ABSTRAL

Ireland - English - HPRA (Health Products Regulatory Authority)

Buy It Now

Active ingredient:
FENTANYL, AS CITRATE SALT
Available from:
Kyowa Kirin Ltd
ATC code:
N02AB03
INN (International Name):
FENTANYL, AS CITRATE SALT
Dosage:
600 Microgram
Pharmaceutical form:
Tablet Sublingual
Prescription type:
Product subject to prescription which may not be renewed (A)
Therapeutic area:
fentanyl
Authorization status:
Marketed
Authorization number:
PA1049/006/006
Authorization date:
2009-05-22

Package leaflet: Information for the patient

Abstral 100 microgram sublingual tablets

Abstral 200 microgram sublingual tablets

Abstral 300 microgram sublingual tablets

Abstral 400 microgram sublingual tablets

Abstral 600 microgram sublingual tablets

Abstral 800 microgram sublingual tablets

Fentanyl

Read all of this leaflet carefully before you start taking this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet:

What Abstral is and what it is used for

What you need to know before you take Abstral

How to take Abstral

Possible side effects

How to store Abstral

Contents of the pack and other information

1.

What Abstral is and what it is used for

Abstral is a treatment for adults who must already regularly be taking strong pain-relieving

medicine (opioids) for their persistent cancer pain, but require treatment for their breakthrough pain.

If you are not sure, talk to your doctor.

Breakthrough pain is pain which occurs suddenly, even though you have taken or used your usual

opioid pain-relieving medicine.

The active substance in Abstral sublingual tablets is fentanyl. Fentanyl belongs to a group of strong

pain-relieving medicines called opioids.

2.

What you need to know before you take Abstral

Do not take Abstral

if you are allergic to fentanyl or any of the other ingredients of this medicine (listed in section 6)

if you have severe breathing problems

If you are not regularly using a prescribed opioid medicine (e.g codeine, fentanyl,

hydromorphone, morphine, oxycodone, pethidine), every day on a regular schedule, for at

least a week, to control your persistent pain. If you have not been using these medicines you

must not use Abstral because it may increase the risk that breathing could become

dangerously slow and/or shallow, or even stop.

If you suffer from short-term pain other than breakthrough pain.

Warnings and precautions

Talk to your doctor or pharmacist before taking Abstral if you have or have recently had any of the

following, as your doctor will need to take account of these when prescribing your dose:

a head injury, because Abstral may cover up the extent of the injury

breathing problems or suffer from myasthenia gravis (a condition characterised by muscle

weakness)

problems with your heart, especially a slow heart rate

low blood pressure

liver or kidney disease, as this may require your doctor to more carefully adjust your dose

a brain tumour and/or raised intracranial pressure (an increase of pressure in the brain which

causes severe headache, nausea/vomiting and blurred vision)

mouth wounds or mucositis (swelling and redness of the inside of the mouth)if you take

antidepressants or antipsychotics please refer to the section ‘Other medicines and Abstral’

if you have ever developed adrenal insufficiency or lack of sex hormones (androgen deficiency)

with opioid use.

When taking Abstral, inform your doctor or dentist that you are taking this medicine, if

you are to have any surgery,

you experience pain or increased sensitivity to pain (hyperalgesia) which does not respond to a

higher dosage of your medicine as prescribed by your doctor

you experience a combination of the following symptoms: nausea, vomiting, anorexia, fatigue,

weakness, dizziness and low blood pressure. Together these symptoms may be a sign of a

potentially life-threatening condition called adrenal insufficiency, a condition in which the

adrenal glands do not produce enough hormones

Other medicines and Abstral

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines

(other than your regular opioid pain-relieving medicine).

Some medicines may increase or decrease the effects of Abstral. Therefore if you start,

change the dose of, or stop therapy with the following medication tell your doctor as they may

need to adjust your dose of Abstral:

Certain types of antifungal medicines containing e.g. ketoconazole or itraconazole (used to treat

fungal infections).

Certain types of antibiotic medicines called macrolides, containing e.g. erythromycin (used to

treat infections).

Certain types of antiviral medicines called protease inhibitors, containing e.g. ritonavir (used to

treat infections caused by viruses).

