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Janssen-Cilag Ltd

50 - 100 Holmers Farm Way, High Wycombe, Bucks, HP12 4EG, UK
Telephone: +44 1494 567 567
Fax: +44 1494 567 568
Medical Information Direct Line: +353 1 800 709 122
Medical Information e-mail: medinfo@janssen-cilag.co.uk
Customer Care direct line: +353 1 620 2300
Medical Information Facsimile: +44 (0) 1494 567 445
Summary of Product Characteristics last updated on medicines.ie: 19/06/2017
SPC Sublimaze 50 micrograms/ml, Solution for Injection

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

Updated on 19/06/2017 and displayed until Current
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 4.5 - 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:   13-Jun-2017
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



4.1       Therapeutic indications

 

As an adjunct in the maintenance of general anaesthesia and analgesia.

 

In conjunction with a neuroleptic agent in the technique of neuroleptanalgesia.

 

As a respiratory depressant/analgesic in patients requiring prolonged assisted ventilation.

 

As the sole intravenous analgesicanaesthetic agent in surgical procedures.

 

4.2       Posology and method of administration

 

Fentanyl should be given only in an environment where the airway can be controlled and by personnel who can control the airway (see section 4.4 Special warnings and precautions).

 

The dosage of fentanyl should be individualised according to age, body weight, physical status, underlying pathological condition, use of other drugs, and type of surgery and anaesthesia.

 

Techniques that involve analgesia in a spontaneously breathing child should only be used as part of an anaesthetic technique, or given as part of a sedation/ analgesia technique, with experienced personnel in an environment that can manage sudden chest wall rigidity requiring intubation, or apnoea requiring airway support (see section 4.4).

 

It is recommended to wear gloves while opening the ampoule (see section 6.6 Special precautions for disposal and other handling).

 

Method of administration:

For intravenous administration.

 

Posology:

As an adjunct in the maintenance of general anaesthesia and analgesia

 

Adults:

0.05 mg supplements as necessary.For both balanced anaesthesia and total intravenous anaesthesia (TIVA), dose amounts and the intervals between doses should be adjusted to account for the duration and severity of the surgical procedure.

 

Bolus administration

 

0.0005-0.01 mg/kg

 

Continuous infusion

 

0.0005-0.005 mg/kg/h

 

Children:

0.001 mg/kg supplements as necessary.

 

In conjunction with a neuroleptic agent in the technique of neuroleptanalgesia

 

Adults:

The usual dose is 0.1 mg initially, with maintenance doses of 0.05 mg as necessary.

 

Children:

0.01 mg/kg initially, with supplemental doses of 0.001 mg/kg.

 

In patients requiring prolonged assisted ventilation

 

Adults:

Up to 0.6 mg initially, with supplemental doses of 0.05 mg to 0.2 mg.

 

Children:

0.001 mg/kg supplements as necessary.

 

As sole IV analgesicanaesthetic agent in surgical procedures

 

Adults:

The usual dose is 0.1 mg to 0.8 mg initially, depending on response, with maintenance doses of 0.05 mg as necessary, in conjunction with controlled ventilation.

 

Children:

The usual dose is 0.01 mg/kg initially, depending on response, with maintenance doses of 0.001 mg/kg as necessary, in conjunction with controlled ventilation.

 

Elderly and debilitated patients:

As with other opioids, the initial dose should be reduced in the elderly (>65 years of age) and in debilitated patients. The effect of the initial dose should be taken into account in determining supplemental doses.

 

Obese patients:

In obese patients there is a risk of overdosing if the dose is calculated based on body weight. Obese patients should have dosage calculated according to their estimated lean body mass.

 

Renal Impairment

            In patients with renal impairment reduced dosing of Sublimaze should be considered and these patients should 
            be observed carefully for signs of fentanyl toxicity (see section 5.2 Pharmacokinetic properties).

 

4.5       Interaction with other medicinal products and other forms of interaction

Effect of other drugs on fentanyl

Central Nervous System (CNS) depressants

 

Drugs such as barbiturates, benzodiazepines, neuroleptics, halogenic gasesgeneral anaesthetics and other, non-selective CNS depressants (e.g., alcohol) may potentiate the respiratory depression of opioids.

When patients have received such drugs, the dose of fentanyl required may be less than usual. Concomitant use with Sublimaze in spontaneously breathing patients may increase the risk of respiratory depression, profound sedation, coma, and death.

