Package leaflet: Information for the user

Carlosafine 35 micrograms/h transdermal patch Carlosafine 52.5 micrograms/h transdermal patch Carlosafine 70 micrograms/h transdermal patch

buprenorphine

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.

What is in this leaflet:

1.    What Carlosafine is and what it is used for

2.    What you need to know before you use Carlosafine

3.    How to use Carlosafine

4.    Possible side effects

5.    How to store Carlosafine

6.    Contents of the pack and other information

1. What Carlosafine is and what it is used for

The active substance of Carlosafine is buprenorphine.

Carlosafine is an analgesic (a pain-relieving medicine) intended to relieve moderate to severe cancer pain and severe pain that has not responded to other types of painkillers. Carlosafine acts through the skin. Buprenorphine is an opioid (strong pain reliever), which reduces pain by acting on the central nervous system (specific nerve cells in the spinal cord and in the brain). The effect of the transdermal patch lasts for up to four days. Carlosafine is not suitable for the treatment of acute (short-lasting) pain.

2. What you need to know before you use Carlosafine

Do not use Carlosafine

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

-    if you are dependent on strong pain relievers (opioids);

-    if you suffer from a disease in which you have or may have great difficulty breathing

-    if you are taking monoamine oxidase (MAO) inhibitors (certain medicines used to treat depression) or you have taken this type of medicine in the last two weeks (see “ Other medicines and Carlosafine”);

-    if you suffer from myasthenia gravis (a certain type of severe muscle weakness);

-    if you suffer from delirium tremens (confusion and trembling caused by abstinence from alcohol following habitual excessive drinking or occurring during an episode of heavy alcohol consumption);

-    if you are pregnant.

Carlosafine must not be used to treat withdrawal symptoms in drug-

dependent persons.

Warnings and precautions

Talk to your doctor or pharmacist before using Carlosafine

-    if you have recently drunk a lot of alcohol;

-    if you suffer from seizures or convulsions (fits)

-    if your consciousness is disturbed (feeling light-headed or faint) for an unknown reason;

-    if you are in a state of shock (cold sweat might be a sign of it);

-    if the pressure in your skull is increased (for instance after head injury or in brain disease), and artificial respiration is not possible;

-    if you have difficulty breathing or are taking other medicines that may make you breathe more slowly or weakly (see “Other medicines and Carlosafine”);

-    if your liver does not work properly;

-    if you are inclined to abuse medicines or drugs.

Also, please be aware of the following precautions:

-    Some people may become dependent on strong pain relievers such as Carlosafine when they use them over a long period of time. They may have withdrawal effects when they stop using them (see “If you stop using Carlosafine”).

-    Fever and external heat may lead to larger quantities of buprenorphine in the blood than normal. Also, external heat may prevent the transdermal patch from sticking properly. Therefore, do not expose yourself to external heat (e.g. sauna, infra-red lamps, electric blankets, hot water bottles) and consult your doctor if you have fever.

Athletes should be aware that this medicine may cause a positive reaction to sports doping control tests.

Children and adolescents

Carlosafine should not be used in persons below the age of 18 years, because no experience has so far been gained in this age group.

Other medicines and Carlosafine

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

-    Carlosafine must not be used together with monoamine oxidase (MAO) inhibitors (certain medicines used to treat depression), or if you have taken this type of medicine for the last 2 weeks.

-    Carlosafine may make some people feel drowsy, sick, or faint or make them breathe more slowly or weakly. These side effects may be intensified if other medicines that may produce the same effects are taken at the same time. These other medicines include other strong pain relievers (opioids), certain sleeping pills, anaesthetics, and medicines used to treat certain psychological diseases such as tranquillizers, antidepressants, and neuroleptics.

-    If Carlosafine is used together with some medicines, the effects of the transdermal patch may be increased. These medicines include e.g. certain anti-infectives/anti-fungals (e.g. containing erythromycin or ketoconazole) or HIV medicines (e.g. containing ritonavir)

-    If Carlosafine is used together with other medicines, the effects of the transdermal patch may be reduced. These medicines include certain products, e.g. dexamethasone; medicines to treat epilepsy (e.g. containing carbamazepine, or phenytoin) or medicines for tuberculosis (e.g. rifampicin).

Carlosafine with food, drink and alcohol

You should not drink alcohol while using Carlosafine. Alcohol may intensify certain side effects of the transdermal patch and you may feel unwell.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

There is insufficient experience regarding the use of Carlosafine in pregnant women. Therefore, you must not use Carlosafine during pregnancy.