Rifampin or rifabutin (medicines used to treat bacterial infections)

Carbamazepine, phenytoin or phenobarbital (medicines used to treat convulsions/fits).

Herbal medicines containing St John’s wort (Hypericum perforatum)

Medicines containing alcohol

Medicines called monoamine-oxidase (MAO) inhibitors, which are used for severe depression

and Parkinson’s disease. Tell your doctor if you have taken this type of medicine within the last

two weeks

Certain types of strong pain killers, called partial agonist/antagonists e.g. buprenorphine,

nalbuphine and pentazocine (medicines for treatment of pain). You could experience symptoms

of withdrawal syndrome (nausea, vomiting, diarrhoea, anxiety, chills, tremor, and sweating)

while using these medicines.

Abstral may add to the effect of medicines that make you feel sleepy, including:

other strong pain-relieving medicines (opioid-type medicines e.g. for pain and cough)

general anaesthetics (used to make you sleep during operations)

muscle relaxants

sleeping tablets

medicines used to treat

depression

allergies

anxiety and psychosis

medicines containing clonidine (used to treat high blood pressure).

The risk of side effects increases if you are taking medicines such as certain antidepressants or

antipsychotics. Abstral may interact with these medicines and you may experience mental status

changes (e.g. agitation, hallucinations, coma), and other effects, such as body temperature above 38°C,

increase in heart rate, unstable blood pressure, and exaggeration of reflexes, muscular rigidity, lack of

coordination and/or gastrointestinal symptoms (e.g nausea, vomiting, diarrhoea). Your doctor will tell

you whether Abstral is suitable for you.

Abstral with food, drink and alcohol

Abstral can make some people feel drowsy. Do not consume alcohol without consulting your doctor

as it might make you feel more drowsy than usual.

Do not drink grapefruit juice while you are prescribed Abstral treatment as it may increase the side

effects of Abstral.

Pregnancy and breast-feeding

You must not use Abstral during pregnancy unless you have been specifically told to by your doctor.

Fentanyl can get into breast milk and may cause side effects in the breast-fed infant. Do not use

Abstral if you are breast-feeding. You should not start breast-feeding until at least 5 days after the last

dose of Abstral.

Ask your doctor or pharmacist for advice before taking any medicine when pregnant or breast-feeding.

Driving and using machines

Abstral may impair your mental and/or physical ability to perform potentially hazardous tasks such as

driving or operating machinery.

If you feel dizzy, sleepy or have blurred vision when you take Abstral, do not drive or use machinery.

Driving in the UK

This medicine can affect your ability to drive as it may make you sleepy or dizzy.

Do not drive while taking this medicine until you know how this medicine affects you.

It may be an offence to drive if your ability to drive safely is affected by taking this medicine.

There is further information for patients who are intending to drive in the UK - go to

https://www.gov.uk/drug-driving-law

Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking

this medicine.

3.

How to take Abstral

Before taking Abstral for the first time your doctor will explain how Abstral should be taken to

effectively treat your breakthrough pain.

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist

if you are not sure.

This product should ONLY be used by you according to your doctor’s instructions. It should not be

used by anyone else as it could present a SERIOUS risk to their health, especially in children.

Abstral is a different type of medication from other medicines you may have used to treat your

breakthrough pain. You must always use the dose of Abstral as prescribed by your doctor – this

may be a different dose from that which you have used with other medicines for breakthrough pain.

Starting Treatment – Finding the most appropriate dose

For Abstral to work successfully, your doctor will need to identify the most appropriate dose for

treating your breakthrough pain. Abstral is available in a range of strengths. You may need to try

different strengths of Abstral over a number of episodes of breakthrough pain to find the most

appropriate dose. Your doctor will help you do this and will work with you to find the best dose to

use.

If you do not get adequate pain relief from one dose your doctor may ask you to take an extra dose to

treat an episode of breakthrough pain. Do not take a second dose unless your doctor tells you to, as

this may result in overdose.

Sometimes your doctor may advise you to take a dose which consists of more than one tablet at a time.

Only do this if directed by your doctor.

Wait at least 2 hours from taking your last dose before treating your next episode of breakthrough pain

with Abstral.

Continuing Treatment - Once you have found the most appropriate dose

Once you and your doctor have found a dose of Abstral that controls your breakthrough pain you

should take this dose no more than four times a day. A dose of Abstral may consist of more than

one tablet.

