Fentanyl Matrix Normon 25 micrograms/h transdermal patches EFG: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

Fentanilo Matrix Normon 25 micrograms/h transdermal patch EFG

Fentanyl

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, consult your doctor, pharmacist, or nurse.
This medicine has been prescribed only for you (or for your child), and you should not give it to others, even if they have the same symptoms as you, because it could harm them.
If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

What Fentanilo Matrix Normon is and what it is used for
What you need to know before using Fentanilo Matrix Normon
How to use Fentanilo Matrix Normon
Possible side effects
How to store Fentanilo Matrix Normon
Contents of the pack and other information

1. What Fentanilo Matrix Normon is and what it is used for

This medicine is called Fentanilo Matrix Normon.

The patches help relieve severe and long-lasting pain:

in adults who require continuous pain treatment
in children over 2 years of age who are already using opioid medication and who require continuous pain treatment.

Fentanilo Matrix Normon contains a medicine called fentanil. It belongs to a group of strong painkillers known as opioids.

2. What you need to know before using Fentanilo Matrix Normon

Do not use Fentanilo Matrix Normon

If you are allergic to fentanyl or any of the other components of this medicine (listed in section 6)
If you have short-term pain, such as sudden pain or pain after surgery
If you have difficulty breathing, with slow or weak breathing

Do not use this medicine if you or your child are in any of the above situations. If you are unsure, consult your doctor or pharmacist before using Fentanilo Matrix Normon.

Warnings and precautions

Fentanilo Matrix Normon may cause life-threatening adverse effects in people who are not regularly using prescribed opioids.
Fentanilo Matrix Normon is a medicine that could be fatal to children, even if the patches have already been used. Please note that a transdermal patch (used or unused) may be attractive to a child, and if it adheres to a child's skin or if the child puts it in their mouth, the result may be fatal.
Keep this medicine in a secure and safe place, out of reach of others. See section 5 for more information.

If the patch adheres to another person

The patch must only be used on the skin of the person for whom the doctor has prescribed it. There have been cases where the patch has accidentally adhered to another family member due to close physical contact or sharing the same bed with the person wearing the patch. If the patch accidentally adheres to another person (particularly a child), the medicine from the patch can pass through the other person's skin and may cause serious adverse effects, such as difficulty breathing, with slow or weak breathing, which may be fatal. If the patch adheres to another person's skin, remove it immediately and seek medical help.

Take special care with Fentanilo Matrix Normon

Consult your doctor or pharmacist before using this medicine if you are in any of the following situations. Your doctor will need to monitor you more closely:

If you have ever had lung or breathing problems
If you have ever had heart, liver, or kidney problems, or low blood pressure
If you have ever had a brain tumor
If you have ever had persistent headaches or a head injury
If you are elderly, as you may be more sensitive to the effects of this medicine
If you have a disorder called "myasthenia gravis", in which muscles become weak and tire easily

If you have any of the above conditions (or if you are unsure), consult your doctor or pharmacist before using Fentanilo Matrix Normon.

While using the patch, inform your doctor if you experience breathing problems during sleep. Opioids such as Fentanilo Matrix Normon can cause sleep-related breathing disorders such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low blood oxygen levels). Talk to your doctor if you, your partner, or caregiver notice any of the following symptoms:

Pauses in breathing during sleep
Waking up at night due to shortness of breath
Difficulty staying asleep
Excessive daytime sleepiness

Your doctor may decide to adjust the dose.

While using the patch, inform your doctor if you notice a change in your pain. If you experience:

The patch no longer relieves your pain
An increase in pain
A change in the way you feel pain (e.g., pain in another part of your body)
Pain from touch to your body that should not cause pain

Do not change the dose on your own. Your doctor may decide to adjust the dose or change your treatment.

Adverse effects and Fentanilo Matrix Normon

Fentanilo Matrix Normon may cause unusual drowsiness and may slow or weaken your breathing. Very rarely, these breathing problems may be life-threatening or even fatal, especially in people who have not previously used strong opioid painkillers (such as Fentanilo Matrix Normon or morphine). If you, your partner, or caregiver notice that the person wearing the patch is unusually drowsy, with slow or weak breathing:
Remove the patch
Call a doctor or go immediately to the nearest hospital
Keep the person moving and talking as much as possible
If you develop a fever while using Fentanilo Matrix Normon, speak to your doctor. This may increase the amount of medicine passing through your skin.
Fentanilo Matrix Normon may cause constipation; speak to your doctor or pharmacist for advice on how to prevent or relieve constipation.

