Carlosafine 52.5 micrograms/h transdermal patch

• 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

• 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.
• if you have pain which lasts only for a short period or pain after having an operation because of the increased risk of dependence and developing serious breathing problems.
  If you are going to have an operation, or have just had an operation, please tell the doctor at the hospital if you are currently treated with Carlosafine transdermal patch to discuss your pain management.

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

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 you have a depression or other conditions that are treated with antidepressants.
  The use of these medicines together with Carlosafine can lead to serotonin syndrome, a potentially life-threatening condition (see “Other medicines and Carlosafine”).
• if your liver does not work properly;
• if you are inclined to abuse medicines or drugs.

Tolerance, dependence, and addiction

This medicine contains buprenorphine which is an opioid medicine. Repeated use of opioids can result in the drug being less effective (you become accustomed to it, known as tolerance).

Repeated use of Carlosafine can also lead to dependence, abuse, and addiction, which may result in life-threatening overdose. The risk of these side effects can increase with a higher dose and longer duration of use.

Dependence or addiction can make you feel that you are no longer in control of how much medicine you need to take or how often you need to take it.

The risk of becoming dependent or addicted varies from person to person. You may have a greater risk of becoming dependent on or addicted to Carlosafine if:

• You or anyone in your family have ever abused or been dependent on alcohol, prescription medicines or illegal drugs (“addiction”).
• You are a smoker.
• You have ever had problems with your mood (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following signs whilst taking Carlosafine, it could be a sign that you have become dependent or addicted:

• You need to take the medicine for longer than advised by your doctor
• You need to take more than the recommended dose
• You might feel that you need to carry on taking your medicine, even when it doesn’t help to relieve your pain.
• You are using the medicine for reasons other than prescribed, for instance, ‘to stay calm’ or ‘help you sleep’
• You have made repeated, unsuccessful attempts to quit or control the use of the medicine
• When you stop using the medicine you feel unwell, and you feel better once taking the medicine again (‘withdrawal effects’)

If you notice any of these signs, speak to your doctor to discuss the best treatment pathway for you, including when it is appropriate to stop and how to stop safely (see section 3, If you stop using Carlosafine).

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.

Carlosafine can cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep related hypoxemia (low oxygen level in the blood). The symptoms can include breathing pauses during sleep, night awakening due to shortness of breath, difficulties to maintain sleep or excessive drowsiness during the day. If you or another person observe these symptoms, contact your doctor. A dose reduction may be considered by your doctor.

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.

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, anti-depressants, and neuroleptics.
• Concomitant use of Carlosafine and sedating medicines such as benzodiazepines or related drugs increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant use should only be considered when other treatment options are not possible.

However if your doctor does prescribe Carlosafine together with sedating medicines the dose and duration of concomitant treatment should be limited by your doctor.

Please tell your doctor about all sedating medicines you are taking, and follow your doctor’s dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms.

• 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).
• Some medicines may increase the side effects of Carlosafine and may sometimes cause very serious reactions. Do not take any other medicines whilst taking Carlosafine without first talking to your doctor, especially anti-depressants, such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepine, or trimipramine. These medicines may interact with Carlosafine and you may experience symptoms such as involuntary, rhythmic contractions of muscles, including the muscles that control movement of the eye, agitation, hallucinations, coma, excessive sweating, tremor, exaggeration of reflexes, increased muscle tension, body temperature above 38°C. Contact your doctor when experiencing such symptoms.
• Gabapentin or pregabalin to treat epilepsy or pain due to nerve problems (neuropathic pain).
• medicines to treat depression;
• medicines used to treat allergies, travel sickness or nausea (antihistamines or antiemetics);
• medicines to treat psychiatric disorders (antipsychotics or neuroleptics);
• muscle relaxants;
• medicines to treat Parkinson’s disease;

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

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 not sufficient experience regarding the use of Carlosafine in pregnant women. Therefore, you do not use Carlosafine if you are pregnant.

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

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 dosage 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.

Carlosafine 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 if this medicine affects your ability to drive.
• However, you would not be committing an offence if:
  • 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 or in the information provided with the medicine and
  • It was not affecting your ability to drive safely

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

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.

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.

The following table shows you when to change your patch:

Apply/change your patch in the morning Apply/change your patch in evening of

Monday Thursday

Tuesday Friday

Wednesday Saturday

Thursday Sunday

Friday Monday

Saturday Tuesday

Sunday Wednesday

Before applying the transdermal patch

• Choose an area of skin which is flat, clean and hairless on your upper body, preferably on the chest below the collar-bone 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 3: Stick the transdermal patch onto 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 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, out of the sight and reach of children.
• 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 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 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 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 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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

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

• 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

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

[35 µg/h:]

“Buprenorphin” and “35 µg/h”

[52.5 µg/h:]

“Buprenorphin” and “52.5 µg/h”

[70 µg/h:]

“Buprenorphin” and “70 µg/h”

Each transdermal patch is sealed in one child-resistant sachet. The patches are available in packs containing 4, 5, 8, 10, 16 or 20 transdermal patches.

Not all pack sizes may be marketed.