1. Name of the medicinal product
Diprivan emulsion for injection or infusion. Order Propofol
2. Qualitative and quantitative composition for example
Propofol 20 mg/ml, 100mg/ml, 200mg/ml, 1000mg/ml.
3. The most important Pharmaceutical form
Emulsion for injection or infusion.
White aqueous isotonic oil-in-water emulsion.
4. Clinical particulars
4.1 Therapeutic indications
Propofol is a short-acting intravenous general anaesthetic for:
- Induction and maintenance of general anaesthesia in adults and children >3 years.
- Sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia in adults and children >3 years.
- Sedation of ventilated patients >16 years of age in the intensive care unit.
4.2 Posology and method of administration
Induction of General Anaesthesia
Administration of Diprivan 2% by bolus injection is not recommended. Therefore Diprivan 2% may be used to induce anaesthesia by infusion but only in those patients who will receive Diprivan 2% for maintenance of anaesthesia.
In unpremedicated and premedicated patients, it is recommended that Diprivan 2% should be titrated (approximately 2 ml [40 mg] every 10 seconds in an average healthy adult by 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 Diprivan 2%. The total dose required can be reduced by lower rates of administration (1-2.5 ml/min [20-50 mg/min]). Over this age, the requirement will generally be less. In patients of ASA Grades 3 and 4, lower rates of administration should be used (approximately 1 ml [20 mg] every 10 seconds).
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other general anaesthetics
In general, falls in mean arterial blood pressure and slight changes in heart rate are observed when Diprivan 2% is administered for induction and maintenance of anaesthesia. However, the haemodynamic parameters normally remain relatively stable during maintenance and the incidence of untoward haemodynamic changes is low.
Although ventilatory depression can occur following administration of Diprivan 2%, any effects are qualitatively similar to those of other intravenous anaesthetic agents and are readily manageable in clinical practice.
As a result Diprivan 2% reduces cerebral blood flow,morever intracranial pressure and cerebral metabolism. The reduction in intracranial pressure is greater in patients with an elevated baseline intracranial pressure.
Clinical efficacy and safety
Recovery from anaesthesia is usually rapid and clear headed with a low incidence of headache and post-operative nausea and vomiting.
In general, there is less post-operative nausea and vomiting following anaesthesia with Diprivan 2% than following anaesthesia with inhalational agents. There is evidence that this may be related to a reduced emetic potential of propofol. However Diprivan 2%, at the concentrations likely to occur clinically, does not inhibit the synthesis of adrenocortical hormones.
5.2 Pharmacokinetic properties
When Diprivan 2% is used to maintain anaesthesia, blood concentrations asymptotically approach the steady-state value for the given administration rate.
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).
The pharmacokinetics are linear over the recommended range of infusion rates of Diprivan 2%.
5.3 Preclinical safety data
As a resulth of published studies in animals demonstrate that the use of anaesthetic agents during the period of rapid brain growth or synaptogenesis results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Morever In neonatal primates, exposure to 3 hours of an anaesthetic regimen that produced a light surgical plane of anaesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer increased neuronal cell loss.