Panitaz 20micrograms/hour transdermal patches

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

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Active ingredient:
Buprenorphine
Available from:
Dr Reddy's Laboratories (UK) Ltd
ATC code:
N02AE01
INN (International Name):
Buprenorphine
Dosage:
20microgram/1hour
Pharmaceutical form:
Transdermal patch
Administration route:
Transdermal
Class:
Schedule 3 (CD No Register)
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 04070200; GTIN: 05036072006492
Authorization number:
PL 08553/0566

Read the complete document

What is in this leaflet:

1.

What Panitaz is and what it is used for

2.

What you need to know before you use Panitaz

3.

How to use Panitaz

4.

Possible side effects

5.

How to store Panitaz

6.

Contents of the pack and other information

1.

What Panitaz is and what it is used for

Panitaz patches contain the active ingredient buprenorphine which belongs to a group of medicines called strong

analgesics or ‘painkillers’. They have been prescribed for you by your doctor to relieve moderate, long-lasting pain

that requires the use of a strong painkiller.

Panitaz patches should not be used to relieve acute pain.

Panitaz patches act through the skin. After application, buprenorphine passes through the skin into the blood.

Each patch lasts for seven days.

2.

What you need to know before you use Panitaz

Do not use Panitaz:

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

if you have breathing problems

if you are addicted to drugs

if you are taking a type of medicine known as a monoamine oxidase inhibitor (examples include

tranylcypromide, phenelzine, isocarboxazid, moclobamide and linezolid), or you have taken this type of

medicine in the last two weeks

if you suffer from myasthenia gravis (a condition in which the muscles become weak)

if you have previously suffered from withdrawal symptoms such as agitation, anxiety, shaking or sweating

upon stopping taking alcohol.

Panitaz must not be used to treat symptoms associated with drug withdrawal.

Warnings and precautions

Talk to your doctor before using Panitaz:

if you suffer from seizures, fits or convulsions

if you have a severe headache or feel sick due to a head injury or increased pressure in your skull (for

instance due to brain disease). This is because the patches may make symptoms worse or hide the extent of a

head injury

if you are feeling light-headed or faint

if you have severe liver problems

if you have ever been addicted to drugs

if you have a high temperature, as this may lead to larger quantities of the active ingredient being absorbed

into the blood than normal.

If you have recently had an operation, please speak to your doctor before using these patches.

Do not expose the patch to extreme heat (e.g. heating pads, electric blanket, heat lamps, sauna, hot tubs, heated

water beds, hot water bottle etc) as this may lead to larger quantities of the active ingredient being absorbed into

the blood than normal. External heat may also prevent the patch from sticking properly.

Children and adolescents

Do not give this medicine to children below 18 years.

Other medicines and Panitaz

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

Panitaz patches must not be used together with a type of medicine known as a monoamine oxidase inhibitor

(examples include tranylcypromide, phenelzine, isocarboxazid, moclobamide and linezolid), or if you have

taken this type of medicine in the last two weeks.

If you take some medicines such as phenobarbital or phenytoin (medicines commonly used to treat seizures,

fits or convulsions), carbamazepine (a medicine to treat seizures, fits or convulsions and certain pain

conditions), or rifampicin (a medicine to treat tuberculosis) the effects of Panitaz patches may be reduced.

Panitaz patches may make some people feel drowsy, sick or faint or make them breathe more slowly or

weakly. These side effects may be made worse if other medicines that produce the same effects are taken at

the same time. These include certain medicines to treat pain, depression, anxiety, psychiatric or mental

disorders, medicines to help you sleep, medicines to treat high blood pressure such as clonidine, other opioids

(which may be found in painkillers or certain cough mixtures e.g. morphine, dextropropoxyphene, codeine,

dextromethorphan, noscapine), antihistamines which make you drowsy, or anaesthetics such as halothane.

Panitaz patches must be used with caution if you are also taking benzodiazepines (medicines used to treat

anxiety or to help you sleep). This combination may cause serious breathing problems which could be fatal in

case of overdose. Tell your doctor if you are taking this combination.

Panitaz with food, drink and alcohol

Alcohol may make some of the side effects worse and you may feel unwell if you drink alcohol whilst wearing

Panitaz patches. Drinking alcohol whilst using Panitaz patches may also affect your reaction time.

Pregnancy and breast-feeding

You should not use Panitaz patches if you are pregnant or are breast-feeding, think you may be pregnant or are

planning to have a baby.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Panitaz patches may affect your reactions to such an extent that you may not react adequately or quickly enough

in the event of unexpected or sudden occurrences. This applies particularly:

at the beginning of treatment

if you are taking medicines to treat anxiety or help you sleep

if your dose is increased.

If you are affected, you should not drive or operate machinery whilst using Panitaz patches, or for 24 hours after

removing the patch.

The 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 it affects you.

It is an offence to drive while you have this medicine in your body over a specified limit unless you have a

defence (called the ‘statutory defence’).

This defence applies when:

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

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

medicine.Please note that it is still an offence to drive if you are unfit because of the medicine (i.e. your ability

to drive is being affected).

Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be found

here: 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 use Panitaz

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

if you are not sure.

Different strengths of Panitaz patches are available. Your doctor will decide which strength of Panitaz patch will suit

you best.

During treatment, your doctor may change the patch you use to a smaller or larger one if necessary, or tell you to

use a combination of up to two patches. You should not apply more than two patches at the same time,

regardless of the patch strength.

Adults and elderly patients

Unless your doctor has told you differently, attach one Panitaz patch (as described in detail below) and change it

every seventh day, preferably at the same time of day. Your doctor may wish to adjust the dose after 3-7 days until

the correct level of pain control has been found. If your doctor has advised you to take other painkillers in addition

to the patch, strictly follow the doctor’s instructions, otherwise you will not fully benefit from treatment with the

Panitaz patch. The patch should be worn for 3 full days before increasing the dose, this is when the maximum

effect of a given dose is established.

Patients under 18 years of age

Panitaz patches should not be used in patients below the age of 18 years.

Patients with kidney disease/dialysis patients

In patients with kidney disease, no change in dose is necessary.

Patients with liver disease

In patients with liver disease, the effects and period of action of the Panitaz patch may be affected and your doctor

will therefore check on you more closely.

Before applying the transdermal patch

Choose an area of non-irritated, intact skin on your upper arm, outer arm, upper chest, upper back or side of

the chest (see illustrations). Ask for assistance if you cannot apply the patch yourself.

The Panitaz patch should be applied to a relatively hairless or nearly hairless skin site. If no suitable hair free

sites are available the hairs should be cut off with a pair of scissors. Do not shave them off.

Avoid skin which is red, irritated or has any other blemishes, for instance large scars.

