Panup

Patient Information Leaflet: Information for the User

Panup 5 micrograms/hour transdermal patch, 10 micrograms/hour transdermal patch, 15 micrograms/hour transdermal patch, 20 micrograms/hour transdermal patch, 25 micrograms/hour transdermal patch, 30 micrograms/hour transdermal patch, 40 micrograms/hour transdermal patch

buprenorphine
For use in adults
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Panup is and what it is used for
2. What you need to know before using Panup
3. How to use Panup
4. Possible side effects
5. How to store Panup
6. Contents of the pack and other information

1. What Panup is and what it is used for

Panup transdermal patches contain the active substance buprenorphine, which belongs to a group of
medicines called strong analgesics or "painkillers".
Panup is used in adults to relieve moderate long-term pain requiring treatment with a strong painkiller.
Panup must not be used to relieve acute pain.

2. What you need to know before using Panup

Do not use Panup

• 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 drug-dependent
• if you are taking a type of medicine known as a monoamine oxidase inhibitor (MAO inhibitor) (examples include tranylcypromine, phenelzine, isocarboxazide, moclobemide and linezolid), or if you have taken such a medicine within the last two weeks
• if you suffer from severe myasthenia (a disorder causing muscle weakness)
• if you are experiencing withdrawal symptoms such as agitation, anxiety, tremor or sweating after stopping alcohol consumption.

Panup must not be used to treat symptoms associated with discontinuation of a medicine.
Warnings and precautions
Talk to your doctor or pharmacist before using Panup in the following cases:

• if you have recently consumed a large amount of alcoholic beverages
• if you suffer from seizures, epileptic attacks or convulsions
• if you have sleep-related breathing disorders (sleep apnoea)
• if you have a severe headache or nausea due to head trauma or increased intracranial pressure (for example, due to a brain disease). This is because the patches may worsen symptoms or mask the severity of a head injury
• if you suffer from dizziness or fainting
• if you have severe liver problems
• if anyone in your family has abused or been dependent on alcohol, prescription medicines or illegal drugs
• if you are a smoker
• if you have ever had mood disorders (depression, anxiety or personality disorder) or have been treated by a psychiatrist for other mental illnesses
• if you have a fever, as this may lead to increased absorption of the active ingredient into the bloodstream compared to normal
• if you are being treated with antidepressants. Using these medicines together with Panup may lead to serotonin syndrome, a potentially life-threatening condition (see "Other medicines and Panup")
• if you suffer from constipation

This medicine may cause reactions at the application site, usually mild to moderate skin inflammation, typically appearing as redness, swelling, itching, rash, small blisters and painful/burning sensation at the application site. Most commonly, this is due to skin irritation, and these reactions disappear after removal of the Panup patch. More severe allergic reactions may appear as blistering with oozing, which may spread beyond the application site and may not resolve quickly after removal of Panup. Chronic allergic reactions may lead to open wounds, bleeding, ulcers, skin discoloration and infections. If you notice any of the above-mentioned skin reactions, contact your doctor.
This medicine may increase your sensitivity to pain, particularly at high doses. Inform your doctor if this occurs. A dose reduction or change in medication may be necessary.
If you have recently undergone surgery, consult your doctor before using these transdermal patches.
Sleep-related breathing disorders: Panup may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (low blood oxygen levels). Symptoms may include pauses in breathing during sleep, nighttime awakenings due to breathlessness, difficulty maintaining sleep or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor, who may consider reducing the dose.
Panup may impair the body's normal production of hormones such as cortisol or sex hormones, particularly if high doses have been used for a prolonged period.
For athletes: using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.
Using Panup as a doping agent may pose health risks.
Children and adolescents
Panup must not be used in children and adolescents under 18 years of age.
Other medicines and Panup
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicine.
Some medicines may increase the side effects of Panup and sometimes may cause serious adverse reactions.
Do not take other medicines while using Panup without first talking to your doctor, especially:

• Panup must not be used in combination with a type of medicine known as a monoamine oxidase inhibitor (MAO inhibitor) (examples include tranylcypromine, phenelzine, isocarboxazide, moclobemide and linezolid), or if you have taken such a medicine within the last two weeks.
• Antidepressants such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepin or trimipramine. These medicines may interact with Panup and you may experience symptoms such as involuntary rhythmic muscle contractions, including muscles controlling eye movement, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle tone, body temperature above 38°C. Contact your doctor if you experience such symptoms.
• If you are taking medicines such as phenobarbital or phenytoin (commonly used to treat seizures, epileptic attacks or convulsions), carbamazepine (used to treat seizures, epileptic attacks or convulsions or certain pain conditions) or rifampicin (a medicine for the treatment of tuberculosis), the effects of Panup may be reduced.
• In some people, Panup may cause drowsiness, nausea or fainting, or may slow down or weaken breathing. These side effects may be worsened by concomitant use of other medicines that produce similar effects. These include certain medicines used to treat pain, depression, anxiety, psychiatric or mental disorders, medicines used to promote sleep, medicines used to treat high blood pressure such as clonidine, other opioids (which may be found in painkillers or some cough medicines, such as morphine, dextropropoxyphene, codeine, dextromethorphan, noscapine), sedating antihistamines, or anaesthetics such as halothane.
• Concomitant use of Panup and sedative medicines such as benzodiazepines or related medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma and