In section 4, you can find the complete list of possible adverse effects.

While wearing the patch, do not expose it to direct heat sources such as heating pads, electric blankets, hot water bottles, heated water beds, or heat or tanning lamps. Do not sunbathe, take prolonged hot baths, or use saunas or hot hydrotherapy baths. Doing so may increase the amount of medicine released from the patch.

Long-term use and tolerance

This medicine contains fentanyl, an opioid. Repeated use of opioid painkillers may make the drug less effective (the body becomes accustomed to it, known as pharmacological tolerance). You may also become more sensitive to pain while using Fentanilo Matrix Normon. This is known as hyperalgesia. Increasing the patch dose may continue to reduce pain for a time, but it may also be harmful. If you notice the medicine is losing effectiveness, consult your doctor. Your doctor will decide whether it is better to increase the dose or gradually reduce the use of Fentanilo Matrix Normon.

Dependence and addiction

Repeated use of Fentanilo Matrix Normon may also lead to dependence, abuse, and addiction, which could result in a potentially fatal overdose. The risk of these adverse effects may be higher with higher doses and prolonged use. Dependence or addiction may cause a feeling of losing control over the amount of medicine you need to use or how often you need to use it. You may feel the need to keep using the medicine even if it no longer helps relieve pain.

The risk of dependence or addiction varies from person to person. The risk of becoming dependent on or addicted to Fentanilo Matrix Normon may be higher if:

You or any member of your family have abused alcohol or have experienced dependence on alcohol, prescription medicines, or illegal drugs ("addiction").
You smoke.
You have ever had mood disorders (depression, anxiety, or a personality disorder) or have received treatment from a psychiatrist for other mental illnesses.

If you notice any of the following symptoms while using Fentanilo Matrix Normon, they could be signs of dependence or addiction:

You need to use the medicine for longer than prescribed by your doctor.
You need to use a higher dose than recommended.
You are using the medicine for reasons other than those prescribed, for example, to stay calm or to help you sleep.
You have made repeated unsuccessful attempts to stop using the medicine or control its use.
You feel unwell when you stop using the medicine, and feel better once you take it again ("withdrawal effects").

If you notice any of these signs, consult your doctor to determine the best treatment approach for you, when it is appropriate to stop the medicine, and how to do so safely.

This medicine contains fentanyl, which is an opioid. It may cause dependence and/or addiction.

Repeated use of Fentanilo Matrix Normon may also lead to dependence, abuse, and addiction, which could result in potentially fatal overdose.

Withdrawal symptoms when stopping Fentanilo Matrix Normon

Do not stop using this medicine abruptly. Withdrawal symptoms may occur, such as restlessness, difficulty sleeping, irritability, agitation, anxiety, awareness of heartbeat (palpitations), increased blood pressure, feeling or being sick, diarrhoea, loss of appetite, tremors, chills, or sweating. If you wish to stop using this medicine, speak to your doctor first. Your doctor will advise you on how to do this, usually by gradually reducing the dose so that unpleasant withdrawal effects are minimized.

Other medicines and Fentanilo Matrix Normon

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This includes medicines purchased without a prescription and herbal remedies. You should also inform your pharmacist that you are using Fentanilo Matrix Normon if you purchase any medicine from the pharmacy.

Your doctor will know which medicines can be safely taken with Fentanilo Matrix Normon. You may need to be closely monitored if you are taking, or stop taking, any of the following types of medicines, as this may affect the dose of Fentanilo Matrix Normon you require.

In particular, inform your doctor or pharmacist if you are taking:

Other pain medicines, such as other opioid analgesics (e.g., buprenorphine, nalbuphine, or pentazocine) and some analgesics for neuropathic pain (gabapentin and pregabalin).
Medicines to help you sleep (such as temazepam, zaleplon, or zolpidem).
Medicines to help you relax (tranquilizers, such as alprazolam, clonazepam, diazepam, hydroxyzine, or lorazepam) and medicines for mental disorders (antipsychotics, such as aripiprazole, haloperidol, olanzapine, risperidone, or phenothiazines).
Medicines to relax muscles (such as cyclobenzaprine or diazepam).
Some medicines used to treat depression called SSRIs or SNRIs (such as citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or venlafaxine). – more information below
Some medicines used to treat depression or Parkinson’s disease called MAOIs (such as isocarboxazid, phenelzine, selegiline, or tranylcypromine). You must not use Fentanilo Matrix Normon within 14 days of stopping these medicines. – more information below
Some antihistamines, especially those causing drowsiness (such as chlorpheniramine, clemastine, cyproheptadine, diphenhydramine, or hydroxyzine).
Some antibiotics used to treat infections (such as erythromycin or clarithromycin).
Medicines used to treat fungal infections (such as itraconazole, ketoconazole, fluconazole, or voriconazole).
Medicines used to treat HIV infection (such as ritonavir).
Medicines used to treat irregular heartbeats (such as amiodarone, diltiazem, or verapamil).
Medicines to treat tuberculosis (such as rifampicin).
Some medicines used to treat epilepsy (such as carbamazepine, phenobarbital, or phenytoin).
Some medicines used to treat nausea or dizziness (such as phenothiazines).
Some medicines used to treat heartburn or ulcers (such as cimetidine).
Some medicines used to treat angina (chest pain) or high blood pressure (such as nicardipine).
Some medicines used to treat blood cancer (such as idelalisib).