Buprenorphine, the active substance contained in the transdermal patch, inhibits milk formation and passes into breast milk. Therefore, you should not use Carlosafine if you are breast-feeding.

Driving and using machines

Carlosafine may make you feel dizzy or drowsy or experience blurred or double vision and 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,

-    when your dose is changed,

-    when you switch to Carlosafine from another pain reliever,

-    if you also use other medicines that act on the brain,

-    if you drink alcohol.

If you are affected, you should not drive or operate machinery whilst using Carlosafine. This applies also at the end of treatment with Carlosafine. Do not drive or operate machinery for at least 24 hours after the patch has been removed.

Discuss with your doctor or pharmacist if you are unsure about anything.

3. How to use Carlosafine

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Carlosafine is available in three strengths: Carlosafine 35 micrograms/h transdermal patch, Carlosafine 52.5 micrograms/h transdermal patch and Carlosafine 70 micrograms/h transdermal patch.

The choice of which strength of Carlosafine will suit you best will be made by your doctor. During treatment your doctor may change which transdermal patch you use to a smaller or larger one if necessary.

The recommended dose is:

Adults

Unless your doctor has told you differently, attach one Carlosafine transdermal patch (as described in detail below) and change it after 4 days at the latest. For convenience of use, you can change the transdermal patch twice a week at the same days, e.g. always on Monday mornings and Thursday evenings. To help you remember when to change your transdermal patch, you should make a note on the calendar on the outer packaging. If your doctor has advised you to take other pain relievers in addition to the transdermal patch, strictly follow the doctor’s instructions, otherwise you will not fully benefit from treatment with Carlosafine.

Elderly patients

No dosage adjustment is needed for elderly patients.

Patients with kidney disease / dialysis patients

In patients with kidney disease and in dialysis patients, no dosage adjustment is necessary.

Patients with liver disease

In patients with liver disease, the intensity and duration of action of Carlosafine may be affected. If this applies to you, your doctor will check on you more closely.

Use in children and adolescents

Carlosafine should not be used in persons below the age of 18 years, because no experience has so far been gained in this age group.

Route of administration

The patch is for transdermal use.

When the transdermal patch is applied to the skin, the active substance buprenorphine passes through the skin into the blood.

Method of administration

Before applying the transdermal

- Choose an area of skin which is flat, clean, free from cuts or scars and hairless on your upper body, preferably on the chest below the collarbone or on the upper part of the back (see adjacent illustrations). Call assistance if you cannot apply the transdermal patch yourself.

-    If the chosen area has hairs, cut them 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 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 transdermal 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.

- 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 4: Press the transdermal patch against your skin with the palm of your hand for about 30 to 60 seconds. Make sure that the whole transdermal patch is in contact with your skin, especially at the edges.

- Step 5: Wash your hands after using the transdermal patch. Do not use any cleansing products.

Wearing the transdermal patch

You may wear the transdermal patch for up to 4 days. Provided that you have applied the transdermal patch correctly, there is little risk of it coming off. You may shower, bathe or swim while wearing it. However, do not expose the transdermal patch to extreme heat (e.g. sauna baths, infra-red lamps, electric blankets, hot water bottles).

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

-    Throw it away carefully.

-    Stick a new transdermal patch on a different skin site (as described above). Wait at least one week before using the same site again.

Duration of treatment

Your doctor will tell you how long you may use Carlosafine. Do not stop using Carlosafine on your own account, because pain may return and you may feel unwell (see also “If you stop using Carlosafine” below).

If you have the impression that the effect of the Carlosafine transdermal patch is too weak or too strong, tell your doctor or pharmacist.

If you use more Carlosafine than you should If this happens there may be signs of an overdose of the substance buprenorphine. An overdose may intensify the side effects of buprenorphine such as drowsiness, nausea, and vomiting. You may get pin-point pupils and breathing may become slow and weak. You may also get cardiovascular collapse.

As soon as you discover that you have used more transdermal patches than you should, remove the excess transdermal patches and talk to a doctor or pharmacist.

If you forget to use Carlosafine

If you forget an application, stick a new transdermal patch on as soon as you remember. You will then need to change your routine, e.g. if you usually apply your transdermal patches on Mondays and Thursdays, but you forget and don’t stick on a new transdermal patch until Wednesday, you will need to change your transdermal patches on Wednesdays and Saturdays from then on. Make a note of the new pair of days on the calendar on the outer packaging. If you are very late changing your transdermal patch, pain may return. In this case please contact your doctor.

Never apply twice the number of transdermal patches to make up for the forgotten application!

If you stop using Carlosafine

If you interrupt or finish using Carlosafine too soon, pain may return. If you wish to stop use on account of unpleasant side effects, please consult your doctor. He/she will tell you what can be done and whether you can be treated with other medicines.