The area of skin you choose must be dry and clean. If necessary, wash it with cold or lukewarm water. Do not

use soap, alcohol, oil, lotions or other detergents. After a hot bath or shower, wait until your skin is completely

dry and cool. Do not apply lotion, cream or ointment to the chosen area. This might prevent your patch from

sticking properly

Applying the transdermal patch

Step 1: Each transdermal patch is sealed in a sachet. Just before use, cut the sachet along

the sealed edge with scissors. Take out the transdermal patch. Do not use the patch if the

sachet seal is broken.

Step 2: The sticky side of the transdermal patch is covered with a transparent protective foil.

Carefully peel off one part of the foil. Try not to touch the sticky part of the transdermal patch.

Step 3: Stick the transdermal patch on to the area of skin you have chosen and remove the

remaining foil.

Step 4: Press the transdermal patch against your skin with the palm of your hand and count

slowly to 30. Make sure that the whole transdermal patch is in contact with your skin,

especially at the edges.

Wearing the transdermal patch

You should wear the patch for seven days. Provided that you have applied the patch correctly, there is little risk of

it coming off. If the edges of the patch begin to peel off, they may be taped down with a suitable skin tape. You

may shower, bathe or swim whilst wearing it.

In the unlikely event that your patch falls off before it needs changing, do not use the same patch again. Stick a

new one on straight away (see “Changing the transdermal patch” below).

Changing the transdermal patch

Take the old transdermal patch off.

Fold it in half with the sticky side inwards.

Open and take out a new patch. Use the empty sachet to dispose of the old patch. Now discard the

sachet safely.

Even used patches contain some active ingredient that may harm children or animals, so make sure your used

patches are always kept out of the reach and sight of them.

Stick a new transdermal patch on a different appropriate skin site (as described above). You should not apply a

new patch to the same site for 3-4 weeks.

Remember to change your patch at the same time of day. It is important that you make a note of the time of day.

Duration of treatment

Your doctor will tell you how long you should be treated with the Panitaz patch. Do not stop treatment without consulting

a doctor, because your pain may return and you may feel unwell (see also “If you stop using Panitaz” below).

If you feel that the effect of the Panitaz patch is too weak or too strong, talk to your doctor or pharmacist.

If you use more Panitaz than you should

As soon as you discover that you have used more patches than you should, remove all patches and call your

doctor or hospital straight away. People who have taken an overdose may feel very sleepy and sick. They may

also have breathing difficulties or lose consciousness and may need emergency treatment in hospital. When

seeking medical attention make sure that you take this leaflet and any remaining patches with you to show to

the doctor.

If you forget to use Panitaz

Stick a new patch on as soon as you remember. Also make a note of the date, as your usual day of changing may

now be different. If you are very late changing your patch, your pain may return. In this case, please contact your

doctor.

Do not apply additional patches to make up for the forgotten application.

If you stop using Panitaz

If you stop using Panitaz patches too soon or you interrupt your treatment your pain may return. If you wish to stop

treatment please consult your doctor. They will tell you what can be done and whether you can be treated with

other medicines.

Some people may have side effects when they have used strong painkillers for a long time and stop using them.

The risk of having effects after stopping Panitaz patches is very low. However, if you feel agitated, anxious,

nervous or shaky, if you are overactive, have difficulty sleeping or digestive problems, tell your doctor.

The pain relieving effect of Panitaz patch is maintained for some time after removal of the patch. You should not

start another opioid analgesic (strong painkiller) within 24 hours after removal of the patch.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects that may be associated with Panitaz patches are similar to those seen with other strong

painkillers and include difficulty in breathing and low blood pressure.

This medicine can cause allergic reactions, although serious allergic reactions are rare. Remove the patch and tell

your doctor immediately if you get any sudden wheeziness, difficulties in breathing, swelling of the eyelids, face or

lips, rash or itching especially those covering your whole body.

This medicine can cause allergic reactions, although serious allergic reactions are rare. Take the patch off and tell

This medicine can cause allergic reactions, although serious allergic reactions are rare. Remove the patch

and tell your doctor immediately if you get any sudden wheeziness, difficulties in breathing, swelling of the

eyelids, face or lips, rash or itching especially those covering your whole body.

As with all strong painkillers, there is a risk that you may become addicted or reliant on Panitaz patches.

In patients treated with Panitaz patches, the following other side effects have been reported:

Very common (may affect more than 1 in 10 people)

headache, dizziness, drowsiness

constipation, dry mouth, feeling or actually being sick

itchy skin, redness, itching at application site

Common (may affect up to 1 in 10 people)

loss of appetite

confusion, depression, difficulty in sleeping, nervousness

tingling or numbness

flushing of the skin

shortness of breath

abdominal pain or discomfort, diarrhoea, indigestion

sweating, rash, skin eruptions

tiredness, a feeling of unusual weakness, muscle weakness, pain, chest pain, swelling of hands, ankles or

feet, redness or rash at the application site

Uncommon (may affect up to 1 in 100 people)

dehydration

mood swings, restlessness, agitation, anxiety, feeling detached from oneself, a feeling of extreme happiness,

hallucinations, nightmares

changes in taste, difficulty in speaking, reduced sensitivity to pain or touch, loss of memory, migraine, fainting,

shaking, problems with concentration or co-ordination

dry eyes, blurred vision

a ringing or buzzing sound in the ears, a feeling of dizziness or spinning

high or low blood pressure, angina (severe chest pain associated with heart disease), fast or irregular heart beat

worsening of breathing problems associated with asthma, cough, hiccups, over breathing, reduced oxygen in

the blood, runny nose, wheezing

wind

weight loss

dry skin, swelling of the face

muscle cramps, spasms, aches and pains

difficulty in passing urine

a flu like illness, high temperature, shivering, generally feeling unwell

an increase in accidental injuries (e.g. falls)

withdrawal symptoms such as agitation, anxiousness, sweating or shaking upon stopping using Panitaz patches

If you need to have blood tests remind your doctor that you are using Panitaz patches. This is important because

Panitaz patches may change the way your liver works and this could affect the results of some blood tests.

Rare (may affect up to 1 in 1,000 people)

decreased sexual drive, mental disorder

difficulties with balance

swelling of the eyelids, a reduction in size of the pupils in the eye

difficulty in breathing

diverticulitis (inflammation of the intestine), difficulty in swallowing

local allergic reaction with marked signs of swelling (in such cases treatment should be stopped)

decreased erection, sexual dysfunction

Very rare (may affect up to 1 in 10,000 people)

muscle twitching

ear pain

blisters

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 Yellow Card Scheme, website

www.mhra.gov.uk/yellowcard. By reporting side effects, you can help provide more information on the safety of

this medicine.

5.

How to store Panitaz

Keep this medicine out of the sight and reach of children.

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

refers to the last day of that month.

Do not store above 25°C.

