Transtec - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Buprenorphine

TRANSTEC 35 micrograms / h / 52.5 micrograms / h / 70 micrograms / h Transdermal Patch

Indications Why is Transtec used? What is it for?

Transtec is an analgesic medicine (for pain relief), indicated for the treatment of cancer pain of moderate to severe intensity and severe pain that does not respond to other types of pain reliever.

TRANSTEC works by crossing the skin. When the transdermal patch is applied to the skin, the active ingredient buprenorphine passes into the blood through the skin. Buprenorphine is an opioid (strong analgesic) that reduces pain by acting on the central nervous system (specific nerve cells in the spinal cord and brain). The effect of the transdermal patch lasts up to four days. Transtec is not indicated for the treatment of acute pain (pain of short duration).

Contraindications When Transtec should not be used

Do not use Transtec

  • 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 diseases that compromise, or that can seriously compromise, respiratory function;
  • if you are taking MAO inhibitors (medicines to treat depression), or have taken any in the last 2 weeks, (see "Other medicines and Transtec");
  • if you suffer from myasthenia gravis (severe form of muscle weakness);
  • if you suffer from delirium tremens (confusion and shaking caused by alcohol withdrawal, after excessive use of alcohol or occasional excessive alcohol consumption).
  • If you are pregnant.

Transtec should not be used to treat withdrawal symptoms in drug addicts.

Precautions for use What you need to know before taking Transtec

Talk to your doctor or pharmacist before using Transtec

  • If you have recently drunk a lot of alcohol
  • if you suffer from fits
  • if you suffer from disturbances of consciousness (light-headedness or fainting) due to unknown causes;
  • if you are in shock (cold sweat could be a symptom);
  • when the pressure in the skull increases (for example as a result of head injuries or brain disorders), without the possibility of artificial respiration;
  • if you have breathing problems or are taking medicines that can slow or weaken your breathing (see "Other medicines and Transtec");
  • if your liver is not functioning properly;
  • if you tend to abuse drugs or narcotic substances; Also follow the following precautions:
  • some people may experience dependence on potent analgesics, such as Transtec, after prolonged treatments. These people may experience withdrawal symptoms at the end of treatment (see "when treatment with Transtec is stopped");
  • Fever and exposure to external heat sources can raise blood concentrations of buprenorphine beyond normal. In addition, excess heat on the skin surface can prevent proper adhesion of the transdermal patch. Ask your doctor for advice if you have a fever and do not expose yourself to external heat sources (eg sauna, infrared lamps, electric blankets, hot water bottles).

For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.

Children and adolescents

Transtec should not be used in patients under 18 years of age, as there is currently no experience on the use of the medicine in this age group.

Interactions Which drugs or foods can modify the effect of Transtec

Other medicines and Transtec

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

  • Transtec must not be used if you are taking MAO inhibitors (medicines to treat depression) or if you have used them in the previous two weeks.
  • TRANSTEC may cause drowsiness, nausea, weakness, or make breathing shorter or weaker in some patients. These side effects can be more intense if you are also taking other medications that can cause the same side effects. Among these other drugs are other potent pain relievers (opioids), some drugs for the treatment of insomnia, anesthetics and drugs used to treat certain psychological illnesses, such as tranquilizers, antidepressants and neuroleptics.
  • If Transtec is used together with certain medications, the effect of the transdermal patch may be enhanced. These medications include for example some anti-infectives / antifungals (eg erythromycin or ketoconazole), or anti-HIV medications (eg ritonavir-based) .
  • If Transtec is used together with other drugs, the effect of the transdermal patch may be reduced. These drugs include certain products, for example, dexamethasone, drugs to treat epilepsy (eg containing carbamazepine or phenytoin) or drugs for the tuberculosis (e.g. rifampicin)

Transtec with food and drink and alcohol

You should not drink alcohol while using Transtec. Alcohol can intensify some undesirable effects of the trandermal patch and make you feel unwell. Drinking grapefruit juice can increase the effect of Transtec.

Warnings It is important to know that:

Pregnancy, breastfeeding 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 taking this medicine. There is insufficient experience with the use of Transtec during pregnancy. Therefore Transtec should not be used during pregnancy. The active substance in the transdermal patch, buprenorphine, inhibits the formation of milk and passes into breast milk. be used while breastfeeding.

Driving and using machines

Transtec can make you feel dizzy, sleepy, blurred or double vision and impair your ability to react in such a way that you cannot react adequately or quickly enough to unexpected or sudden situations. This is especially true:

  • at the beginning of the treatment;
  • when changing the dosage
  • when you start using Transtec to replace another analgesic;
  • if you also use other medicines that affect the brain;
  • if you drink alcohol.

If you experience these effects, you should not drive or operate machinery while using Transtec. This recommendation also applies at the end of treatment with Transtec. Do not drive or use machines for at least 24 hours after removing the patch.

Talk to your doctor or pharmacist if you have any concerns.

Dose, Method and Time of Administration How to use Transtec: Posology

Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist. Transtec is available in three strengths: Transtec 35 micrograms / h transdermal patches, Transtec 52.5 micrograms / h transdermal patches, Transtec 70 micrograms / h transdermal patches. The choice of which strength of Transtec is best for you should be made by your doctor. During treatment, your doctor may decide to change the transdermal patch to a larger or smaller one if necessary.

The recommended dosage is:

Adults

Unless otherwise prescribed, apply a TRANSTEC transdermal patch (following the instructions described below) and replace it after 4 days at the latest. For convenience, you can change the transdermal patch twice a week, at regular intervals, for example always on Monday morning and Thursday evening. In order not to forget when to change the transdermal patch, mark the days of replacement of the transdermal patch on the calendar on the pouch. If your doctor prescribes other analgesics in addition to the transdermal patch, strictly follow his instructions, otherwise you may not get the benefit from the transdermal patch. use of TRANSTEC.

Use in children and adolescents

Transtec should not be used by people under the age of 18, as there is no experience on the use of the medicine in this age group.

Elderly patients

It is not necessary to adjust the dose for elderly patients.

Patients with kidney disease and dialysis patients

In patients with kidney disease and on dialysis, no dosage adjustment is required.

Patients with liver disease

In patients with liver disease, the intensity and duration of the effect of Transtec may be affected. In this case the doctor will carry out more frequent checks

Method of application

Before applying the patch

  • Choose an area of ​​flat, clean, hairless skin on the upper body, preferably on the chest in the subclavicular area or on the upper back (see illustrations opposite). Get help if you cannot apply the patch on your own.
  • If the chosen area is not free of hair, any hair should be cut with scissors, and not shaved. THORAX BACK
  • Do not apply the patch to skin that is red, irritated or has other changes, such as extensive scars.
  • The area of ​​skin chosen for the application must be dry and clean. If necessary, wash the area with cold or lukewarm water. Do not use soaps or other cleansers. After a hot bath or shower, wait until the skin is completely dry and cool before applying the patch. Do not use lotions, creams or ointments. This could prevent proper adhesion of the transdermal patch in the chosen area.

Application of the transdermal patch

  1. 1Each transdermal patch is individually sealed in a sachet. Open the sachet only immediately before use by tearing it along the incision. Remove the transdermal patch.
  2. The sticky side of the transdermal patch is covered with a silver colored protective film. Carefully peel off the liner in half, avoiding touching the adhesive layer of the transdermal patch.
  3. Stick the transdermal patch on the skin area chosen for application and remove the rest of the protective film.
  4. Press the transdermal patch onto the skin with the palm of your hand for approximately 30 seconds. Make sure that all of the transdermal patch adheres to the skin, especially along the edges.
Put on the transdermal patch

The transdermal patch should be worn for a maximum of 4 days. Make sure it has been applied correctly; there is a minimal risk that it may detach. You can shower, bathe or swim while wearing it. However, do not expose the transdermal patch to excessive heat sources (such as saunas, infrared lamps, electric blankets and hot water bottles).

In the unlikely event that the transdermal patch falls off before the next change, the same transdermal patch cannot be used again, a new patch must be attached immediately (see "Changing the transdermal patch").

Changing the transdermal patch

  • Remove the old transdermal patch
  • Fold it in half making the adhesive surfaces adhere.
  • Throw away the transdermal patch, out of the sight and reach of children.
  • Apply a new transdermal patch to a different area of ​​the skin as described above. Do not apply another one to the same area of ​​skin for a week or so.

Duration of treatment

Your doctor will tell you how long you will need to use Transtec for. Do not stop treatment on your own, as the pain may come back, making you feel unwell (see "When you stop taking Transtec"). If you have the impression that the analgesic effect of Transtec transdermal patches is too weak or too strong, consult your doctor or pharmacist.

Overdose What to do if you have taken too much Transtec

If you use more TRANSTEC than you should

In this case, symptoms of buprenorphine overdose may occur. An overdose can aggravate the side effects of buprenorphine, such as: sleepiness, nausea and vomiting. He may have pinpoint pupils and his breathing may become slow and weak. Cardiovascular collapse can occur. When you realize that you have used more transdermal patches than necessary, remove the excess transdermal patches and consult your doctor or pharmacist immediately.

If you forget to apply TRANSTEC

If you have forgotten a transdermal patch, put on a new one as soon as possible. In this case you will have to change your habits, for example if you usually apply the transdermal patch on Mondays and Thursdays, but have forgotten it and therefore change the transdermal patch on Wednesday, remember that from that moment on you will have to change it on Wednesday and Saturday. Make a note of the two new days on the pouch calendar. If you change your patch very late, the pain may return. In this case, contact your doctor. Do not double the number of patches you apply to make up for not applying!

If you stop taking Transtec

If you stop or stop treatment with Transtec earlier than necessary, the pain may return. If you wish to stop treatment due to side effects, please consult your doctor, who will inform you about what can be done and whether you can be treated with other medicines. Some people may experience withdrawal symptoms when they have used strong pain relievers for a long time and then stop them. The risk of having such effects after stopping treatment with Transtec is very low. However, in case of agitation, anxiety, nervousness, tremors, hyperactivity, insomnia and digestive disorders, consult your doctor. If you have any questions about the use of this medicine. ask your doctor or pharmacist.

Side Effects What are the side effects of Transtec

Like all medicines, this medicine can cause side effects, although not everybody gets them. Undesirable effects are classified as follows:

Very common: more than 1 in 10 people

Common: more than 1 in 100 people; less than 1 in 10 people

Uncommon More than 1 in 1,000 people. Less than 1 in 100 people

Rare: more than 1 in 10,000 people; less than 1 in 1,000 people

Very rare: less than 1 in 10,000 people

The following side effects have been reported:

Disorders of the immune system

Very rare: severe allergic reactions (see below).

Metabolism and nutrition disorders

Rare: loss of appetite.

Psychiatric disorders

Uncommon: confusion, sleep disturbances, restlessness.

Rare: false sensations such as hallucinations, anxiety, nightmares, decreased libido.

Very rare: addiction, mood swings.

Nervous System Pathologies

Common: dizziness, headache.

Uncommon: sedation of varying severity (calm), from fatigue to drowsiness.

Rare: difficulty concentrating, speech disturbances, numbness, disturbed balance, abnormal sensations of the skin (feeling of numbness, tingling or burning).

Very rare: muscle spasms, taste disturbance.

Eye disorders

Rare: visual disturbances, blurred vision, swollen eyelids.

Very rare: pinpoint pupils.

Ear disorders

Very rare: ear pain.

Cardiovascular pathologies

Uncommon: circulatory disorders (such as hypotension or, rarely, even circulatory collapse).

Rare: hot flashes.

Chest and lung disorders

Common: short breath

Rare: difficulty in breathing (respiratory depression).

Very rare: breathing too fast, hiccups.

Gastrointestinal disorders

Very common: nausea.

Common: vomiting, constipation.

Uncommon: dry mouth.

Rare: heartburn.

Very rare: retching.

Skin disorders (usually at the application site)

Very common: redness, itching.

Common: skin changes (rash, usually after long treatments), sweating.

Uncommon: rash.

Rare: hives

Very rare: pustules and small vesicles.

Urinary disorders

Uncommon: disturbed urination, urinary retention (less urine than normal).

Pathologies of the reproductive system

Rare: difficulty with erection.

Systemic pathologies

Common: edema (for example swelling in the legs), tiredness.

Uncommon: weakness.

Rare: withdrawal symptoms (see below), administration site reactions.

Very rare: chest pain.

If you notice any of the listed side effects, please contact your doctor as soon as possible. In some cases, delayed allergic reactions may occur, with obvious signs of inflammation. In this case, stop treatment with Transtec after talking to your doctor.

If you experience swelling in your hands, feet, ankles, face, lips, mouth or throat which cause you difficulty in swallowing or breathing, hives, fainting, yellowing of the skin or eyes (also called jaundice), remove the patch. transdermal and call your doctor immediately or go to the emergency room of the nearest hospital. These could be symptoms of a very rare severe allergic reaction.

Withdrawal symptoms may occur in some people when strong pain relievers are used for a long time and then discontinued. The risk of having such withdrawal effects after stopping treatment with Transtec is low. However, in case of agitation, anxiety, nervousness, tremors, hyperactivity, insomnia and digestive disorders, consult your doctor.

Reporting of side effects

If you get any side effects, please tell your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it. By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

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" (month / year). The expiry date refers to the last day of that month

This medicine does not require any special storage conditions. Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Composition and pharmaceutical form

What Transtec contains

The active ingredient is buprenorphine.

TRANSTEC 35 micrograms / h transdermal patch Each transdermal patch contains 20 mg of buprenorphine and releases approximately 35 micrograms of buprenorfinal "per hour. The surface area of ​​the transdermal patch that contains the active substance is 25 cm2. TRANSTEC 52.5 micrograms / h transdermal patch Each transdermal patch contains 30 mg of buprenorphine and releases approximately 52.5 micrograms of buprenorphine per hour. The surface area of ​​the transdermal patch containing the active ingredient is 37.5 cm2. TRANSTEC 70 micrograms / h transdermal patch Each transdermal patch contains 40 mg of buprenorphine and releases approximately 70 micrograms of buprenorphine per hour. The surface area of ​​the transdermal patch that contains the active ingredient is 50 cm2.

The other ingredients are:

adhesive matrix: [(Z) -octadec-9-en-1-yl] oleate, povidone K90, 4-oxopentanoic acid, poly [acrylic-co-butylacrylate-co- (2-ethylxyl) acrylate-co-vinylacrylate- tato] (5: 15: 75: 5) cross-linked (area containing buprenorphine) or non-cross-linked, (area without buprenorphine); separation foil between the two matrices: poly (ethylene terephthalate) - support layer: poly (ethylene terephthalate) fabric. The protective coating (to be removed before applying the transdermal patch) consists of a poly (ethylene terephthalate) foil, silicone coated and coated with aluminum on one side.

What TRANSTEC looks like and what the pack contains

TRANSTEC transdermal patches are flesh-colored with rounded corners printed with:

Transtec 35 micrograms / h, buprenorphinum 20 mg.

Transtec 52.5 micrograms / h, buprenorphinum 30 mg.

Transtec 70 micrograms / h, buprenorphinum 40 mg.

TRANSTEC is contained in cartons with: 3, 5, 10 30 transdermal patches contained in single sachets.

Not all pack sizes may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Transtec can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER 09 .0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS AND QUALITY CONTROLS

01.0 NAME OF THE MEDICINAL PRODUCT

TRANSTEC TRANSDERMAL PATCH

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Transtec 35 mcg / h transdermal patch:

1 transdermal patch contains 20 mg of buprenorphine.

Surface containing the active principle: 25 cm2.

Nominal quantity released: 35 mcg of buprenorphine per hour (for a period of 96 h).

Transtec 52.5 mcg / h transdermal patch:

1 transdermal patch contains 30 mg of buprenorphine.

Surface containing the active principle: 37.5 cm2.

Nominal quantity released: 52.5 mcg of buprenorphine per hour (for a period of 96 h).

Transtec 70 mcg / h transdermal patch:

1 transdermal patch contains 40 mg of buprenorphine.

Surface containing the active principle: 50 cm2.

Nominal quantity released: 70 mcg of buprenorphine per hour (for a period of 96 h).

For the full list of excipients, see section 6.1

03.0 PHARMACEUTICAL FORM

Skin-colored transdermal patch with rounded corners, bearing the words:

Transtec 35 mcg / h, buprenorphinum 20 mg

Transtec 52.5 mcg / h, buprenorphinum 30 mg

Transtec 70 mcg / h, buprenorphinum 40 mg

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Treatment of moderate to severe cancer pain and severe pain unresponsive to non-opioid analgesics.

Transtec is not indicated for the treatment of acute pain.


04.2 Posology and method of administration

Dosage

Patients over 18 years of age

Transtec dosage should be adapted to the individual patient's condition (pain intensity, suffering, individual response). The lowest possible dosage should be used to ensure adequate pain relief. Three different strengths of transdermal patches are available to provide therapy tailored to the patient's condition: Transtec 35 mcg / h, Transtec 52.5 mcg / h and Transtec 70 mcg / h.

Choice of starting dose: Patients who have not previously received analgesics should start with the lower strength transdermal patch (Transtec 35 mcg / h). Patients who have previously used a WHO step I (non-opioid) or step II (weak opioid) analgesic should also start with Transtec 35 mcg / h. According to the recommendations of the WHO it is possible to continue to administer a non-opioid analgesic depending on the general medical condition of the patient.

When switching from a step III analgesic (strong opioid) to Transtec and choosing the starting transdermal patch strength, the nature of the previous drug, the route of administration and the average daily dose should be taken into account in order to avoid the pain returns.

In general, it is advisable to adjust the dose individually starting with the lowest strength transdermal patch (TRANSTEC 35 mcg / h). Clinical experience has shown that patients previously treated with a high daily dose strong opioid (corresponding to approximately 120 mg of oral morphine) can initiate therapy with the next higher dose transdermal patch (see also section 5.1).

To allow for individual dosage adjustment over an adequate period of time, sufficient additional immediate-release analgesics should be made available during dose adjustment.

The required dosage of Transtec should be tailored to the individual needs of the patient and monitored at regular intervals.

After application of the first Transtec transdermal patch, serum concentrations of buprenorphine slowly increase in both patients previously treated with analgesics and in those who have not received analgesics. Therefore, the effect is unlikely to occur rapidly initially. Consequently, an initial assessment of the analgesic effect should only be made after 24 hours. The previously used analgesic drug (with the exception of transdermal opioids) should be administered at the same dosage during the first 12 hours after switching to Transtec. appropriate rescue medications should be made available over the next 12 hours.

Dose adjustment and maintenance therapy

Transtec must be replaced after 96 hours (4 days) at the latest. For convenience, the transdermal patch can be changed twice a week at regular intervals, for example always on Monday morning and Thursday evening. The dose should be individually determined until analgesic efficacy is achieved. If analgesia is insufficient, the dose may be increased at the end of the initial application period by applying more than one transdermal patch of the same strength or by switching to the next higher strength. of transdermal patch. Do not apply more than 2 transdermal patches at the same time, regardless of the strength used.

Before applying Transtec with the next dosage, the amount of opioid drugs used in addition to the previous transdermal patch should be considered, i.e. the total amount of opioids needed, adjusting the dosage accordingly. Patients who require additional analgesic (e.g. for excruciating pain during maintenance therapy) can take, in addition to the transdermal patch, for example one to two sublingual tablets of 0.2 mg buprenorphine every 24 h. If regular addition of 0.4-0.6 mg buprenorphine sublingually is required, the next dosage should be used.

Pediatric population

Since Transtec has not been studied in patients under the age of 18, it is not recommended for use in patients below this age limit.

Elderly patients

There is no need to adjust the dose with Transtec for elderly patients.

Patients with renal insufficiency

Since the pharmacokinetics of buprenorphine are not altered in renal insufficiency, the drug can also be used in patients with renal insufficiency including patients on dialysis.

Patients suffering from hepatic insufficiency

Buprenorphine is metabolised in the liver. In patients with impaired hepatic function, the intensity and duration of its action may be affected. Therefore patients with hepatic insufficiency should be carefully monitored during treatment with Transtec.

Application procedure

Transtec should be applied to non-irritated skin on a flat, hairless surface, but not to areas of the skin with extensive scars. Preferable areas of the upper body are: upper back and sub-clavicular area of ​​the chest.

Any fluff should be cut with a pair of scissors and not shaved. If it is necessary to clean the application site, this should be done with water. Soap or other detergents should not be used. influence the adhesion of the transdermal patch to the area chosen for the application of Transtec.

The skin must be completely dry before applying the patch. Transtec must be applied immediately after removing it from the sachet. After removing the protective liner, the transdermal patch should be pressed firmly in place with the palm of the hand for approximately 30 seconds. The transdermal patch will not come off when bathing, showering or swimming. However, it must not be exposed to excessive heat (e.g. sauna, infrared radiation).

Transtec should be worn continuously for up to 4 days. A new transdermal patch should be applied to a different site from the previous one, after removing the previous transdermal patch. At least one week should elapse before applying a new transdermal patch to the same skin area.

Duration of administration

Transtec should under no circumstances be administered for longer than strictly necessary. If, in consideration of the nature and severity of the disease, it is necessary to use Transtec for prolonged pain therapy, careful and regular checks (if necessary with treatment interruptions) should be carried out to determine if and to what extent it is necessary to continue the therapy. .

Transtec discontinuation

Once Transtec is removed, the serum levels of buprenorphine gradually decrease and therefore the analgesic effect is maintained for a certain period of time. This should be taken into consideration when Transtec therapy is to be followed by other opioids. As a general rule, this should not be done. You must administer another opioid within 24 hours after the removal of Transtec At present, only limited information is available on the starting dose of other opioids given after Transtec has been discontinued.


04.3 Contraindications

Transtec is contraindicated in case of:

- hypersensitivity to the active substance or to any of the excipients (listed in section 6.1);

- patients dependent on opioids and in the treatment of narcotic withdrawal;

- conditions in which the respiratory system and functionality are seriously compromised or which may become so;

- patients taking or have taken MAO inhibitors within the last two weeks (see section 4.5);

- patients with myasthenia gravis;

- patients with delirium tremens;

- pregnancy (see section 4.6).


04.4 Special warnings and appropriate precautions for use

Transtec should only be used with particular caution in acute alcoholic intoxication, in seizure disorders, in patients with head injuries, shock, decreased level of consciousness of uncertain origin, increased intracranial pressure without the possibility of ventilation.

Occasionally, buprenorphine causes respiratory depression. Therefore, caution should be exercised when treating patients with impaired respiratory function or patients taking medications that can cause respiratory depression.

