Last Updated on eMC 07-12-2017 View medicine  | Aspen Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:04-12-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text

Text strikethrough = deleted text

 

 

4.5       Interaction with other medicinal products and other forms of interaction

 

 

Diprivan 2% has been used in association with spinal and epidural anaesthesia and with commonly used premedicants, neuromuscular blocking drugs, inhalational agents and analgesic agents; no pharmacological incompatibility has been encountered. Lower doses of Diprivan 2% may be required where general anaesthesia is used as an adjunct to regional anaesthetic techniques. Profound hypertension has been reported following anaesthetic with propofol in patients treated with rifampicin.

 

The concurrent administration of other CNS depressants such as pre-medication drugs, inhalation agents, analgesic agents may add to the sedative, anaesthetic and cardiorespiratory depressant effects of Diprivan 2% (see Section 4.4).

 

A need for lower propofol doses has been observed in patients taking valproate. When used concomitantly, a dose reduction of propofol may be considered.

See Section 4.2.5 Administration.

 

10.       DATE OF REVISION OF THE TEXT

31/01/2017 04/12/2017

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:31-01-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text
Text strikethrough = deleted text

 

 

Marketing Authorisation holder

Aspen Pharma Trading Limited,

3016 Lake Drive,

Citywest Business Campus,

Dublin 24

 

AstraZeneca UK Limited,

600 Capability Green,

Luton, LU1 3LU, UK.

 

 

 

Marketing authorisation number(s)

PL 39699/0075

17901/0008

 

Date of revision of the text

27 Feb 2015

 

31 Jan 2017

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:31-01-2017

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new text
Text strikethrough = deleted text

 

 

Marketing Authorisation holder

Aspen Pharma Trading Limited,

3016 Lake Drive,

Citywest Business Campus,

Dublin 24

 

AstraZeneca UK Limited,

600 Capability Green,

Luton, LU1 3LU, UK.

 

 

 

Marketing authorisation number(s)

PL 39699/0076

PL 17901/0009

 

 

Date of revision of the text

31/01/2017

 

2nd January 2015

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.8 - Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.3 - Shelf life
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:27-02-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 2: updates in line with QRD

Section 4.2: updates in line with QRD

Section 4.2: treatment with rifampicin – profound hypotension reported following anaesthesia with propofol(in line with CSP)

Section 4.2: updates in line with QRD, amended of text to include that an alternative effect-site mode of administration may be accessible on some Diprifusors, but its safety and efficacy have not yet been established.

Section 4.2: deletion of historical text (sedation during intensive care)

Section 4.3: QRD update and update in line with CSP update

Section 4.4: addition of dependence on in line with CSP update

section 4.4 text on blood lipid level monitoring in patients at risk of fat overload (in line with CSP) moved lower down

section 4.4. qrd update

-section 4.4 addition of text on propofol not being used in patients of 16 years or younger for sedation for intensive care (in line with CSP)

Section 4.4 removal of text regarding safety and efficacy of diprivan in children younger than 16 years(in line with CSP)

Section 4.4 addition of text regarding use of propfol emulsion infusions for ICU sedation associated with metabolic derangements and organ system failures may result in death(in line with CSP)

Section 4.4 additional text added in reference to propofol infusion syndrome (CSP update)

Section 4.4 text added to take caution in patients with fat metabolism disorders(in line with CSP)

Section 4.4 additional precaution text added regarding caution when treating patients with mitochondrial disease(in line with CSP)

Section 4.6 – updated in line with QRD

Section 4.7 – updated in line with QRD

Section 4.8- addition of drug dependence in undesireable effects (psychiatric disorders) (in line with CSP)

Section 4.8 –addition of respiratory depression as an undesireable effect (not known frequency) (in line with CSP)

Section 4.8 – addtion of tissue necrosis and local pain, swelling to undesireable effects (very rare and not known respectively) (in line with CSP)

Section 4.8 – addition of ADR wording

Section 5.1 – updated in line with QRD

Section 5.2 – updated in line with QRD

Section 6.3 – updated in line with QRD

Section 6.6 – updated in line with QRD

Section 9 – updated in line with QRD

Section 10 – update to date of revision

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.6 - Pregnancy and Lactation
  • Change to section 4.7 - Effects on Ability to Drive and Use Machines
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:19-01-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4

 

Several amendments to Special Warning and Precautions for Use

 

Section 4.6

 

Pregnancy and Lactation sections updated

 

Section 4.7

 

Additional text

 

Diprivan 2% induced impairment is not generally detectable beyond 12 hours (Section 4.4).

 

Section 4.8

 

Table and text updated. Footnotes to table updated

 

Section 10

 

Date of Revision changed to 19th January 2012.

Reasons for adding or updating:

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 5.2 - Pharmacokinetic Properties

Date of revision of text on the SPC:07-09-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



SPC Changes Diprivan 2% PFS PAI 10 0041

 

Section 4.1

 

Diprivan 2% 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.

Section 4.2.1, Children

New 2nd and 3rd paragraphs, sub-section now reads as,

“Diprivan 2% is not recommended for induction of anaesthesia in children less than 3 years of age.

For induction of anaesthesia in children over 3 years of age, Diprivan 2% 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 2% for induction of anaesthesia. In younger children, dose requirements may be higher (2.5–4 mg/kg body weight).

