Active ingredients: Fentanyl
MATRIFEN 12 micrograms / hour transdermal patches
MATRIFEN 25 micrograms / hour transdermal patches
MATRIFEN 50 micrograms / hour transdermal patches
MATRIFEN 75 micrograms / hour transdermal patches
MATRIFEN 100 micrograms / hour transdermal patches
Indications Why is Matrifen used? What is it for?
Matrifen transdermal patch contains the active substance fentanyl. Fentanyl belongs to a group of powerful pain-relieving drugs called opioids and works by blocking pain signals coming to the brain. Fentanyl is gradually released from the patch, passes through the skin and into the body.
Matrifen is used for:
Adults: long-lasting pain that can only be adequately treated with strong analgesics.
Children: Long-term treatment of severe chronic pain in children aged 2 years and over who are already on opioid therapy.
One transdermal patch relieves pain for 72 hours (3 days).
Matrifen patches can be used for children between 2 and 16 years of age who have previously used opioid pain relievers to treat pain. If the patches were prescribed for your child, the term "you" is listed below. , should be interpreted as "his son".
Contraindications When Matrifen should not be used
Do not use Matrifen:
- If you are allergic to fentanyl or any of the other ingredients of this medicine (listed in section 6).
- If you have short-term pain (for example, after surgery).
- If you have severe breathing difficulties.
- If your central nervous system (e.g. your brain or spinal cord) is severely compromised, for example from brain damage.
Precautions for use What you need to know before taking Matrifen
ATTENTION
Matrifen is a medicine that can be life-threatening for children.
This also applies to transdermal patches that have already been used.
Keep in mind that the appearance of this medicine may be tempting for children and this could be deadly.
Matrifen can have life-threatening side effects in people who do not routinely use prescribed opioid drugs.
Transfer of the patch to another person
The patch should only be used on the skin of patients for whom it has been prescribed by their doctor. There are some cases where a patch has been accidentally attached to a family member following close physical contact or sharing the same bed with a patient wearing the patch. Transferring a patch to a person who is not using it (particularly a child) can lead to an overdose.
Should a patch transfer to the skin of another person occur, the patch should be removed immediately and a doctor consulted.
Before you start using Matrifen, tell your doctor if you have any of the following conditions:
- asthma, respiratory depression (reduced ability to breathe) or any lung disease
- irregular heartbeat
- low blood pressure
- impaired liver function
- impaired renal function
- a recent head injury or brain disease (e.g. a tumor)
- if you have a disease that causes muscle fatigue and weakness (myasthenia gravis).
- Matrifen can cause constipation, ask your doctor or pharmacist to know how to prevent it.
Tell your doctor if you get a fever during treatment, as an increase in body temperature can cause the medicine to pass through the skin too much. For the same reason, you must avoid exposing the patch applied to the skin to direct heat, as in the case of using heating pads, electric blankets, hot water bags, heated water beds, saunas, sun lamps, solariums, hot baths or thermal baths with hydromassage with hot water.
You can shower while wearing the patch and you are allowed to stay outdoors in the sun, provided you protect the patch with a layer of fabric during hot summer days.
The transdermal patch must not be divided or cut.
If you use Matrifen for a prolonged period you may develop less pain relief (tolerance to the drug) and physical or mental dependence. However, this is rarely seen during the treatment of pain of neoplastic origin.
Elderly patients should be monitored when using Matrifen.
Children
Matrifen should not be given to children under 2 years of age or to children who have not previously been treated with potent pain relievers such as morphine.
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.
Interactions Which drugs or foods can modify the effect of Matrifen
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.
Some medicines can affect Matrifen or be affected by it. Some of these are:
- Pain relievers (e.g. opioids such as morphine and codeine) as well as pentazocine, nalbuphine and buprenorphine
- medicines for anxiety and tranquilizers, sleep medicines and general anesthetics, phenothiazines (medicines for psychosis)
- Sedative antihistamines (some allergy or car sickness medicines cause drowsiness)
- Medicines used to relax muscles
- some medicines used to treat epilepsy (such as carbamazepine, phenobarbital or phenytoin)
- Rifampicin (to treat tuberculosis)
- Ritonavir and nelfinavir (against the HIV virus).
- Itraconazole, ketoconazole, fluconazole and voriconazole (against fungal infections).
- MAO inhibitors (eg moclobemide for depression or selegiline for Parkinson's disease) You must not take Matrifen for 14 days after stopping these medicines.
- Some medicines used to treat depression (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine)
- Macrolide antibiotics (e.g. erythromycin, troleandomycin and clarithromycin)
- Nefazodone (against depression)
- Medicines that treat an irregular heartbeat, such as amiodarone, diltiazem or verapamil.
Matrifen with alcohol
Do not drink alcohol while using Matrifen patches as this may increase the risk of serious side effects and cause difficulty in breathing, a drop in blood pressure, severe sleepiness and coma.
Warnings It is important to know that:
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.
Safe use of Matrifen during pregnancy has not been established. Fentanyl should not be used during childbirth as fentanyl can cause breathing difficulties in the newborn. Fentanyl is excreted in breast milk and can cause sedation and respiratory depression (reduced breathing capacity) in breastfed babies. Breastfeeding should therefore be stopped for at least 72 hours after removing the patch. Do not use Matrifen if you are pregnant or breastfeeding unless your doctor has considered that the risk of not using it outweighs. the risk of taking Matrifen. Prolonged treatment during pregnancy may cause withdrawal symptoms in the newborn. If you become pregnant while taking Matrifen, consult your doctor.
Driving and using machines
Fentanyl transdermal patch may cause drowsiness; if this happens, do not drive a car, do not use tools or machinery.
Dose, Method and Time of Administration How to use Matrifen: Posology
Always use this medicine exactly as your doctor has told you. If you are unsure, ask your doctor or pharmacist.
The dose is determined by your doctor, who will adapt it to your individual needs. Always follow your doctor's instructions.
The recommended dose is one patch every three days. Depending on your reaction, the dose of drug contained in the patch or the number of patches may need to be adjusted. The effect is obtained within 24 hours of applying the first patch. Do not stop the treatment without consulting your doctor.