Wait at least 2 hours from taking your last dose before treating your next episode of breakthrough pain

with Abstral.

If you think that the dose of Abstral that you are using is not controlling your breakthrough pain

satisfactorily tell your doctor, as he may need to adjust your dose.

You must not change your dose of Abstral unless directed by your doctor.

Taking the medicine

Abstral should be used sublingually. This means that the tablet should be placed under the tongue

where it dissolves rapidly in order to allow fentanyl to be absorbed across the lining of the mouth.

Once absorbed, fentanyl starts to work to relieve pain.

When you get an episode of breakthrough pain, take the dose advised by your doctor as follows:

If your mouth is dry, take a sip of water to moisten it. Spit out or swallow the water.

Remove the tablet(s) from the blister pack immediately before use as follows.

Separate one of the blister squares from the pack by tearing along the dotted

lines/perforations (keep the remaining blister squares together)

Peel back the edge of the foil where the arrow is shown and gently remove the tablet. Do

not try to push Abstral sublingual tablets through the foil top, as this will damage them

Place the tablet under your tongue as far back as you can and let it dissolve completely.

Abstral will dissolve rapidly under the tongue and be absorbed in order to provide pain relief. It

is therefore important that you do not suck, chew or swallow the tablet.

You should not drink or eat anything until the tablet has completely dissolved under your

tongue.

If you take more Abstral than you should

remove any remaining tablets from your mouth

tell your carer or another person what has happened

you or your carer should immediately contact your doctor, pharmacist or local hospital and

discuss what action to take

while waiting for the doctor, keep the person awake by talking to or shaking her/him now and

then

Symptoms of overdose include:

extreme drowsiness

slow, shallow breathing

If these occur, seek emergency medical help immediately.

If you think someone has taken Abstral by accident seek emergency medical help immediately.

If you stop taking Abstral

You should discontinue Abstral when you no longer have any breakthrough pain. You must however

continue to take your usual opioid pain relieving medicine to treat your persistent cancer pain as

advised by your doctor. You may experience withdrawal symptoms similar to the possible side effects

of Abstral when discontinuing Abstral. If you experience withdrawal symptoms or if you are

concerned about your pain relief you should contact your doctor. Your doctor will evaluate if you need

medicine to reduce or eliminate the withdrawal symptoms.

4.

Possible side effects

Like all medicines, Abstral can cause side-effects, although not everybody gets them.

If you start to feel unusually or extremely sleepy or your breathing becomes slow or shallow, you

or your carer should immediately contact your doctor or local hospital for emergency help (see

also section 3 “If you take more Abstral than you should”).

Very common side effects (may affect more than 1 in 10 people) include:

nausea

Common side effects (may affect up to 1 in 10 people) include:

dizziness, headache, excessive sleepiness

breathlessness/shortness of breath

inflammation inside the mouth, vomiting, constipation, dry mouth

sweating, weary/tired/lack of energy

Uncommon side effects (may affect up to 1 in 100 people) include:

allergic reaction, trembling/shaking, disturbed or blurred vision, fast or slow heart beat, low

blood pressure, memory loss

depression, suspicious thoughts/ feeling afraid for no reason, feeling confused, feeling

disorientated, feeling anxious/unhappy/restless, feeling unusually happy/healthy, mood swings

feeling full all the time, stomach ache, indigestion

mouth ulcers, problems with tongue, pain in mouth or throat, tightness in throat, lip or gum

ulcers

loss of appetite, loss of or change in sense of smell/taste

difficulty sleeping or disturbed sleep, disturbance in attention/easily distracted, lack of

energy/weakness/loss of strength

abnormality in skin, rash, itchiness, night sweats, decreased sensitivity to touch, bruising easily

joint pain or stiffness, stiffness in muscles

drug withdrawal symptoms, (may manifest by the occurrence of the following side effects:

nausea, vomiting, diarrhoea, anxiety, chills, tremor, and sweating), accidental overdose, in

males an inability to get and/or keep an erection, feeling generally unwell

Side effects of frequency not known: (frequency cannot be estimated from the available data)

swollen tongue, severe breathing problems, fall, flushing, feeling very warm, diarrhoea,

convulsion (fits), swelling of arms or legs, seeing or hearing things that are not really there

(hallucinations), fever, drug dependence (addiction), drug abuse.

