Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

Propofol-Lipuro 1% 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 patent airway, artificial ventilation, oxygen enrichment and other resuscitative facilities should be readily available at all times. Propofol-Lipuro 1% should not be administered by the person conducting the diagnostic or sur- gical procedure.

Abuse of, and dependence on Propofol-Lipuro 1%, predominantly by health care professionals, have been reported. As with other general anaesthetics, the administration of Propofol-Lipuro 1% without airway care may result in fatal respiratory complications.

When Propofol-Lipuro 1% is administered for conscious sedation, for surgical and diagnostic proce- dures, patients should be continually monitored for early signs of hypotension, airway obstruction and oxygen desaturation.

As with other sedative agents, when Propofol-Lipuro 1% is used for sedation during operative proce- dures, 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 Propofol-Lipuro 1%. Very rarely the use of Propofol-Lipuro 1% may be associated with the develop- ment of a period of postoperative 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 spon- taneous, appropriate care of an unconscious patient should be administered.

Propofol-Lipuro 1% induced impairment is not generally detectable beyond 12 hours. The effects of Propofol-Lipuro 1%, the procedure, concomitant medications, the age and the condition of the patient should be considered when advising patients on:
• The advisability of being accompanied on leaving the place of administration 
•   The timing of recommencement of skilled or hazardous tasks such as driving 
•   The use of other agents that may sedate (Eg. benzodiazepines, opiates, alcohol.) 
As with other intravenous anaesthetic agents, caution should be applied in patients with cardiac, res- piratory, renal or hepatic impairment or in hypovolaemic or debilitated patients.
Propofol-Lipuro 1% clearance is blood flow dependent, therefore, concomitant medication that re- duces cardiac output will also reduce Propofol-Lipuro 1% clearance.

Propofol-Lipuro 1% lacks vagolytic activity and has been associated with reports of bradycardia (oc- casionally profound) and also asystole. The intravenous administration of an anticholinergic agent be- fore induction, or during maintenance of anaesthesia should be considered, especially in situations where vagal tone is likely to predominate, or when Propofol-Lipuro 1% is used in conjunction with other agents likely to cause a bradycardia.

As with other intravenous anaesthetic and sedative agents, patients should be instructed to avoid alco- hol before and for at least 8 hours after administration of Propofol-Lipuro 1%.

During bolus administration for operative procedures, extreme caution should be exercised in patients with acute pulmonary insufficiency or respiratory depression.

Concomitant use of central nervous system depressants e.g., alcohol, general anaesthetics, narcotic an- algesics will result in accentuation of their sedative effects. When Propofol-Lipuro 1% is combined with centrally depressant drugs administered parenterally, severe respiratory and cardiovascular de- pression may occur. It is recommended that Propofol-Lipuro 1% is administered following the analge- sic and the dose should be carefully titrated to the patient's response (see section 4.5).

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 admin- istration of Propofol-Lipuro 1% during the period of anaesthetic maintenance.
When Propofol-Lipuro 1% 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.
The benefits and risks of the proposed procedure should be considered prior to proceeding with repeated or prolonged use (>3 hours) of propofol in young children (< 3 years) and in pregnant women as there have been reports of neurotoxicity in preclinical studies, see Section 5.3.

Paediatric population
The use of Propofol 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 re- duced 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.

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 meta- bolic 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 oxy- gen delivery to tissues; serious neurological injury and/or sepsis; high dosages of one or more of the following pharmacological agents - vasoconstrictors, steroids, inotropes and/or Propofol-Lipuro 1% (usually at dose rates greater than 4 mg/kg/h for more than 48 hours).

Prescribers should be alert to these events in patients with the above risk factors and immediately dis- continue propofol- when the above signs develop. All sedative and therapeutic agents used in the in- tensive care unit (ICU), should be titrated to maintain optimal oxygen delivery and haemodynamic pa- rameters. 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 appropri- ately 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 Propofol-Lipuro 1% contains approximately 0.1 g of fat.
This medicinal product contains less than 1 mmol (23 mg) sodium in 100 ml, i.e. essentially ‘sodium free’.

Additional Precautions
Caution should be taken when treating patients with mitochondrial disease. These patients may be sus- ceptible 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 infu- sion syndrome’ may be similar.

Propofol-Lipuro 1% contains no antimicrobial preservatives and supports growth of micro-organisms.

When Propofol-Lipuro 1% is to be aspirated, it must be drawn aseptically into a sterile syringe or giv- ing set immediately after opening the ampoule or breaking the vial seal. Administration must commence without delay. Asepsis must be maintained for both Propofol-Lipuro 1% and infusion equipment throughout the infusion period. Any infusion fluids added to the Propofol-Lipuro 1% line must be administered close to the cannula site. Propofol-Lipuro 1% must not be administered via a mi- crobiological filter.

Propofol-Lipuro 1% and any syringe containing Propofol-Lipuro 1% are for single use in an individual patient. In accordance with established guidelines for other lipid emulsions, a single infusion of propofol must not exceed 12 hours. At the end of the procedure or at 12 hours, whichever is the sooner, both the reservoir of propofol and the infusion line must be discarded and replaced as appro- priate.

Effects on Driving

4.7   Effects on ability to drive and use machines

Propofol-Lipuro 1% 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 im- paired for some time after general anaesthesia.

Propofol-Lipuro 1% induced impairment is not generally detectable beyond 12 hours (Section 4.4).