Some people may experience withdrawal-effects when they have used strong pain relievers for a long time and stop using them. The risk of having effects after you stop using Carlosafine is very low. However, if you feel agitated, anxious, nervous or shaky, if you are overactive, have difficulty sleeping or digestion problems, tell your doctor.

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

4. Possible side effects

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

If you experience swelling of the hands, feet, ankles, face, lips, mouth, or throat which may cause difficulty in swallowing or breathing, hives, fainting, yellowing of the skin and eyes (also called jaundice), remove the transdermal patch and call your doctor immediately or seek help at the casualty department of the nearest hospital. These can be symptoms of a very rare serious allergic reaction.

The following side effects have been reported:

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

•    nausea (feeling sick)

•    redness, itching

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

•    dizziness, headache

•    shortness of breath

•    vomiting, constipation

•    skin changes (exanthema, generally on repeated use), sweating

•    oedema (e.g. swelling of the legs), tiredness

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

•    confusion, sleep disorder, restlessness

•    various degrees of sedation (calmness), ranging from tiredness to muzziness

•    circulation disorders (such as low blood pressure or, rarely, even circulatory collapse)

•    dry mouth

•    rash

•    difficulty in passing water, urinary retention (less urine than normal)

•    weariness

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

•    loss of appetite

•    illusions such as hallucinations, anxiety and nightmares, reduced sex drive

•    difficulties concentrating, speech disorder, muzziness, disturbed balance, abnormal skin sensations (numbness, prickling or burning sensations)

•    visual disturbance, blurred vision, swollen eyelids

•    hot flushes

•    difficulty breathing (respiratory depression)

•    heartburn

•    hives

•    erection difficulties

•    withdrawal symptoms (see below), administration site reactions

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

•    serious allergic reactions (see below)

•    dependence, mood swings

•    muscle twitching, taste disorders

•    pin-point pupils

•    ear pain

•    abnormally rapid breathing, hiccups

•    retching

•    pustules, small blisters

•    chest pain

If you notice any of the side effects listed above, tell your doctor as soon as possible.

In some cases delayed allergic reactions occurred with marked signs of inflammation. In such a case you should stop using Carlosafine after you have talked to your doctor.

Some people may have withdrawal symptoms when they have used strong pain relievers for a long time and stop using them. The risk of having withdrawal effects when you stop using Carlosafine is low. However, if you feel agitated, anxious, nervous or shaky, if you are overactive, have difficulty sleeping or digestion problems, tell your doctor.

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 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 Carlosafine

•    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.

•    This medicine does not require any special storage conditions.

•    After removing a patch, fold it in half with the sticky sides inwards and press them together. Return the used patch to its sachet and carefully dispose the transdermal patch.

•    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 Carlosafine contains

-    The active substance is buprenorphine.

[35 micrograms /h:]

Each transdermal patch of 25 cm2 contains 20 mg of buprenorphine and releases 35 micrograms of buprenorphine per hour.

[52.5 micrograms /h:]

Each transdermal patch of 37.5 cm2 contains 30 mg of buprenorphine and releases 52.5 micrograms of buprenorphine per hour.

[70 micrograms /h:]

Each transdermal patch of 50 cm2 contains 40 mg of buprenorphine and releases 70 micrograms of buprenorphine per hour.

-    The other ingredients are:

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-glycidylmethacrylate-co-(2-hydroxyethyl)acrylate-co-vinylacetate]

(68:0,15:5:27),

Separating foil between adhesive matrices with and without buprenorphine: Polyethylene terephthalate film,

Backing foil: polyester,

Release liner: Polyethylene terephthalate film, siliconised Blue printing ink

What Carlosafine looks like and contents of the pack

Each transdermal patch is rectangular beige coloured with rounded corners and is imprinted

[35 Mg/h:]

“Buprenorphin” and “35 Mg/h”

[52.5 Mg/h:]

“Buprenorphin” and “52.5 Mg/h”

[70 Mg/h:]

“Buprenorphin” and “70 Mg/h”

Each transdermal patch is sealed in one child-resistant sachet. The patches are available in packs containing [For DE/H/5080/001-003/DC]

4, 5, 8, 10, 16 or 20 transdermal patches.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Glenmark Pharmaceuticals Europe Limited

Laxmi House

2B Draycott Avenue

Kenton, Middlesex

HA3OBU

United Kingdom

Manufacturer

Tesa Labtec GmbH Heykenaukamp 1O 21147 Hamburg Germany

This leaflet was last revised in November 2015