Prolonged treatment with fentanyl during pregnancy may cause withdrawal symptoms in the newborn

which can be life-threatening (see section 2).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects

not listed in this leaflet. You can also report side effects directly via the national reporting system

listed below. By reporting side effects you can help provide more information on the safety of this

medicine.

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

5.

How to store Abstral

The pain-relieving medicine in Abstral is very strong and could be life-threatening if taken

accidentally by a child. Abstral must be kept out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister after EXP. The expiry date

refers to the last day of that month.

Do not store above 25°C.

Store in the original blister in order to protect from moisture.

It is recommended to keep Abstral in a locked storage space.

Any unused product should be taken, if possible, to your pharmacist to be disposed of safely. Do not

throw away any medicines via wastewater or household waste. These measures will help protect the

environment.

6.

Contents of the pack and other information

What Abstral contains

The active substance is fentanyl. One sublingual tablet contains either

100 micrograms fentanyl (as citrate)

200 micrograms fentanyl (as citrate)

300 micrograms fentanyl (as citrate)

400 micrograms fentanyl (as citrate)

600 micrograms fentanyl (as citrate)

800 micrograms fentanyl (as citrate)

The other ingredients are mannitol (E421), silicified microcrystalline cellulose, croscarmellose sodium

and magnesium stearate.

What Abstral looks like and contents of the pack

Abstral is a small white sublingual tablet to be inserted under the tongue. It comes in a range of

different strengths and shapes. Your doctor will prescribe the strength (shape) and number of tablets

suitable for you.

The 100 microgram tablet is a white round tablet

The 200 microgram tablet is a white oval-shaped tablet

The 300 microgram tablet is a white triangle-shaped tablet

The 400 microgram tablet is a white diamond-shaped tablet

The 600 microgram tablet is a white “D”-shaped tablet

The 800 microgram tablet is a white capsule-shaped tablet

Abstral tablets are contained in blisters, available in cartons of 10 or 30 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:

Marketing authorisation holder:

Kyowa Kirin Ltd

Galabank Business Park

Galashiels

TD1 1QH

Tel : +44 (0)1896 664000

Fax : +44(0)1896 664001

Manufacturer:

Recipharm Stockholm AB

Lagervägen 7

136 50 Jordbro

Sweden

Tel. +46 8 6025200

Aesica Queenborough Ltd.

North Road

Queenborough

Kent

ME11 5EL

United Kingdom

This medicinal product is authorised in the Member States of the EEA under the following

names:

Abstral:

Belgium, Cyprus, Denmark, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg,

Netherlands, Norway, Portugal, Slovenia, Spain, Sweden, UK.

Lunaldin:

Czech Republic, Estonia, Latvia, Lithuania, Slovak Republic, Romania

This leaflet was last revised in: 05-2018

Summary of Product Characteristics

1 NAME OF THE MEDICINAL PRODUCT

Abstral 600 microgram sublingual tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each sublingual tablet contains:

600 micrograms fentanyl (as citrate)

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Sublingual tablet

600 microgram sublingual tablet is a white “D”-shaped tablet

4 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Management of breakthrough pain in adult patients using opioid therapy for chronic cancer pain.

Breakthrough pain is

a transient exacerbation of otherwise controlled chronic background pain.

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:

Abstral sublingual tablets should be administered directly under the tongue at the deepest part.

Abstral sublingual

tablets should not be swallowed, but allowed to completely dissolve in the sublingual cavity without chewing or

sucking.

Patients should be advised not to eat or drink anything until the sublingual tablet is completely dissolved.

In patients who have a dry mouth water may be used to moisten the buccal mucosa before taking Abstral.

Dose titration:

The object of dose titration is to identify an optimal maintenance dose for ongoing treatment of breakthrough pain

episodes. This optimal dose should provide adequate analgesia with an acceptable level of adverse reactions.

The optimal dose of Abstral will be determined by upward titration, on an individual patient basis.

Several doses are

available for use during the dose titration phase. The initial dose of Abstral used should be 100 micrograms, titrating

upwards as necessary through the range of available dosage strengths.

Patients should be carefully monitored until an optimal dose is reached.