 

Cytochrome P450 3A4 (CYP3A4) inhibitors

 

Fentanyl, a high clearance drug, is rapidly and extensively metabolised mainly by CYP3A4. When Sublimaze is used, the concomitant use of a CYP3A4 inhibitor may result in a decrease in fentanyl clearance. With single-dose Sublimaze administration, the period of risk for respiratory depression may be prolonged, which may require special patient care and longer observation. With multiple-dose Sublimaze administration, the risk for acute and/or delayed respiratory depression may be increased, and a dose reduction of Sublimaze may be required to avoid accumulation of fentanyl. Oral ritonavir (a potent CYP3A4 inhibitor) reduced the clearance of a single intravenous Sublimaze dose by two thirds, although peak plasma concentrations of fentanyl were not affected. However, itraconazole (another potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of a single intravenous Sublimaze dose. Co-administration of other potent or less potent CYP3A4 inhibitors, such as voriconazole or fluconazole, and Sublimaze may also result in an increased and/or prolonged exposure to fentanyl.

Itraconazole (a potent CYP3A4 inhibitor) at 200 mg/day given orally for 4 days had no significant effect on the pharmacokinetics of IV fentanyl.

Oral ritonavir (one of the most potent CYP3A4 inhibitors) reduced the clearance of IV fentanyl by two thirds; however, peak plasma concentrations after a single dose of IV fentanyl were not affected. Co-administration of fluconazole or voriconazole and fentanyl may result in an increased exposure to fentanyl. When fentanyl is used in a single dose, the concomitant use of potent CYP3A4 inhibitors requires special patient care and observation.

With continuous treatment, dose reduction of fentanyl may be required to avoid accumulation of fentanyl, which may increase the risk of prolonged or delayed respiratory depression.

Pretreatment with, or concurrent administration of, cimetidine may increase plasma levels of fentanyl, when repeated doses of both drugs are used.

Bradycardia may be intensified by pretreatment with, or concurrent use of, drugs such as beta-blockers, suxamethonium, halothane, vecuronium, which may themselves cause bradycardia.

Serotonergic Drugs

Coadministration of fentanyl with a serotonergic agent, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition (see section 4.3 Contraindications).

Effect of fentanyl on other drugs

Following the administration of fentanyl, the dose of other CNS depressant drugs should be reduced. This is particularly important after surgery, because profound analgesia is accompanied by marked respiratory depression, which can persist or recur in the postoperative period. Administration of a CNS depressant, such as a benzodiazepine, during this period may disproportionally increase the risk for respiratory depression.

Plasma concentrations of etomidate increased considerably (by a factor of 2-3) when combined with fentanyl. The total plasma clearance and volume of distribution of etomidate is decreased by a factor 2 to 3 without a change in half-life when administered with fentanyl.

Simultaneous administration of fentanyl and intravenous midazolam results in an increase in the terminal plasma half-life and a reduction in the plasma clearance of midazolam.  When these drugs are co-administered with fentanyl their dose may need to be reduced.

 

Updated on 15/04/2015 and displayed until 19/06/2017
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 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   10-Apr-2015
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



. QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Also contains sodium.

 

 

4.2           Posology and method of administration

 

Elderly and debilitated patients:

As with other opioids, the initial dose should be reduced in the eElderly (>65 years of age) and in debilitated patients will required reduced dose. The effect of the initial dose should be taken into account in determining supplemental doses.

 

Obese patients:

In obese patients there is a risk of overdosing if the dose is calculated based on body weight. Obese patients should have dosage calculated according to their estimated lean body mass.

 

Renal Impairment

In patients with renal impairment reduced dosing of Sublimaze should be considered and these patients should be observed carefully for signs of fentanyl toxicity (see section 5.2 Pharmacokinetic properties).

 

 

4.3           Contraindications

 

 

Use in patients with h Hypersensitivity or idiosyncratic response to the active ingredient substance  to any of the excipients listed in section 6.1 or other morphinomimetics.opioids.

Use in patients with rRespiratory depression, cyanosis, excessive bronchial exudation, bronchoconstriction (reversible or irreversible) or chronic pulmonary disease.

Use in patients a After operative interventions in the biliary tract.

Use in patients who are receiving, or have within two weeks received, monoamine oxidase inhibitors.