can be life-threatening. For this reason, concomitant use should only be considered when no other therapeutic options are available.
However, if your doctor prescribes Panup together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor.
Inform your doctor about all sedative medicines you are taking and follow carefully the dose recommended by your doctor. It may be helpful to inform friends and family to watch for the signs and symptoms listed above. Contact your doctor if such symptoms occur.
Panup and alcohol
Alcohol may worsen some of the side effects, and you may feel unwell if you consume alcohol while using Panup. Drinking alcohol while using Panup may also affect your reaction time.
Pregnancy and breastfeeding
You must not use Panup if you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, unless otherwise directed by your doctor, who will have carefully evaluated the benefits and risks for both mother and unborn child.
Ask your doctor or pharmacist for advice before using this medicine.
Driving and using machines
Panup may affect your reaction ability to such an extent that you may not be able to react adequately or quickly enough in case of unexpected or sudden events. This is particularly true:

• at the beginning of treatment
• if you are taking medicines for anxiety or to promote sleep
• if your dose is increased

If this applies to you (for example, if you experience dizziness, drowsiness or blurred vision), you must not drive or operate machinery while using Panup, nor during the 24 hours following removal of the transdermal patch.

3. How to use Panup transdermal patch

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Several dosage strengths of Panup are available. Your doctor will decide which strength of buprenorphine transdermal patch is most suitable for your condition.
When people first start using buprenorphine transdermal patches, they often experience nausea and vomiting (see section 4). These symptoms usually resolve after the first week of treatment. It is advisable to schedule a follow-up visit with your doctor one or two weeks after starting Panup transdermal patches to ensure you are receiving the correct dose and to manage any side effects.
During treatment, your doctor may replace the transdermal patch you are using with a smaller or larger one if necessary, or instruct you to use a combination of two patches. Do not cut or divide the patch or use a higher dose than recommended. Do not apply more than two transdermal patches at the same time, up to a total maximum dose of 40 micrograms/hour.
If you feel that the effect of Panup is too weak or too strong, consult your doctor or pharmacist.

Adults and elderly patients
Unless otherwise directed by your doctor, apply one Panup transdermal patch (as described in detail below) and replace it every seven days, preferably at the same time of day. Your doctor may decide to adjust the dose after 3–7 days to achieve optimal pain control. If your doctor has advised you to take additional painkillers alongside the transdermal patch, follow their instructions carefully; otherwise, you may not fully benefit from treatment with Panup. The transdermal patch must be used for 3 full days before increasing the dose: this is the time required for a given dose to exert its maximum effect.

Patients with liver disease
In patients with liver disease, the effects and duration of action of Panup may be altered, and your doctor will therefore monitor you more closely.

Use in children and adolescents
Panup transdermal patches must not be used in patients under 18 years of age.

Method of administration
Panup is for transdermal use.
Panup works through the skin. After application, buprenorphine passes into the bloodstream through the skin.

Before applying the Panup transdermal patch

• Choose an intact, non-irritated area of skin on the upper arm, outer arm, upper chest, upper back, or lateral side of the torso (see illustrations below). If you are unable to apply the patch yourself, ask for assistance.

• The buprenorphine transdermal patch should be applied to a relatively hair-free or nearly hair-free area of skin. If suitable hair-free areas are not available, trim the hair with scissors. Do not use a razor to remove hair.
• Avoid red, irritated skin or skin with other abnormalities, such as large scars.
• The selected skin area must be dry and clean. If necessary, wash with cool or lukewarm water. Do not use soap, alcohol, oil, lotions, or other detergents. After a hot bath or shower, wait until the skin is completely dry and cool. Do not apply lotions, creams, or ointments to the selected area: this could prevent the transdermal patch from adhering properly.

Applying the transdermal patch
Step 1: Each transdermal patch is sealed in a pouch. Just before use, open the pouch by tearing at the indicated spot. Remove the transdermal patch. Do not use the patch if the pouch seal is already broken.

Step 2: The adhesive side of the transdermal patch is covered with a transparent protective liner. Carefully remove half of the liner. Avoid touching the adhesive surface of the patch.