Switching from other fentanyl containing products to Abstral must not occur at a 1:1 ratio because of different

absorption profiles. If patients are switched from another fentanyl containing product, a new dose titration with Abstral

is required.

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

1

The following dose regimen is recommended for titration, although in all cases the physician should take into account

the clinical need of the patient, age and concomitant illness.

All patients must start therapy with a single 100 microgram sublingual tablet.

If adequate analgesia is not obtained

within 15-30 minutes of administration of a single sublingual tablet, a supplemental (second) 100 microgram sublingual

tablet may be administered.

If adequate analgesia is not obtained within 15-30 minutes of the first dose an increase in

dose to the next highest tablet strength should be considered for the next episode of breakthrough pain (Refer to figure

below).

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.

If adequate analgesia is achieved at the higher dose, but undesirable effects are considered unacceptable, an

intermediate dose (using the 100 microgram sublingual tablet where appropriate) may be administered.

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.

Strength (micrograms) of first sublingual tablet per

episode of breakthrough pain

Strength (micrograms) of supplemental (second)

sublingual tablet to be taken 15-30 minutes after

first tablet, if required

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

2

In order to minimise the risk of opioid–related adverse reactions and to identify the appropriate dose, it is imperative

that patients be monitored closely by health professionals during the titration process.

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

Maintenance therapy:

Once an appropriate dose has been established, which may be more than one tablet, patients should be maintained on

this dose and should limit consumption to a maximum of four Abstral doses per day.

During the maintenance period patients should wait at least 2 hours before treating another episode of breakthrough

pain with Abstral.

Dose re-adjustment:

If the response (analgesia or adverse reactions) to the titrated Abstral dose markedly changes,

an adjustment of dose

may be necessary to ensure that an optimal dose is maintained.

If more than four episodes of breakthrough pain are experienced per day over a period of more than four consecutive

days, then the dose of the long acting opioid used for persistent pain should be re-evaluated.

If the long acting opioid

or dose of long acting opioid is changed the Abstral dose should be re-evaluated and re-titrated as necessary to ensure

the patient is on an optimal dose.

It is imperative that any dose re-titration of any analgesic is monitored by a health professional.

In absence of adequate pain control, the possibility of hyperalgesia, tolerance and progression of underlying disease

should be considered (see section 4.4).

Discontinuation of therapy:

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 avoid

the possibility of abrupt withdrawal effects.

Use in children and adolescents:

Abstral must not be used in patients less than 18 years of age due to a lack of data on safety and efficacy.

Use in older people

Dose titration needs to be approached with particular care and patients observed carefully for signs of fentanyl toxicity

(see section 4.4).

Use in patients with renal and hepatic impairment

Patients with kidney or liver dysfunction should be carefully observed for signs of fentanyl toxicity during the Abstral

titration phase (see section 4.4).

4.3 Contraindications

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

Patients without maintenance opioid therapy as there is an increased risk of respiratory depression.

Severe respiratory depression or severe obstructive lung conditions.

Treatment of acute pain other than breakthrough pain.

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

3

4.4 Special warnings and precautions for use

Patients and their carers must be instructed that Abstral contains an active substance in an amount that can be fatal to a

child, and therefore to keep all tablets out of the reach and sight of children.

Due to the potentially serious undesirable effects that can occur when taking an opioid therapy such as Abstral, patients

and their carers should be made fully aware of the importance of taking Abstral correctly and what action to take

should symptoms of overdose occur.

Before Abstral therapy is initiated, it is important that the patient’s long-acting opioid treatment used to control their

persistent pain has been stabilised.

Upon repeated administration of opioids such as fentanyl, tolerance and physical and/or psychological dependence may

develop.

Iatrogenic addiction following therapeutic use of opioids is known to occur.

In common with all opioids, there is a risk of clinically significant respiratory depression associated with the use of

Abstral.

Particular caution should be exercised during dose titration with Abstral in patients with chronic obstructive

pulmonary disease or other medical conditions predisposing them to respiratory depression (e.g. myasthenia gravis)

because of the risk of further respiratory depression, which could lead to respiratory failure.

Abstral should only be administered with extreme caution in patients who may be particularly susceptible to the

intracranial effects of hyperkapnia, such as those showing evidence of raised intracranial pressure, reduced

consciousness, coma or brain tumours.

