Posology : מינונים

4.2 Posology and method of administration
Propofol 1% MCT Fresenius must only be given in hospitals or adequately equipped day therapy units by physicians trained in anaesthesia or in the care of patients in intensive care.
Circulatory and respiratory functions should be constantly monitored (e.g. ECG, pulse oxymetry) and facilities for maintenance of patient airways, artificial ventilation, and other resuscitation facilities should be immediately available at all times.

For sedation during surgical and diagnostic procedures Propofol 1% MCT Fresenius should not be administered by the same person conducting the surgical or diagnostic procedure.

The dose of Propofol 1% MCT Fresenius should be individualised based on the response of the patient and premedications used.

Supplementary analgesic agents are generally required in addition to Propofol 1% MCT Fresenius

Posology

General anaesthesia in adults
Induction of anaesthesia:

For induction of anaesthesia Propofol 1% MCT Fresenius should be titrated (approximately 20 - 40 mg propofol every 10 seconds) against the response of the patient until clinical signs show the onset of anaesthesia.

Most adult patients aged less than 55 years are likely to require 1.5 to 2.5 mg propofol/kg bodyweight.

In patients over this age and in patients of ASA grades III and IV, especially those with impaired cardiac function, the requirements will generally be less and the total dose of Propofol 1% MCT Fresenius may be reduced to a minimum of 1 mg propofol/kg bodyweight. Lower rates of administration of Propofol 1% MCT Fresenius should be used (approximately 2 ml of the 10mg/ml emulsion (20 mg propofol) every 10 seconds).

Maintenance of anaesthesia:

Anaesthesia can be maintained by administering Propofol 1% MCT Fresenius either by continuous infusion or repeat bolus injections.

For maintenance of anaesthesia generally doses of 4 to 12 mg propofol/kg bodyweight/h should be given. A reduced maintenance dose of approximately 4 mg propofol/kg bodyweight/h may be sufficient during less stressful surgical procedures such as minimal invasive surgery.

In elderly patients, patients in unstable general conditions, patients with impaired cardiac function or hypovolaemic patients and patients of ASA grades III and IV the dosage of Propofol 1% MCT Fresenius may be reduced further depending on the severity of the patient’s condition and on the performed anaesthetic technique.

For maintenance of anaesthesia with Propofol 1% MCT Fresenius using repeat bolus injections dose increments of 25 to 50 mg propofol (= 2.5 – 5 ml Propofol 1% MCT Fresenius) should be given according to clinical requirements.

Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardiopulmonary depression.

General anaesthesia in children over 1 month of age

Induction of anaesthesia:
For induction of anaesthesia Propofol 1% MCT Fresenius should be titrated slowly until clinical signs show the onset of anaesthesia.
The dose should be adjusted according to age and/or bodyweight. Most patients over 8 years of age require approximately 2.5 mg/kg bodyweight Propofol 1% MCT Fresenius for induction of anaesthesia. In younger children, especially between the age of 1 month and 3 years, dose requirements may be higher (2.5 – 4 mg/kg bodyweight).

Maintenance of general anaesthesia:

Anaesthesia can be maintained by administering Propofol 1% MCT Fresenius by infusion or repeated bolus injection 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, especially between the age of 1 month and 3 years, dose requirements may be higher.

For ASA III and IV patients lower doses are recommended (see also section 4.4).

Sedation for diagnostic and surgical procedures in adult patients 
To provide sedation during surgical and diagnostic procedures, doses and administration rates should be adjusted according to the clinical response. Most patients will require 0.5 - 1 mg propofol/kg bodyweight over 1 to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating Propofol 1% MCT Fresenius to the desired level of sedation. Most patients will require 1.5 - 4.5 mg propofol/kg bodyweight/h. The infusion may be supplemented by bolus administration of 10 – 20 mg propofol (1 – 2 ml Propofol 1% MCT Fresenius) if a rapid increase of the depth of sedation is required.

In patients older than 55 years and in patients of ASA grades III and IV lower doses of Propofol 1% MCT Fresenius may be required and the rate of administration may need to be reduced.

Sedation for diagnostic and surgical procedures in children over 1 month of age

Doses and administration rates should be adjusted according to the required depth of sedation and the clinical response. Most paediatric patients require 1 – 2 mg/kg bodyweight propofol for onset of sedation. Maintenance of sedation may be accomplished by titrating Propofol 1% MCT Fresenius infusion to the desired level of sedation. Most patients require 1.5 - 9 mg/kg/h propofol. With Propofol 1% MCT Fresenius the infusion may be supplemented by bolus administration of up to 1 mg/kg bodyweight if a rapid increase of depth of sedation is required.

In ASA III and IV patients lower doses may be required.