Do not use the patch if the sachet seal is broken.

Used patches must be folded over on themselves with the adhesive layer inwards, and discarded safely out of

sight and reach of children.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away

medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Panitaz patches contain

The active substance is buprenorphine.

Each 5 micrograms/h transdermal patch contains 5 mg of buprenorphine in a patch size of 6.25 cm2 and releases

about 5 micrograms of buprenorphine per hour (over a period of 7 days).

Each 10 micrograms/h transdermal patch contains 10 mg of buprenorphine in a patch size of 12.5 cm2 and

releases about 10 micrograms of buprenorphine per hour (over a period of 7 days).

Each 20 micrograms/h transdermal patch contains 20 mg of buprenorphine in a patch size of 25 cm2 and releases

about 20 micrograms of buprenorphine per hour (over a period of 7 days).

The other ingredients are polyacrylate, povidone K90, levulinic acid, oleyl oleate, PET film, polyester web, blue

printing ink.

What Panitaz patches look like and contents of the pack

Transdermal patch.

Three sizes are available.

Each 5 micrograms/h transdermal patch is beige coloured with rounded corners and is imprinted with

“Buprenorphin” and “5 μg/h”.

Each 10 micrograms/h transdermal patch is beige coloured with rounded corners and is imprinted with

“Buprenorphin” and “10 μg/h”.

Each 20 micrograms/h transdermal patch is beige coloured with rounded corners and is imprinted with

“Buprenorphin” and “20 μg/h”.

One transdermal patch is sealed in one child-resistant sachet. The patches are available in cartons containing 4

transdermal patches.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Dr. Reddy’s Laboratories (UK) Ltd., 6 Riverview Road, Beverley, East Yorkshire, HU17 0LD, United Kingdom

Manufacturer

betapharm Arzneimittel GmbH, Kobelweg 95, Augsburg, 86156, Germany

This leaflet was last revised in 07/2017

Package leaflet: Information for the user

Panitaz 5 micrograms/h, 10 micrograms/h, 20 micrograms/h Transdermal Patches

Buprenorphine

Important things you need to know about Panitaz

These patches contain a strong pain killer.

Ensure that old patches are removed before applying a new one.

Patches must not be cut.

Do not expose the patches to a heat source (such as a hot water bottle).

Do not soak in a hot bath or take a hot shower whilst wearing a patch.

If you develop a fever tell your doctor immediately.

Follow the dosage instructions carefully and only change your patch on the same day and at the same time 7 days later.

If your breathing becomes shallow and weak take the patch off and seek medical help

Read all of this leaflet carefully before you start using 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.

480 mm

280 mm

60 mm

70 mm

70 mm

70 mm

70 mm

What is in this leaflet:

1.

What Panitaz is and what it is used for

2.

What you need to know before you use Panitaz

3.

How to use Panitaz

4.

Possible side effects

5.

How to store Panitaz

6.

Contents of the pack and other information

1.

What Panitaz is and what it is used for

Panitaz patches contain the active ingredient buprenorphine which belongs to a group of medicines called strong

analgesics or ‘painkillers’. They have been prescribed for you by your doctor to relieve moderate, long-lasting pain

that requires the use of a strong painkiller.

Panitaz patches should not be used to relieve acute pain.

Panitaz patches act through the skin. After application, buprenorphine passes through the skin into the blood.

Each patch lasts for seven days.

2.

What you need to know before you use Panitaz

Do not use Panitaz:

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

if you have breathing problems

if you are addicted to drugs

if you are taking a type of medicine known as a monoamine oxidase inhibitor (examples include

tranylcypromide, phenelzine, isocarboxazid, moclobamide and linezolid), or you have taken this type of

medicine in the last two weeks

if you suffer from myasthenia gravis (a condition in which the muscles become weak)

if you have previously suffered from withdrawal symptoms such as agitation, anxiety, shaking or sweating

upon stopping taking alcohol.

Panitaz must not be used to treat symptoms associated with drug withdrawal.

Warnings and precautions

Talk to your doctor before using Panitaz:

if you suffer from seizures, fits or convulsions

if you have a severe headache or feel sick due to a head injury or increased pressure in your skull (for

instance due to brain disease). This is because the patches may make symptoms worse or hide the extent of a

head injury

if you are feeling light-headed or faint

if you have severe liver problems

if you have ever been addicted to drugs

if you have a high temperature, as this may lead to larger quantities of the active ingredient being absorbed

into the blood than normal.

If you have recently had an operation, please speak to your doctor before using these patches.

Do not expose the patch to extreme heat (e.g. heating pads, electric blanket, heat lamps, sauna, hot tubs, heated

water beds, hot water bottle etc) as this may lead to larger quantities of the active ingredient being absorbed into

the blood than normal. External heat may also prevent the patch from sticking properly.

Children and adolescents

Do not give this medicine to children below 18 years.

Other medicines and Panitaz

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

Panitaz patches must not be used together with a type of medicine known as a monoamine oxidase inhibitor

(examples include tranylcypromide, phenelzine, isocarboxazid, moclobamide and linezolid), or if you have

taken this type of medicine in the last two weeks.

If you take some medicines such as phenobarbital or phenytoin (medicines commonly used to treat seizures,

fits or convulsions), carbamazepine (a medicine to treat seizures, fits or convulsions and certain pain

conditions), or rifampicin (a medicine to treat tuberculosis) the effects of Panitaz patches may be reduced.

Panitaz patches may make some people feel drowsy, sick or faint or make them breathe more slowly or

weakly. These side effects may be made worse if other medicines that produce the same effects are taken at

the same time. These include certain medicines to treat pain, depression, anxiety, psychiatric or mental

disorders, medicines to help you sleep, medicines to treat high blood pressure such as clonidine, other opioids

(which may be found in painkillers or certain cough mixtures e.g. morphine, dextropropoxyphene, codeine,

dextromethorphan, noscapine), antihistamines which make you drowsy, or anaesthetics such as halothane.

Panitaz patches must be used with caution if you are also taking benzodiazepines (medicines used to treat

anxiety or to help you sleep). This combination may cause serious breathing problems which could be fatal in

case of overdose. Tell your doctor if you are taking this combination.

Panitaz with food, drink and alcohol

Alcohol may make some of the side effects worse and you may feel unwell if you drink alcohol whilst wearing

Panitaz patches. Drinking alcohol whilst using Panitaz patches may also affect your reaction time.

Pregnancy and breast-feeding

You should not use Panitaz patches if you are pregnant or are breast-feeding, think you may be pregnant or are

planning to have a baby.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Panitaz patches may affect your reactions to such an extent that you may not react adequately or quickly enough

in the event of unexpected or sudden occurrences. This applies particularly:

at the beginning of treatment

if you are taking medicines to treat anxiety or help you sleep

if your dose is increased.