In patients with head injuries, the clinical course may be masked by the use of

opioids.

In such a case, opioids should be used only if absolutely necessary.

As with other opioids, in case of insufficient pain control in response to an increased dose of fentanyl, the possibility of

opioid-induced hyperalgesia should be considered. A fentanyl dose reduction or discontinuation of fentanyl treatment

or treatment review may be indicated.

Cardiac disease

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

bradyarrythmias.

Data from intravenous studies with fentanyl suggest that older patients may have reduced clearance, a prolonged half-

life and they may be more sensitive to the active substance than younger patients.

Older, cachectic, or debilitated

patients should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary.

Abstral should be administered with caution to patients with liver or kidney dysfunction, especially during the titration

phase.

The use of Abstral in patients with hepatic or renal impairment may increase the bioavailability of fentanyl and

decrease its systemic clearance, which could lead to accumulation and increased and prolonged opioid effects.

Care should be taken in treating patients with hypovolaemia and hypotension.

Abstral has not been studied in patients with mouth wounds or mucositis. There may be a risk of increased systemic

drug exposure in such patients and therefore extra caution is recommended during dose titration.

There should be no noticeable effects on cessation of treatment with Abstral, but possible symptoms of withdrawal are

anxiety, tremor, sweating, paleness, nausea and vomiting.

Serotonin Syndrome

Caution is advised when Abstral

is coadministered with drugs that

affect

the serotoninergic neurotransmitter

systems.

The development

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

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

4

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.

4.5 Interaction with other medicinal products and other forms of interaction

Fentanyl is metabolised by CYP3A4.

Active substances that inhibit CYP3A4 activity such as macrolide antibiotics

(e.g. erythromycin), azole antifungal agents (e.g. ketoconazole, itraconazole) or certain protease inhibitors (e.g.

ritonavir) may increase the bioavailability of fentanyl by decreasing its systemic clearance, potentially enhancing or

prolonging opioid effects.

Grapefruit juice is also known to inhibit CYP3A4.

Coadministration with agents that induce

CYP3A4 activity such as antimycobacterials (e.g. rifampin, rifabutin), anticonvulsants (e.g. carbamazepine, phenytoin,

and phenobarbital) herbal products (e.g. St John’s wort, Hypericum perforatum) may reduce the efficacy of fentanyl.

CYP3A4 inducers exert their effect in a time-dependent manner, and may take at least 2 weeks to reach maximal effect

after introduction. Conversely, on discontinuation, CYP3A4 induction may take at least 2 weeks to decline. Patients

receiving fentanyl who stop therapy with, or decrease the dose of CYP3A4 inducers may be at risk of increased

fentanyl activity or toxicity. Fentanyl should therefore be given to patients with caution if administered concomitantly

with CYP3A4 inhibitors and/or inducers.

Concomitant use of other CNS depressants, such as other morphine derivatives (analgesics and antitussives), general

anaesthetics, skeletal muscle relaxants, sedative antidepressants, sedative H1 antihistamines, barbiturates, anxiolytics

(ie benzodiazepines), hypnotics, antipsychotics, clonidine and related substances may produce increased CNS

depressant effects.

Respiratory depression, hypotension and profound sedation may occur.

Alcohol potentiates the sedative effects of morphine-based analgesics, therefore concomitant administration of

alcoholic beverages or medicinal products containing alcohol with Abstral is not recommended.

Abstral is not recommended for use in patients who have received monoamine oxidase (MAO) inhibitors within 14

days because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

The concomitant use of partial opioid agonists/antagonists (e.g. buprenorphine, nalbuphine, pentazocine) is not

recommended. They have high affinity to opioid receptors with relatively low intrinsic activity and therefore partially

antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependent patients.

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.

4.6 Fertility, pregnancy 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.

Long-term treatment during pregnancy may cause withdrawal symptoms in the new-born infant.

Fentanyl should not be used during labour and delivery (including caesarean section) since fentanyl crosses the

placenta and may cause respiratory depression in the foetus or in the new-born infant.

Breast-feeding

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

5

Fentanyl passes into breast milk and 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 5 days after the last

administration of fentanyl.

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.