Other sections :

Removal of naloxone as an example of an opioid antagonist. Update to advice on managing potential respiratory depression in the mother and infant following administration during childbirth.  Rewording of the overdose warning. Update to pharmacokinetic information in obese and renal patients. Toxicology text moved from Section 5.2 to Section 5.3 preclinical safety data.

Updated on 19/09/2014 and displayed until 15/04/2015
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 4.4 - Special warnings and precautions for use
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   15-Sep-2014
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company

Sections 4.2 and 6.6 regarding handling of the ampoules, deletion of droperidol, QRD changes plus ADR reporting
Updated on 26/06/2013 and displayed until 19/09/2014
Reasons for adding or updating:
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • 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:   21-Jun-2013
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company

setion 4.4 addition of;

 

Serotonin syndrome

 

Caution is advised when fentanyl is coadministered with drugs that affect the serotonergic neurotransmitter systems.

 

The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic drugs such as Selective Serotonin Re-uptake Inhibitors (SSRIs) and Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs), and with drugs which impair metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]). This may occur within the recommended dose.

 

Serotonin syndrome may include mental-status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., hyper-reflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea).

 

If serotonin syndrome is suspected, rapid discontinuation of fentanyl should be considered.


Section 4.5 addition of:

Serotonergic Drugs

Coadministration of fentanyl with a serotonergic agent, such as a Selective Serotonin Re-uptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition.

Section 4.8 addition of

Cases of serotonin syndrome have been reported when products containing fentanyl are administered concomitantly with highly serotonergic drugs (see sections 4.4 and 4.5)

Updated on 24/03/2011 and displayed until 26/06/2013
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 4.5 - 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:   21-Mar-2011
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



Change to section 4.2 - Posology and method of administration

The dosage of fentanyl should be individualised according to age, body weight, physical status, underlying pathological condition, use of other drugs, and type of surgery and anaesthesia.

 

Elderly and debilitated patients:

Elderly and debilitated patients will require reduced doses. The effect of the initial dose should be taken into account in determining supplemental doses.

 

Change to section 4.4 - Special warnings and precautions for use

It is recommended to reduce the dosage in the elderly and in debilitated patients.

 

If fentanyl is administered with a neuroleptic, such as droperidol, the user should be familiar with the special properties of each drug, particularly the difference in duration of action.

 

As with other opioids, due to the anti-cholinergic effects, administration of fentanyl may lead to increases of bile duct pressure and, in isolated cases, spasms of the Sphincter of Oddi might be observed. 

 

In patients with myasthenia gravis, careful consideration should be applied in the use of certain anticholinergic agents and neuromuscular-blocking pharmaceutical agents prior to, and during, the administration of a general anaesthetic regimen which includes administering intravenous fentanyl. 

 

Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Plasma concentrations of etomidate increased considerably (by a factor 2-3) when combined with fentanyl.

 

Change to section 10 - Date of revision of the text

21 March 2011

Updated on 03/08/2010 and displayed until 24/03/2011
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 10 - Date of revision of the text
Date of revision of text on the SPC:   27-Jul-2010
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



Change to section 4.2 - Posology and method of administration

Inclusion of precautionary statements as follows:

 

Fentanyl should be given only in an environment where the airway can be controlled and by personnel who can control the airway (see section 4.4).

 

Techniques that involve analgesia in a spontaneously breathing child should only be used as part of an anaesthetic technique, or given as part of a sedation/ analgesia technique, with experienced personnel in an environment that can manage  sudden chest wall rigidity requiring intubation, or apnoea requiring airway support (see section 4.4).

Change to section 4.4 - Special warnings and precautions for use

Inclusion of precautionary statements as follows:

 

Sublimaze should be given only in an environment where the airway can be controlled and by personnel who can control the airway.

 

Paediatric population

Techniques that involve analgesia in a spontaneously breathing child should only be used as part of an anaesthetic technique, or given as part of a sedation/ analgesia technique, with experienced personnel in an environment that can manage sudden chest wall rigidity requiring intubation, or apnoea requiring airway support.

Change to section 10 - Date of revision of the text

27 July 2010

Updated on 03/08/2009 and displayed until 03/08/2010
Reasons for adding or updating:
  • Change to section 10 - Date of revision of the text
  • Change to section 5.3 - Preclinical safety data
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
Date of revision of text on the SPC:   21-Jul-2009
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



4.4

Special Warnings and Precautions for Use

Term “asystole” changed to “cardiac arrest”

4.5

Interaction with other medicinal products and other forms of interaction

Addition of interaction with fluconazole /voriconazole and effect of fentanyl on other drugs

 

4.6

Pregnancy and Lactation

Addition of statement: Fentanyl can cross the placenta in early pregnancy.