If you are affected, you should not drive or operate machinery whilst using Panitaz patches, or for 24 hours after

removing the patch.

The 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 it affects you.

It is an offence to drive while you have this medicine in your body over a specified limit unless you have a

defence (called the ‘statutory defence’).

This defence applies when:

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

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

medicine.Please note that it is still an offence to drive if you are unfit because of the medicine (i.e. your ability

to drive is being affected).

Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be found

here: 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 use Panitaz

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

if you are not sure.

Different strengths of Panitaz patches are available. Your doctor will decide which strength of Panitaz patch will suit

you best.

During treatment, your doctor may change the patch you use to a smaller or larger one if necessary, or tell you to

use a combination of up to two patches. You should not apply more than two patches at the same time,

regardless of the patch strength.

Adults and elderly patients

Unless your doctor has told you differently, attach one Panitaz patch (as described in detail below) and change it

every seventh day, preferably at the same time of day. Your doctor may wish to adjust the dose after 3-7 days until

the correct level of pain control has been found. If your doctor has advised you to take other painkillers in addition

to the patch, strictly follow the doctor’s instructions, otherwise you will not fully benefit from treatment with the

Panitaz patch. The patch should be worn for 3 full days before increasing the dose, this is when the maximum

effect of a given dose is established.

Patients under 18 years of age

Panitaz patches should not be used in patients below the age of 18 years.

Patients with kidney disease/dialysis patients

In patients with kidney disease, no change in dose is necessary.

Patients with liver disease

In patients with liver disease, the effects and period of action of the Panitaz patch may be affected and your doctor

will therefore check on you more closely.

Before applying the transdermal patch

Choose an area of non-irritated, intact skin on your upper arm, outer arm, upper chest, upper back or side of

the chest (see illustrations). Ask for assistance if you cannot apply the patch yourself.

The Panitaz patch should be applied to a relatively hairless or nearly hairless skin site. If no suitable hair free

sites are available the hairs should be cut off with a pair of scissors. Do not shave them off.

Avoid skin which is red, irritated or has any other blemishes, for instance large scars.

The area of skin you choose must be dry and clean. If necessary, wash it with cold or lukewarm water. Do not

use soap, alcohol, oil, lotions or other detergents. After a hot bath or shower, wait until your skin is completely

dry and cool. Do not apply lotion, cream or ointment to the chosen area. This might prevent your patch from

sticking properly

Applying the transdermal patch

Step 1: Each transdermal patch is sealed in a sachet. Just before use, cut the sachet along

the sealed edge with scissors. Take out the transdermal patch. Do not use the patch if the

sachet seal is broken.

Step 2: The sticky side of the transdermal patch is covered with a transparent protective foil.

Carefully peel off one part of the foil. Try not to touch the sticky part of the transdermal patch.

Step 3: Stick the transdermal patch on to the area of skin you have chosen and remove the

remaining foil.

Step 4: Press the transdermal patch against your skin with the palm of your hand and count

slowly to 30. Make sure that the whole transdermal patch is in contact with your skin,

especially at the edges.

Wearing the transdermal patch

You should wear the patch for seven days. Provided that you have applied the patch correctly, there is little risk of

it coming off. If the edges of the patch begin to peel off, they may be taped down with a suitable skin tape. You

may shower, bathe or swim whilst wearing it.

In the unlikely event that your patch falls off before it needs changing, do not use the same patch again. Stick a

new one on straight away (see “Changing the transdermal patch” below).

Changing the transdermal patch

Take the old transdermal patch off.

Fold it in half with the sticky side inwards.

Open and take out a new patch. Use the empty sachet to dispose of the old patch. Now discard the

sachet safely.

Even used patches contain some active ingredient that may harm children or animals, so make sure your used

patches are always kept out of the reach and sight of them.

Stick a new transdermal patch on a different appropriate skin site (as described above). You should not apply a

new patch to the same site for 3-4 weeks.

Remember to change your patch at the same time of day. It is important that you make a note of the time of day.

Duration of treatment

Your doctor will tell you how long you should be treated with the Panitaz patch. Do not stop treatment without consulting

a doctor, because your pain may return and you may feel unwell (see also “If you stop using Panitaz” below).

If you feel that the effect of the Panitaz patch is too weak or too strong, talk to your doctor or pharmacist.

If you use more Panitaz than you should

As soon as you discover that you have used more patches than you should, remove all patches and call your

doctor or hospital straight away. People who have taken an overdose may feel very sleepy and sick. They may

also have breathing difficulties or lose consciousness and may need emergency treatment in hospital. When

seeking medical attention make sure that you take this leaflet and any remaining patches with you to show to

the doctor.

If you forget to use Panitaz

Stick a new patch on as soon as you remember. Also make a note of the date, as your usual day of changing may

now be different. If you are very late changing your patch, your pain may return. In this case, please contact your

doctor.

Do not apply additional patches to make up for the forgotten application.

If you stop using Panitaz

If you stop using Panitaz patches too soon or you interrupt your treatment your pain may return. If you wish to stop

treatment please consult your doctor. They will tell you what can be done and whether you can be treated with

other medicines.

Some people may have side effects when they have used strong painkillers for a long time and stop using them.

The risk of having effects after stopping Panitaz patches is very low. However, if you feel agitated, anxious,

nervous or shaky, if you are overactive, have difficulty sleeping or digestive problems, tell your doctor.

The pain relieving effect of Panitaz patch is maintained for some time after removal of the patch. You should not

start another opioid analgesic (strong painkiller) within 24 hours after removal of the patch.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects that may be associated with Panitaz patches are similar to those seen with other strong

painkillers and include difficulty in breathing and low blood pressure.

This medicine can cause allergic reactions, although serious allergic reactions are rare. Remove the patch and tell

your doctor immediately if you get any sudden wheeziness, difficulties in breathing, swelling of the eyelids, face or

lips, rash or itching especially those covering your whole body.

This medicine can cause allergic reactions, although serious allergic reactions are rare. Take the patch off and tell

This medicine can cause allergic reactions, although serious allergic reactions are rare. Remove the patch

and tell your doctor immediately if you get any sudden wheeziness, difficulties in breathing, swelling of the

eyelids, face or lips, rash or itching especially those covering your whole body.

As with all strong painkillers, there is a risk that you may become addicted or reliant on Panitaz patches.