4.8 Undesirable effects

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 and/or other fentanyl-containing compounds:

The Following adverse reactions have been reported with Abstral and/or other fentanyl-containing compounds

during clinical studies and from post-marketing experience. They 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.

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

Decreased appetite

Psychiatric

disorders

Depression

Paranoia

Confusional state

Disorientation

Mental status changes

Anxiety

Euphoric mood

Dysphoria

Emotional lability

Hallucination

Drug dependence

(addiction)

Drug abuse

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

6

Disturbance in attention

Insomnia

Nervous system

disorders

Dizziness

Headache

Somnolence

Amnesia

Parosmia

Dysgeusia

Tremor

Lethargy

Hypoaesthesia

Sleep disorder

Convulsion

Eye disorders

Vision blurred

Cardiac

disorders

Tachycardia

Bradycardia

Vascular

disorders

Hypotension

Respiratory,

thoracic

and mediastinal

disorders

Dyspnoea

Oropharyngeal pain

Throat tightness

Respiratory

depression

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

Swollen Tongue

Diarrhoea

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

Fatigue

*Drug withdrawal

syndrome

Asthenia

Malaise

Flushing and hot

flush

Peripheral oedema

Pyrexia

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

7

* opioid withdrawal symptoms such as nausea,

vomiting,

diarrhoea,

anxiety,

chills,

tremor,

and sweating have been

observed with transmucosal fentanyl

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;

Fax: +353 1 6762517.

Website: www.hpra.ie; e-mail: medsafety@hpra.ie

4.9 Overdose

The symptoms of fentanyl overdose are an extension of its pharmacological actions, the most serious effect being

respiratory depression, which may lead to respiratory arrest.

Management of opioid overdose in the immediate term includes removal of any remaining Abstral sublingual tablets

from the mouth, physical and verbal stimulation of the patient and an assessment of the level of consciousness.

A patent airway should be established and maintained.

If necessary an oropharyngeal airway or endotracheal tube

should be inserted, oxygen administered and mechanical ventilation initiated, as appropriate.

Adequate body

temperature and parenteral fluid intake should be maintained.

For the treatment of accidental overdose in opioid-naïve individuals, naloxone or other opioid antagonists should be

used as clinically indicated and in accordance with their Summary of Product Characteristics.

Repeated administration

of the opioid antagonist may be necessary if the duration of respiratory depression is prolonged.

Care should be taken when using naloxone or other opioid antagonists to treat overdose in opioid-maintained patients,

due to the risk of precipitating an acute withdrawal syndrome.

If severe or persistent hypotension occurs, hypovolaemia should be considered, and the condition should be managed

with appropriate parenteral fluid therapy.

Muscle rigidity interfering with respiration has been reported with fentanyl and other opioids.

In this situation,

endotracheal intubation, assisted ventilation and administration of opioid antagonists as well as muscle relaxants may

be requested.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics; Opioids; Phenylpiperidine derivatives

ATC code: N02AB03

Fentanyl is a potent µ-opioid analgesic with rapid onset of analgesia 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 function are typical of opioid analgesics and are considered to be class

effects. These can include respiratory depression, bradycardia, hypothermia, constipation, miosis, physical dependence

and euphoria.

site conditions

Neonatal

withdrawal

syndrome

Injury, poisoning

and procedural

complications

Accidental overdose

Fall

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

8

Opioids may influence the hypothalamic-pituitary-adrenal or –gonadal axes. Some changes that can be seen include an

increase in serum prolactin, and decreases in plasma cortisol and testosterone. Clinical signs and symptoms may be

manifest from these hormonal changes.

The analgesic effects of fentanyl are related to the blood level of the active substance; in opioid-naïve patients,

minimum effective analgesic serum concentrations of fentanyl range from 0.3-1.2 ng/ml, while blood levels of 10-

20 ng/ml produce surgical anaesthesia and profound respiratory depression.

In patients with chronic cancer pain on stable maintenance doses of opioids, statistically significant improvement in

pain intensity difference was seen with Abstral versus placebo from 10 minutes after administration onwards (see

figure 1 below), with a significantly lower need for rescue analgesic therapy.