Step 3: Apply the transdermal patch to the selected skin area and remove the remaining protective liner.

Step 4: Press the transdermal patch onto the skin with the palm of your hand and count slowly to 30. Ensure that the entire patch is in full contact with the skin, especially at the edges.

Wearing the transdermal patch
You must wear the transdermal patch for seven days. Provided it has been correctly applied, it is unlikely to come loose. If the edges of the patch begin to lift, they may be secured with specific skin tape. You may take showers, bathe, or swim while wearing the transdermal patch.
Do not expose the transdermal patch to extreme temperatures (such as heating pads, electric blankets, heat lamps, saunas, hot tubs, heated water beds, hot water bottles, etc.), as this may cause increased absorption of the active ingredient into the bloodstream beyond normal levels. External heat may also prevent the patch from adhering properly. If you develop a fever, this may alter the effects of Panup (see section “Warnings and precautions” above).
In the unlikely event that the transdermal patch detaches before it is due to be replaced, do not reuse the same patch. Immediately apply a new one (see “Replacing the transdermal patch” below).

Replacing the transdermal patch

• Remove the old transdermal patch.
• Fold it in half with the adhesive side inward.
• Open and remove a new transdermal patch. Use the empty pouch to dispose of the old patch. Dispose of the pouch safely.
• Used patches still contain some active ingredient, which could be dangerous for children or animals. Ensure used patches are kept out of their reach and sight.
• Apply a new transdermal patch to a suitable and different skin site from the previous one (as described above). Do not apply a new patch to the same skin area for 3–4 weeks.
• Remember to replace the patch at the same time of day. It is important to note the exact time.

Duration of treatment
Your doctor will tell you how long you should be treated with Panup. Do not stop treatment without consulting your doctor, as your pain may return and you may feel unwell (see also “If you stop treatment with Panup” below).

If you use more Panup than you should
As soon as you realize you have used more transdermal patches than prescribed, remove all patches and contact your doctor or hospital immediately. People who have taken an excessive dose of buprenorphine may experience severe drowsiness and nausea. You may also have difficulty breathing or lose consciousness, requiring emergency treatment in hospital. When seeking medical help, make sure to bring this patient information leaflet and any remaining patches to show the doctor.

If you forget to apply Panup
Apply a new transdermal patch as soon as you remember. Also note the date, as your usual replacement day may now be different. If you delay replacing the patch significantly, your pain may return. In this case, contact your doctor.
Do not apply additional transdermal patches to make up for a missed application.

If you stop treatment with Panup
If you stop treatment with Panup too early or discontinue it, your pain may return. If you wish to stop treatment, consult your doctor. They will advise you on what to do and whether you can switch to another medication.
Some people may experience side effects when they stop using strong painkillers after long-term use. The risk of experiencing such effects after stopping Panup is very low. However, if you feel restless, anxious, nervous, or experience tremors, hyperactivity, difficulty sleeping, or digestive problems, inform your doctor.
The pain-relieving effect of Panup persists for some time after removal of the transdermal patch. You must not start taking another opioid analgesic (strong painkiller) within 24 hours after removing the transdermal patch.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The serious side effects that may be associated with Panup are similar to those observed with other strong painkillers and include difficulty breathing and low blood pressure.
This medicine may cause allergic reactions, although severe reactions are rare. If you experience sudden shortness of breath, difficulty breathing, swelling of the eyelids, face or lips, rash or itching, especially if affecting the whole body, remove the transdermal patch immediately and contact your doctor without delay.
There is a risk that you may become dependent on Panup.
The following side effects have also been reported in patients treated with Panup:
Very common (may affect more than 1 in 10 people)

• headache, dizziness, drowsiness
• constipation, nausea and vomiting
• itchy skin, skin redness
• skin rash, itching, redness, inflammation or swelling at the application site

Common (may affect up to 1 in 10 people)

• loss of appetite
• confusion, depression, anxiety, sleep disorders, restlessness, tremor
• shortness of breath
• abdominal pain or discomfort, diarrhea, indigestion, dry mouth
• sweating, rash, skin eruptions
• fatigue, unusual weakness, muscle weakness, edema (for example swelling of the hands, ankles or feet)

Uncommon (may affect up to 1 in 100 people)

• restlessness, agitation, feelings of extreme happiness, hallucinations, nightmares, decreased sexual desire, aggression
• altered taste, difficulty speaking, reduced sensitivity to pain or touch, tingling or numbness
• memory loss, migraine, fainting, problems with concentration or coordination
• dry eyes, blurred vision
• ringing or buzzing in the ears
• sensation of vertigo or dizziness
• high or low blood pressure, chest pain, rapid heartbeat, awareness of heartbeat, hot flushes
• cough, hiccups, wheezing
• flatulence
• weight loss
• dry skin
• spasms, discomfort and pain
• difficulty starting urination, difficulty passing urine, involuntary urination
• fever
• increased incidence of accidental injuries (e.g. falls)
• withdrawal symptoms such as restlessness, anxiety, sweating or tremor after stopping Panup