In patients treated with Panitaz patches, the following other side effects have been reported:

Very common (may affect more than 1 in 10 people)

headache, dizziness, drowsiness

constipation, dry mouth, feeling or actually being sick

itchy skin, redness, itching at application site

Common (may affect up to 1 in 10 people)

loss of appetite

confusion, depression, difficulty in sleeping, nervousness

tingling or numbness

flushing of the skin

shortness of breath

abdominal pain or discomfort, diarrhoea, indigestion

sweating, rash, skin eruptions

tiredness, a feeling of unusual weakness, muscle weakness, pain, chest pain, swelling of hands, ankles or

feet, redness or rash at the application site

Uncommon (may affect up to 1 in 100 people)

dehydration

mood swings, restlessness, agitation, anxiety, feeling detached from oneself, a feeling of extreme happiness,

hallucinations, nightmares

changes in taste, difficulty in speaking, reduced sensitivity to pain or touch, loss of memory, migraine, fainting,

shaking, problems with concentration or co-ordination

dry eyes, blurred vision

a ringing or buzzing sound in the ears, a feeling of dizziness or spinning

high or low blood pressure, angina (severe chest pain associated with heart disease), fast or irregular heart beat

worsening of breathing problems associated with asthma, cough, hiccups, over breathing, reduced oxygen in

the blood, runny nose, wheezing

wind

weight loss

dry skin, swelling of the face

muscle cramps, spasms, aches and pains

difficulty in passing urine

a flu like illness, high temperature, shivering, generally feeling unwell

an increase in accidental injuries (e.g. falls)

withdrawal symptoms such as agitation, anxiousness, sweating or shaking upon stopping using Panitaz patches

If you need to have blood tests remind your doctor that you are using Panitaz patches. This is important because

Panitaz patches may change the way your liver works and this could affect the results of some blood tests.

Rare (may affect up to 1 in 1,000 people)

decreased sexual drive, mental disorder

difficulties with balance

swelling of the eyelids, a reduction in size of the pupils in the eye

difficulty in breathing

diverticulitis (inflammation of the intestine), difficulty in swallowing

local allergic reaction with marked signs of swelling (in such cases treatment should be stopped)

decreased erection, sexual dysfunction

Very rare (may affect up to 1 in 10,000 people)

muscle twitching

ear pain

blisters

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 Yellow Card Scheme, website

www.mhra.gov.uk/yellowcard. By reporting side effects, you can help provide more information on the safety of

this medicine.

5.

How to store Panitaz

Keep this medicine out of the sight and reach of children.

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

refers to the last day of that month.

Do not store above 25°C.

Do not use the patch if the sachet seal is broken.

Used patches must be folded over on themselves with the adhesive layer inwards, and discarded safely out of

sight and reach of children.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away

medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Panitaz patches contain

The active substance is buprenorphine.

Each 5 micrograms/h transdermal patch contains 5 mg of buprenorphine in a patch size of 6.25 cm2 and releases

about 5 micrograms of buprenorphine per hour (over a period of 7 days).

Each 10 micrograms/h transdermal patch contains 10 mg of buprenorphine in a patch size of 12.5 cm2 and

releases about 10 micrograms of buprenorphine per hour (over a period of 7 days).

Each 20 micrograms/h transdermal patch contains 20 mg of buprenorphine in a patch size of 25 cm2 and releases

about 20 micrograms of buprenorphine per hour (over a period of 7 days).

The other ingredients are polyacrylate, povidone K90, levulinic acid, oleyl oleate, PET film, polyester web, blue

printing ink.

What Panitaz patches look like and contents of the pack

Transdermal patch.

Three sizes are available.

Each 5 micrograms/h transdermal patch is beige coloured with rounded corners and is imprinted with

“Buprenorphin” and “5 μg/h”.

Each 10 micrograms/h transdermal patch is beige coloured with rounded corners and is imprinted with

“Buprenorphin” and “10 μg/h”.

Each 20 micrograms/h transdermal patch is beige coloured with rounded corners and is imprinted with

“Buprenorphin” and “20 μg/h”.

One transdermal patch is sealed in one child-resistant sachet. The patches are available in cartons containing 4

transdermal patches.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Dr. Reddy’s Laboratories (UK) Ltd., 6 Riverview Road, Beverley, East Yorkshire, HU17 0LD, United Kingdom

Manufacturer

betapharm Arzneimittel GmbH, Kobelweg 95, Augsburg, 86156, Germany

This leaflet was last revised in 07/2017

480 mm

280 mm

Read the complete document

Object 1

Panitaz 20 micrograms/h Transdermal Patches

Summary of Product Characteristics Updated 08-Aug-2016 | Dr. Reddy's Laboratories (UK) Ltd

1. Name of the medicinal product

Panitaz 20 micrograms/h Transdermal Patches

2. Qualitative and quantitative composition

Each transdermal patch contains 20 mg buprenorphine.

Area containing active substance: 25 cm

Nominal release rate: 20 micrograms per hour (over a period of 7 days).

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Transdermal patch

Rectangular patch with rounded edges, a beige coloured web backing layer imprinted with

“Buprenorphin“ and “20 μg/h “ in blue colour, a transparent adhesive matrix laminated with a central

placed transparent matrix and a transparent release liner with a cut to facilitate the application.

4. Clinical particulars

4.1 Therapeutic indications

Treatment of non-malignant pain of moderate intensity when an opioid is necessary for obtaining

adequate analgesia.

Panitaz is not suitable for the treatment of acute pain.

4.2 Posology and method of administration

Posology

Panitaz should be administered every 7

day.

Patients aged 18 years and over:

The lowest Panitaz dose (Panitaz 5 micrograms/h transdermal patch) should be used as the initial dose.

Consideration should be given to the previous opioid history of the patient (see section 4.5) as well as to

the current general condition and medical status of the patient.

Titration:

During initiation and titration with Panitaz, patients should use the usual recommended doses of short-

acting supplemental analgesics (see section 4.5) as needed until analgesic efficacy with Panitaz is

attained.

The dose should not be increased before 3 days, when the maximum effect of a given dose is established.

Subsequent dosage increases may then be titrated based on the need for supplemental pain relief and the

patient's analgesic response to the patch.

To increase the dose, a larger patch should replace the patch that is currently being worn, or a

combination of patches should be applied in different places to achieve the desired dose. It is

recommended that no more than two patches are applied at the same time, regardless of the patch

strength. A new patch should not be applied to the same skin site for the subsequent 3-4 weeks (see

section 5.2). Patients should be carefully and regularly monitored to assess the optimum dose and

duration of treatment.

Conversion from opioids:

Panitaz can be used as an alternative to treatment with other opioids. Such patients should be started on

the lowest available dose (Panitaz 5 micrograms/h transdermal patch) and continue taking short-acting

supplemental analgesics (see section 4.5) during titration, as required.

Patients under 18 years of age:

As Panitaz has not been studied in patients under 18 years of age the use of Panitaz in patients below this

age is not recommended.

Elderly:

No dosage adjustment of Panitaz is required in elderly patients.

Renal impairment:

No special dose adjustment of Panitaz is necessary in patients with renal impairment.