Apply and change the patch
Each patch contains enough medication to last 3 days (72 hours). You should always change the patch on the third day, unless your doctor tells you to do otherwise. Always remove the used patch before applying a new one. Always change the 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, so you will remember when it is time to change it. The following table will show you which day of the week you need to change the patch:
Where to apply the patch
Adults
- Apply the patch to a flat surface on the upper body or arm
Children
- Always apply the patch to the upper back, so that it is more difficult for the child to touch or remove it
- Even so, check often that the patch remains stuck to the skin
- It is important that the child does not remove the patch and does not put it in the mouth, as this could be life-threatening or even fatal.
- It may take some time for the patch to be fully effective. Your child may therefore need additional pain reliever until then. Your doctor will advise you if necessary.
- Children should be monitored very carefully for 48 hours after:
- the application of the first patch
- when a higher strength patch is used
For you and your child, do not apply the patch:
- In the same area twice in a row
- On sensitive areas, often subject to movement, skin with small wounds, spots or other skin irregularities
- Skin with a lot of hair. If so, don't shave them (shaving irritates the skin). Instead, the hair should be cut as close to the skin as possible with scissors.
It will take several days before you can apply a new patch to the same area of skin.
Apply the patch
Step 1 Prepare the skin
- Make sure your skin is perfectly dry, clean and cool before applying the patch on it.
- If you need to cleanse your skin, use only cold water
- Do not use soap or any other cleanser, creams, lotions, oils or talc before applying the patch
- Do not apply the patch after a hot bath or shower.
Step 2 Open the sachet
- Each patch is sealed in a sachet
- Tear or cut the sachet near the sealed edge, as shown by the arrow
- Gently open the flaps of the sachet completely (if using scissors, cut along the sealed edge of the sachet to avoid damaging the patch)
- Do not use the patch if it has been dismembered, cut or if it looks damaged
- Never divide or cut the patch.
Step 3 Detach and press
- Make sure that the patch is then covered with a loose dress and not stuck under a tight or elasticated bandage.
- Carefully peel off one half of the glossy protective film starting from the center of the patch. Try not to touch the sticky side of the patch.
- Press the sticky side of the patch onto your skin.
- Remove the other part of the protective film and press the entire patch onto the skin with the palm of your hand
- Keep it pressed for at least 30 seconds. Make sure it adheres well to the skin, especially along the edges.
Step 4 Disposal of the patch
- Immediately after removing the patch, fold it tightly in half on itself, so that the sticky side closes back on itself.
- Put the folded patch in its original sachet and throw it in the drug collection bin at pharmacies
- As used patches still contain some medicine which can be dangerous for children and even fatal, keep used patches out of the sight and reach of children.
Step 5 Washing
- Then wash your hands with clean water.
How fast does the patch work?
- It can take up to a day for the first patch to work fully
- Your doctor may additionally give you painkillers to use for the first or more days
- The patch will then relieve your pain continuously so you can stop taking any other pain relievers. However, your doctor may still prescribe a pain reliever from time to time.
If the patch sticks to another person (see also section 2)
- Use the patch only on the skin of the person for whom it was prescribed
- Make sure the patch does not come off and adheres to another person or child, especially if you share a bed or are very close
- If the patch accidentally sticks to another person, peel it off immediately and call your doctor. How long should you use the patch? Matrifen patches are for long-lasting pain. Your doctor will tell you how long to use them.
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 additional pain relievers (or both).
- If an increase in patch strength does not work, your doctor may decide to discontinue patch therapy.
If you forget to use or change the patch:
You should change the patch at the same time every three days if you have not been instructed otherwise by your doctor. If you forget to do this, change it as soon as you remember.
If you change your patch very late you should contact your doctor as you may need some additional painkillers, but do not put on another patch.
If you stop using Matrifen
- 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 them suddenly could make her feel sick
- If you stop using the patches, do not start using them again without asking your doctor first. 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 where the patch is.
- If your doctor agrees, you can do gymnastics or sports while wearing the patch
- You can also swim while applying the patch, but:
- do not use heated whirlpools
- do not put a tight or elastic band over the patch
- Do not expose the patch to direct heat sources such as fan heaters, hot water bottles, electric blankets, heated water beds, heat or tanning beds, 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, pharmacist or nurse.
Overdose What to do if you have taken too much Matrifen
If you have attached more patches than prescribed, remove the patches and contact your doctor or hospital immediately asking their opinion on the risk.
The most common sign of overdose is a reduced ability to breathe. Symptoms consist of slowed or weakened breathing. If this happens, remove the patches and contact a doctor immediately. While waiting for the doctor, the person should be kept awake by talking to him or shaking him from time to time.
Other signs or symptoms of overdose are sleepiness, drop in body temperature, slow heart rate, drop in blood pressure, deep sedation, loss of muscle coordination, constriction of the pupils (small pupils) and seizures.
Signs of an overdose include difficulty in breathing or shallow breathing, excessive sleepiness, inability to think clearly, walk or speak normally, and feel faint, lightheaded, or confused.
Side Effects What are the side effects of Matrifen
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the following serious side effects occur, remove the patch and contact your doctor or go to a hospital immediately. 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 potent opioid pain relievers (such as Matrifen or morphine) before. If you or your partner or caregiver notice that you or your baby are breathing more slowly or weakly, keep moving and talk as much as possible
- Sudden swelling of the face or throat, severe irritation, redness or blistering of the skin. These could be signs of a severe allergic reaction. This only happens in a small number of people.
- Convulsions, seizures. These effects occur in less than 1 in 100 people.
- Decreased consciousness or loss of consciousness. These effects occur in less than 1 in 100 people.
Other side effects
Very common: may affect more than 1 in 10 people):
- drowsiness,
- dizziness,
- headache,
- feeling sick, vomiting
- constipation.
Common: may affect up to 1 in 10 people
- hypersensitivity,
- loss of appetite, difficulty falling asleep,
- confusion, depression, anxiety, hallucinations,
- chills,
- stinging sensation on the skin (paraesthesia),
- dizziness,
- irregular heartbeat, fast heartbeat,
- high blood pressure,
- diarrhea, dry mouth, gastric changes,
- sweating,
- itching, rash, redness,
- muscle spasm,
- difficulty urinating,
- tiredness,
- swelling of the hands, ankles or feet,
- weakness,
- feeling sick, feeling cold.
Uncommon: may affect up to 1 in 100 people:
- Memory loss,
- feeling agitated, disoriented, excited, or unusually carefree
- feeling of decreased sensitivity especially on the skin,
- slow heart rate
- bluish discoloration of the skin,
- low blood pressure,
- bowel obstruction,
- eczema and / or other skin conditions including skin reactions at the patch application site,
- muscle twitching,
- sexual dysfunctions,
- fever, flu syndrome, changes in body temperature, withdrawal effects (vomiting, retching, diarrhea, anxiety or chills).
Rare: may affect up to 1 in 1,000 people):
- shrunken pupils,
- partial obstruction of the small or large intestine.
Additional side effects in children and adolescents
Very common: may affect more than 1 in 10 people
- headache,
- feeling unwell,
- constipation, diarrhea,
- itch.
Common: 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 are not there),
- dizziness
- tremor, decreased sensation especially of the skin,
- dry mouth,
- rash, excessive sweating, redness of the skin,
- muscle spasms,
- difficulty urinating,
- swelling of the hands, ankles or feet,
- skin reactions in the patch application area.
Uncommon: may affect up to 1 in 100 people
- confusion,
- tingling sensation,
- shrunken 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 nausea, feeling sick, diarrhea, anxiety or chills), flu-like symptoms.
Other adverse reactions
Reduced analgesic action (tolerance), physical and psychological dependence may develop during long-term use of fentanyl.
Opioid withdrawal symptoms (such as: nausea, vomiting, diarrhea, anxiety and chills) may occur in some patients who switch from their previous opioid analgesics to Matrifen transdermal patch.
Skin rashes, itching or sweating (affects less than 1 in 10 people). You may notice a rash, redness or mild 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.
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. Side effects can also be reported 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 unused and used patches out of the sight and reach of children. High amounts of the drug remain in the transdermal patches even after use.
Do not use Matrifen after the expiry date which is stated on the pack. The expiry date refers to the last day of the month.
This medicinal product does not require any special storage conditions.
Handle the patch
Accidental exposure to unused or used patches, especially in children, can lead to a fatal outcome. Used patches must be folded in half so that the sticky part closes on itself and must be disposed of safely. Unused patches should be returned to the hospital or pharmacy.
Do not dispose of any medicines via wastewater or household waste. This will help protect the environment.
Deadline "> Other information
What Matrifen transdermal patch contains
The active ingredient is: Fentanyl.
There are 5 different patch strengths (see table below)
Other components are: Dipropylene glycol, hydroxypropylcellulose, dimethicone, adhesive silicone (amino-resistant), ethylene vinyl acetate (EVA, release membrane), polyethylene terephthalate (PET, cover film), fluoropolymer coated polyester (protective film) and printing ink .
What Matrifen looks like and contents of the pack
Matrifen is a clear, rectangular patch; each patch is packaged in a heat sealed pouch made of paper, aluminum and polyacrylonitrile (PAN). The transdermal patches are printed in color with the name, active substance name and strength:
- 12 micrograms / hour patch: brown print
- 25 micrograms / hour patch: red print
- 50 micrograms / hour patch: green print
- 75 micrograms / hour patch: blue print
- 100 micrograms / hour patch: gray print
The patches are supplied in a pack containing 1, 2, 3, 4, 5, 8, 10, 16 and 20 patches.
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.
01.0 NAME OF THE MEDICINAL PRODUCT -
MATRIFEN TRANSDERMAL PATCH
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Matrifen 12 mcg / hour: Each transdermal patch contains 1.38 mg of fentanyl in a 4.2 cm² patch and releases 12 mcg / hour of fentanyl
Matrifen 25 mcg / hour: Each transdermal patch contains 2.75 mg of fentanyl in an 8.4 cm² patch and releases 25 mcg / hour of fentanyl
Matrifen 50 mcg / hour: Each transdermal patch contains 5.50 mg of fentanyl in a 16.8 cm² patch and releases 50 mcg / hour of fentanyl
Matrifen 75 mcg / hour: Each transdermal patch contains 8.25 mg of fentanyl in a 25.2 cm² patch and releases 75 mcg / hour of fentanyl
Matrifen 100 mcg / hour: Each transdermal patch contains 11.0 mg of fentanyl in a 33.6 cm² patch and releases 100 mcg / hour of fentanyl
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Transdermal patch.
Rectangular, translucent patch with a removable protective film. The protective film is wider than the patch.
The patches are marked with a color print bearing the name and dosage:
12 mcg / hour patch: brown print
25 mcg / hour patch: red print
50 mcg / hour patch: green print
75 mcg / hour patch: blue print
100 mcg / hour patch: gray print
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Adults:
Chronic severe pain, which can only be adequately treated with opioid analgesics.
Children:
Long-term treatment of severe chronic pain in children from 2 years of age already being treated with opioids.
04.2 Posology and method of administration -
Dosage
The fentanyl transdermal patches release the active ingredient within 72 hours. The release rate of fentanyl is 12, 25, 50, 75 and 100 mcg / hour and the corresponding active surface is 4.2 - 8.4 - 16.8 - 25.2 and 33.6 cm².
The required dose of fentanyl is individually adjusted and should be evaluated regularly after each administration.
Selection of starting dosage:
The fentanyl dosage level is based on previous opioid use and takes into account the possible development of tolerance, concomitant drug treatment, the patient's general state of health and the degree of disease severity.
Adults
Opioid-tolerant patients
For dosing in opioid-tolerant patients who switch from oral or parenteral treatment to treatment with Matrifen, refer to the following Equianalgesic Efficacy Conversion table. The dosage can be titrated subsequently, with increases or decreases, if required, with variations of 12 or 25 mcg / hour, in order to reach the most appropriate minimum dose of Matrifen, based on the response and further analgesic demand.
Opioid-naïve patients
The initial dosage should not exceed 12 mcg / hour when the mode of response of the painful condition to opioids is not fully known.
Clinical experience with fentanyl-based transdermal patches is limited in opioid-naive patients. If therapy with fentanyl-based transdermal patches is considered appropriate in opioid-naïve patients, it is recommended that these patients be titrated to the highest dose. low immediate-release opioids (such as morphine, hydromorphone, oxycodone, tramadol and codeine) to achieve the equianalgesic dose corresponding to the fentanyl-based transdermal patches. These patients may then be prescribed a fentanyl-based transdermal patch. The dosage may subsequently be titrated with increases or decreases, if required, with variations of 12 or 25 mcg / hour in order to reach the most appropriate minimum dose of fentanyl-based transdermal patches, based on the response and the additional analgesic requirement. (see also section 4.4 "Special warnings and precautions for use" - Opioid naive patients and non-tolerant states anza to opioids).
Conversion of Equianalgesic Efficacy
1. Calculate the analgesic dose required within the previous 24 hours.
2. Convert the resulting amount to the equianalgesic dose of oral morphine using Table 1 All the IM and oral doses in this table are considered equivalent in analgesic effect to 10 mg of IM morphine.
3. To derive the Matrifen dose corresponding to the calculated 24-hour morphine dose, use Table 2 or Dose Conversion Table 3 as specified below.
Table 2 indicates the doses for adult patients who have been on stable therapy with oral morphine or another immediate-release opioid for several weeks and who require opioid rotation (conversion ratio of oral morphine to transdermal fentanyl is approximately 150: 1).
Table 3 indicates doses for adult patients who have been on stable and well-tolerated opioid therapy for a long time and who require opioid rotation (conversion ratio of oral morphine to transdermal fentanyl is approximately 100: 1).
Tables 2 and 3 should not be used to switch from transdermal fentanyl treatment to treatment with another opioid.
Table 1. Conversion of equianalgesic of ica potency
* Based on single dose studies, where the i.m. of the mentioned agent was compared with morphine to achieve equivalent efficacy. Oral doses are those recommended when changing from parenteral to oral administration.
** The 3: 1 efficacy ratio for morphine IM / oral doses is based on a study conducted in chronic pain patients.
Table 2. Recommended starting dose of Matrifen based on oral daily morphine dose (for patients who have been on stable oral morphine or immediate-release opioid therapy for several weeks and who require an opioid rotation)
Conversion schemes are based on clinical studies. Schemes based on other studies have been found to be useful in clinical practice and can be used.
Table 3 Recommended starting dose of Matrifen based on daily oral morphine dose (for patients on long-term stable and well-tolerated opioid therapy and requiring opioid rotation)
Previous analgesic therapies should be progressively discontinued after application of the first transdermal patch until the analgesic efficacy of Matrifen is achieved. For both opioid-naïve (opioid-naive) and opioid-tolerant patients, the initial assessment of the analgesic effect of Matrifen should not be carried out before the patch has been applied for at least 24 hours since the concentrations plasma levels of fentanyl gradually increase over this period.
Dose titration and maintenance therapy
The patch should be replaced every 72 hours. The dose should be determined individually until a balance is achieved between analgesic efficacy and tolerability. In patients where there is a marked decrease in analgesic efficacy in the period from 48 to 72 hours after application it may be necessary to replace fentanyl after 48 hours. The dose of 12 mcg / hour is appropriate for dose adjustment in the " If analgesia is insufficient after the initial application period, the dose may be increased after 3 days until the desired effect is achieved in each patient. Further dose adjustments should normally be made in increments of 12 mcg / hr or 25 mcg / hr, although additional analgesics needed and the extent of the patient's pain should be taken into account. More than one patch may be used at a time for dose adjustments and for doses above 100 mcg / hour. Patients may periodically need supplemental doses of a short-acting analgesic in case of breakthrough pain. Additional or alternative methods of analgesia or alternative opioid administration should be considered when the dose of Matrifen exceeds 300 mcg / hour.
Opioid withdrawal symptoms (see section 4.8 "Undesirable effects") have been described by switching from long-term morphine to transdermal fentanyl despite adequate analgesic efficacy. In case of withdrawal symptoms it is recommended to treat them with low doses. of short-acting morphine.
Matrifen discontinuation
If it is necessary to discontinue the patch, its replacement with other opioid drugs should be gradual, starting with a low dose and gradually increasing. Fentanyl levels gradually decrease after the patch is removed; it takes at least 17 hours for the patch to decrease. serum concentration of fentanyl decreases by 50% (see section 5.2).
As a general rule, discontinuation of opioid analgesia should be gradual in order to prevent withdrawal symptoms (nausea, vomiting, diarrhea, anxiety, muscle tremors).
Tables 2 and 3 should not be used for conversion from Matrifen to other therapies to avoid overestimating the new analgesic dose with a potential risk of overdose.
Use in the elderly
Elderly or cachectic patients should be closely monitored and the dosage reduced if necessary (see section 4.4).
Use in patients with hepatic or renal impairment
Patients with impaired hepatic or renal function should be carefully observed for symptoms of overdose and the dose should possibly be reduced (see section 4.4).
Use in patients with fever
Dosage adjustments may be required in patients during febrile episodes (see section 4.4).
Use in the pediatric population
Children 16 years of age or older: Follow adult dosage
Children between the ages of 2 and 16:
Matrifen should only be given to opioid-tolerant pediatric patients (2 to 16 years of age) who are already receiving a drug at a dose of at least equivalent to 30 mg oral morphine per day. For switching pediatric patients from oral opioids to Matrifen, refer to "Conversion of equianalgesic potency of drugs" (Table 1), and "Recommended starting dose of Matrifen based on an oral daily dose of morphine" (Table 4).
Table 4: Recommended starting dose of Matrifen based on an oral daily dose of morphine¹
¹ In clinical trials these daily oral dose ranges of morphine were used as the basis for conversion to Matrifen
² Conversion to Matrifen doses greater than 25 mcg / hour is the same for both adults and pediatric patients.
There is currently little information from clinical trials about children receiving more than 90 mg of morphine per day. In pediatric studies, the required dose of fentanyl transdermal patch was calculated in the traditional way: 30 mg to 44 mg oral per day of morphine or an equivalent opioid dose was replaced by a 12 mcg / hour fentanyl patch. It should be noted that this conversion designed for children only applies to the switch from oral morphine (or its equivalent) to fentanyl patches. The studied conversion cannot be used to convert the switch from fentanyl to other opioids, as it could cause an overdose.
The analgesic effect of the first dose of Matrifen patch will not be optimal within the first 24 hours. Then, during the first 12 hours after switching to Matrifen, patients should be given their regular dose of their previous pain relievers. Over the next 12 hours, patients should be given their regular dose of their previous pain relievers. these analgesics should be administered as needed.
As fentanyl levels peak after 12 - 24 hours of treatment, it is recommended that the patient be monitored for adverse events, which may include hypoventilation, for at least 48 hours after initiating Matrifen therapy or after recovery. - dose titration (see also section 4.4 Special warnings and precautions for use).
Dose titration and maintenance
If the analgesic effect of Matrifen is insufficient, an additional dose of morphine or another short-acting opioid should be given. Depending on the increased analgesic needs and pain experienced by the child, a decision may be made to increase the dose. L " dose adjustment should be done gradually with 12 mcg / hour patches.
Method of administration
For transdermal use
Fentanyl 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 preferred application site to minimize the risk of the child removing the patch. Before applying the patch, the hairs must be trimmed (unshaven) in the application area (a "hairless" area is preferable). If the place where the patch is to be applied needs cleaning before application, this is done with running water. Soaps, oils, lotions, alcohol or any other agent that may irritate the skin or alter its characteristics should not be used. The skin must be perfectly dry before applying the patch.
Patches should be checked prior to use. Transdermal patches should not be divided or cut (see section 4.4). Cut, split or damaged patches should not be applied.
Since the transdermal patch is protected on the outside by a waterproof protective film, it is possible to wear the patch during a quick shower.
The Matrifen patch must be removed from the protective pouch by first folding the notch (located near the arrowhead on the pouch label) and then carefully tearing the pouch along the notch. If you use scissors to open the pouch, you need to cut near the sealed edge so as not to damage the patch inside.
The fentanyl transdermal patch should be applied as soon as the package is opened, avoiding touching the sticky side of the patch.
After removing the protective layer, the transdermal patch should be firmly pressed for about 30 seconds with the palm of the hand open on the application area, making sure that the contact on the application area is total, especially along the edges. Additional fixation of the transdermal patch may be required. Then wash your hands with clean water.
The fentanyl transdermal patch should be worn continuously for 72 hours, after which the transdermal patch should be replaced. A new transdermal patch should always be placed in a different area from the previous one. The same application site can only be reused after an interval of at least 7 days.
For disposal instructions, see section 6.6.
04.3 Contraindications -
Matrifen is contraindicated in patients with known hypersensitivity to fentanyl or to any of the excipients listed in section 6.1.
Acute or postoperative pain, as dose titration is not possible in short-term use and may result in a risk of severe or life-threatening hypoventilation.
Severe respiratory depression.
04.4 Special warnings and appropriate precautions for use -
Patients who have experienced serious adverse events should be monitored for 24 hours following removal of the transdermal patch as serum concentrations of fentanyl gradually decrease and are reduced by approximately 50% after 17 hours (range 13-22).
Fentanyl transdermal patches should be kept out of the sight and reach of children before and after use.
Do not cut the transdermal patches. A patch that has been split, cut or damaged in any way should not be used.
Respiratory depression
As with all other potent opioids, significant respiratory depression may occur in some patients with fentanyl transdermal patch; Patients should be observed for these effects. Respiratory depression may persist even after removal of the patch. The incidence of respiratory depression increases with increasing fentanyl dosage (see section 4.9 Overdose, related to depression CNS-active drugs may increase respiratory depression (see section 4.5 Interaction with other medicinal products and other forms of interaction).
Serotonin syndrome
Caution is advised when fentanyl transdermal patches are co-administered with drugs that affect the serotonergic systems.
The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic medicinal products such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs) and certain drugs that alter the metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]) Serotonin syndrome can occur even at recommended doses.
Serotonin syndrome may include changes in mental status (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, unstable blood pressure, hyperthermia), neuromuscular changes (e.g. hyperreflexia, motor incoordination, rigidity) and / o gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).
If serotonin syndrome is suspected, fentanyl transdermal patches should be promptly discontinued.
Chronic lung diseases
Fentanyl can cause more severe side effects in patients with chronic obstructive respiratory disease, or other lung diseases. In such patients, opioids can reduce respiratory rate and increase airway resistance.
Dependence on the drug and potential for abuse
Tolerance, physical and psychological dependence can occur in the case of repeated administration of opioids such as fentanyl. The onset of iatrogenic dependence following opioid administration is rare. Patients with a previous history of drug addiction / alcohol abuse are at increased risk of developing addiction and abuse during opioid treatment. Patients at increased risk of abuse may still be treated appropriately with modified-release opioid formulations, however these patients will need to be monitored for identification of misuse, abuse, or addiction. Fentanyl can be abused in a similar way to other opioid agonists. Intentional abuse or misuse of Matrifen can result in overdose and / or death.
Increased intracranial pressure
Matrifen should be used with caution in patients who may be particularly sensitive to the intracranial effects of CO2 retention, such as those with evidence of intracranial hypertension, impaired consciousness, or coma. Fentanyl should be used with caution in patients with brain tumors.
Heart disease
Fentanyl can cause bradycardia and should therefore be administered with caution in patients suffering from bradyarrhythmias.
Opioids can cause hypotension, especially in patients with acute hypovolaemia. In case of concomitant symptomatic hypotension and / or hypovolaemia these should be corrected before starting treatment with transdermal fentanyl patches.
Hepatic insufficiency
Because fentanyl is metabolised to inactive metabolites in the liver, liver failure may delay its elimination. If patients with hepatic impairment use transdermal fentanyl, they should be closely monitored for signs of fentanyl toxicity and the fentanyl dosage reduced if necessary (see section 5.2 Pharmacokinetic properties).
Kidney failure
Less than 10% of fentanyl is excreted unchanged by the kidneys and, unlike morphine, there are no known active metabolites eliminated by the kidney. If patients with renal insufficiency receive transdermal fentanyl these should be carefully observed for signs of fentanyl toxicity and the dosage reduced if necessary (see section 5.2 Pharmacokinetic properties).
Fever / application of external heat
A pharmacokinetic model suggests that fentanyl serum concentrations can increase by about one third if skin temperature reaches 40 ° C. Therefore, patients with fever should be monitored for opioid side effects and the dosage of fentanyl adjusted as necessary. There is a possibility that temperature-dependent increases in the release of fentanyl from the system lead to possible overdose and death. A clinical pharmacology study conducted in healthy adult subjects showed that the application of heat to a fentanyl transdermal system increased the mean AUC values of fentanyl by 120% and the mean Cmax values by 61%.
All patients should be advised that while wearing the patch, avoid exposing the fentanyl transdermal patch application site to a direct external source of heat, such as heating pads, electric blankets, hot water beds, heat lamps or tanning beds. intensive sun baths, hot water bottles, prolonged hot baths, saunas and hot water whirlpool spas because the temperature can potentially increase the release of fentanyl from the patch.
Interactions with other medicines
Interactions with CYP3A4 inhibitors:
Concomitant use of transdermal fentanyl with cytochrome P450 3A4 (CYP3A4) inhibitors (eg ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, erythromycin, nelfinavir, nefazodone, verapamil, diltiazole and plasma concentrations) may lead to increased plasma concentrations of fentanyl, which may increase or prolong both therapeutic and side effects, and may cause severe respiratory depression. Particular attention and observation of the patient is warranted in this situation. Therefore, the concomitant use of transdermal fentanyl and CYP3A4 inhibitors does not is recommended unless the patient is closely monitored. Patients, especially those taking transdermal fentanyl and CYP3A4 inhibitors, should be monitored for signs of respiratory depression and any dose adjustments should be made if necessary.
Elderly patients
Results from intravenous studies with fentanyl indicate that elderly patients may have a lower elimination capacity, a prolonged drug half-life, and may be more sensitive to the drug than younger patients. If elderly patients are treated with transdermal fentanyl , they should be closely observed for signs of fentanyl toxicity and the dosage should be reduced if necessary (see section 5.2 Pharmacokinetic properties).
Gastrointestinal tract
Opioids increase tone and decrease propulsive contractions of the smooth muscle of the gastrointestinal tract. The resulting prolongation of gastrointestinal transit time may be responsible for constipation caused by fentanyl. Patients should be informed about measures to prevent constipation and the use of laxative prophylaxis should be considered. Care should be taken in patients with chronic constipation. If paralytic ileus is known or suspected. treatment with fentanyl patches should be discontinued.
Accidental exposure by patch transfer
Accidental transfer of a fentanyl patch to the skin of a person who is not using the patch (particularly a child), while sleeping in the same bed or in close physical contact, may result in an opioid overdose for the person does not use the patch. Patients should be advised that should a patch transfer occur, the transferred patch should be removed immediately from the skin of the non-user (see section 4.9 "Overdose").
Use in pediatric patients
Matrifen must not be administered to pediatric patients who have never taken opioids (see section 4.2 Posology and method of administration). The potential for severe or life-threatening hypoventilation exists regardless of the dose of Matrifen transdermal system administered.
Fentanyl transdermal patch has not been studied in children under 2 years of age. Matrifen should only be given to children 2 years of age or older who tolerate opioids (see section 4.2 Posology and method of administration). Matrifen should not be used in children under 2 years of age.
To avoid accidental ingestion by children, use caution when choosing the application site of Matrifen (see section 4.2 Posology and method of administration) and check that the patch is well adhered.
Feeding time
Since fentanyl is excreted in breast milk, breastfeeding should be discontinued during treatment with transdermal fentanyl (see also section 4.6).
Patients with myasthenia gravis
Non-epileptic (myo) clonic reactions may occur. Exercise caution when treating patients with myasthenia gravis.
Concomitant use of agonists / antagonists
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, hypnotics, general anesthetics, phenothiazines, tranquilizers, muscle relaxants, sedative antihistamines, and alcoholic beverages may produce additive depressant effects; they may hypoventilation, hypotension and profound sedation, coma or death occur. Concomitant use of transdermal fentanyl with any of these drugs therefore requires special patient attention and observation.
Fentanyl, a high-clearance drug, is rapidly and extensively metabolised primarily by CYP3A4.
Concomitant use of transdermal fentanyl with cytochrome P450 3A4 (CYP3A4) inhibitors (eg, ritonavir, ketoconazole, itraconazole, fluconazole, voriconazole, troleandomycin, clarithromycin, nelfinavir, nefazodone, verapzemil plasma concentrations of fentanyl, which may increase or prolong both therapeutic and adverse effects, and may lead to severe respiratory depression. Particular attention and observation of the patient are appropriate in this situation. The concomitant use of transdermal fentanyl and blood inhibitors CYP3A4 is not recommended unless the patient is closely monitored (see also Special warnings and precautions for use, section 4.4).
Concomitant use of inducers of cytochrome CYP3A4 (eg rifampicin, carbamazepine, phenobarbital, phenytoin) may lead to decreased plasma concentrations of fentanyl and decreased therapeutic effect. This may require a dose adjustment of transdermal fentanyl. After discontinuation of treatment with inducers of cytochrome CYP3A4, the effects caused by induction gradually decrease and this may lead to increased plasma concentrations of fentanyl with possible consequent increase or prolongation of both therapeutic and undesirable effects and possible severe depression. respiratory. In this case, careful monitoring and dose adjustment should be performed if warranted.
Monoamine Oxidase Inhibitors (MAOIs):
The use of transdermal fentanyl is not recommended in patients requiring concomitant administration of a MAOI. Serious and unexpected interactions with MAOIs, such as potentiation of opioid effects or potentiation of serotonergic effects, have been reported. For this reason, fentanyl it should not be used for 14 days after stopping treatment with MAOIs.
Serotonergic drugs
Co-administration of transdermal fentanyl with serotonergic agents, such as a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-Noradrenaline Reuptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI) may increase the risk of serotonin syndrome , a potentially life-threatening condition
Concomitant use of agonists / antagonists
Concomitant use of buprenorphine, nalbuphine or pentazocine is not recommended. They have a high affinity for opioid receptors with a relatively low intrinsic activity and thus partially antagonize the effect of fentanyl and may induce withdrawal symptoms in patients. opioid dependent (see also section 4.4).
04.6 Pregnancy and breastfeeding -
Pregnancy
There are insufficient data on the use of transdermal fentanyl in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3 Preclinical safety data). The potential risk in humans is unknown, although it has been shown that fentanyl administered as anesthetic ev it passes through the placenta in women in the early stages of pregnancy. Neonatal withdrawal syndrome has been found in infants whose mothers had chronic use of transdermal fentanyl during pregnancy. Fentanyl should not be used during pregnancy unless clearly needed.
The use of transdermal fentanyl during delivery is not recommended as it should not be used in the treatment of acute or postoperative pain (see section 4.4, Special warnings and precautions for use). In addition, since fentanyl passes through the placenta, the use of transdermal fentanyl during delivery can cause respiratory depression in the newborn.
Feeding time
Fentanyl is excreted in breast milk and can cause sedation and respiratory depression in the nursing infant. Breastfeeding should therefore be discontinued during treatment with transdermal fentanyl and for at least 72 hours after removal of the patch.
04.7 Effects on ability to drive and use machines -
Transdermal fentanyl may reduce the mental and / or physical abilities required for performing potentially hazardous activities such as driving vehicles or using machines.
04.8 Undesirable effects -
The safety of transdermal fentanyl was evaluated in 1854 subjects who participated in 11 clinical trials (double-blind transdermal fentanyl [placebo or active control] and / or open label transdermal fentanyl [no control or active control]) focusing on the treatment of chronic malignant or non-malignant pain. These subjects had taken at least 1 dose of transdermal fentanyl and are the source of the safety data.
Based on safety data collected from these clinical studies, the most commonly reported adverse drug reactions (ADRs) were (with% incidence): nausea (35.7%), vomiting (23.2%), constipation ( 23.1%), somnolence (15.0%), dizziness (13.1%) and headache (11.8%).
The ADRs recorded in these clinical trials with the use of transdermal fentanyl, including the ADRs mentioned above, and those reported in post-marketing experience are listed below.
The frequency categories listed use the following convention:
very common (≥ 1/10); common (≥ 1/100,
Table 5: Adverse Drug Reactions in Adult and Pediatric Subjects
As with other opioid analgesics, tolerance, physical dependence and psychological dependence may occur with repeated use of fentanyl (see section 4.4, Special warnings and precautions for use).
Symptoms of opioid withdrawal syndrome (such as nausea, vomiting, diarrhea, anxiety and tremors) may occur in some patients after switching from their previous opioid analgesics to fentanyl transdermal patches or if therapy is stopped abruptly (see section 4.2 , Posology and method of administration) There have been very rare cases of neonatal abstinence syndrome in neonates when mothers had chronic use of transdermal fentanyl during pregnancy (see section 4.6, Fertility, pregnancy and lactation).
Pediatric subjects
The characteristics of adverse events in children and adolescents treated with fentanyl transdermal patch are similar to those seen in adults. In the pediatric population, no risks other than those expected with the use of opioids for the relief of pain associated with serious illness have been identified and there do not appear to be any specific pediatric risks associated with the use of the fentanyl transdermal patch in children 2 years of age or older. of age when used appropriately. Very common adverse events reported in pediatric clinical trials were fever, vomiting and nausea.
The safety of fentanyl transdermal patches was evaluated in 289 pediatric subjects (
Based on the pooled safety data from these 3 clinical trials in pediatric subjects, the most commonly reported adverse drug reactions (ADRs) (e.g. incidence ≥10%): were (with% incidence): vomiting (33 , 9%), nausea (23.5%). headache (16.3%), constipation (13.5%), diarrhea (12.8%) and pruritus (12.8%). Table 6 shows all ADRs reported in pediatric subjects treated with fentanyl transdermal patches in the previously mentioned clinical studies.
For the allocation to the frequency categories of ADRs in the pediatric population reported in Table 6, the same criteria applied for Table 5 were used.
Table 6 Adverse drug reactions in pediatric subjects in clinical studies
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 an overdose of fentanyl consist in an enhancement of its pharmacological actions, the most serious effect that can occur is respiratory depression.
Treatment
Immediate countermeasures for the treatment of respiratory depression include removal of the patch and physical or verbal stimulation of the patient. These actions can be followed by the administration of a specific opioid antagonist such as naloxone.
Respiratory depression resulting from an overdose may exceed the duration of action of the opioid antagonist. The interval between doses of the i.v. must be carefully established due to the possibility of re-narcotization following removal of the patch; repeated administration or continuous infusion of naloxone may be required. Nulling the effect of the narcotic may result in acute onset of pain and release of catecholamines.
If the clinical situation justifies it, a patent airway should be ensured and maintained, possibly with an oropharyngeal or endotracheal tube, and oxygen administered and breathing assisted or controlled, as appropriate. Appropriate body temperature and fluid intake should be maintained.
If severe or persistent hypotension develops, the possibility of hypovolaemia should be considered and the condition treated with "adequate parenteral fluid therapy."
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: analgesics, opioids
ATC code: N02AB03
Matrifen is a transdermal patch that releases fentanyl continuously. Fentanyl is an opioid analgesic with predominantly affinity for the μ receptor. The predominant pharmacological effects are pain reduction and sedation. Patients not previously exposed to opioids will have a reduction in pain with fentanyl concentrations between 0.3 and 1.5 ng / ml. In this patient group the frequency of adverse effects will increase with serum concentrations above 2 ng / ml. Both the minimal effective concentration of fentanyl and the concentration associated with adverse reactions will increase with the development of progressive tolerance. The development of tolerance varies considerably from one subject to another.
Pediatric population
The safety of transdermal fentanyl was evaluated in three open clinical studies with 289 pediatric patients with chronic pain, aged 2 to 18 years; of these, 66 children were aged between 2 and 6 years. In these studies, a daily dose of 30 mg to 45 mg oral morphine was replaced by a 12 mcg / hour fentanyl transdermal patch. A starting dose of 25 mcg / hour or more was used on 181 patients who were previously taking daily opioid doses of at least 45 mg per oral morphine dose.
05.2 "Pharmacokinetic properties -
Fentanyl transdermal patch allows the systemic release of fentanyl during the application period of 72 hours.
Absorption:
After the first application of the patch, serum concentrations of fentanyl gradually increase, generally leveling off between 12 and 24 hours and remaining relatively constant for the remainder of the 72 hours of application. After the second 72-hour application, a steady-state serum concentration is achieved which is maintained during subsequent applications of a patch of the same size. Absorption of fentanyl may be somewhat different from one application site to another. Relatively lower absorption (approximately 25%) of fentanyl was observed in studies with healthy volunteers after applying the patch to the chest compared to upper arm and back.
Distribution:
The plasma protein binding of fentanyl is 84%.
Biotransformation:
Fentanyl exhibits linear kinetics and is metabolised primarily in the liver via CYP3A4. The major metabolite, norfentanyl, is not active.
Elimination:
Once the fentanyl patch is removed, plasma concentrations of fentanyl gradually decrease and fall by approximately 50% over 13 - 22 hours in adults or 22 - 25 hours in children. Continued absorption of fentanyl from the skin accounts for a slower disappearance of the drug from the serum than after an intravenous infusion. About 75% of fentanyl is excreted in the urine, mostly as metabolites, and less than 10% as unchanged drug. Approximately 9% of the dose is recovered in the faeces, mainly in the form of metabolites.
Pharmacokinetics in special groups
Impaired hepatic or renal function could cause increased serum concentrations. Elderly, cachectic or generally poor patients may have reduced clearance of fentanyl, which could cause a longer terminal half-life of the compound (see sections 4.2 and 4.4).
