporarily stops the infusion to allow concentrations to decrease and reach a new target more quickly.