Hepatic impairment:

Buprenorphine is metabolised in the liver. The intensity and duration of its action may be affected in

patients with impaired liver function. Therefore patients with hepatic insufficiency should be carefully

monitored during treatment with Panitaz.

Patients with severe hepatic impairment may accumulate buprenorphine during treatment. Consideration

of alternate therapy should be considered, and Panitaz should be used with caution, if at all, in such

patients.

Method of administration

Panitaz is for transdermal use.

Patch application:

Panitaz should be applied to non-irritated, intact skin of the upper outer arm, upper chest, upper back or

the side of the chest, but not to any parts of the skin with large scars. Panitaz should be applied to a

relatively hairless or nearly hairless skin site. If none are available, the hair at the site should be cut with

scissors, not shaven.

If the application site must be cleaned, it should be done with clean water only. Soaps, alcohol, oils,

lotions or abrasive devices must not be used. The skin must be dry before the patch is applied. Panitaz

should be applied immediately after removal from the sealed sachet. Following removal of the protective

layer, the transdermal patch should be pressed firmly in place with the palm of the hand for

approximately 30 seconds, making sure the contact is complete, especially around the edges. If the edges

of the patch begin to peel off, the edges may be taped down with suitable skin tape.

The patch should be worn continuously for 7 days.

Bathing, showering, or swimming should not affect the patch. If a patch falls off, a new one should be

applied.

Duration of administration:

Panitaz should under no circumstances be administered for longer than absolutely necessary. If long-term

pain treatment with Panitaz is necessary in view of the nature and severity of the illness, then careful and

regular monitoring should be carried out (if necessary with breaks in treatment) to establish whether and

to what extent further treatment is necessary.

Discontinuation:

After removal of the patch, buprenorphine serum concentrations decrease gradually and thus the analgesic

effect is maintained for a certain amount of time. This should be considered when therapy with Panitaz is

to be followed by other opioids. As a general rule, a subsequent opioid should not be administered within

24 hours after removal of the patch. At present, only limited information is available on the starting dose

of other opioids administered after discontinuation of the transdermal patch (see section 4.5).

4.3 Contraindications

Panitaz is contraindicated in:

patients with known hypersensitivity to the active substance buprenorphine or to any of the excipients

(see section 6.1)

opioid dependent patients and for narcotic withdrawal treatment

conditions in which the respiratory centre and function are severely impaired or may become so

patients who are receiving MAO inhibitors or have taken them within the last two weeks (see section

4.5)

patients suffering from myasthenia gravis

patients suffering from delirium tremens.

4.4 Special warnings and precautions for use

Panitaz should be used with particular caution in patients with convulsive disorders, head injury, shock, a

reduced level of consciousness of uncertain origin, intracranial lesions or increased intracranial pressure,

or in patients with severe hepatic impairment (see section 4.2).

Significant respiratory depression has been associated with buprenorphine, particularly by the intravenous

route. A number of overdose deaths have occurred when addicts have intravenously abused

buprenorphine, usually with benzodiazepines concomitantly. Additional overdose deaths due to ethanol

and benzodiazepines in combination with buprenorphine have been reported.

Panitaz is not recommended for analgesia in the immediate post-operative period or in other situations

characterised by a narrow therapeutic index or a rapidly varying analgesic requirement.

Controlled human and animal studies indicate that buprenorphine has a lower dependence liability than

pure agonist analgesics. In humans limited euphorigenic effects have been observed with buprenorphine.

This may result in some abuse of the product and caution should be exercised when prescribing to

patients known to have, or suspected of having, a history of drug abuse.

As with all opioids, chronic use of buprenorphine can result in the development of physical dependence.

Withdrawal (abstinence syndrome), when it occurs, is generally mild, begins after 2 days and may last up

to 2 weeks. Withdrawal symptoms include agitation, anxiety, nervousness, insomnia, hyperkinesia,

tremor and gastrointestinal disorders.

Patients with fever or exposed to external heat:

While wearing the patch, patients should be advised to avoid exposing the application site to external heat

sources, such as heating pads, electric blankets, heat lamps, sauna, hot tubs, and heated water beds, etc.,

as an increase in absorption of buprenorphine may occur. When treating febrile patients, one should be

aware that fever may also increase absorption resulting in increased plasma concentrations of

buprenorphine and thereby increased risk of opioid reactions.

4.5 Interaction with other medicinal products and other forms of interaction

Panitaz must not be used concomitantly with MAOIs or in patients who have received MAOIs within the

previous two weeks (see section 4.3).

Effect of other active substances on the pharmacokinetics of buprenorphine:

Buprenorphine is primarily metabolised by glucuronidation and to a lesser extent (about 30%) by

CYP3A4.

Concomitant treatment with CYP3A4 inhibitors may lead to elevated plasma concentrations with

intensified efficacy of buprenorphine.

A drug interaction study with the CYP3A4 inhibitor ketoconazole did not produce clinically relevant

increases in mean maximum (C

) or total (AUC) buprenorphine exposure following buprenorphine

with ketoconazole as compared to buprenorphine alone.

The interaction between buprenorphine and CYP3A4 enzyme inducers has not been studied.

Co-administration of buprenorphine and enzyme inducers (e.g. phenobarbital, carbamazepine, phenytoin

and rifampicin) could lead to increased clearance which might result in reduced efficacy.

Reductions in hepatic blood flow induced by some general anaesthetics (e.g. halothane) and other

medicinal products may result in a decreased rate of hepatic elimination of buprenorphine.

Pharmacodynamic interactions:

Panitaz should be used cautiously with:

Benzodiazepines: This combination can potentiate respiratory depression of central origin, with risk of

death in case of overdose (see section 4.4).

Other central nervous system depressants: other opioid derivatives (analgesics and antitussives containing

e.g. morphine, dextropropoxyphene, codeine, dextromethorphan or noscapine). Certain antidepressants,

sedative H1-receptor antagonists, alcohol, anxiolytics, neuroleptics, clonidine and related substances.

These combinations increase the CNS depressant activity.

Buprenorphine is a partial mu-receptor agonist but it is described to function as a pure mu receptor

agonist at typical analgesic doses. These doses produce buprenorphine exposures comparable to or greater

than those produced by buprenorphine 5, 10, and 20 micrograms/h transdermal patches. In buprenorphine

clinical studies, where subjects receiving full mu agonist opioids (up to 90 mg oral morphine or oral

morphine equivalents per day) were transferred to buprenorphine, there were no reports of abstinence

syndrome or opioid withdrawal during conversion from entry opioid to buprenorphine (see section 4.4).

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data from the use of buprenorphine in pregnant women. Studies in animals have shown

reproductive toxicity (see Section 5.3). The potential risk for humans is unknown.

Towards the end of pregnancy high doses of buprenorphine may induce respiratory depression in the

neonate even after a short period of administration. Long-term administration of buprenorphine during the

last three months of pregnancy may cause a withdrawal syndrome in the neonate.