4.8

Undesirable effects

Revision of data and new presentation of ADR

5.2

Pharmacokinetic properties

New presentation and addition of special populations data (Paediatrics, Adult patients with burns) 

5.3

Preclinical Safety Data

Addition of a long-term study data

 

10.

DATE OF REVISION OF THE TEXT

 

Changed to 21 July 2009

 

 

Updated on 12/06/2009 and displayed until 03/08/2009
Reasons for adding or updating:
  • Change to section 3 - Pharmaceutical form
Date of revision of text on the SPC:   17-Feb-2009
Legal Category:   Product subject to medical prescription which may not be renewed (A)

Free-text change information supplied by the pharmaceutical company



3.

PHARMACEUTICAL FORM

Correction

Updated on 24/02/2009 and displayed until 12/06/2009
Reasons for adding or updating:
  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   02/2009
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

6.3

Shelf life

Decrease in unopened shelf life from 5 years to 3 years.

10.

DATE OF REVISION OF THE TEXT

 

Changed to Feb 2009.

 

Updated on 13/11/2008 and displayed until 24/02/2009
Reasons for adding or updating:
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 6.2 - Incompatibilities
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 7 - Marketing authorisation holder
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   07/2008
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

 

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Correction

3.

PHARMACEUTICAL FORM

Correction

 

6.2

Incompatibilities

Correction

6.6

Instructions for use, handling and disposal

Correction

 

7.

MARKETING AUTHORISATION HOLDER

Change of address

 

 

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Correction

 

10.

DATE OF REVISION OF THE TEXT

 

Date change

 

Updated on 24/06/2008 and displayed until 13/11/2008
Reasons for adding or updating:
  • Change to section 4.8 - Undesirable effects
  • 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:   06/2008
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

Change to section 4.8 – Undesirable effects

Update to MeDdra convention and addition of Loss of consciousness and seizure as ADR

Change to section 5.1 - Pharmacodynamic properties

Addition of ATC code and group

Change to section 10 – Date of revision of text

June 2008

Updated on 07/03/2007 and displayed until 24/06/2008
Reasons for adding or updating:
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.3 - Preclinical safety data
  • Change to section 9 - Date of renewal of authorisation
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   02/2007
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

Change to section 4.4 – Special Warnings and Precautions for Use

Additional statement regarding potential for abuse.

“Fentanyl can be abused in a manner similar to other opioid agonists.”

Change to section 5.3 - Preclinical Safety Data

Correction of statement to delete

 , like other opioid analgesics,”

from first sentence.

Change to section 9 – Date of Renewal of Authorisation

Correction of date of first authorisation to “1st April 1978”

Change to section 10 – Date of revision of text

Change to “February 2007”

Updated on 01/09/2006 and displayed until 07/03/2007
Reasons for adding or updating:
  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 8 - MA number
  • Change to section 10 - Date of revision of the text
Date of revision of text on the SPC:   11/2005
Legal Category:   prescription only

Free-text change information supplied by the pharmaceutical company

Section 1. - Addition of strength into product name as agreed during renewal.

Section 2. - Amalgamation of licence numbers for both the 2ml and 10 ml ampoule as agreed during renewal

Section 6.4 - Updated during renewal

Section 6.6 - Updated during renewal

Section 8. - PA numbers amalgamated during renewal

Section 10. - November 2005

 

Updated on 17/06/2004 and displayed until 01/09/2006
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 4.8 - Undesirable effects
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text
Updated on 11/11/2003 and displayed until 17/06/2004
Reasons for adding or updating:
  • Change to section 6.1 - List of excipients
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text
Updated on 07/11/2003 and displayed until 11/11/2003
Reasons for adding or updating:
  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text
Updated on 06/11/2003 and displayed until 07/11/2003
Reasons for adding or updating:
  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text
Updated on 04/11/2003 and displayed until 06/11/2003
Reasons for adding or updating:
  • Change to section 10 - Date of revision of the text
  • Change to section 6.3 - Shelf life
Updated on 05/06/2003 and displayed until 04/11/2003
Reasons for adding or updating:
  • New SPC for medicines.ie

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Active Ingredients

 
   fentanyl citrate