Section 4.1

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Sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia in adults and children over one month of age.

Sedation of ventilated patients over 16 years of age in the intensive care unit.

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Diprivan may also be used for sedation of ventilated patients receiving intensive care in adults, only for a period of 48 hours, or in rare cases up to a maximum of 7 days.
Diprivan may also be used for conscious sedation for surgical and diagnostic procedures in adults only.

Section 4.2

A. Adults

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Diprivan 2% should be used to induce anaesthesia by infusion and only in those patients who will receive Diprivan 2% for maintenance of anaesthesia.

Continuous Infusion:

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or Diprivan 2%

Repeat Bolus Injection:

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It is recommended that only Diprivan 1% is used.

C. Children

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Diprivan 2% is not recommended for induction and maintenance of anaesthesia in children between 1 month and 3 years of age since the 2% strength is difficult to be accurately titrated in small children, due to the small volumes needed. For these patients it is recommended to use Diprivan 1%.
Induction of General Anaesthesia:

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For induction of anaesthesia in children over 1 month of age, Diprivan 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 Diprivan 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).

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When used to induce anaesthesia in children, it is recommended that Diprivan is given slowly until the clinical signs show the onset of anaesthesia. The dose should be adjusted for age and/or weight. Most patients over 8 years of age are likely to require approximately 2.5 mg/kg of Diprivan for induction of anaesthesia. Under this age the requirement may be more. Lower dosage is recommended for children of ASA grades 3 and 4.

Maintenance of General Anaesthesia:

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Anaesthesia can be maintained by administering Diprivan 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).

Conscious Sedation for Surgical and Diagnostic Procedures:

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

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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.

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Sedation During Intensive Care: Diprivan is not recommended for sedation in children as safety and efficacy have not been demonstrated. Although no causal relationship has been established, serious adverse events (including fatalities) have been observed from spontaneous reports of unlicensed use and these events were seen most often in children with respiratory tract infections given doses in excess of those recommended for adults.

D) Administration

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Administration of Diprivan 2% by bolus injection is not recommended.

E) Target Controlled Infusion – Administration of Diprivan by Diprifusor TCI System in Adults

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or 2%

Section 4.3

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Diprivan 1% must not be used in patients of 16 years of age or younger for sedation in intensive care (see section 4.4).

Section 4.4

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Propofol clearance is blood flow dependent, therefore, concomitant medication that reduces cardiac output will also reduce propofol clearance.

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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 (see sections 4.2 and 4.8).

Section 5.1

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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

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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

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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

Date of Revision changed to 27th June 2011

Section 2

Additional text:

Contains sodium 0.0018 mmol/ml.

Contains soya-bean oil, refined 100 mg/ml.

Section 4.3

Additional text:

Diprivan contains soya oil and should not be used in patients who are hypersensitive to peanut or soya.

Section 4.4

At end of section there are Additional precautions

Section 6.6

Text for Additional precautions moved to section 4.4

Section 9

Renewal of authorisation: 6 November 2007

Section 10

Revision date of text: 4 July 2008

Section 4.6

Current text:

Pregnancy: Diprivan should not be used in pregnancy. Diprivan has been used, however, during termination of pregnancy in first trimester.

Obstetrics: Diprivan crosses the placenta and may be associated with neonatal depression. It should not be used for obstetric anaesthesia.

Lactation: Safety to the neonate following the use of Diprivan in mothers who are breast‑feeding has not been established.

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Pregnancy: The safety of Diprivan during pregnancy has not been established. Therefore, Diprivan should not be used in pregnant women unless clearly necessary. Propofol crosses the placenta and may be associated with neonatal depression. High doses (more than 2.5 mg/kg for induction or 6 mg/kg/h for maintenance of anaesthesia) should be avoided.

Lactation: Safety to the neonate following the use of Diprivan in mothers who are breast‑feeding has not been established. Studies in breast‑feeding women showed that propofol is excreted in small amounts into the milk. Therefore, mothers should stop breast‑feeding and discard breast milk for 24 hours after administration of propofol.

Section 10