Sedation in patients over 16 years of age adults during intensive care 
When used to provide sedation for ventilated patients under intensive care conditions, it is recommended that Propofol 1% MCT Fresenius should be given by continuous infusion. The dose should be adjusted according to the depth of sedation required. Usually satisfactory sedation is achieved with administration rates in the range of 0.3 to 4.0 mg propofol/kg bodyweight/h. Rates of infusion greater than 4.0 mg propofol/kg bodyweight/h are not recommended (see section 4.4).

Administration of propofol by a target controlled infusion (TCI) system is not advised for sedation in the intensive care unit (ICU).

Duration of administration

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

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

Containers should be shaken before use.
If two layers can be seen after shaking the emulsion should not be used.
Use only homogeneous preparations and undamaged containers.
Propofol 1% MCT Fresenius can be used for infusion undiluted or diluted (for dilution see section 6.6).

When Propofol 1% MCT Fresenius is infused, it is recommended that equipment such as burettes, drop counter, syringe pumps (including TCI systems) or volumetric infusion pumps should always be used to control infusion rates.

Prior to use, the ampoule neck or rubber membrane should be cleaned using an alcohol spray or a swab dipped in alcohol. After use, tapped containers must be discarded.

Propofol 1% MCT Fresenius is a lipid containing emulsion without antimicrobial preservatives and may support rapid growth of micro-organisms.
The emulsion must be drawn aseptically into a sterile syringe or giving set immediately after opening the ampoule or breaking the vial seal. Administration must commence without delay.

Asepsis must be maintained for both Propofol 1% MCT Fresenius and infusion equipment throughout the infusion period. Co-administration of other medicinal products or fluids added to the Propofol 1% MCT Fresenius infusion line must occur close to the cannula site using a Y-piece connector or a three-way valve. For instructions on co-administration of the medicinal product, see section 6.6.

Propofol 1% MCT Fresenius must not be administered via a microbiological filter.

Propofol 1% MCT Fresenius and any infusion equipment containing Propofol 1% MCT Fresenius are for single administration in an individual patient. After use remaining solution of Propofol 1% MCT Fresenius has to be discarded.

Infusion of undiluted Propofol 1% (10 mg/1 ml) MCT Fresenius: 
As usual for fat emulsions, the infusion of Propofol 1% MCT Fresenius via one infusion system must not exceed 12 hours. After 12 hours, the infusion system and reservoir of Propofol 1% MCT Fresenius must be discarded or replaced if necessary.

Infusion of diluted Propofol 1% MCT Fresenius:

For administering infusion of diluted Propofol 1% MCT Fresenius, burettes, drop counters or volumetric infusion pumps should always be used to control infusion rates and to avoid the risk of accidentally uncontrolled infusion of large volumes of diluted Propofol 1% MCT Fresenius. This risk has to be taken into account when the decision for the maximum dilution in the burette is made.

The maximum dilution must not exceed 1 part of Propofol 1% (10 mg/1 ml) MCT Fresenius with 4 parts of 5% w/v glucose solution or 0.9% w/v sodium chloride solution (minimum concentration 2 mg propofol per ml). The mixture should be prepared aseptically (controlled and validated conditions preserved) immediately prior to administration and must be administered within 6 hours after preparation.
Propofol 1% (10 mg/1 ml) MCT Fresenius must not be mixed with other solutions for infusion or injection. However, co-administration of a 5% w/v glucose solution or 0.9% w/v sodium chloride solution or 0.18% w/v sodium chloride and 4% w/v glucose solution with Propofol 1% (10 mg/1 ml) MCT Fresenius is permitted via a Y-piece connector close to the injection site.

To reduce pain on the injection site, lidocaine may be injected immediately before the use of Propofol 1% MCT Fresenius (see section 4.4). Alternatively, Propofol 1% MCT Fresenius may be mixed, immediately for use, with preservative free lidocaine injection (20 parts of Propofol 1% MCT Fresenius with up to 1 part of 1% lidocaine injection solution) under controlled and validated aseptical conditions. The mixture has to be administered within 6 hours after preparation.

Muscle relaxants like atracurium and mivacurium should only be administered after flush of the same infusion site used for Propofol 1% MCT Fresenius.

If Propofol 1% MCT Fresenius is injected into a vein by electric pumps, appropriate compatibility should be ensured.

Target Controlled Infusion – Administration of Propofol 1% MCT Fresenius by pumps (for 20 ml plastic and 50 ml plastic syringe only):

Administration of Propofol 1% MCT Fresenius by a Target Controlled Infusion system is restricted to induction and maintenance of general anaesthesia in adults.
It is not recommended for use in ICU sedation or sedation for surgical and diagnostic procedures or in children.

Propofol 1% MCT Fresenius may be administered by a Target Controlled Infusion system incorporating appropriate Target Controlled Infusion software. Users must be familiar with the infusion pump users' manual, and with the administration of Propofol 1% MCT Fresenius by Target Controlled Infusion.

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

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

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

Induction and Maintenance of General Anaesthesia during target controlled infusion

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

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

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

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