Therefore Panitaz should not be used during pregnancy and in women of childbearing potential who are

not using effective contraception.

Breastfeeding

Studies in rats have shown that buprenorphine may inhibit lactation. Excretion of buprenorphine into the

milk in rats has been observed. Data on excretion into human milk are not available. Therefore the use of

Panitaz during lactation should be avoided.

4.7 Effects on ability to drive and use machines

Panitaz has a major influence on the ability to drive and use machines. Even when used according to

instructions, Panitaz may affect the patient's reactions to such an extent that road safety and the ability to

operate machinery may be impaired. This applies particularly in the beginning of treatment and in

conjunction with other centrally acting substances including alcohol, tranquillisers, sedatives and

hypnotics. An individual recommendation should be given by the physician. A general restriction is not

necessary in cases where a stable dose is used.

In patients who are affected, such as during treatment initiation or titration to a higher dose, these patients

should not drive or use machines, nor for at least 24 hours after the patch has been removed.

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 you have this medicine in your body over a specified limit unless you

have a defence (called the 'statutory defence').

This defence applies when:

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

- You have taken it according to the instructions given by the prescriber and in the information provided

with the medicine.

Please note that it is still an offence to drive if you are unfit because of the medicine (i.e. your ability to

drive is being affected).“

Details regarding a new driving offence concerning driving after drugs have been taken in the UK may be

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

4.8 Undesirable effects

Serious adverse reactions that may be associated with buprenorphine therapy in clinical use are similar to

those observed with other opioid analgesics, including respiratory depression (especially when used with

other CNS depressants) and hypotension (see section 4.4).

The following undesirable effects have occurred:

Very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000,

<1/1000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Immune system disorders

Uncommon

hypersensitivity

Very rare

anaphylactic reaction, anaphylactoid reactions

Metabolism and nutrition disorders

Common

anorexia

Uncommon

dehydration

Psychiatric disorders

Common

confusion, depression, insomnia, nervousness

Uncommon

sleep disorder, restlessness, agitation, depersonalisation, euphoric mood, affect

lability, anxiety, hallucinations, nightmares

Rare

psychotic disorders, decreased libido

Very rare

drug dependence, mood swings

Nervous system disorders

Very common

headache, dizziness, somnolence

Common

paraesthesia

Uncommon

sedation, dysgeusia, dysarthria, hypoaesthesia, memory impairment, migraine,

syncope, tremor, abnormal co-ordination, disturbance in attention

Rare

balance disorder, speech disorder

Very rare

involuntary muscle contractions

Eye disorders

Uncommon

dry eye, blurred vision

Rare

visual disturbance, eyelid oedema, miosis

Ear and labyrinth disorders

Uncommon

tinnitus, vertigo

Very rare

ear pain

Cardiac disorders

Uncommon

angina pectoris, palpitations, tachycardia

Vascular disorders

Common

vasodilatation

Uncommon

hypotension, circulatory collapse, hypertension, flushing

Respiratory, thoracic and mediastinal disorders

Common

dyspnoea

Uncommon

asthma aggravated, cough, hypoxia, rhinitis, wheezing, hyperventilation,

hiccups

Rare

respiratory depression, respiratory failure

Gastrointestinal disorders

Very common

constipation, dry mouth, nausea, vomiting

Common

abdominal pain, diarrhoea, dyspepsia

Uncommon

flatulence

Rare

diverticulitis, dysphagia, ileus

Hepatobiliary disorders

Rare

biliary colic

Skin and subcutaneous tissue disorders

Very common

pruritus, erythema

Common

rash, sweating, exanthema

Uncommon

dry skin, face oedema, urticaria

Very rare

pustules, vesicles

Musculoskeletal and connective tissue disorders

Uncommon

muscle cramp, myalgia, muscular weakness, muscle spasms

Renal and urinary disorders

Uncommon

urinary retention, micturition disorders

Reproductive system and breast disorders

Rare

erectile dysfunction, sexual dysfunction

General disorders and administration site conditions

Very common

application site pruritus, application site reaction

Common

tiredness, asthenia, pain, peripheral oedema, application site erythema,

application site rash, chest pain

Uncommon

fatigue, influenza-like illness, pyrexia, rigors, malaise, oedema, drug

withdrawal syndrome

Rare

application site inflammation*

Investigations

Uncommon

alanine aminotransferase increased, weight decreased

Injury, poisoning and procedural complications

Uncommon

accidental injury, fall

* In some cases delayed local allergic reactions occurred with marked signs of inflammation. In such

cases treatment with buprenorphine should be terminated.

Buprenorphine has a low risk of physical dependence. After discontinuation of buprenorphine,

withdrawal symptoms are unlikely. This may be due to the very slow dissociation of buprenorphine from

the opioid receptors and to the gradual decrease of buprenorphine plasma concentrations (usually over a

period of 30 hours after removal of the last patch). However, after long-term use of buprenorphine,

withdrawal symptoms similar to those occurring during opioid withdrawal cannot be entirely excluded.

These symptoms include agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and

gastrointestinal disorders.

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 the Yellow Card Scheme, website:

www.mhra.gov.uk/yellowcard.

4.9 Overdose

Symptoms:

Symptoms similar to those of other centrally acting analgesics are to be expected. These include

respiratory depression, sedation, drowsiness, nausea, vomiting, cardiovascular collapse and marked

miosis.

Treatment:

Remove any patches from the patient's skin. Establish and maintain a patent airway, assist or control

respiration as indicated and maintain adequate body temperature and fluid balance. Oxygen, intravenous

fluids, vasopressors and other supportive measures should be employed as indicated.

A specific opioid antagonist such as naloxone may reverse the effects of buprenorphine. The dose of

naloxone may be in the range 5 to 12 mg intravenously. The onset of the naloxone effect may be delayed

by 30 minutes or more. Maintenance of adequate ventilation is more important than treatment with

naloxone.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Analgesics, opioids; ATC code: N02AE01

Buprenorphine is a partial agonist opioid, acting at the mu opioid receptor. It also has antagonistic activity

at the kappa opioid receptor.

Efficacy has been demonstrated in five pivotal phase III studies of up to 12 weeks duration in patients

with non-malignant pain of various aetiologies. These included patients with moderate and severe OA and

back pain. Buprenorphine demonstrated clinically significant reductions in pain scores (approximately 3

points on the BS-11 scale) and significantly greater pain control compared with placebo.

A long term, open-label extension study (n=384) has also been performed in patients with non-malignant

pain. With chronic dosing, 63% of patients were maintained in pain control for 6 months, 39% of patients

for 12 months, 13% of patients for 18 months and 6% for 21 months. Approximately 17% were stabilised

on the 5 mg dose, 35% on the 10 mg dose and 48% on the 20 mg dose.

