” Diprivan 1% is not recommended for surgical and diagnostic procedures in children aged less than 1 month.
In children over 1 month of age, doses and adminisation 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 Diprivan 1% for onset of sedation. Maintenance of sedation may be accomplished by titrating Diprivan 1% infusion to the desired level of sedation. Most patients require 1.5–9 mg/kg/h Diprivan 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.”
Section 4.3
Changed text to second paragraph, now reads as,
Diprivan 1% 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
Changed text to 12th paragraph, now reads as,
“As with other intravenous anaesthetic agents, caution should be applied in patients with cardiac, respiratory, renal or hepatic impairment or in hypovolaemic, elderly or debilitated patients. Propofol clearance is blood flow dependent, therefore, concomitant medication that reduces cardiac output will also reduce propofol clearance.”
Changed text to 18th paragraph, now reads as,
“The use of Diprivan 1% 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.”
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
Changes to second paragraph and additional 4th and 5th paragraphs, section now reads as,
“The decline in propofol concentrations following a bolus dose or following the termination of an infusion can be described by a three compartment open model with very rapid distribution (half-life 2 –4 minutes), rapid elimination (half-life 30 – 60 minutes), and a slower final phase, representative of redistribution of propofol from poorly perfused tissue.
Propofol is extensively distributed and rapidly cleared from the body (total body clearance 1.5–2 litres/minute). Clearance occurs by metabolic processes, mainly in the liver where it is blood flow dependent, to form inactive conjugates of propofol and its corresponding quinol, which are excreted in urine.
When Diprivan 1% is used to maintain anaesthesia, blood concentrations asymptotically approach the steady-state value for the given administration rate. The pharmacokinetics are linear over the recommended range of infusion rates of Diprivan 1%.
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