If you are due to have blood tests, remember to inform your doctor that you are using Panup. This is important because Panup may affect how the liver functions, which could influence the results of certain blood tests.
Rare (may affect up to 1 in 1,000 people)

• angina (chest pain associated with heart disease)
• mental disorders
• difficulty maintaining balance
• swelling of the eyelids or face, reduced pupil size
• difficulty breathing, worsening of asthma, hyperventilation
• feeling faint, especially when standing
• skin flushing
• difficulty swallowing, ileus
• local allergic reaction with marked swelling (in such cases treatment must be discontinued)
• swelling and irritation inside the nose
• reduced erection, sexual dysfunction
• flu-like illness
• dehydration

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

• muscle contractions
• mood changes
• ear pain
• blisters
• drug dependence

Frequency not known (frequency cannot be estimated from the available data)

• Breathing problems during sleep (sleep apnoea syndrome), see section 2 “Warnings and precautions”
• Convulsions, epileptic seizures or fits
• Inflammation of the intestinal wall. Symptoms may include fever, vomiting and stomach pain or discomfort.
• Increased sensitivity to pain
• Abdominal pain or discomfort resembling colic
• Feeling detached from oneself
• Withdrawal symptoms in babies born to mothers who took Panup during pregnancy may include high-pitched crying, irritability and restlessness, agitation (tremors), feeding difficulties, sweating and failure to gain weight
• Contact dermatitis (rash with inflammation which may include a burning sensation), skin color changes

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Panup

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 on the sachet, after
Exp. The expiry date refers to the last day of that month.
Do not store above 25°C.
Do not use the transdermal patch if you notice that the seal of the sachet is broken.
Used transdermal patches must be folded in half with the adhesive layer facing inwards and safely disposed of.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Panup contains

• The active substance is buprenorphine.

Panup 5 micrograms/hour transdermal patch
Each transdermal patch contains 5 mg of buprenorphine for 6.25 cm, releasing 5 micrograms of
buprenorphine per hour.
Panup 10 micrograms/hour transdermal patch
Each transdermal patch contains 10 mg of buprenorphine for 12.5 cm, releasing 10 micrograms of
buprenorphine per hour.
Panup 15 micrograms/hour transdermal patch
Each transdermal patch contains 15 mg of buprenorphine for 18.75 cm, releasing 15 micrograms of
buprenorphine per hour.
Panup 20 micrograms/hour transdermal patch
Each transdermal patch contains 20 mg of buprenorphine for 25 cm, releasing 20 micrograms of
buprenorphine per hour.
Panup 25 micrograms/hour transdermal patch
Each transdermal patch contains 25 mg of buprenorphine for 31.25 cm, releasing 25 micrograms of
buprenorphine per hour.
Panup 30 micrograms/hour transdermal patch
Each transdermal patch contains 30 mg of buprenorphine for 37.5 cm, releasing 30 micrograms of
buprenorphine per hour.
Panup 40 micrograms/hour transdermal patch
Each transdermal patch contains 40 mg of buprenorphine for 50 cm, releasing 40 micrograms of
buprenorphine per hour.

• Other components are:
  Protective liner (to be removed before applying the patch): poly(ethylene terephthalate) sheet, siliconized
  Adhesive matrix (containing buprenorphine): levulinic acid, oleyl oleate, povidone K90, poly[acrylic acid-co-butyl acrylate-co-(2-ethylhexyl)acrylate-co-vinyl acetate] (5:15:75:5)
  Separating liner (between adhesive matrices with and without buprenorphine): poly(ethylene terephthalate) sheet
  Patch backing: acrylic adhesive, polyurethane support film, printing ink

Description of the appearance of Panup and contents of the pack
Panup is a rectangular transdermal patch of light brown/yellowish colour, with rounded edges.
The transdermal patch bears the following inscriptions:
Buprenorphinum 5 µg/h
Buprenorphinum 10 µg/h
Buprenorphinum 15 µg/h
Buprenorphinum 20 µg/h
Buprenorphinum 25 µg/h
Buprenorphinum 30 µg/h
Buprenorphinum 40 µg/h
Each transdermal patch is individually packed in a child-resistant pouch.
Pack sizes containing 4, 8 or 12 transdermal patches.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Sandoz S.p.A.
Largo Umberto Boccioni 1
21040 Origgio (VA)
Italy

Manufacturer
Hexal AG
Industriestrasse 25, 83607 Holzkirchen
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names: