“Diprivan 2% must not be used in patients of 16 years of age or younger for sedation in intensive care (See 4.4 Special warnings and precautions for use).”
Section 4.4
Changes throughout section, now reads as,
“Diprivan 2% should be given by those trained in anaesthesia, or where appropriate, doctors trained in the care of patients in Intensive Care. Facilities for maintenance of a patent airway, artificial ventilation and oxygen enrichment should be available.
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 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 general anaesthesia. Very rarely the use of Diprivan 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.
When Diprivan 2% is administered to an epileptic patient, there may be a risk of convulsion.
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. Propofol clearance is blood flow dependent, therefore, concomitant medication that reduces cardiac output will also reduce propofol clearance.
The risk of relative vagal overactivity may be increased because Diprivan 2% lacks vagolytic activity. Diprivan 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.
Appropriate care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsions must be used cautiously.
Use is not recommended with electroconvulsive treatment.
As with other anaesthetics sexual disinhibition may occur during recovery.
Diprivan 2% is not advised for general anaesthesia in children younger than 1 month of age. The safety and efficacy of Diprivan 2% for (background) sedation in children younger than 16 years of age have not been demonstrated. Although no causal relationship has been established, serious undesirable effects with (background) sedation in patients younger than 16 years of age (including cases with fatal outcome) have been reported during unlicensed use. In particular these effects concerned occurrence of metabolic acidosis, hyperlipidemia, rhabdomyolysis and/or cardiac failure. These effects were most frequently seen in children with respiratory tract infections who received dosages in excess of those advised in adults for sedation in the intensive care unit.
The use of Diprivan 2% is not recommended for newborn infants for induction and maintenance of anaesthesia as this patient population has not been fully investigated. Pharmacokinetic data (see Section 5.2) indicate that clearance is considerably reduced in neonates with a very high inter-individual variability. Relative overdose could occur administering doses recommended for older children resulting in severe cardiovascular depression.
Diprivan 2% is not recommended for diagnostic and surgical procedures in children <3 years of age since the 2% strength is difficult to be adequately titrated in small children due to the extremely small volumes needed.
Very rare reports have been received of occurrence of metabolic acidosis, rhabdomyolysis, hyperkalaemia and/or rapidly progressive cardiac failure (in some cases with fatal outcome) in adults who were treated for more than 58 hours with dosages in excess of 5 mg/kg/h. This exceeds the maximum dosage of 4 mg/kg/h currently advised for sedation in the intensive care unit. The patients affected were mainly (but not only) seriously head-injured patients with raised ICP. The cardiac failure in such cases was usually unresponsive to inotropic supportive treatment. Treating physicians are reminded if possible not to exceed the dosage of 4 mg/kg/h. Prescribers should be alert to these possible undesirable effects and consider decreasing the Diprivan 2% dosage or switching to an alternative sedative at the first sign of occurrence of symptoms. Patients with raised ICP should be given appropriate treatment to support the cerebral perfusion pressure during these treatment modifications.
Diprivan 2% contains 0.0018 mmol sodium per ml.
EDTA is a chelator of metal ions, including zinc. The need for supplemental zinc should be considered during prolonged administration of Diprivan, particularly in patients who are predisposed to zinc deficiency, such as those with burns, diarrhoea and/or major sepsis.
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.”
Section 5.1
New final paragraph, reads as,
”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.”
Section 5.2
New 4th and 5th paragraphs, reads as,
“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).”
Section 10
7th September 2010