For ASA 3 and 4 patients lower doses are recommended (see also Section 4.4).

Administration of Diprivan 2% by a ‘Diprifusor’ TCI system is not recommended for induction of general anaesthesia in children.”

Section 4.2.2, Children
Additional text in 2nd paragraph and new 3rd paragraph, sub-section now reads as,

” Diprivan 2% is not recommended for maintenance of anaesthesia in children less than 3 years of age.

Anaesthesia can be maintained in children over 3 years of age by administering Diprivan 2% by infusion 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, dose requirements may be higher.

For ASA 3 and 4 patients lower doses are recommended (see also Section 4.4).

Administration of Diprivan 2% by a 'Diprifusor' TCI System is not recommended for maintenance of general anaesthesia in children.”

Section 4.2.4, Sedation for Surgical and Diagnostic Procedures

 

New sub-section, now reads as,

Adults

To provide sedation for surgical and diagnostic procedures, rates of administration should be individualised and titrated to clinical response.

 

Most patients will require 0.5–1 mg/kg over 1–5 minutes for onset of sedation.

 

Maintenance of sedation may be accomplished by titrating Diprivan 2% infusion to the desired level of sedation - most patients will require 1.5–4.5 mg/kg/h. In addition to the infusion, bolus administration of 10–20 mg may be used if a rapid increase in the depth of sedation is required. In patients of ASA Grades 3 and 4 the rate of administration and dosage may need to be reduced.

 

Administration of Diprivan 2% by a ‘Diprifusor’ TCI system is not recommended for sedation for surgical and diagnostic procedures.

Elderly Patients

When Diprivan 2% is used for sedation the rate of infusion or ‘target concentration’ should also be reduced. Patients of ASA grades 3 and 4 will require further reductions in dose and dose rate. Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardiorespiratory depression.

 

Children

Diprivan 2% is not recommended for surgical and diagnostic procedures in children aged less than 3 years.

 

In children over 3 years 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 2% for onset of sedation. Maintenance of sedation may be accomplished by titrating Diprivan 2% infusion to the desired level of sedation. Most patients require 1.5–9 mg/kg/h Diprivan 2%.

In ASA 3 and 4 patients lower doses may be required.”

Section 4.3
Changed text to second paragraph, now reads as,

“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

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:28-07-2009

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 5.1 Pharmacodynamic Properties

Additional wording at the end of the first paragraph:
"However, propofol is thought to produce its sedative/anaesthetic effects by the positive modulation of the inhibitory function of the neurotransmitter GABA through the ligand-gated GABAA receptors."

Section 10
"28th July 2009"

Reasons for adding or updating:

  • Change to section 6.1 - List of Excipients
  • Change to section 4.4 - Special warnings and precautions for Use

Date of revision of text on the SPC:21-08-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4

Additional text:

 

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.

 

Section  6.1

Additional excipient:

Disodium Edetate Ph Eur

 

Section 10

Date of revision of text: 21 August 2008

Reasons for adding or updating:

  • Change to section 1 -Name of the Medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 6.1 - List of Excipients
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-05-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 1

Change of name from Diprivan 2% to

Diprivan 20 mg/ml (2%) emulsion for injection or infusion.

 

Section 3

Current text - Oil in water emulsion for intravenous injection.

New text –

Emulsion for injection or infusion.

White aqueous isotonic oil-in-water emulsion.

 

Section 4.3

Current text:

Known hypersensitivity for any of the components of Diprivan 1% or Diprivan 2%.

 

Diprivan 2% is contraindicated for sedation in intensive care of patients of 16 years of age or younger (See 4.4 Special warnings and precautions for use).

 

New text:

Diprivan is contraindicated in patients with a known hypersensitivity to propofol or any of the excipients.

 

Diprivan 2% is contraindicated for sedation in intensive care of patients of 16 years of age or younger (See 4.4 Special warnings and precautions for use).

 

Diprivan 2% contains soya oil and should not be used in patients who are hypersensitive to peanut or soya.

 

 Section 4.4

New additional sentence last paragraph before heading “Additional Precautions”

Diprivan 2% contains 0.0018 mmol sodium per ml.

 

Section 6.1

Addition of the word “Refined” in the Soya-bean Oil excipient

 

Section 10

New revision date of text: 14th May 2007

 

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change from BAN to rINN

Date of revision of text on the SPC:01-02-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.8
Add sentence to 3rd last paragraph: 
 
Dystonia/dyskinesia have been reported.
 
Section 10
New revision date of text - 21 February 2007

Reasons for adding or updating:

  • Change to section 4.2 - Posology and Method of Administration
  • Change to section 4.3 - Contra-indications
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects

Reasons for adding or updating:

  • Change to section 4.2 - Posology and Method of Administration
  • Change to section 4.3 - Contra-indications
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects

Reasons for adding or updating:

  • Change to section 4.2 - Posology and Method of Administration
  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects

Reasons for adding or updating:

  • Change to section 9 - Date of Renewal of Authorisation

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder

Reasons for adding or updating:

  • Change to section 4.3 - Contra-indications
  • Change to section 4.2 - Posology and Method of Administration

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC