FENTANYL - GENERIC DRUG - PACKAGE LEAFLET - LEAFLETS

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Fentanyl - Generic Drug - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Fentanyl

Fentanyl Zentiva 25 micrograms / h transdermal patch
Fentanyl Zentiva 50 micrograms / h transdermal patch
Fentanyl Zentiva 75 micrograms / h transdermal patch
Fentanyl Zentiva 100 micrograms / h transdermal patch

Why is Fentanyl used - Generic drug? What is it for?

The name of the medicine is Fentanyl Zentiva transdermal patch. In this leaflet it will be called Fentanyl Zentiva or just patch. The patch helps relieve severe and persistent pain.

Fentanyl Zentiva transdermal patch contains a medicine called fentanyl. Fentanyl belongs to a group of powerful pain relievers called opiates.

The medicine passes slowly from the patch to the body through the skin.

Contraindications When Fentanyl should not be used - Generic drug

Do not use Fentanyl Zentiva transdermal patch if

you are allergic to fentanyl or any of the other ingredients of this medicine listed in section 6;
the pain he suffers from is short-lived; - If your central nervous system (brain and spinal cord) is severely compromised, for example due to brain trauma;
if you have difficulty breathing (slower and weaker breathing) and feel unusually sleepy.

Do not use this medicine if any of the above conditions apply to you or your child. If you are not sure ask your doctor or pharmacist before using Fentanyl Zentiva.

Precautions for use What you need to know before taking Fentanyl - Generic drug

What you need to know before you use Fentanyl Zentiva transdermal patch

Fentanyl Zentiva transdermal patch can be used in children from 2 years of age who have previously used opioid pain relievers.

If your child has been prescribed the patch, the term "yours" below should be understood as "your child".

Talk to your doctor or pharmacist before using Fentanyl Zentiva. Fentanyl Zentiva is a medicinal product that is life-threatening for children.

This also applies to unused transdermal patches. Please note that the form of this medicinal product may be attractive to a child and this can lead to a fatal outcome in some cases.

Fentanyl Zentiva may have side effects in people who do not routinely use prescribed opioid medicines.

Interactions Which drugs or foods can modify the effect of Fentanyl - Generic drug

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

In particular, tell your doctor or pharmacist if you are using:

Other pain medications such as other opioid pain relievers (brupenorphine, nalbuphine or pentazocine)
Medicines that help you sleep
Medicines that help you calm down (tranquilizers) and medicines for mental disorders
Medicines to relax the muscles
Some medicines used to treat depression (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine)
Some medicines used to treat depression (called MAOIs). You should not use Fentanyl Zentiva for 14 days after stopping these medicines
Nefazodone, a medicine used to treat depression
Some antihistamines (especially those that can make you sleepy)
Some antibiotics used to treat infections, such as erythromycin, clarithromycin, or troleandomycin
Medicines used to treat fungal infections, such as itraconazole, ketoconazole, fluconazole or voriconazole
Medicines used to treat HIV infections, such as ritonavir or nelfinavir
Medicines used to treat irregular heartbeats, such as amiodarone, diltiazem or verapamil
Rifampicin (to treat tuberculosis)
Some medicines used to treat epilepsy (such as carbamazepine, phenobarbital or phenytoin).

Tell your doctor if you are using certain medicines to treat depression, known as Serotonia Reuptake Inhibitors (SSRIs), Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) or MAO inhibitors. Your doctor needs to know the use of these medicines as concomitant use of Fentanyl may increase the risk of developing serotonin syndrome, a potentially life-threatening condition.

Your doctor knows which medicines are safe while using Fentanyl Zentiva. You may need to be closely monitored if you are taking any of these types of medicines listed above or if you have stopped taking certain types of medicines listed above. as this may affect the dosage of Fentanyl you need.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using Fentanyl Zentiva.

Surgery or clinical examinations

If you are planning to administer an anesthetic, tell your doctor or dentist that you are using Fentanyl Zentiva.

Fentanyl Zentiva transdermal patch with food, drink and alcohol

Don't drink alcohol unless you have talked to your doctor first. Fentanyl Zentiva can make you sleepy or breathe much slower. Drinking alcohol can make these effects worse.

Warnings It is important to know that:

Transfer of the patch to another person

The patch should only be used on the skin of people for whom it has been prescribed by their doctor. There have been reports of accidental adhesion of a patch to a family member of a user due to close contact or sharing of the same bed. Sticking the patch to another person (especially a child) can cause an overdose. If the patch sticks to another person's skin, remove the patch immediately and contact your doctor.

As with other strong pain relievers, Fentanyl Zentiva can cause drowsiness, and slower or weaker breathing. Very rarely, these breathing difficulties can be life-threatening or fatal in people who have never used strong morphine-related pain relievers (such as Fentanyl Zentiva) or morphine itself. If you or your partner or caregiver notice that you or your child are breathing much more slowly or weakly then:
- Remove the patch
- Contact your doctor or go directly to the nearest hospital
- Move and talk as much as possible
If you experience fever while applying Fentanyl Zentiva, talk to your doctor as this can affect the way the medicine passes through the skin.
Do not expose the patch to direct heat such as heating pads, hot water bottles, electric blankets, beds with heated water mattresses, heat or tanning lamps, intense sun, prolonged hot baths, sauna, or swimming pool with hot water. affect the absorption of the medicine through the skin.
Check with your doctor or pharmacist before using this medicine if you have or have ever had:
- Lung or breathing problems
- Problems with your heart, blood pressure or blood volume, liver or kidney
- Brain tumors
- Persistent headaches or brain injuries

Your doctor may need to check you more carefully

If you are very ill, very thin or elderly, you may be more sensitive to the effects of the patch
If you have a condition where the muscles are weak or fatigue easily, known as myasthenia gravis, talk to your doctor or pharmacist before taking Fentanyl Zentiva.
Like many other strong pain relievers, repeated use of the patches can lead to drug tolerance or development of dependence on the drug.
Talk to your doctor if you have abused or been addicted to alcohol, prescription medications, or illegal drugs
Fentanyl Zentiva can cause constipation, talk to your doctor or pharmacist who will tell you how to prevent constipation.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using Fentanyl Zentiva.

Children and adolescents

Fentanyl Zentiva should not be used in children less than 2 years of age.

Fentanyl Zentiva should not be used in children who have not previously been treated with strong pain relievers such as morphine.

Other types of patches

There are other types of fentanyl transdermal patches available, but they are not exactly the same. If the patch looks different than what you have used previously, talk to your doctor or pharmacist before using it.

Pregnancy and breastfeeding

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 have been reports of babies born having withdrawal effects after the mother used Fentanyl for a long period of time during pregnancy. Fentanyl Zentiva should not be used during childbirth as the medicine may affect the baby's breathing. Do not breast-feed while taking Fentanyl Zentiva. You should not breast-feed for 3 days after removing the Fentanyl Zentiva patch. This is because small amounts of the medicine can pass into breast milk.

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

Driving and using machines

Fentanyl Zentiva can make you sleepy. If it occurs, do not drive or use any tools or machinery.

Dosage and method of use How to use Fentanyl - Generic drug: Dosage

Always use this medicine always exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.

Use and replacement of patches

There is enough medicine in each patch for at least 3 days (72 hours)
You must always change the patch on the third day, unless your doctor tells you to do otherwise
Always remove the old patch before applying a new one
Always change your patch at the same time of day every 3 days (72 hours)
If you are using more than one patch, change all patches at the same time
Make a note of the day, date and time you apply the patch to remember when you need to change it
The following table shows you which day of the week to change the patch:

Apply the patch on Change the patch at the same time on Monday Thursday Tuesday Friday Wednesday Saturday Thursday Sunday Friday Monday Saturday Tuesday Sunday Wednesday

Where to apply the patch

Adults

Apply the patch to the flat surface of the child's upper body or arm
Always apply the patch to the upper back to make it difficult for your child to touch or remove it
Check very often that the patch remains attached to the skin
It is important that your child does not remove the patch and put it in the mouth as it could be life-threatening or even fatal
It may take some time for the patch to be fully effective. Therefore, your child may need an additional pain reliever until the patch is effective. Your doctor will inform you if this is necessary.
Children should be closely monitored up to 48 hours after:
- The application of the first patch
- The application of a high-dose patch

For you or your child, do not put the patch on:

The same area twice in a row
Sensitive areas of the skin that are in motion, cut skin, blemishes or other skin imperfections
Skin with a lot of hair. If there are hairs do not shave it (shaving can irritate the skin), instead cut the hair as close to the skin as possible.

It takes several days before applying the patch to the same area of skin.

Apply the patch on

Phase 1: skin preparation

Be sure your skin is completely dry, clean and cool before applying the patch on top
If you need to cleanse your skin, use cold water only
Do not use soap or other cleansers, creams, foams, oils or talc before applying the patch
Do not stick the patch directly on the skin after a hot bath or shower

Step 2: opening the sachet

Each patch is sealed in its own sachet
Tear or cut to open the sachet
Gently cut or tear the edge of the sachet completely (if using scissors, cut as close as possible to the edge of the sachet to avoid damaging the patch
Grasp both sides to open the sachet and pull
Take the patch and use it immediately
Keep the sachet empty to dispose of the used patch later
Use each patch only once
Do not take the patch out of its sachet until you are ready to use it
Check the patch for damage
Do not use the patch if it has been divided, cut or looks damaged
Never cut or divide the patch

Step 3: Peel off and press

make sure the patch will be covered by loose clothing and not stuck under a tight or elastic band
carefully peel off one half of the plastic backing away from the center of the patch. Try not to touch the sticky side of the patch
press the sticky part of the patch to the skin
Remove the other part of the backing and press the entire patch onto the skin with the palm of your hand
Hold it for at least 30 seconds. Make sure it is glued well, especially the margins.

Step 4: Disposal of the patch

Immediately after removing the patch, fold it back on itself in half so that the adhesive applied side closes on itself
Place the patch in its original sachet and dispose of it in household waste
As used patches contain some medicine which may be dangerous for children, keep used patches out of the reach and sight of children.

Step 5: washing

Wash your hands with clean water afterwards. Learn more about Fentanyl Zentiva patches How quickly the patch works
It can take up to 1 day for the first patch to work completely
Your doctor may give you a second pain reliever for the first day or more
After that, the patch should help you relieve pain continuously so that you can stop taking other pain relievers. However, your doctor may still prescribe another pain reliever from time to time.

If you forget to change your patch

If you forget, change the patch as soon as you remember and make a note of the day and time. Change the patch again after 3 days (72 hours) as usual.
If you are very late in changing your patch, you should speak to your doctor as you may need an additional pain reliever, but do not put on an extra patch.

If a patch falls off

If a patch falls off before it's time to change it, stick a new one on immediately and make a note of the day and time. Use a new area of skin on:
- The upper part of his body or arms
- Your baby's upper back
Leave it for another 3 days (72 hours) before changing it for another patch as usual
If your patches keep falling off, talk to your doctor, nurse or pharmacist.

If the patch sticks to another person

Use the patch only on the skin of the person for whom it was prescribed
Make sure the patch does not come off and stick to another person or child especially while sharing a bed or in close contact
If a patch accidentally sticks to another person, remove it immediately and call your doctor.

How long should the patch be used for?

Fentanyl Zentiva patches are for long lasting pain. Your doctor will tell you how long to use it.

If the pain gets worse

If the pain gets worse while using these patches, your doctor may prescribe a higher strength patch, or give you an additional pain reliever (or both).
If an increase in the patch strength does not work, your doctor may decide to stop therapy.

If you want to stop using the patches

Talk to your doctor before you stop using these patches
If you have been using them for some time, your body may have gotten used to it. Stopping suddenly can make you feel sick
If you stop using the patches, do not start it again without first asking your doctor. You may need a patch with a different strength when you start again.

Daily activities while using the patches

The patches are water resistant
You can shower or bathe while wearing the patch, but do not rub on the patch
If your doctor agrees, you can do gymnastics or sports while applying the patch
You can swim while applying the patch but:
- Do not use swimming pools with hot water
- Do not put an elastic or tight band over the patch
Do not expose the patch to direct heat sources such as heating pads, hot water bottles, electric blankets, heated water beds, heat or tanning lamps, intense sun, prolonged hot baths, or saunas. These can affect the absorption of the medicine through the skin.

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

Overdose What to do if you have taken an overdose of Fentanyl - Generic Medication

If you have applied more than one patch or the strength of the patch is wrong, remove the patch and contact your doctor or go to the nearest hospital. Signs of an overdose include difficulty in breathing or shallow breathing, tiredness, excessive sleepiness, inability to think clearly, walk or speak normally, and feel faint, lightheaded, or confused.

Side Effects What are the side effects of Fentanyl - Generic Drug

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

Remove the patch and contact your doctor or go to the nearest hospital immediately if you notice or suspect any of the effects listed below. You may need urgent medical treatment.

If you feel unusually sleepy, breathe slower or weaker than usual. Very rarely these breathing difficulties can be life-threatening or even fatal especially in patients who have never used strong opioid pain relievers (such as fentanyl or morphine) before. If you or your partner or caregiver notice that you or your baby are breathing more slowly or weakly, follow the instructions above and keep moving and talk as much as possible.
Sudden swelling of the face or throat, severe irritation, redness or blistering of the skin. These can be signs of a severe allergic reaction. This only occurs in a small number of people.
Convulsions, seizures.These effects may affect up to 1 in 100 people.
Reduced consciousness or loss of consciousness, these effects may affect up to 1 in 100 people.

The following side effects have been reported

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

Feeling sick (nausea), or being sick (vomiting), constipation
Dizziness, sleepiness, or not being able to sleep
Headache

Common (may affect up to 1 in 10 people)

Allergic reactions
Noticing that you have an unusual heartbeat (also called palpitations), fast heartbeat
High blood pressure - Loss of appetite or dry mouth
Sedation, feeling nervous, worried or depressed
Confusion, hallucinations (seeing or hearing things that are not there)
Tingling sensation, tremor, feeling lightheaded
Muscle spasms
Stomach pain, indigestion, difficulty urinating
Diarrhea
Feeling cold, sweating excessively
General feeling of malaise, tiredness, weakness
Swelling of the hands, ankles or feet
Itchy skin, rash or red skin

Uncommon (may affect up to 1 in 100 people)

Flu-like symptoms
Low heart rate
Low blood pressure
Decreased sensitivity, especially of the skin
Blurred vision
Bluish tint of the skin
Feeling agitated, disoriented, excited or unusually carefree
Loss of memory, difficulty speaking
Eczema and / or other skin disorders including dermatitis in the patch application area
Sexual dysfunctions
Complete obstruction of the intestine
Muscle contractions
Fever, altered body temperature
Drug withdrawal effects (such as getting sick, feeling sick, diarrhea, anxiety, or chills)

Rare side effects (may affect up to 1 in 1000 people)

Blurred vision due to narrowing of the pupils
Hiccup
Partial obstruction of the small or large intestine
Irregular heartbeats
Dilation of blood vessels

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

Painful swelling - Loss of coordination and balance
Lazy eye
Bladder pain, reduced passage of urine compared to normal during the day

The following side effects have been reported in clinical trials in children (up to 18 years of age):

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

Headache
Feeling or being sick
Constipation, diarrhea
Itching

Common side effects (may affect up to 1 in 10 people)

Allergic reactions
Loss of appetite, stomach pain
Difficulty sleeping, sleepiness, tiredness, feeling weak
Feeling worried or depressed, hallucinating (seeing or hearing things that aren't there) dizziness
Tremor, decreased sensation especially of the skin
Dry mouth
Rash, excessive sweating, redness of the skin
Muscle spasms
Difficulty passing urine
Swelling of the hands, ankles or feet
Skin reactions in the patch application area

Uncommon side effects (may affect up to 1 in 100 people)

Confusion
Tingling sensation
Decrease in the size of the pupils
Feeling dizzy
Bluish discoloration of the skin, eczema and / or other skin disorders including dermatitis in the patch application area
Drug withdrawal effects (such as getting sick, feeling sick, diarrhea, anxiety or chills) flu-like symptoms

If you experience any of these side effects, talk to your doctor, nurse or pharmacist.

Skin rash, itching or sweating (may affect up to 1 in 10 people). You may notice a slight rash, redness or itching of the skin in the patch application area. This is usually mild and resolves after the patch is removed. If this does not happen, or if the patch is very irritating to your skin, please tell your doctor.

There have been reports of withdrawal effects in newborn babies following use of Fentanyl by the mother for a long time during pregnancy.

Like many different powerful pain relievers, repeated use of the patches can lead to drug tolerance or addiction.

If any of the side effects occur, please tell your doctor, nurse or pharmacist.

If you switch from a different pain reliever to Fentanyl Zentiva patches, effects such as malaise, feeling sick, diarrhea, anxiety or chills may occur. Tell your doctor if you notice any of these effects.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. 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, even after using them. High quantities of the active ingredient remain in the transdermal patches even after their use.

Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

Do not store above 30 ° C.

Handling of the patch

Used patches should be folded in such a way that the sticky part of the patch adheres to itself and must then be safely discarded. Accidental exposure of used and unused patches can cause fatal outcome especially in children. Unused patches should be returned to the pharmacy (hospital).

Other_information "> Other information

What Fentanyl Zentiva contains

The active ingredient is fentanyl

Fentanyl Zentiva 25 micrograms / h transdermal patch

Each patch releases 25 micrograms of fentanyl per hour. Each 7.5 cm2 patch contains 4.125 mg of fentanyl.

Fentanyl Zentiva 50 micrograms / h transdermal patch

Each patch releases 50 micrograms of fentanyl per hour. Each patch of 15 cm2 contains 8.25 mg of fentanyl.

Fentanyl Zentiva 75 micrograms / h transdermal patch

Each patch releases 75 micrograms of fentanyl per hour. Each patch of 22.5 cm2 contains 12.375 mg of fentanyl.

Fentanyl Zentiva 100 micrograms / h transdermal patch

Each patch releases 100 micrograms of fentanyl per hour. Each 30 cm2 patch contains 16.5 mg of fentanyl.

The other ingredients are: Adhesive layer: Polyacrylate adhesive layer. Backing film: Polypropylene sheet, blue printing ink.

Release membrane: Polyethylene terephthalate (siliconized) sheet.

What Fentanyl Zentiva transdermal patch looks like and contents of the pack

Fentanyl Zentiva transdermal patch is a transparent transdermal patch with an adhesive surface through which it can adhere to the skin. The transdermal patches have a blue print indicating the strength.

Fentanyl Zentiva transdermal patch is available in packs of 3, 5, 10 or 20 transdermal patches.

Not all pack sizes may be marketed.

NOTE

It is not possible to achieve all required strengths with Fentanyl Zentiva transdermal patch. There are other fentanyl patches available that allow you to achieve these different dosages.

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.

More information on Fentanyl - Generic drug 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 the 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 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 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 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

FENTANYL ZENTIVA TRANSDERMAL PATCH

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

Fentanyl Zentiva 25 mcg / h transdermal patch

Every patch releases 25 mcg of fentanyl per hour. Each 7.5 cm² patch contains 4.125 mg of fentanyl.

Fentanyl Zentiva 50 mcg / h transdermal patch

Every patch releases 50 mcg of fentanyl per hour. Each patch of 15 cm² contains 8.25 mg of fentanyl.

Fentanyl Zentiva 75 mcg / h transdermal patch

Every patch releases 75 mcg of fentanyl per hour. Each patch of 22.5 cm² contains 12.375 mg of fentanyl.

Fentanyl Zentiva 100 mcg / h transdermal patch

Every patch releases 100 mcg of fentanyl per hour. Each patch of 30 cm² contains 16.5 mg of fentanyl.

For the full list of excipients, see section 6.1

03.0 PHARMACEUTICAL FORM -

Transdermal patch

Fentanyl Zentiva 25 mcg / h transdermal patch

Clear and colorless patch with blue print on the protective film: "fentanyl 25 mcg / h".

Fentanyl Zentiva 50 mcg / h transdermal patch

Clear and colorless patch with blue print on the protective film: "fentanyl 50 mcg / h".

Fentanyl Zentiva 75 mcg / h transdermal patch

Clear and colorless patch with blue print on the protective film: "fentanyl 75 mcg / h".

Fentanyl Zentiva 100 mcg / h transdermal patch

Clear and colorless patch with blue print on the protective film: "fentanyl 100 mcg / h".

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Fentanyl Zentiva transdermal patch is indicated:

Adults:

• In severe chronic pain that can only be adequately managed with opioid analgesics

Children:

- in the long-term management of severe chronic pain in children from 2 years of age on opioid therapy.

04.2 Posology and method of administration -

For transdermal use

Fentanyl Zentiva transdermal patch should be applied to non-irritated, non-irradiated skin on a smooth surface of the trunk or upper arm. In young children, the upper back is the most suitable place to apply the patch, to minimize the possibility of the child removing it. A hairless area should be selected. If this is not possible, the hairs on the application area must be trimmed (not shaved) before application. If the area chosen for the application of Fentanyl Zentiva transdermal patch needs to be cleaned before applying the patch, it should be cleaned with water. Soaps, oils, lotions or any other agent that may irritate the skin or alter its characteristics should not be used. The skin must be completely dry before applying the patch. Patches should be checked before use. Patches that are cut, split, or otherwise damaged should not be used.

The Fentanyl Zentiva transdermal patch must be removed from the protective wrapping by first folding the notch (located near the arrowhead on the sachet label) and then carefully tearing off the wrapping material. If scissors are used to open the wrap, the cut should be made close to the sealed edge so as not to damage the patch inside.

Fentanyl Zentiva transdermal patch should be applied immediately after removal from the sealed pouch. Avoid touching the sticky side of the patch. After removing both parts of the protective layer, the transdermal patch should be pressed firmly onto the application site with the palm of your hand for about 30 seconds, making sure that contact is complete, especially around the edges, then wash your hands with clean water.

Fentanyl Zentiva transdermal patch should remain on for 72 consecutive hours. A new patch should then be applied to a different skin area after the previous transdermal patch has been removed. It may take several days before a new patch can be applied to the same skin area.

The need for continued treatment should be assessed at regular intervals.

Selection of the starting dose

The appropriate starting dose of Fentanyl Zentiva transdermal patch should be based on the patient's current opioid use.

It is recommended that Fentanyl Zentiva transdermal patch be used in patients who have demonstrated opioid tolerance. Other factors that need to be considered are the patient's current general condition and medical condition, including body mass, age and degree of debilitation as well as the degree of opioid tolerance.

Adults

Opioid-tolerant patients

For conversion of opioid-tolerant patients from oral or parenteral opioids to Fentanyl Zentiva transdermal patch please refer to the table of conversion of equianalgesic potency shown below. Dosage can, accordingly, be titrated up or down, if required, in increments of either 12.5 or 25 mcg / h to achieve the lowest appropriate dose of Fentanyl Zentiva transdermal patch based on response. and the dose of additional analgesic needed.

Opiate-naïve patients

In opioid-naive patients, the normal starting dose of Fentanyl should not exceed 25 mcg / h.

Clinical experience with Fentanyl Zentiva transdermal patch is limited in patients naive to opiates. In situations where Fentanyl Zentiva transdermal patch therapy is considered appropriate in opioid-naive patients, it is recommended that these patients are initially treated with low-dose immediate-release opioids (e.g. morphine, hydromorphine, oxycodone, tramadol and codeine) to achieve an equianalgesic dosage of Fentanyl Zentiva transdermal patch with a release rate of 25 mcg / h. Patients may then switch to treatment with the Fentanyl Zentiva 25 mcg / h transdermal patch. Thereafter, the dose can be titrated up or down as needed in 12.5 or 25 mcg / h increments to reach the lowest appropriate dose of Fentanyl Zentiva transdermal patch based on response and need for additional analgesics (see also section 4.4).

Equianalgesic power conversion

• Calculate the analgesic dose required within the previous 24 hours.

• Convert this amount to the oral dose of morphine equivalent using table 1. All oral and intramuscular (IM) doses are considered equivalent to 10 mg of morphine IM for analgesic effect.

• To derive the Fentanyl Zentiva transdermal patch strength corresponding to the 24 hour calculation of the equianalgesic morphine dose, use the dose conversion in Table 2 or Table 3 as follows:

Table 2 is for adult patients for whom an oral dose of morphine or another immediate-release opioid has been defined over several weeks and who require an opioid rotation (conversion ratio of oral morphine to transdermal fentanyl approximately equal to 150: 1).

Table 3 is for highly opioid-tolerant adult patients who have a long-term stable and well-tolerated opioid regimen, and who require opioid rotation (conversion ratio of oral morphine to transdermal fentanyl approximately equal to 100: 1 ).

Tables 2 and 3 should not be used to switch from transdermal fentanyl to another opioid treatment.

Table 1: conversion of equianalgesic potency

Name of the substance Equianalgesic dose (mg) IM * oral morphine 10 30-40 (taken in repeated doses) ** Hydromorphone 1,5 7,5 methadone 10 20 oxycodone 15 30 levorphanol 2 4 oxymorphone 1 10 (rectal) diamorphone 5 60 pethidine 75 --- codeine 130 200 buprenorphine 0,4 0.8 (sublingual)

* Based on single dose studies in which an IM dose of each listed substance was compared with morphine to define relative potency. Oral doses are those recommended when switching from parenteral to oral route.

** Oral potency / IM potency for morphine is based on clinical experience in patients with chronic pain.

References: adapted from the Foley KM. The treatment of cancer pain. NEJM 1985; 313: 84-95, and updates.

Table 2: Recommended Initial Dosage of Fentanyl Zentiva Transdermal Patch Based on Daily Oral Morphine Dosage¹ (for patients stabilized on oral morphine or immediate-release opioids for several weeks and requiring an opioid rotation)

Morphine orally over 24 hours (mg / day) Fentanyl Zentiva transdermal patch (mcg / h) 25 135 - 224 50 225 - 314 75 315 - 404 100 405 - 494 125 495 - 584 150 585 - 674 175 675 - 764 200 765 - 854 225 855 - 944 250 945 - 1034 275 1035 - 1124 300

¹ In clinical studies these daily oral dose ranges of morphine were used as the basis for conversion to fentanyl transdermal patch.

Table 3: Recommended starting dosage of Fentali Zentiva transdermal patch based on daily oral morphine dosage (for patients with stable and well-tolerated opioid therapy for long periods and who need opioid rotation)

Oral dose of morphine in 24 hours (mg / day) Dosage of Fentanyl Zentiva transdermal patch (mcg / h) 12,5 45-89 25 90-149 50 150-209 75 210-269 100 270-329 125 330-389 150 390-449 175 450-509 200 510-569 225 570-629 250 630-689 275 690-749 300

Previous analgesic therapy should be withdrawn gradually from the time of the first patch application until analgesic efficacy with Fentanyl Zentiva transdermal patch is achieved. For both potent opioid-naive and opioid-tolerant patients, the initial assessment of "Analgesic effect of Fentanyl Zentiva transdermal patch should not be performed for 24 hours after patch application" due to the gradual increase in serum concentrations of fentanyl up to that point.

Dose titration and maintenance therapy

Fentanyl Zentiva transdermal patch should be replaced every 72 hours. The dose should be individually titrated until a balance between analgesic effect and tolerability is achieved. In patients who have experienced a marked decrease within 48-72 hours after application, replacement of fentanyl may be necessary after 48 hours. If analgesia is insufficient at the end of the first application period, the dose can be increased. Dose adjustment, when necessary, should normally be performed by the following titration steps from 25 mcg / h up to 75 mcg / h: 25 mcg / h, 37 mcg / h, 50 mcg / h, 62.5 mcg / h and 75 mcg / h; Thereafter, dose adjustments should normally be made in increments of 25 mcg / h, although the additional analgesic effects needed (oral morphine 90 mg / day ≈ Fentanyl Zentiva transdermal patch 25 mcg / h) and the extent of the patient's pain. More than one Fentanyl Zentiva transdermal patch may be used to achieve the desired dose. Patients may periodically need additional doses of a short-acting pain reliever for transient painful exacerbations. When the dose of Fentanyl Zentiva transdermal patch exceeds 300 mcg / h, the use of additional or alternative methods of analgesia should be considered.

Discontinuation of Fentanyl Zentiva transdermal patch therapy

If discontinuation of Fentanyl Zentiva transdermal patch therapy is required, its replacement with other opioid drugs should be gradual, starting with a low dose and slowly increasing. This is because the concentration of fentanyl gradually decreases after removal of Fentanyl Zentiva, and it takes 17 hours or more for serum fentanyl concentrations to decrease by 50% (see section 5.2). As a general rule, discontinuation of opioid-type analgesia should be gradual to prevent the onset of withdrawal symptoms.

Opioid withdrawal symptoms (see section 4.8) may occur in some patients after conversion or dose adjustment.

Table 2 and Table 3 should not be used for conversion from Fentanyl Zentiva transdermal patch to other therapies to avoid overestimation of the new analgesic dose and potentially lead to overdose.

Use in elderly patients

Data from intravenous studies with fentanyl suggest that elderly patients may have reduced clearance, a prolonged half-life, and may be more sensitive to the drug than younger patients. Elderly, cachectic, or debilitated patients should be carefully monitored for regarding signs of fentanyl toxicity and, if necessary, the dose should be reduced (see section 5.2).

Pediatric population

Children aged 16 and over : follow the dosages established for adults.

Children between the ages of 2 and 16 :

Fentanyl Zentiva transdermal patch should only be given to opioid-tolerant pediatric patients (ages 2-16 years) who are already receiving at least the equivalent of 30 mg morphine per day orally. For conversion of pediatric patients from treatment. with oral opioids Fentanyl Zentiva transdermal patch refer to Table 4 "Recommended dose of Fentanyl Zentiva transdermal patch based on daily oral morphine dose".

Table 4: Recommended dose of the Fentanyl Zentiva transdermal patch based on the oral daily dose of morphine ¹

Morphine orally over 24 hours (mg / day) Fentanyl Zentiva transdermal patch (mcg / h) For pediatric patients² 30-44 12 45-134 25

¹ In clinical trials these daily dose ranges of oral morphine were used as a starting point for switching to the fentanyl transdermal patch.

² Conversion to Fentanyl Zentiva transdermal patch doses greater than 25 mcg / h is the same for adults and pediatric patients.

For children who have received morphine doses greater than 90 mg oral daily, only limited information is available from clinical studies. In pediatric studies the required dose of fentanyl transdermal patch was calculated according to the following conversion: 30 mg to 44 mg of oral morphine per day or its equivalent opioid dose was replaced with a 12-gauge fentanyl transdermal patch. that the conversion table only applies to children who need to switch from oral morphine (or its equivalent) to Fentanyl Zentiva patches. The established conversion should not be used to switch from Fentanyl Zentiva transdermal patch to other opioids due to the overdose that may occur.

The analgesic effect of the first dose of the Fentanyl Zentiva patch is not optimal during the first 24 hours. Then during the first 12 hours after switching to the fentanyl transdermal patch, the patient should take the previous analgesics in the usual dose. Over the next 12 hours. these analgesics should be administered according to clinical need.

Since the maximum peak of fentanyl is achieved after 12 or 24 hours of treatment, it is recommended that the patient be monitored for adverse events, including hypoventilation, for at least 48 hours after initiation of Fentanyl transdermal patch therapy or until titration of the dose (see also section 4.4).

Dose titration and maintenance

If the analgesic effect of Fentanyl Zentiva transdermal patch is insufficient, an additional dose of morphine or other short-acting opioid should be administered. Depending on the need for an additional analgesic effect and the child's pain status, it may be decided to increase the dose. The dose is adjusted using 12 mcg / h at a time.

04.3 Contraindications -

- Hypersensitivity to the active substance or to any of the other excipients listed in section 6.1.

- Fentanyl Zentiva transdermal patch is a prolonged-release formulation indicated for the treatment of chronic untreatable pain and is contraindicated in acute or postoperative pain, because it is not possible to titrate the dosage during short-term use and the possibility of severe respiratory depression or life-threatening.

- Severe impairment of the central nervous system.

- Severe respiratory depression

04.4 Special warnings and appropriate precautions for use -

PATIENTS WHO HAVE MANIFESTED SERIOUS ADVERSE EVENTS SHOULD BE MONITORED FOR AT LEAST 24 HOURS OR MORE "AFTER REMOVAL OF FENTANIL ZENTIVA TRANSDERMAL PATCH DUE TO CLINICAL SYMPTOMS BECAUSE THE SIERIC CONCENTRATION OF FENTANIL DECREASES BY INTERVALLOUS AND ABOUT 50% AFTER 13-22) (see paragraph 5.2).

Keep Fentanyl Zentiva transdermal patch out of the reach and sight of children at all times before and after use.

Fentanyl Zentiva transdermal patch should not be cut. A patch that is split, cut, or damaged in any way should not be used.

The use of Fentanyl Zentiva in opioid-naive patients has been associated with very rare cases of major and / or fatal respiratory depression when used as initial opioid therapy. The potential risk of severe or potentially life-threatening hypoventilation exists even if used the lowest dose of Fentanyl Zentiva in the initial treatment of opioid-naïve patients It is recommended that Fentanyl Zentiva be used in patients who have demonstrated opioid tolerance (see section 4.2).

When Fentanyl Zentiva is administered for chronic untreatable pain that will require prolonged treatment, it is strictly recommended that the physician define the treatment goals for pain relief and functional improvement in accordance with local guidelines for pain management. The physician and the patient must agree on the interruption of treatment if these objectives are not achieved.

Respiratory depression

As with all potent opioids, severe respiratory depression may occur in some patients with Fentanyl Zentiva transdermal patch; patients should be monitored in case of onset of this effect. Respiratory depression may persist even after the patch is removed. The incidence of respiratory depression increases with increasing fentanyl dosage (see section 4.9). CNS-active drugs may increase respiratory depression (see section 4.5).

Serotonin syndrome

Caution is advised when Fentanyl Zentiva is co-administered with medicinal products that affect the serotonergic neurotransmitter system.

The development of potentially life-threatening serotonin syndrome may occur with concomitant use of serotonergic drugs such as serotonin reuptake inhibitors (SSRIs) and with serotonin and norepinephrine reuptake inhibitors (SNRIs) and with drugs that impair metabolism serotonin (including monoamine oxidase inhibitors (MAOIs)) This can occur at the recommended dose.

Serotonin syndrome may include changes in mental status (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, unstable blood pressure, hyperthermia), neuromuscular abnormalities (e.g. hyperreflexia, incoordination, rigidity) and / or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).

If serotonin syndrome is suspected, "discontinuation of Fentanyl Zentiva should be considered.

Chronic lung disease

Fentanyl, like other opiates, may cause more serious adverse reactions in patients with chronic obstructive diseases or other lung diseases; in such patients, opioids can reduce respiratory rate and increase airway resistance.

Drug addiction and potential for abuse

Tolerance, physical dependence and psychological dependence can develop with repeated administration of opiates such as fentanyl. Iatrogenic dependence following opioid administration is rare. Patients with a previous history of drug dependence / alcohol abuse are more at risk of developing dependence and abuse during opioid treatment. Patients with increased risk of opioid abuse can still be treated appropriately with modified-release opioid formulations; however, these patients will require monitoring for telltale signs of misuse, abuse or dependence. Abuse of fentanyl can occur in the same way as with other opioid agonists. Abuse or intentional misuse of Fentanyl Zentiva transdermal patch can lead to ovedoses and / or death.

Increased intracranial pressure

Fentanyl Zentiva transdermal patch should be used with caution in patients who are particularly sensitive to the intracranial effects of CO2 retention, such as those with obvious signs of increased intracranial pressure, impaired consciousness or in a coma.

Fentanyl Zentiva transdermal patch should be used with caution in patients with brain tumors.

Heart disease

Opiates can cause hypotension, especially in patients with acute hypovolaemia. Pre-existing symptomatic hypotension and / or hypovolaemia should be corrected before starting treatment with fentanyl transdermal patches. Fentanyl can induce bradycardia and Fentanyl Zentiva should therefore be administered with caution to patients suffering from bradyarrhythmias.

Hepatic impairment

As fentanyl is metabolised to inactive metabolites in the liver, hepatic impairment may delay its elimination. If patients with hepatic impairment use Fentanyl Zentiva they should be carefully monitored for symptoms of fentanyl toxicity and the Fentanyl dose should be reduced if necessary (see section 5.2).

Renal impairment

Less than 10% of fentanyl is excreted unchanged by the kidneys and, unlike morphine, there are no known active metabolites excreted by the kidney. If transdermal fentanyl is to be administered to patients with renal impairment, they should be closely monitored for signs of fentanyl toxicity and the dose should be reduced if necessary (see section 5.2).

Patients with fever / exposed to external heat sources

A pharmacokinetic model suggests that fentanyl serum concentrations can increase by about one third if body temperature rises to 40 ° C.

Therefore patients with fever should be monitored for opioid side effects and the dosage of Fentanyl transdermal patch should be adjusted if necessary.

There is a potential temperature-dependent increase in the amount of fentanyl released from the transdermal system which can lead to possible overdose and death.

A clinical pharmacology study conducted in healthy adult subjects showed that the application of heat to the Fentanyl Zentiva transdermal system increased the mean fentanyl AUC values by 120% and the mean C values by 61%.

All patients should be advised to avoid exposure of the Fentanyl Zentiva transdermal patch application site to direct external heat sources, such as heating pads, hot water bottles, electric blankets, heated water beds, heat or tanning lamps. , intense sun, prolonged hot baths, sauna, or swimming pool with hot water while the patch is applied as there is a potential temperature-dependent increase in the release of fentanyl from the patch.

Interactions with other medicinal products

Interactions with CYP3A4 inhibitors

Concomitant use of fentanyl with cytochrome P450 3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandromycin, clarithromycin, erythromycin, nelfinavir, nefazodone, verapamil, diltiazole and plasma concentrations) may lead to increased plasma concentrations of fentanyl which may cause an increase or prolongation of both the therapeutic effects and the undesirable effects which may cause severe respiratory depression. Particular patient care and careful observation are appropriate in this situation. Therefore concomitant use of the fentanyl transdermal patch with cytochrome P4503A4 inhibitors is not recommended unless the patient is closely monitored. Patients, especially those receiving fentanyl and CYP3A4 inhibitors, should be monitored for signs of depression. and if necessary a dose adjustment should be made.

Accidental exposure due to patch transfer

Accidental transfer of a fentanyl patch to the skin of a non-patch wearer (particularly a child), while sharing a bed or in close physical contact with a patch wearer, can lead to an opiate overdose for a non-carrier. Patches. Patients should be advised that if an accidental patch transfer occurs, the transferred patch should be removed immediately from the skin of the non-patch wearer (see section 4.9).

Elderly patients

Data from intravenous studies with fentanyl suggest that elderly patients may have reduced clearance and a prolonged drug half-life and may be more sensitive to the drug than young patients. If elderly patients receive Fentanyl Zentiva, they should be kept. under careful monitoring for signs of fentanyl toxicity and, if necessary, the dose reduced (see section 5.2).

Gastrointestinal system

Opiates increase muscle tone and decrease the propulsive contractions of the smooth cells of the gastrointestinal tract. The result is a prolongation of the transit time which may be responsible for the constipating effect of fentanyl. Patients should be informed about measures to prevent constipation and the use of laxatives as prophylaxis should be considered. Extreme caution should be used in patients with chronic constipation. If paralytic ileus is present or suspected, treatment with Fentanyl Zentiva should be used. be interrupted.

Pediatric patients

Fentanyl must not be administered transdermally to opioid-naive pediatric patients (see section 4.2).The potential for severe or life-threatening hypoventilation exists regardless of the dose of transdermal fentanyl administered (see Table 2 in section 4.2).

Transdermal fentanyl has not been studied in children younger than 2 years of age, so it should not be used in these children. Fentanyl Zentiva transdermal patch should only be given to children 2 years of age or older who tolerate opioids (see section 4.2).

In order to prevent accidental ingestion by children, use caution when selecting the application area of the Fentanyl Zentiva transdermal patch (see section 4.2) and carefully monitor the adhesion of the patch.

Discarding the patch

The used patch may contain significant residues of the active ingredient. So after the removal of the used patch, the patch should be folded firmly in half with the adhesive layer inside so that the adhesive layer is not external, and discarded safely and out of reach of children according to the instructions in the box.

Feeding time

Since fentanyl is excreted in breast milk, breastfeeding should be discontinued during treatment with Fentanyl Zentiva (see also section 4.6).

Patients with myasthenia gravis

Non-epileptic (myo) clonic reactions may occur. Caution is required when treating patients with myasthenia gravis.

Concomitant use of agonist / antagonist combinations

The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended (see also section 4.5).

04.5 Interactions with other medicinal products and other forms of interaction -

Concomitant use of other central nervous system depressants, including opioids, sedatives, anxiolytics, hypnotics, general anesthetics, phenothiazines, tranquilizers, antipsychotics, musculoskeletal relaxants, sedative antihistamines, and alcoholic beverages may produce additional depressing effects; hypoventilation may occur. , hypotension and profound sedation, coma or death. Concomitant use of any of the above medicines therefore requires special care and observation.

Fentanyl, a medicinal product with high clearance, is rapidly and extensively metabolised by CYP3A4 mainly. Concomitant use of fentanyl transdermal patch with cytochrome P450 3A4 (CYP3A4) inhibitors (eg ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandromycin, clarithromycin, erythromycin, nelemfinavir, increased plasma concentrations of fentanyl which may increase or prolong both therapeutic and adverse effects and may cause severe respiratory depression. Special patient care and observation is indicated in this situation. The concomitant use of CYP3A4 inhibitors and transdermal fentanyl not is recommended unless there is close patient monitoring (see section 4.4).

Concomitant use with CYP3A4 inducers (eg rifampicin, carbamazepine, phenobarbital, phenytoin) may lead to decreased plasma concentrations of fentanyl and decreased therapeutic effect. This may require an adjustment of the transdermal fentanyl dose. After discontinuation of treatment with a CYP3A4 inducer, the effect of the inducer gradually decreases and may result in increased plasma concentrations of fentanyl which may increase or prolong both therapeutic and adverse effects and may cause severe respiratory depression. In this situation careful monitoring and dose adjustment should be made if necessary.

Concomitant use with agonist / antagonist combinations

The concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended. These substances have a high affinity for opioid receptors with a relatively low intrinsic activity and therefore partially antagonize the analgesic effect of fentanyl and may induce withdrawal symptoms in patients. opioid dependent (see also section 4.4).

Monoamine Oxidase Inhibitors (MAO-Inhibitors)

The concomitant use of fentanyl in patients receiving MAOIs is not recommended.

Serious and unexpected reactions with MAO inhibitors have been reported, including potentiation of opioid effects or potentiation of serotonergic effects.

Therefore fentanyl should not be used in the first 14 days after stopping treatment with MAO-Inhibitors.

Serotonergic medicines

Co-administration of fentanyl transdermal patch with serotonergic medicinal products, such as Serotonin Reuptake Inhibitors (SSRIs) or Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) or Monoamine Oxidase Inhibitors (MAOIs), may potentially increase the risk of a serotonin syndrome. life-threatening.

04.6 Pregnancy and breastfeeding -

Insufficient data are available for the use of Fentanyl Zentiva in pregnant women. Studies in animals have shown some reproductive toxicity (see section 5.3). The potential risk to humans is unknown although in other formulations, fentanyl administered as an intravenous anesthetic may cross the placenta in the early stages of human pregnancy.

Neonatal abstinence syndrome has been reported in newborn babies whose mothers chronically used Fentanyl Zentiva during pregnancy.

Fentanyl should not be used during pregnancy unless clearly needed.

Therefore, the use of fentanyl during delivery is not recommended as it should not be used for the management of acute or postoperative pain (see sections 4.3 and 4.4).

Furthermore, as fentanyl passes through the placenta, the use of Fentanyl Zentiva during delivery could lead to respiratory depression in the newborn.

Fentanyl is excreted in breast milk and can cause sedation and respiratory depression in the breastfed infant. Breastfeeding should therefore be discontinued during treatment with Fentanyl and for at least 72 hours after removal of the transdermal patch.

04.7 Effects on ability to drive and use machines -

Fentanyl Zentiva can impair the mental and / or physical abilities required to perform potentially dangerous actions such as driving cars or operating machinery.

04.8 Undesirable effects -

The safety of fentanyl was evaluated in 1854 adult and pediatric subjects who participated in 11 clinical trials (double-blind fentanyl [placebo or control drug] and / or open-label fentanyl [no control or control drug] used in the management of chronic malignant or non-malignant pain.

These patients received at least 1 dose of fentanyl and were evaluated for safety. Based on a pool of safety data from these clinical trials, the most commonly reported adverse drug reactions (ADRs) (e.g. ≥ 10% incidence) (with% incidence) were: nausea (35.7 %), vomiting (23.2%), constipation (23.1%), somnolence (15.0%), dizziness (13.1%), headache and insomnia (10.2%).

The ADRs reported with the use of fentanyl from these clinical trials, including the adverse reactions indicated above and those from post marketing experience are listed in Table A below.

The frequency categories shown use the following convention.

Very common (≥1 / 10),

Common (≥1 / 100,

Uncommon (≥1 / 1,000 to

Rare (≥1 / 10,000,

Very rare (

Not known (frequency cannot be estimated from the available clinical data)

Table A: Adverse Drug Reactions in Adult and Pediatric Subjects System and organ classification Frequency category Adverse drug reactions Disorders of the immune system common Hypersensitivity Not known Anaphylactic shock, anaphylactic reaction, anaphylactoid reaction Metabolism and nutrition disorders common Anorexia Psychiatric disorders Very common Insomnia, sleepiness common Sedation, depression, anxiety, confusion, hallucinations Uncommon Agitation, disorientation, euphoria Nervous system disorders Very common Dizziness, headache common Tremor, paraesthesia, Uncommon Hypoesthesia, convulsion (including clonic convulsion and grand mal convulsion), amnesia, speech disturbances Very rare Ataxia Eye disorders Rare Miosis Very rare Amblyopia Ear and labyrinth disorders common Vertigo Cardiac pathologies common Palpitations, tachycardia Uncommon Bradycardia, cyanosis Rare Arrhythmia Vascular pathologies common Hypertension Uncommon Hypotension Rare Vasodilation Respiratory, thoracic and mediastinal disorders common Dyspnea, Uncommon Respiratory depression, respiratory distress Rare Apnea, hypoventilation Not known Bradypnea Gastrointestinal disorders Very common Nausea, vomiting, constipation common Diarrhea, dry mouth, abdominal pain, upper abdominal pain, dyspepsia. Uncommon Ileus Rare Subileo, sob Very rare Painful flatulence Skin and subcutaneous tissue disorders common Hyperhidrosis, pruritus, rash, erythema Uncommon Eczema, allergic dermatitis, skin diseases, dermatitis, contact dermatitis Musculoskeletal and connective tissue disorders common Muscle spasms Uncommon Muscle contractions Renal and urinary disorders common Urinary retention Very rare Oliguria, cystalgia Diseases of the reproductive system and breast Uncommon Erectile dysfunction, sexual dysfunction General disorders and administration site conditions common Fatigue, peripheral edema, asthenia, malaise, cold sensation Uncommon Application site reactions, application site hypersensitivity, flu-like syndrome, sensation of body temperature change, drug withdrawal syndrome, pyrexia Rare Application site dermatitis, application site eczema

Pediatric subjects

The adverse event profile in children and adolescents treated with fentanyl transdermal patches is similar to that seen in adults. No risks have been identified in the pediatric population other than those expected with the use of opioids to relieve pain associated with serious illness, and there does not appear to be a specific risk for the pediatric population associated with the use of the fentanyl transdermal patch in children of 2 years, when used according to the instructions. Very common adverse events reported in pediatric clinical trials were fever, vomiting and nausea.

The safety of fentanyl transdermal patch was evaluated in 289 pediatric subjects (

Based on pooled clinical data from these 3 clinical trials in pediatric subjects, the most common (i.e. ≥ 10% incidence) adverse drug reactions (ADRs) were (% incidence): vomiting (33.9%), nausea ( 23.5%), headache (16.3%), constipation (13.5%), diarrhea (12.8%), and itching (12.8%). Table B shows all ADRs reported with fentanyl transdermal patch in pediatric subjects in the mentioned clinical studies.

The ADRs in Table B for the pediatric population were assigned frequency categories using the same convention used for Table A.

Table B: Adverse Drug Rations in Clinical Studies in Pediatric Subjects System and organ classification Frequency category Adverse drug reactions Disorders of the immune system common Hypersensitivity Metabolism and nutrition disorders common Anorexia Psychiatric disorders common Insomnia, Somnolence, Anxiety, Depression, Hallucinations Uncommon Confusional state Nervous system disorders Very common Headache common Dizziness, tremors, hypoesthesia Uncommon Paresthesia Eye disorders Uncommon Miosis Ear and labyrinth disorders Uncommon Vertigo Cardiac pathologies Uncommon Cyanosis Respiratory, thoracic and mediastinal disorders common Respiratory depression Gastrointestinal disorders Very common Vomiting, Nausea, constipation, Diarrhea common Abdominal pain, Abdominal pain upper, dry mouth Skin and subcutaneous tissue disorders Very common Itching common Eruption, Hyperhidrosis, Erythema Uncommon Contact dermatitis, Skin disorders, Allergic dermatitis, Eczema Musculoskeletal and connective tissue disorders common Muscle spasms Renal and urinary disorders common Urinary retention General disorders and administration site conditions common Peripheral edema, Fatigue, Application site reactions, Asthenia Uncommon Drug withdrawal syndrome, flu-like illness

As with other opioid analgesics, tolerance, physical dependence and psychological dependence may develop with repeated use of the fentanyl transdermal patch (see section 4.4).

Opioid withdrawal symptoms (such as nausea, vomiting, diarrhea, anxiety, chills) are possible in some patients after conversion from their previous opioid analgesic to fentanyl transdermal patch or when therapy is stopped abruptly (see section 4.2).

There have been reports of newborn babies with withdrawal syndrome if mothers used fentanyl trandermal patch during pregnancy (see section 4.6).

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 www.agenziafarmaco.gov.it/it/responsabili.

04.9 Overdose -

Symptoms

The manifestations of fentanyl overdose are an extension of its pharmacological actions, the most severe effect being respiratory depression.

Treatment

Immediate countermeasures should be taken to treat respiratory depression, including removal of the patch and physical or verbal stimulation of the patient. These actions can be followed by the administration of a specific opiate antagonist such as naloxone.

Respiratory depression caused by an overdose may last beyond the action of the opioid antagonist.

The interval between doses of the intravenous antagonist must be carefully considered because of the possible re-narcotization after removal of the patch; it may be necessary to administer naloxone in repeated doses or by continuous infusion.

Canceling the narcotic effect can result in exacerbation of pain and release of catecholamines.

If the clinical situation justifies it, a patency of the airways must be established and maintained, possibly via the oropharyngeal route or with an endotracheal cannula, and oxygen must be administered and the assistance or control of respiration must proceed, as needed. An "adequate body temperature and" appropriate hydration should be maintained.