Use of Fentanilo Matrix Normon with antidepressants

The risk of adverse effects increases if you are taking medicines such as certain antidepressants. Fentanilo Matrix Normon may interact with these medicines, and you may experience changes in mental state such as agitation, seeing, feeling, hearing, or smelling things that are not present (hallucinations), and other effects such as changes in blood pressure, rapid heartbeat, high body temperature, hyperactive reflexes, lack of coordination, muscle stiffness, nausea, vomiting, and diarrhoea (these could be signs of serotonin syndrome). If used together, your doctor may want to monitor you closely for these side effects, especially when starting treatment or when the dose of medicine is changed.

Use with central nervous system depressants, including alcohol and some narcotic medicines

Concomitant use of Fentanilo Matrix Normon and sedative medicines such as benzodiazepines or related medicines increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use should only be considered when no other treatment options are possible.

However, if your doctor prescribes Fentanilo Matrix Normon together with sedative medicines, your doctor should limit the dose and duration of concomitant treatment.

Inform your doctor about all sedative medicines you are taking, and strictly follow your doctor's dosing recommendations. It may be helpful to inform friends or family members so they are aware of the signs and symptoms mentioned above. Contact your doctor if you experience these symptoms.

Do not drink alcohol while using Fentanilo Matrix Normon unless you have discussed it with your doctor.

Use in athletes

Athletes are advised that this medicine contains a component that may lead to a positive analytical finding in doping controls.

Surgery

If you are scheduled to receive anaesthesia, inform your doctor or dentist that you are using Fentanilo Matrix Normon.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Fentanilo Matrix Normon should not be used during pregnancy unless you have discussed it with your doctor.

Fentanilo Matrix Normon should not be used during childbirth, as the medicine may affect the newborn's breathing.

Prolonged use of Fentanilo Matrix Normon during pregnancy may cause withdrawal symptoms (such as high-pitched crying, restlessness, seizures, poor feeding, and diarrhoea) in your newborn baby, which could be potentially fatal if not recognized and treated. Speak to your doctor immediately if you think your baby may have withdrawal symptoms.

Do not use Fentanilo Matrix Normon while breastfeeding. You must not breastfeed for 3 days after removing the Fentanilo Matrix Normon patch. This is because the medicine can pass into breast milk.

Driving and using machines

Fentanilo Matrix Normon may affect your ability to drive and operate machinery or tools, as it may cause drowsiness or dizziness. If so, do not drive or operate tools or machinery. Do not drive while using this medicine until you know how it affects you.

Talk to your doctor or pharmacist if you have any doubts about whether it is safe for you to drive while using this medicine.

3. How to use Fentanilo Matrix Normon

Follow exactly the administration instructions for this medicine as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

Your doctor will decide which concentration of Fentanilo Matrix Normon is most suitable for you, taking into account the intensity of your pain, your general condition, and the type of pain treatment you have previously received.

Before starting treatment and regularly during treatment, your doctor will also explain to you what you can expect from using Fentanilo Matrix Normon, when and for how long you should use it, when you should contact your doctor, and when you should stop using it (see also section 2, «Withdrawal syndrome when interrupting treatment with Fentanilo Matrix Normon»).

How to apply and change the patches

Each patch contains a sufficient amount of medicine for 3 days (72 hours).
You must change the patch every three days, unless your doctor has instructed 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 of them at the same time.
Record the day of the week, date, and time each time you apply a patch, so you remember when to change it.
The table below shows when you should change the patch:

Apply the patch on		Change the patch 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 a flat area of the trunk or arm (never over a joint).