Pediatric population
Depending on weight, clearance (L / h / kg) in pediatric patients appears to be 82% higher in children between 2 and 5 years, and 25% higher in children between 6 and 10 years, when compared to children between 11 and 16 years, who appear to have the same clearance as adults These findings were taken into account in setting dosing precautions in pediatric patients.
05.3 Preclinical safety data -
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.
Reduced fertility and increased mortality in rat fetuses were observed in animal studies. However, no teratogenic effects have been demonstrated.
Mutagenicity tests in bacteria and rodents gave negative results. Like other opioids, fentanyl has shown mutagenic effects in mammalian cells in vitro. A mutagenic risk under therapeutic conditions seems unlikely as these effects were induced only by very high concentrations.
Long-term carcinogenicity studies have not been conducted.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Dipropylene glycol
Hydroxypropylcellulose
Dimethicone
Adhesive silicone (amino-resistant)
Release membrane, ethylene vinyl acetate (EVA)
Cover film, polyethylene terephthalate (PET) film
Removable protective film, fluoropolymer coated polyester film
Printing ink
06.2 Incompatibility "-
To avoid interference with the adhesive properties of Matrifen, creams, oils, lotions or powders or other powders should not be used in the area of the skin where the Matrifen patch is to be applied.
06.3 Period of validity "-
3 years
06.4 Special precautions for storage -
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package -
Each transdermal patch is packaged in a heat-sealed paper, aluminum and polyacrylonitrile (PAN) pouch.
Packs of:
1 patch, 3 patches, 5 patches, 10 patches and 20 patches
Not all pack sizes may be marketed
06.6 Instructions for use and handling -
For instructions on how to apply the patch refer to section 4.2. No safety and pharmacokinetic data are available for other application sites.
High amounts of fentanyl remain in the transdermal patches even after use. Used transdermal patches must be folded with the adhesive surfaces on the inside, so that the release membrane is not exposed, and, for safety and environmental reasons, must be disposed of. according to local regulations or returned to the pharmacy or hospital. Any unused medicine should be disposed of according to local regulations or returned to the pharmacy or hospital.
Wash your hands with water after applying or removing the patch.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
GRÜNENTHAL ITALIA S.r.l. Via Carlo Bo n. 11 -20143 Milan
08.0 MARKETING AUTHORIZATION NUMBER -
12 mcg / hour:
12 mcg / hour Transdermal patches 1 patch - AIC n. 037405014 / M
12 mcg / hour Transdermal patches 2 patches - AIC n. 037405267 / M
12 mcg / hour Transdermal patches 3 patches - AIC n. 037405026 / M
12 mcg / hour Transdermal patches 4 patches - AIC n. 037405279 / M
12 mcg / hour Transdermal patches 5 patches - AIC n. 037405038 / M
12 mcg / hour Transdermal patches 8 patches - AIC n. 037405281 / M
12 mcg / hour Transdermal patches 10 patches - AIC n. 037405040 / M
12 mcg / hour Transdermal patches 16 patches - AIC n. 037405293 / M
12 mcg / hour Transdermal patches 20 patches - AIC n. 037405053 / M
25 mcg / hour:
25 mcg / hour Transdermal patches 1 patch - AIC n. 037405065 / M
25 mcg / hour Transdermal patches 2 patches - AIC n. 037405305 / M
25 mcg / hour Transdermal patches 3 patches - AIC n. 037405077 / M
25 mcg / hour Transdermal patches 4 patches - AIC n. 037405317 / M
25 mcg / hour Transdermal patches 5 patches - AIC n. 037405089 / M
25 mcg / hour Transdermal patches 8 patches - AIC n. 037405329 / M
25 mcg / hour Transdermal patches 10 patches - AIC n. 037405091 / M
25 mcg / hour Transdermal patches 16 patches - AIC n. 037405331 / M
25 mcg / hour Transdermal patches 20 patches - AIC n. 037405103 / M
50 mcg / hour:
50 mcg / hour Transdermal patches 1 patch - AIC n. 037405115 / M
50 mcg / hour Transdermal patches 2 patches - AIC n. 037405343 / M
50 mcg / hour Transdermal patches 3 patches - AIC n. 037405127 / M
50 mcg / hour Transdermal patches 4 patches - AIC n. 037405356 / M
50 mcg / hour Transdermal patches 5 patches - AIC n. 037405139 / M
50 mcg / hour Transdermal patches 8 patches - AIC n. 037405368 / M
50 mcg / hour Transdermal patches 10 patches - AIC n. 037405141 / M
50 mcg / hour Transdermal patches 16 patches - AIC n. 037405370 / M
50 mcg / hour Transdermal patches 20 patches - AIC n. 037405154 / M
75 mcg / hour:
75 mcg / hour Transdermal patches 1 patch - AIC n. 037405166 / M
75 mcg / hour Transdermal patches 2 patches - AIC n. 037405382 / M
75 mcg / hour Transdermal patches 3 patches - AIC n. 037405178 / M
75 mcg / hour Transdermal patches 4 patches - AIC n. 037405394 / M
75 mcg / hour Transdermal patches 5 patches - AIC n. 037405180 / M
75 mcg / hour Transdermal patches 8 patches - AIC n. 037405406 / M
75 mcg / hour Transdermal patches 10 patches - AIC n. 037405192 / M
75 mcg / hour Transdermal patches 16 patches - AIC n. 037405418 / M
75 mcg / hour Transdermal patches 20 patches - AIC n. 037405204 / M
100 mcg / hour:
100 mcg / hour Transdermal patches 1 patch - AIC n. 037405216 / M
100 mcg / hour Transdermal patches 2 patches - AIC n. 037405420 / M
100 mcg / hour Transdermal patches 3 patches - AIC n. 037405228 / M
100 mcg / hour Transdermal patches 4 patches - AIC n. 037405432 / M
100 mcg / hour Transdermal patches 5 patches - AIC n. 037405230 / M
100 mcg / hour Transdermal patches 8 patches - AIC n. 037405444 / M
100 mcg / hour Transdermal patches 10 patches - AIC n. 037405242 / M
100 mcg / hour Transdermal patches 16 patches - AIC n. 037405457 / M
100 mcg / hour Transdermal patches 20 patches - AIC n. 037405255 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
First authorization: 10 October 2007
Renewal: 16 September 2010
10.0 DATE OF REVISION OF THE TEXT -
17 October 2015