Figure 1 Mean Pain Intensity Difference from baseline (± SE) for Abstral Compared with Placebo (measured by a 0-10

Likert scale)

The safety and efficacy of Abstral have been evaluated in patients taking the drug at the onset of the breakthrough pain

episode. Pre-emptive use of Abstral for predictable pain episodes was not investigated in the clinical trials.

Fentanyl, in common with all µ-opioid receptor agonists, produces dose dependent respiratory depression.

This risk is

higher in opioid-naïve subjects than in patients experiencing severe pain or receiving chronic opioid therapy.

Long-

term treatment with opioids typically leads to development of tolerance to their secondary effects.

While opioids generally increase the tone of urinary tract smooth muscle, the net effect tends to be variable, in some

cases producing urinary urgency, in others, difficulty in urination.

Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract

leading to a prolongation in gastrointestinal transit time, which may be responsible for the constipating effect of

fentanyl.

5.2 Pharmacokinetic properties

Fentanyl is a highly lipophilic drug absorbed very rapidly through the oral mucosa and more slowly through the

gastrointestinal tract.

Orally administered fentanyl undergoes pronounced hepatic and intestinal first pass effects.

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.

About 80-85% of fentanyl is bound by plasma proteins, mainly

1-glycoprotein and to a lesser extent albumin and

lipoprotein.

The volume of distribution of fentanyl at steady state is about 3-6 l/kg.

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

9

Fentanyl is metabolised primarily via CYP3A4 to a number of pharmacologically inactive metabolites, including

norfentanyl.

Within 72 hours of intravenous fentanyl administration around 75% of the dose is excreted into the urine,

mostly as metabolites, with less than 10% as unchanged drug.

About 9% of the dose is recovered in the faeces,

primarily as metabolites.

Total plasma clearance of fentanyl is about 0.5 l/h/kg.

After Abstral administration, the main elimination half-life of fentanyl is about 7 hours (range 3-12.5 hours) and the

terminal half-life is about 20 hours (range 11.5-25 hours).

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.

Renal/hepatic impairment

Impaired hepatic or renal function could cause increased serum concentrations.

Older, cachectic or generally impaired

patients may have a lower fentanyl clearance, which could cause a longer terminal half-life for the compound (see

sections 4.2 and 4.4).

5.3 Preclinical safety data

Safety pharmacology and repeated dose toxicity data reveal no special hazard for humans that is not already covered by

other sections of this SPC.

Animal studies have shown reduced fertility and increased mortality in rat foetuses.

Teratogenic effects have, however, not been demonstrated.

Mutagenicity testing in bacteria and in rodents yielded negative results.

Like other opioids fentanyl showed mutagenic

effects in vitro in mammalian cells.

A mutagenic risk with therapeutic use seems unlikely since effects were induced

only at very high concentrations.

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.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Mannitol (E421)

Silicified microcrystalline cellulose

Croscarmellose sodium

Magnesium stearate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 25°C.

Store in the original blister package in order to protect from moisture.

6.5 Nature and contents of container

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

1

0

Abstral sublingual tablets are packaged in child resistant blisters of OPA/Aluminium/PVC pockets with

paper/polyester/Aluminium lidding contained in a cardboard outer carton.

The packaging is colour-coded for each

Abstral sublingual tablet strength.

Pack size: Packs of 10 or 30 sublingual tablets. Not all pack sizes may be marketed

6.6 Special precautions for disposal

Waste material should be disposed of safely.

Patients/carers should be encouraged to return any unused product to the

Pharmacy, where it should be disposed of in accordance with national and local requirements.

7 MARKETING AUTHORISATION HOLDER

ProStrakan Limited

Galabank Business Park

Galashiels TD1 1QH

United Kingdom

8 MARKETING AUTHORISATION NUMBER

PA1049/006/006

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of First Authorisation: 22

May 2009

Date of last renewal: 28

February 2013

10 DATE OF REVISION OF THE TEXT

July 2018

H

e

a

l

t

h

P

r

o

d

u

c

t

s

R

e

g

u

l

a

t

o

r

y

A

u

t

h

o

r

i

t

y

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

_

D

a

t

e

P

r

i

n

t

e

d

3

1

/

0

7

/

2

0

1

8

C

R

N

2

2

0

7

6

1

1

p

a

g

e

n

u

m

b

e

r

:

1

1

Similar products

Search alerts related to this product

View documents history

Share this information