Should severe or persistent hypotension arise, the possibility of hypovolemia should be considered and the condition should be managed with adequate parenteral fluids.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

Pharmacotherapeutic group: opiates; phenylpiperidine derivatives

ATC code: N02AB03

Fentanyl is an opioid analgesic with high affinity for m-opioid receptors.

Pediatric patients

The safety of transdermal fentanyl was evaluated in three open studies involving 289 chronic pain pediatric patients aged 2 to 18 years, of which 66 children were aged 2 to 6 years. . In these studies, morphine administered orally in doses of 30 mg to 44 mg per day was replaced with a patch with a release rate of 12 mcg / h.

Initial doses of 25 mcg / h or higher have been used in 181 patients who were previously on daily opioid therapy of at least 45 mg oral morphine dose.

05.2 "Pharmacokinetic properties -

Adults

Fentanyl Zentiva transdermal patch provides continuous systemic release of fentanyl for the administration period of more than 72 hours. Fentanyl is released at a relatively constant rate. The concentration gradient between the matrix and the lowest concentration in the skin determines the release of the drug.

After the first application of Fentanyl Zentiva transdermal patch, serum concentrations of fentanyl gradually increase, generally leveling out between 12 and 24 hours and remaining relatively constant for the remainder of the 72 hours of application. The serum concentrations of fentanyl achieved are proportional to the size of the fentanyl patch. With the second 72-hour application, steady state serum concentration is achieved, which is maintained during subsequent applications of a patch of the same size.

A pharmacokinetic model has suggested that fentanyl serum concentrations may increase by 14% (range 0-26%) if a new patch is applied after 24 hours rather than after the recommended 72-hour application.

Distribution

Fentanyl is approximately 84% bound to plasma proteins.

Biotransformation

Fentanyl has a high clearance and is rapidly and extensively metabolised primarily in the liver by CYP3A4. The major metabolite, norfentanyl, is not active. The skin does not appear to metabolise transdermally administered fentanyl.This was determined in human keratinocyte cells examined and in clinical studies in which 92% of the dose delivered by the system was as unchanged fentanyl which was found in the systemic circulation.

Elimination

After removal of Fentanyl Zentiva transdermal patch, serum concentrations of fentanyl gradually decrease, decreasing by approximately 50% in approximately 17 hours (range 13-22) following a 24 hour application. After a 72-hour application, the mean half-life interval was 20-27 hours. Continuous transdermal absorption of fentanyl results in a slower disappearance of the drug from the serum than after intravenous infusion, where the "Apparent half-life is approximately 7 hours (range 3-12 hours). Fentanyl is primarily metabolised by the liver. Within 72 hours of intravenous administration of fentanyl, approximately 75% of the fentanyl dose is excreted in the urine, mostly under form of metabolites, with less than 10% in the form of unchanged active substance. Approximately 9% of the dose is recovered in the faeces, mainly as metabolites. The mean values of the unbound fraction of fentanyl in plasma are estimated to be between 13 and 21%.

Special populations

Senior citizens

Data from intravenous studies with fentanyl suggest that elderly patients may have decreased clearance and prolonged half-life, and may be more sensitive to the drug than younger patients. In a study conducted with fentanyl transdermal patch, subjects Healthy elderly had fentanyl pharmacokinetic parameters that did not differ significantly from those of healthy young subjects, although peak serum concentrations tended to be lower and mean half-life values were prolonged to approximately 34 hours. Elderly patients should be carefully observed for signs of fentanyl toxicity and the dose reduced if necessary (see section 4.2).

Pediatric patients

The clearance (l / h / kg) in pediatric patients corrected for body weight appears to be 82% higher in children between 2 and 5 years of age and 25% higher in children between 6 and 10 years of age. age compared to children 11-16 years of age, who are likely to have the same clearance as adults This result was obtained by taking into consideration the recommended dose determined for pediatric patients.

Hepatic impairment

In a study conducted with patients with liver cirrhosis, the pharmacokinetics of a single application of 50 micrograms / h of fentanyl transdermal patch was evaluated. Although tmax and t1 / 2 did not change, the mean plasma AUC C values were increased by approximately 35% and 73%, respectively, in these patients. Patients with hepatic impairment should be carefully observed for symptoms of toxicity and reduced fentanyl patch dose if necessary (see section 4.4).

Renal impairment

Data obtained from studies with intravenously administered fentanyl in renal transplant patients suggest that fentanyl clearance may be reduced in this patient population. If patients with renal impairment receive fentanyl transdermal patch, they should be carefully observed for signs of fentanyl toxicity and the dose reduced if necessary (see section 4.4).

05.3 Preclinical safety data -

In vitro studies have shown, like other opioid analgesics, mutagenic effects in cultured mammalian cells only at cytotoxic and metabolically activated concentrations. Fentanyl shows no evidence of mutagenicity when evaluated in in vivo studies in rodents and bacterial methods.

In a two-year carcinogenicity study in rats, fentanyl was not associated with an increase in the incidence of tumors at the subcutaneous dose of up to 33 mcg / kg / day in males or 100 mcg / kg / day in females. Exposure overall achieved (AUC0-24 h) in these studies was maximum tolerated plasma concentration in rats.

Fentail was evaluated for effects on fetal development in rats and rabbits. Some examinations on female rats showed reduced fertility as well as embryonic mortality and transient developmental delay.

These findings were related to maternal toxicity and not to a direct effect of the drug on embryonic development. These changes were observed at steady-state plasma concentrations equivalent to (Css, rat / Css, human = 1.1) of those observed in the clinic following the use of 100 mcg / h patch. No effect was observed. in rabbits, where a maximum plasma concentration of 6.6 times the steady-state plasma concentration of fentanyl was achieved in humans. The daily exposure ratio (AUC4-24, rabbit / human AUC 0-24 = 1.1) was equivalent to those observed in the clinic following the use of 100 mcg / h of patch. There is no evidence of teratogenic effects.

06.0 PHARMACEUTICAL INFORMATION -

06.1 Excipients -

Adhesive layer:

polyacrylic adhesive layer

Reinforcement film:

polypropylene sheet, blue printing ink

Release membrane:

polyethylene terephthalate sheet (siliconized)

06.2 Incompatibility "-

Not relevant

06.3 Period of validity "-

36 months

06.4 Special precautions for storage -

Do not store above 30 ° C.

06.5 Nature of the immediate packaging and contents of the package -

Each transdermal patch is individually packaged in a sachet. The laminated sheet is composed of the following layers (from the outside to the inside): coated paper, low density polyethylene sheet, aluminum foil, Surlyn (copolymer of thermoplastic ethylene-methacrylic acid).

Fentanyl Zentiva 25 mcg / h transdermal patch

Fentanyl Zentiva 50 mcg / h transdermal patch

Fentanyl Zentiva 75 mcg / h transdermal patch

Fentanyl Zentiva 100 mcg / h transdermal patch

Pack containing 3, 5, 10, 20 transdermal patches

Pack containing 7 transdermal patches

Pack containing 14 transdermal patches

Not all pack sizes may be marketed.

06.6 Instructions for use and handling -

Refer to section 4.2 for instructions on how to apply the patch. There are no safety and pharmacokinetic data for other application sites.

After removal, the used patch should be folded in half with the adhesive side inwards so that the adhesive layer is not exposed, placed in the original sachet and disposed of safely and out of the reach of children.

Wash your hands with water only after applying or removing the patch.