Buprenorphine has a significantly lower dependency tendency than pure opioid agonists. In studies conducted with Transtec in healthy volunteers and patients, no withdrawal reactions were observed. However, after prolonged use of Transtec, withdrawal symptoms similar to those occurring during opioid withdrawal cannot be completely ruled out (see section 4.8). These symptoms include: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal disorders.

In opioid abusers, substitution with buprenorphine can prevent withdrawal symptoms. This has led to some cases of buprenorphine abuse; Caution should be exercised in prescribing it to patients suspected of having drug abuse problems.

Buprenorphine is metabolized in the liver. In patients with liver function disorders, the intensity and duration of the effect may be affected. Therefore such patients should be closely monitored during treatment with Transtec.

Athletes should be advised that this medicine may cause a positive reaction to doping tests

Pediatric population

Since Transtec has not been studied in patients under the age of 18, it is not recommended to use the medicine in patients below this age limit.

Patients with fever / exposure to external heat sources

Fever and heat exposure can increase skin permeability. In these cases, theoretically, there could be an increase in serum concentrations of buprenorphine during treatment with Transtec. Therefore, attention should be paid to the increased possibility of opioid reactions in patients who are feverish or have an increase in skin temperature due to other causes during treatment with Transtec.


04.5 Interactions with other medicinal products and other forms of interaction

Following administration of MAO inhibitors in the 14 days prior to administration of the opioid pethidine, life-threatening interactions have been observed in the patient's central nervous system and respiratory and cardiovascular function. The same interactions between MAO inhibitors and Transtec cannot be excluded (see section 4.3).

The effects on the central nervous system may be intensified when Transtec is administered together with other opioids, anesthetics, hypnotics, sedatives, antidepressants, neuroleptics and, in general, with medicinal products that depress the respiratory function and the central nervous system. This also applies to alcohol.

Concomitant administration with inhibitors or inducers of cytochrome CYP 3A4 may potentiate (inhibitors) or reduce (inducers) the efficacy of Transtec.


04.6 Pregnancy and breastfeeding

Pregnancy

No data are available on the use of Transtec in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk to humans is unknown.

Towards the end of pregnancy, high doses of buprenorphine can induce respiratory depression in the newborn even after a short period of administration. Prolonged administration of buprenorphine during the last three months of pregnancy can cause withdrawal syndrome in the newborn. Transtec is therefore contraindicated during pregnancy.

Feeding time

Buprenorphine is excreted in human milk. In rats, buprenorphine inhibits lactation. Transtec should not be used during breastfeeding.

Fertility

There is no known effect of buprenorphine on fertility in animals (see section 5.3).


04.7 Effects on ability to drive and use machines

Transtec markedly affects the ability to drive and use machines.

Transtec, even when administered according to instructions, can affect the patient's reactions to the point of compromising road safety and the ability to use machinery.

This is especially true at the start of treatment, in the event of any dose changes, and when TRANSTEC is used in combination with other centrally acting substances, including alcohol, tranquilizers, sedatives and hypnotics.

Affected patients (experiencing, for example, dizziness, sleepiness or blurred or double vision) should not drive or operate machinery while taking Transtec and for at least 24 hours after removing the patch.

Patients stabilized at specific doses will not necessarily be restricted if no symptoms listed above are present.


04.8 Undesirable effects

The following adverse reactions have been reported in clinical studies following administration of Transtec and during post-marketing surveillance.

Their frequency is defined as follows:

very common (≥ 1/10)

common (≥ 1/100,

uncommon (≥ 1/1000,

rare (≥ 1/10000,

very rare (≤ 1/10000)

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

a) The most commonly reported systemic adverse reactions were nausea and vomiting. The most commonly reported local adverse reactions were erythema and pruritus.

Disorders of the immune system

Very rare: severe allergic reactions *

Metabolism and nutrition disorders

Rare: loss of appetite

Psychiatric disorders

Uncommon: confusion, sleep disturbances, restlessness

Rare: psychoticomimetic effects (e.g. hallucinations, anxiety, nightmares), decreased libido

Very rare: addiction, mood changes

Nervous system disorders

Common: dizziness, headache

Uncommon: sedation, somnolence

Rare: reduced ability to concentrate, slurred speech, numbness, lack of balance, paraesthesia (for example, burning or tingling of the skin)

Very rare: muscle fasciculations, parageusia

Eye disorders

Rare: visual disturbances, blurred vision, eyelid edema

Very rare: miosis

Ear and labyrinth disorders

Very rare: ear pain

Cardiovascular pathologies

Uncommon: circulatory disorders (such as hypotension or, rarely, even circulatory collapse)

