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Abstral Sublingual Tablets

Last Updated on eMC 18-Jul-2016 View document  | Kyowa Kirin Ltd 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.

Updated on 18-Jul-2016 and displayed until Current

Reasons for adding or updating:

  • Change to section 6.3 - Shelf life
  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 31-May-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 6.3 - Change of shelf life from 3 years to 2 years.
Section 7 - Change of the MAH from ProStrakan to Kyowa Kirin Ltd.
Section 10 - Date of revision of the text to May 2016.

Updated on 01-Sep-2015 and displayed until 18-Jul-2016

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.6 - Fertility, pregnancy and lactation
  • 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: 01-Jul-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

In Section 4.2 Posology and method of administration under the heading Discontinuation of therapy the paragraph has been amended as follows:

Abstral should be discontinued immediately if the patient no longer experiences breakthrough pain episodes. The treatment for the persistent background pain should be kept as prescribed. If discontinuation of all opioid therapy is required, the patient must be closely followed by the doctor in order to prevent the possibility of abrupt withdrawal effects. For patients no longer requiring opioid therapy, the Abstral dose should be taken into consideration before a gradual downward titration of opioids to minimise possible withdrawal effects.
In patients who continue to take their chronic opioid therapy for persistent pain but no longer require treatment for breakthrough pain, Abstral therapy may usually be discontinued immediately.


In Section 4.6 Fertility, pregnancy and lactation under the heading Breast-feeding the follow has been changed:

Fentanyl passes into breast milk and may cause sedation and respiratory depression in the breast-fed child. Fentanyl should not be used by breast feeding women and breast feeding should not be restarted until at least 48 hours 5 days after the last administration of Fentanyl.

In Section 4.8 Undesirable effects the following changes have been made:

Heading:         Psychiatric disorders - Insomnia has been added
                       Nervous system disorders - Insomnia has been removed
                       General disorders and administration site conditions - Pyrexia has been added 

In Section 5.1 Pharmacodynamic properties the paragraph has been amended as follows:

Fentanyl is a potent µ-opioid analgesic with rapid onset and short duration of action. Fentanyl is approximately 100-fold more potent than morphine as an analgesic. Secondary effects of fentanyl on central nervous system (CNS), respiratory and gastro-intestinal functions are typical of opioid analgesics and are considered to be class effects. These can include respiratory depression, bradycardia, hypothermia, constipation, miosis, physical dependency and euphoria.

Section 10. DATE OF REVISION OF THE TEXT has been updated as follows:

04 04 2014 July 2015

Updated on 10-Sep-2014 and displayed until 01-Sep-2015

Reasons for adding or updating:

  • 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 - 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 5.3 - Preclinical safety data
  • 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: 04-Apr-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

In Section 4.2 (Posology and method of administration) - "Use in elderly patients" has been changed to "Use in older people"

In Section 4.3 (contraindications) - The sentence "Opioid naïve patients because of the risk of life threatening respiratory depressionhad been replaced with "Patients without maintenance opioid therapy as there is an increased risk of respiratory depression".

The line "Treatment of acute pain other than breakthrough pain."
has been added.

In Section 4.4 (Special warnings and precautions for use) -


Cardiac disease the line "Intravenous fentanyl has been shown to cause bradycardia. Abstral should be used with caution in patients with bradyarrythmias. has been

replaced with "Fentanyl may produce bradycardia. Fentanyl should be used with caution in patients with previous or pre-existing bradyarrythmias."

In the paragraph beginning "Data from..." the word "elderly" has been replaced with "older" on two occasions...

"Data from intravenous studies with fentanyl suggest that elderly older patients may have reduced clearance, a prolonged half-life and they may be more sensitive to the active substance than younger patients.  Elderly older, cachectic, or debilitated patients should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary.



Serotonin Syndrome - the following paragraph has been added...

Serotonin Syndrome
·     Caution is advised when Abstral is coadministered with drugs that affect the serotoninergic 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., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhoea).

 

If serotonin syndrome is suspected, treatment with Abstral should be discontinued.