5.2 Pharmacokinetic properties

There is evidence of enterohepatic recirculation.

Studies in non-pregnant and pregnant rats have shown that buprenorphine passes the blood-brain and

placental barriers. Concentrations in the brain (which contained only unchanged buprenorphine) after

parenteral administration were 2-3 times higher than after oral administration. After intramuscular or oral

administration buprenorphine apparently accumulates in the foetal gastrointestinal lumen “ presumably

due to biliary excretion, as enterohepatic circulation has not fully developed.

Each patch provides a steady delivery of buprenorphine for up to seven days. Steady state is achieved

during the first application. After removal of buprenorphine, buprenorphine concentrations decline,

decreasing approximately 50% in 12 hours (range 10“24 h).

Absorption:

Following buprenorphine application, buprenorphine diffuses from the patch through the skin. In clinical

pharmacology studies, the median time for “buprenorphine 10 μg/h“ to deliver detectable buprenorphine

concentrations (25 picograms/ml) was approximately 17 hours. Analysis of residual buprenorphine in

patches after 7-day use shows 15% of the original load delivered. A study of bioavailability, relative to

intravenous administration, confirms that this amount is systemically absorbed. Buprenorphine

concentrations remain relatively constant during the 7-day patch application.

Application site:

A study in healthy subjects demonstrated that the pharmacokinetic profile of buprenorphine delivered by

buprenorphine is similar when applied to upper outer arm, upper chest, upper back or the side of the chest

(midaxillary line, 5th intercostal space). The absorption varies to some extent depending on the

application site and the exposure is at the most approximately 26 % higher when applied to the upper

back compared to the side of the chest.

In a study of healthy subjects receiving buprenorphine repeatedly to the same site, an almost doubled

exposure was seen with a 14 day rest period. For this reason, rotation of application sites is

recommended, and a new patch should not be applied to the same skin site for 3-4 weeks.

In a study of healthy subjects, application of a heating pad directly on the transdermal patch caused a

transient 26 - 55% increase in blood concentrations of buprenorphine. Concentrations returned to normal

within 5 hours after the heat was removed. For this reason, applying direct heat sources such as hot water

bottles, heat pads or electric blankets directly to the patch is not recommended. A heating pad applied to a

buprenorphine site immediately after patch removal did not alter absorption from the skin depot.

Distribution:

Buprenorphine is approximately 96% bound to plasma proteins.

Studies of intravenous buprenorphine have shown a large volume of distribution, implying extensive

distribution of buprenorphine. In a study of intravenous buprenorphine in healthy subjects, the volume of

distribution at steady state was 430 l, reflecting the large volume of distribution and lipophilicity of the

active substance.

Following intravenous administration, buprenorphine and its metabolites are secreted into bile, and within

several minutes, distributed into the cerebrospinal fluid. Buprenorphine concentrations in the

cerebrospinal fluid appear to be approximately 15% to 25% of concurrent plasma concentrations.

Biotransformation and elimination:

Buprenorphine metabolism in the skin following buprenorphine application is negligible. Following

transdermal application, buprenorphine is eliminated via hepatic metabolism, with subsequent biliary

excretion and renal excretion of soluble metabolites. Hepatic metabolism, through CYP3A4 and

UGT1A1/1A3 enzymes, results in two primary metabolites, norbuprenorphine and buprenorphine 3-O-

glucuronide, respectively. Norbuprenorphine is glucuronidated before elimination. Buprenorphine is also

eliminated in the faeces. In a study in post-operative patients, the total elimination of buprenorphine was

shown to be approximately 551/h.

Norbuprenorphine is the only known active metabolite of buprenorphine.

Effect of buprenorphine on the pharmacokinetics of other active substances:

Based on in vitro studies in human microsomes and hepatocytes, buprenorphine does not have the

potential to inhibit metabolism catalysed by the CYP450 enzymes CYP1A2, CYP2A6 and CYP3A4 at

concentrations obtained with use of buprenorphine 20μg/h transdermal patch. The effect on metabolism

catalysed by CYP2C8, CYP2C9 and CYP2C19 has not been studied.

5.3 Preclinical safety data

In single- and repeat-dose toxicity studies in rats, rabbits, guinea pigs, dogs and minipigs, buprenorphine

caused minimal or no adverse systemic events, whereas skin irritation was observed in all species

examined. No teratogenic effects were observed in rats or rabbits. However, perinatal mortality was

reported in the literature for rats treated with buprenorphine.

A standard battery of genotoxicity tests indicated that buprenorphine is non-genotoxic.

In long-term studies in rats and mice there was no evidence of any carcinogenic potential relevant for

humans.

Toxicological data available did not indicate a sensitising potential of the additives of the transdermal

patches.

6. Pharmaceutical particulars

6.1 List of excipients

Adhesive matrix (containing buprenorphine):

povidone K90

levulinic acid

oleyl oleate

Poly[acrylic acid-co-butylacrylate-co-(2-ethylhexyl)acrylate-co-vinylacetate] (5:15:75:5)

Adhesive matrix (without buprenorphine):

Poly[(2-ethylhexyl)acrylate-co-glycidylmethacrylat-co-(2-hydroxyethyl)acrylate-co-vinylacetate]

(68:27:5:0,15)

Separating foil between adhesive matrices with and without buprenorphine: PET film

Backing web: polyester

Release liner: PET film (to be removed before applying the patch)

Blue printing ink

6.2 Incompatibilities

Not applicable

6.3 Shelf life

30 months

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

Type of container:

Each child-proof sachet is made of a composite layer material consisting of Paper/ PET/ PE/ Aluminium/

Surlyn. One sachet contains one transdermal patch.

Pack sizes:

Packs containing 4 individually sealed transdermal patches.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The patch should not be used if the seal is broken.

Disposal after use:

When changing the patch, the used patch should be removed, the adhesive layer folded inwards on itself,

and the patch disposed of safely and out of sight and reach of children.

7. Marketing authorisation holder

Dr. Reddy's Laboratories (UK) Ltd.

6 Riverview Road

Beverley

East Yorkshire

HU17 0LD

United Kingdom

8. Marketing authorisation number(s)

PL 08553/0566

9. Date of first authorisation/renewal of the authorisation

15/06/2016

10. Date of revision of the text

15/06/2016

Company Contact Details

Dr. Reddy's Laboratories (UK) Ltd

Address

6 Riverview Road, Beverley, Hull, HU17 0LD

Telephone

+44 (0)1482 860228

Medical Information Direct Line

+44 (0)1748 828873

Customer Care direct line

+44 (0)1482 389858

http://www.drreddys.com/united-kingdom

+44 (0)1482 860204

Medical Information e-mail

[email

protected]

Medical Information Fax

+44 (0)1748 828801

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