Rare: hot flashes

Respiratory, thoracic and mediastinal disorders

Common: dyspnoea

Rare: respiratory depression

Very rare: hyperventilation, hiccups

Gastrointestinal disorders

Very common: nausea

Common: vomiting, constipation

Uncommon: dry mouth

Rare: heartburn

Very rare: retching

Skin and subcutaneous tissue disorders

Very common: erythema, pruritus

Common: rash, sweating

Uncommon: rash

Rare: urticaria

Very rare: pustules, vesicles

Renal and urinary disorders

Uncommon: urinary retention, urination disturbances

Diseases of the reproductive system and breast

Rare: reduced erection

General disorders and administration site conditions

Common: edema, fatigue

Uncommon: weakness

Rare: withdrawal symptoms * administration site reactions

Very rare: chest pain

* see section c)

c) In some cases delayed allergic reactions have appeared with evident signs of inflammation. In such cases the treatment with Transtec should be discontinued.

Buprenorphine has a low risk of addiction. After discontinuation of Transtec, withdrawal symptoms are unlikely. This is due to the very slow dissociation of buprenorphine from opiate receptors and the gradual decrease in serum concentrations of buprenorphine (usually within 30 hours after removal of the last transdermal patch). However, after long-term use of Transtec, it is not The appearance of withdrawal symptoms, similar to those occurring during opioid withdrawal, can be totally excluded.These symptoms include: agitation, anxiety, nervousness, insomnia, hyperkinesis, tremors and gastrointestinal disturbances.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.


04.9 Overdose

Buprenorphine has a large safety margin. Due to the controlled release of small amounts of buprenorphine into the bloodstream it is unlikely that elevated or toxic blood levels of buprenorphine will be achieved. The maximum serum concentration of buprenorphine following the application of Transtec 70 mcg / h transdermal patch is approximately 6 times lower than that obtained following intravenous administration of the therapeutic dose of 0.3 mg of buprenorphine.

Symptoms

In principle, symptoms similar to those of other centrally acting analgesics (opioids) should be expected in the event of a buprenorphine overdose. These include: respiratory depression, sedation, somnolence, nausea, vomiting, cardiovascular collapse, marked miosis.

Treatment

General emergency measures apply. Keep the airways open (aspiration!), Maintain breathing and circulation, depending on the symptoms. Naloxone has "limited utility" on the respiratory depressant effect of buprenorphine. There is a need for high doses as repeated boluses or as an infusion (e.g. starting from a bolus administration of 1-2 mg intravenously. After adequate antagonistic effect is achieved, administration by infusion is recommended to maintain constant levels. levels of naloxone) Therefore, adequate ventilation should be established.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: opioids, oripavine derivatives.

ATC code: N02AE01.

Buprenorphine is a strong opioid with mu opioid receptor agonist activity and kappa opioid receptor antagonist activity. Buprenorphine appears to have the general characteristics of morphine but with its own specific pharmacological and clinical peculiarities.

Furthermore, numerous factors, such as clinical indications and conditions, route of administration and interindividual variability, have an impact on analgesia and must therefore be considered when comparing analgesics.

In daily clinical practice, the different opiates are classified with respect to relative potency, although this should be considered a simplification.

The relative potency of buprenorphine in different forms of administration and in different clinical situations has been described as follows in the literature:

- morphine os: BUP i.m. as 1: 67-150 (single dose, in the acute pain model)

- morphine os: BUP s.l. as 1: 60-100 (single dose, acute pain model, multiple doses, chronic pain, cancer pain)

- morphine os BUT TTS as 1: 75-115 (multiple doses, chronic pain)

Abbreviations:

os = oral; i.m. = intramuscular; s.l. = sublingual; TTS = transdermal; BUP = buprenorphine

Adverse reactions are similar to those of other potent opioid analgesics. Buprenorphine appears to have a lower dependency tendency than morphine.


05.2 "Pharmacokinetic properties

a) General characteristics of the active ingredient

Buprenorphine has a plasma protein binding of approximately 96%.

Buprenorphine is metabolised in the liver into No.-dealkylbuprenorphine (norbuprenorphine) and glucurono-conjugated metabolites. 2/3 of the active substance is excreted unchanged in the faeces and 1/3 is excreted as a conjugate of unchanged or dealkylated buprenorphine via the urinary system. There is evidence of enterohepatic recirculation.

Studies in non-pregnant and pregnant rats have shown that buprenorphine crosses the blood brain and placental barrier. Brain concentrations (where only unchanged buprenorphine is found), following parenteral administration, were 2-3 times higher than those obtained after oral administration.

Accumulation of buprenorphine in the gastrointestinal lumen of the fetus has been observed following intramuscular or oral administration, probably due to biliary excretion, since the enterohepatic circulation is not fully developed.

b) Characteristics of Transtec in healthy volunteers

After application of Transtec, buprenorphine is absorbed through the skin. Continuous release of buprenorphine into the systemic circulation occurs by controlled release from the polymer-based adhesive matrix system.

After the initial application of Transtec, plasma concentrations of buprenorphine gradually increase, reaching the minimum effective concentration of 100 pg / ml, after 12-24 h.

In studies performed on healthy volunteers with Transtec, 35 mcg / h, the mean Cmax was found to be between 200 - 300 pg / ml with a mean Tmax between 60-80 h. In a study of TRANSTEC 35 mcg / h and Transtec volunteers, 70 mcg / h were applied following a cross-over design. This study demonstrated dose-proportionality for the different dosages.

Once Transtec is removed, plasma concentrations of buprenorphine steadily decrease and are eliminated with a "half-life of approximately 30 hours (range 22-36). Continuous absorption of buprenorphine from the skin depot results in" slower than that which occurs after intravenous administration.


05.3 Preclinical safety data

Standard toxicological studies did not reveal any particular potential risks for humans. In experiments conducted on rats with repeated doses of buprenorphine, weight growth was slowed down.

Studies on fertility and general reproductive capacity in rats did not show harmful effects. Studies in rats and rabbits revealed signs of fetotoxicity and increased post-implantation loss.

Studies in rats have shown decreased intrauterine growth, delayed development of some neurological functions, and high peri- and postnatal mortality in infants following treatment of the mothers during gestation or lactation. There is evidence that these effects contribute to complications of childbirth and reduced lactation. There was no evidence of embryotoxic effects, including teratogenicity, in rats and rabbits.

In vitro and in vivo tests on the mutagenic potential of buprenorphine did not indicate clinically relevant effects.

There was no evidence of carcinogenic potential relevant to humans in long-term studies in rats and mice.

The toxicological data available do not indicate a sensitization potential of the excipients of the transdermal patch.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Adhesive matrix (containing buprenorphine): [(Z) -octadec-9-en-1-yl] oleate, povidone K90, 4-oxopentanoic acid, poly [acrylic-co-butylacrylate-co- (2-ethylhexyl) acrylate-co-vinyl acetate] (5 : 15: 75: 5), united by cross-links.

Adhesive matrix (without buprenorphine): poly [acrylic-co-butylacrylate-co- (2-ethylhexyl) acrylate-co-vinyl acetate] (5: 15: 75: 5), joined by non-cross links.

Separation foil between the adhesive matrices with and without buprenorphine: poly (ethylene terephthalate) foil.

Support layer: poly (ethylene terephthalate) fabric.

Protective coating (of the adhesive matrix containing buprenorphine): poly (ethylene terephthalate) foil, siliconized and aluminum coated on one side.


06.2 Incompatibility

Not relevant.


06.3 Period of validity

3 years.


06.4 Special precautions for storage

No special storage precautions.


06.5 Nature of the immediate packaging and contents of the package

Container type:

Sealed sachet, consisting of an identical top and bottom layer in heat-sealable laminate, comprising (from the outside to the inside) paper, low density polyethylene, aluminum and poly- (acrylic-co-ethylene) acid. (= surlyn)

Packaging:

Packs of 3, 5, 10, 30 individually sealed transdermal patches.

Not all pack sizes may be marketed.


06.6 Instructions for use and handling

Unused medicines and waste derived from such medicines must be disposed of in accordance with local regulations

07.0 MARKETING AUTHORIZATION HOLDER

GRÜNENTHAL ITALIA S.r.l. - Via Carlo Bo, 11 - 20143 Milan

08.0 MARKETING AUTHORIZATION NUMBER

3 transdermal patches 35 mcg / h - A.I.C. n. 035568017 / M

5 transdermal patches 35 mcg / h - A.I.C. n. 035568029 / M

10 transdermal patches 35 mcg / h - A.I.C. n. 035568031 / M

3 transdermal patches 52.5 mcg / h - A.I.C. n. 035568043 / M

5 transdermal patches 52.5 mcg / h - A.I.C. n. 035568056 / M

10 transdermal patches 52.5 mcg / h - A.I.C. n. 035568068 / M

3 transdermal patches 70 mcg / h - A.I.C. n. 035568070 / M

5 transdermal patches 70 mcg / h - A.I.C. n. 035568082 / M

10 transdermal patches 70 mcg / h - A.I.C. n. 035568094 / M

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

Date of first authorization: April 18, 2003

Date of last renewal: October 24, 2007

10.0 DATE OF REVISION OF THE TEXT

December 2014

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

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