In Section 4.5 (Interaction with other medicinal products and other forms of interactions) - the following paragraph has been added...

Serotoninergic Drugs

Coadministration of fentanyl with a serotoninergic 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.

In Section 4.6 (Fertility, pregnancy and lactation) - the following sentences Fentanyl is excreted into breast milk and may cause sedation and respiratory depression in the breast fed child. Fentanyl should only be used by breast feeding women if the benefits clearly outweigh the potential risks for both mother and child. have been replaced with

Breast-feeding
    
Fentanyl passes into breast milk any may cause sedation and respiratory depression in the breast-fed child. Fentanyl should not be used by breastfeeding women and breastfeeding should not be  restarted until at least 48 hours after the last administration of fentanyl.

In Section 4.7 (Effects on ability to drive and use machines) - the following text has been added...

This medicine can impair cognitive function and can affect a patient’s ability to drive safely. This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients should be told:

  •         The medicine is likely to affect your ability to drive
  •         Do not drive until you know how the medicine affects you
  •         It is an offence to drive while under the influence of this medicine
  •         However, you would not be committing an offence (called ‘statutory defence’) if:

o   The medicine has been prescribed to treat a medical or dental problem and

o   You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and

o   It was not affecting your ability to drive safely



In Section 4.8 (Undesirable effects) -

The paragraph beginning "Tabulated Summary of Adverse Reactions..." has been amended as follows...

Tabulated Summary of Adverse Reactions with Abstral and/or other fentanyl-containing compounds:

The following aAdverse reactions from patient safety and efficacy studies have been reported with Abstral and/or other fentanyl-containing compounds with a suspected relationship to treatment,  during clinical studies and from post-marketing experience. They are listed below by system organ class and frequency (very common ³ 1/10; common ³1/100 to < 1/10; uncommon ³1/1,000 to <1/100; not known (cannot be estimated from available data)). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

The ability to assign Abstral a dose relationship to the adverse reactions from the clinical studies is limited by the titration schemes used in these studies.

 

Within the table content itself the following additions have been made:

Psychiatric orders - Not known (cannot be estimated from available data) - Hallucination
Nervous system disorders - Not known (cannot be estimated from available data)  - Convulsion
Respiratory, thoracic and mediastinal disorders - Not known (cannot be estimated from available data) - Respiratory depression
Gastrointestinal disorders - Not known (cannot be estimated from available data) - 1 Swollen tongue, Diarrhoea
General disorders and administration site conditions - Not known (cannot be estimated from available data) - Flushing and hot flush, Peripheral oedema.
Injury, poisoning and procedural complications - Not known (cannot be estimated from available data) - Fall

The footnote "1Observed in post marketing experience only" has been removed.

At the bottom of the table the following paragraph has been added...

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme
: www.mhra.gov.uk/yellowcard

In Section 5.2 (Pharmacokinetic properties)

In the paragraph Renal/hepatic impairment the word elderly has been replaced with older.

In Section 5.3 (Preclinical safety data)

The last paragraph in the section has been amended as follows...

Long-term carcinogenicity studies have not been performed.

Carcinogenicity studies (26-week dermal alternative bioassay in Tg.AC transgenic mice; two-year subcutaneous carcinogenicity study in rats) with fentanyl did not reveal any findings indicative of oncogenic potential. Evaluation of brain slides from the carcinogenicity study in rats revealed brain lesions in animals administered high doses of fentanyl citrate. The relevance of these findings to humans is unknown.


In Section 9 - DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION the following changes have been made...

Date of first authorisation: 19/09/2008
Date of latest renewal: 28-02-2013

In Section 10 - DATE OF REVISION OF THE TEXT - the following changes have been made...

01/10/2012 04/04/2014

The following have been deleted...
LEGAL CATEGORY
CD (Sch2), POM









 

 

Updated on 24-Apr-2013 and displayed until 10-Sep-2014

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 4.6 - 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 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 10 - Date of revision of the text

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

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Changes to Abstral SPC: New text in SPC is shown in red and any additional explanations in bold.  In each section, only affected paragraphs are shown. For ease of reading, deleted text is not shown.

