Posology : מינונים

4.2 Posology and method of administration

Posology

Propofol must be used only in well equipped hospitals or medical centers by doctors trained in anaesthesia or the treatment of intensive care patients.
Continual monitoring of the circulation and the respiration (for example, ECG pulse oxymeter) is necessary. Provisions for prevention of airway obstruction, artificial respiration and other resuscitation provisions must be immediately available at all times. As regards sedation during surgical or diagnostic operations propofol must not be administered by the same person who performs the surgical or diagnostic operation.
Additional analgesics are generally necessary in combination with propofol.

4.2.1 Induction of General Anaesthesia

Adults

In unpremedicated and premedicated patients, it is recommended that Diprofol 1% should be titrated (approximately 4 ml [40 mg] every 10 seconds in an average healthy adult by bolus injection or 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 Diprofol 1%. The total dose required can be reduced by lower rates of administration (2–5 ml/min [20–50 mg/min]).
In patients over this age and in patients of ASA grades III 3 and IV 4, especially those with impaired cardiac function, the dosage requirements will be less and the total dose of Diprofol 1% may be reduced to a minimum of 1 mg/kg body weight. In these patients lower rates of administration should be applied (approximately 2 ml, corresponding to 20 mg every 10 seconds).

Elderly

In older people the dose requirement for induction of anaesthesia with Diprofol 1% 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

Diprofol 1% is not indicated for induction of anaesthesia in children aged less than 1 month.

For induction of anaesthesia in children over 1 month of age, Diprofol 1% 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 Diprofol 1% 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 body weight).

For ASA 3 and 4 patients lower doses are recommended (see also Section 4.4).

4.2.2 Maintenance of General Anaesthesia

Adults

Anaesthesia can be maintained by administering Diprofol 1% either by continuous infusion or by repeat bolus injections to prevent the clinical signs of light anaesthesia. Recovery from anaesthesia is typically rapid and it is therefore important to maintain Diprofol 1% administration until the end of the procedure.

Continuous Infusion

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

Repeat Bolus Injections

If a technique involving repeat bolus injections is used, increments of 25 mg (2.5 ml) to 50 mg (5.0 ml) may be given according to clinical need.

Elderly

When Diprofol 1% 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

Diprofol 1% is not indicated for maintenance of anaesthesia in children aged less than 1 month.

Anaesthesia can be maintained in children over 1 month of age by administering Diprofol 1% 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 3 and 4 patients lower doses are recommended (see also Section 4.4).

4.2.3 Sedation During Intensive Care

Adults
For sedation during intensive care it is advised that Diprofol 1% 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 Diprofol 1% (see section 4.4 Special warnings and precautions for use). Diprofol 1% is not indicated for sedation in intensive care of patients of 16 years of age or younger (see 4.3 Contraindications).

It is recommended that blood lipid levels be monitored should Diprofol 1% be administered to patients thought to be at particular risk of fat overload.
Administration of Diprofol 1% 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 Diprofol 1% formulation; 1.0 ml of Diprofol 1% contains approximately 0.1g of fat.

If the duration of sedation is in excess of 3 days, lipids should be monitored in all patients.

Elderly

When Diprofol 1% is used for sedation 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

Diprofol 1% 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 Diprofol 1% 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.

Elderly

When Diprofol 1% is used for sedation the rate of infusion or 'target concentration' should also be reduced. Patients of ASA grades 3 and 4 will require further reductions in dose and dose rate. Rapid bolus administration (single or repeated) should not be used in older people as this may lead to cardiorespiratory depression.

Paediatric population

Diprofol 1% is not indicated for surgical and diagnostic procedures in children aged less than 1 month.

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 body weight of Diprofol 1% for onset of sedation. Maintenance of sedation may be accomplished by titrating Diprofol 1% infusion to the desired level of sedation. Most patients require 1.5–9 mg/kg/h Diprofol 1%. The infusion may be supplemented by bolus administration of up to 1 mg/kg body weight if a rapid increase of depth of sedation is required.

In ASA 3 and 4 patients lower doses may be required.

4.2.5 Method of administration

Method of administration

Propofol 10 mg/ml should be administered intravenously as injection or as continuous infusion, either undiluted or diluted with an infusion solution with glucose 5% or sodium chloride 0.9%.
Both solutions in glass bottles and in PVC sachets can be used, but must be mixed well before administration.

Ampoules and vials should be shaken before use.

Before use the neck of the ampoule and the rubber stopper of the infusion vial must be disinfected with medicinal alcohol (spray or tissues). After use, any remaining medicine must be destroyed.
Propofol does not contain any preservatives and promotes the growth of micro-organisms.
After opening of an ampoule or piercing of a vial, the contents must therefore immediately be put aseptically into a sterile syringe or infusion system and then administered directly.
During the infusion period the sterility of both propofol and the infusion system should be maintained.

Medicines or fluids that are added to a running propofol infusion must be added close to the cannula. Propofol must not be administered via infusion systems that are provided with microbial filters. The contents of an ampoule or a vial of propofol and any syringe of propofol are intended for single administration to one patient. Any remaining medicine must be destroyed after use.

Infusion of undiluted propofol 10 mg/ml

When propofol is administered by means of a continuous infusion, control of the infusion rate by means of a burette, drop counter, syringe pump or volumetric infusion pump is recommended. As is the case for parenteral administration of all kinds of fat emulsions, the duration of use of one infusion system for a continuous infusion with propofol must remain limited to 12 hours. The infusion system and the container must be removed and replaced after a maximum of 12 hours. Residues of propofol left over at the end of the infusion period or after changing of the system must be destroyed.

Infusion of diluted Propofol 10 mg/ml

When propofol 10 mg/ml is administered diluted by means of a continuous infusion, control of the rate of infusion by means of a burette, drop counter, syringe pump or volumetric infusion pump is recommended to prevent accidental administration of too large doses of diluted propofol 10mg/ml.

The maximum dilution must not be more than 1 part propofol 10 mg/ml in 4 parts glucose 5% or sodium chloride 0.9% infusion solution (minimum concentration 2 mg propofol/ml) The mixture must be prepared aseptically immediately before administration and must be used within 6 hours after preparation.

Propofol 10 mg/ml must not be mixed with other injection or infusion fluids except those mentioned in heading 6.6. However, simultaneous administration of propofol 10 mg/ml and propofol 20 mg/ml together with an infusion of glucose 5% or sodium chloride 0.9% via Y-connector close to the injection site is possible.
In order to diminish pain at the beginning of the injection, propofol 10 mg/ml can be mixed with lidocaine 1% solution for injection without preservatives (mix 20 parts propofol 10 mg/ml with 1 part lidocaine 1% solution for injection).

Before administering the muscle relaxant, atracurium, after administration of propofol through the same infusion system, it is recommended to flush out the infusion system.


Duration of administration

Propofol can be administered for a maximum of 7 days.