Section 2 (QUALITATIVE AND QUANTITATIVE COMPOSITION)

For the full list of excipients, see section 6.1.

Section 4.2 (Posology and method of administration)

Abstral should only be administered to patients who are considered tolerant to their opioid therapy for persistent cancer pain.  Patients can be considered opioid  tolerant if they take at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour,  at least 30 mg of oxycodone daily, at least 8  mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

Method of administration:

Dose titration:

Dose escalation should continue in a stepwise manner until adequate analgesia with tolerable adverse reactions is achieved.  The dose strength for the supplemental (second) sublingual tablet should be increased from 100 to 200 micrograms at doses of 400 micrograms and higher.  This is illustrated in the schedule below.  No more than two (2) doses should be administered for a single episode of breakthrough pain during this titration phase.

During titration, patients can be instructed to use multiples of 100 microgram tablets and/or 200 microgram tablets for any single dose. No more than four (4) tablets should be used at any one time.

The efficacy and safety of doses higher than 800 micrograms have not been evaluated in clinical studies in patients.

During titration patients should wait at least 2 hours before treating another episode of breakthrough pain with Abstral.

Maintenance therapy:

During the maintenance period patients should wait at least 2 hours before treating another episode of break through pain with Abstral.

Section 4.3 (Contraindications)

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Section 4.6 (Fertilitypregnancy and lactation) 

The safety of fentanyl in pregnancy has not been established. Studies in animals have shown reproductive toxicity, with impaired fertility in rats (see section 5.3).  The potential risk for humans is unknown.  Fentanyl should only be used during pregnancy when clearly necessary.

Section 4.7 (Effects on ability to drive and use machines)

No studies on the effects on the ability to drive and use machines have been performed with Abstral.

However, opioid analgesics are known to impair the mental or physical ability to perform potentially hazardous tasks such as driving or operating machinery. Patients should be advised not to drive or operate machinery if they become dizzy or drowsy or experience blurred or double vision while taking Abstral.

Section 4.8 (Undesirable effects): 

This section has been amended to provide updated safety information. The tabulation below replaces the previous listings of adverse reactions.

Undesirable effects typical of opioids are to be expected with Abstral; they tend to decrease in intensity with continued use. The most serious potential adverse reactions associated with opioid use are respiratory depression (which could lead to respiratory arrest), hypotension and shock.

The clinical trials of Abstral were designed to evaluate safety and efficacy in treating patients with breakthrough cancer pain; all patients were taking concomitant opioids, such as sustained-release morphine, sustained-release oxycodone or transdermal fentanyl, for their persistent pain. Therefore it is not possible to definitively separate the effects of Abstral alone.

The most frequently observed adverse reactions with Abstral include typical opioid adverse reactions, such as nausea, constipation, somnolence and headache.

Tabulated Summary of Adverse Reactions with Abstral:

Adverse reactions from patient safety and efficacy studies with Abstral with a suspected relationship to treatment, and from post-marketing experience are listed below by  system organ class and frequency (very common ≥ 1/10; common ≥ 1/100 to < 1/10; uncommon ≥1/1,000 to <1/100; not known (cannot be estimated from available data)). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

The ability to assign Abstral a dose-relationship to the adverse reactions from the clinical studies is limited by the titration schemes used in these studies.

System Organ Class

Adverse Reaction by Frequency

 

Very common

≥ 1/10

Common

≥ 1/100 to < 1/10

Uncommon

≥ 1/1,000 to < 1/100

Not known (cannot be estimated from available data)

Immune system disorders

 

 

Hypersensitivity

 

Metabolism and nutrition disorders

 

 

Anorexia

Decreases appetite

 

Psychiatric disorders

 

 

Depression

Paranoia

Confusional state

Disorientation

Mental status changes

Anxiety

Euphoric mood

Dysphoria

Emotional lability Disturbance in attention

 

Nervous system disorders

 

Dizziness

Headache

Somnolence

Amnesia

Parosmia

Dysgeusia

Tremor

Lethargy

Hypoaesthesia

Insomnia

Sleep disorder

 

Eye disorders

 

 

Vision blurred

 

Cardiac disorders

 

 

Tachycardia

Bradycardia

 

Vascular disorders

 

 

Hypotension

 

Respiratory, thoracic and mediastinal disorders

 

Dyspnoea

Oropharyngeal pain

Throat tightness

 

Gastrointestinal disorders

Nausea

Stomatitis

Vomiting

Constipation

Dry mouth

Mouth ulceration

Gingival ulceration

Lip ulceration

Impaired gastric emptying

Abdominal pain

Dyspepsia

Stomach discomfort

Tongue disorder

Aphthous stomatitis

1Swollen Tongue

Skin and subcutaneous tissue disorders

 

Hyperhidrosis

Skin lesion

Rash

Pruritus allergic

Pruritus

Night sweats

Increased tendency to bruise

 

Musculoskeletal and connective tissue disorders

 

 

Arthralgia

Musculoskeletal stiffness

Joint stiffness

 

Reproductive system and breast disorders

 

 

Erectile dysfunction

 

General disorders and administration site conditions

 

Fatigue

Drug withdrawal syndrome

Asthenia

Malaise

 

Injury, poisoning and procedural complications

 

 

Accidental overdose

 

 

1Observed in post-marketing experience only

Section 5.1 (Pharmacodynamic properties)

Pharmacotherapeutic group: Analgesics; Opioids; Phenylpiperidine derivatives.

ATC code: N02AB03

Section 5.2 (Pharmacokinetic properties)

Abstral is a quick dissolving sublingual tablet formulation.  Rapid absorption of fentanyl occurs over about 30 minutes following administration of Abstral.  The absolute bioavailability of Abstral has been calculated to be 54 %.  Mean maximal plasma concentrations of fentanyl range from 0.2 to 1.3 ng/ml (after administration of 100 to 800 µg  Abstral) and are reached within 22.5 to 240 minutes.

The pharmacokinetics of Abstral have been shown to be dose proportional over the dose range of 100 to 800 µg.  Pharmacokinetic studies have shown that multiple tablets are bioequivalent to single tablets of the equivalent dose.

Section 10 (DATE OF REVISION OF THE TEXT)

01/10/2012

Updated on 25-Jan-2013 and displayed until 24-Apr-2013

Reasons for adding or updating:

  • Removal of black triangle

Date of revision of text on the SPC: 02-Nov-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Removal of black triangle

Updated on 07-Mar-2012 and displayed until 25-Jan-2013

Reasons for adding or updating:

  • Change to section 6. 3 - Shelf Life

Date of revision of text on the SPC: 02-Nov-2011

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

In section 6.3, the shelf-life has been changed from 2 to 3 years.

Updated on 03-Jun-2010 and displayed until 07-Mar-2012

Reasons for adding or updating:

  • Change to section 5.1 - Pharmacodynamic Properties
  • Change to section 6. 5 - Nature and Contents of Container
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC: 17-Feb-2010

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:



In section 5.1, the text has been updated to reflect new data showing that the onset of action is 10 minutes following administration. A graphic illustration of this data has been added.

In section 6.5, the description of the container has been expanded to include full details of packaging components. The container itself is unchanged.

Updated on 23-Mar-2010 and displayed until 03-Jun-2010

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration

Date of revision of text on the SPC: 14-Oct-2009

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Clarification of dosage schedule.

Updated on 08-Jan-2009 and displayed until 23-Mar-2010

Reasons for adding or updating:

  • New SPC for new product

Legal Category:POM

Black Triangle (CHM): YES

Company contact details

Kyowa Kirin Ltd

Company image
Address

Galabank Business Park, Galashiels, TD1 1QH

Medical Information e-mail
Medical Information Direct Line

+ 44 (0)1896 664 000

Before you contact this company: often several companies will market medicines with the same active ingredient. Please check that this is the correct company before contacting them. Why?

Active ingredients

fentanyl citrate

Legal categories

POM - Prescription Only Medicine

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