Children

Always apply the patch to the upper back so that your child has difficulty reaching or removing it.
Check regularly that the patch remains adhered to the skin.
It is important that the child does not remove the patch and put it in their mouth, as this could endanger their life or be fatal.
Keep your child under close observation for 48 hours after:
Applying the first patch
Applying a patch with a higher dose
The patch may take some time to reach its full effect. Therefore, your child may need additional painkillers until the patch becomes effective. Your doctor will explain this to you.

Adults and children:

Do not apply the patch to

The same site twice in a row.
Areas that move a lot (joints), or to irritated or wounded skin.
Areas of skin with excessive hair. If hair is present, do not shave it (shaving may irritate the skin). Instead, cut the hair as close to the skin as possible.

How to apply the patch

Preparing the skin

Before applying the patch, ensure the skin is completely dry, clean, and cool
If washing is necessary, use only cold water
Do not use soap or other cleansers, creams, moisturizers, oils, or talcum powder before applying the patch
Do not apply the patch immediately after a hot bath or shower

Diagram with four illustrated steps: cut the pouch, remove the protective film, apply the patch to the skin, and press with the palm

Disposing of the patch

Immediately after removing the patch, fold it in half so that the adhesive side sticks to itself
Place it back into the original pouch and dispose of it according to your pharmacist's instructions
Keep used patches out of sight and out of reach of children; even when used, patches still contain medication that could harm children and may even be fatal

Washing hands

Always wash your hands with water only after handling patches

More information on the use of Fentanilo Matrix Normon

Daily activities while using patches

The patches are water-resistant
You may shower or bathe with the patch in place, but do not rub it
If your doctor agrees, you may exercise or engage in sports while wearing the patch
You may also swim with the patch in place, but:
Do not use hot tubs or whirlpool baths
Do not cover the patch with elastic or tight-fitting fabrics
While wearing the patch, do not expose it to direct heat sources such as heating pads, electric blankets, hot water bottles, heated water beds, or heat or tanning lamps. Do not sunbathe, take prolonged hot baths, or use saunas. Doing so may increase the amount of medication released from the patch.

How long do the patches take to work?

The first patch may take some time to reach its full effect.
Your doctor may provide additional painkillers during the first few days.
Afterwards, the patch should help provide continuous pain relief, allowing you to stop taking other painkillers. However, your doctor may occasionally prescribe additional painkillers.

How long will you need to use the patches?

Fentanilo Matrix Normon patches are indicated for long-term pain. Your doctor will advise you on how long you can expect to use the patches.

If pain worsens

If your pain suddenly worsens after applying the last patch, check the patch. If it no longer adheres properly or has come off, replace the patch (see also the section If the patch comes off ).
If your pain worsens over time while using the patches, your doctor may try patches with a higher dose or prescribe additional painkillers (or both).
If increasing the patch dose does not help, your doctor may decide to stop using the patches.

If you use too many patches or a patch with the wrong dose

If you have applied too many patches or a patch with the wrong dose, remove them immediately and contact your doctor right away or call the Toxicology Information Service at (91) 562 04 20, stating the medication and amount applied, or go to the hospital.

Signs of overdose include difficulty breathing or weak breathing, fatigue, extreme drowsiness, inability to think clearly or to walk or speak normally, and dizziness, lightheadedness, or confusion. An overdose may also cause a brain disorder known as toxic leukoencephalopathy.

If you forget to change the patch

If you forget to change the patch, change it as soon as you remember and note the date and time. Then resume changing the patch every 3 days (72 hours) as usual.
If you are significantly delayed, you should speak with your doctor, as you may need additional painkillers, but do not apply extra patches.

If the patch comes off

If the patch falls off before it is time to change it, apply a new one immediately and note the date and time. Choose a new skin site:
On the trunk or arm
On the upper back of your child
Inform your doctor and leave the patch in place for another 3 days (72 hours) or for the time your doctor specifies, before changing the patch in the usual way
If patches tend to fall off frequently, consult your doctor, pharmacist, or nurse

If you wish to stop using the patches

Do not stop using this medication abruptly. If you wish to stop using this medication, speak with your doctor first. Your doctor will advise you on how to do so, usually by gradually reducing the dose to minimize unpleasant withdrawal symptoms. See also section 2, “Withdrawal symptoms when stopping Fentanilo Matrix Normon”.
If you stop using the patches, do not reuse them without first consulting your doctor. You may require a different dose when restarting treatment.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

If you, or your partner or caregiver, notice any of the following signs in the person wearing the patch, remove the patch immediately and call a doctor or go straight to the nearest hospital. Urgent medical treatment may be needed.

Unusual drowsiness, slower or weaker breathing than expected.

Follow the above recommendations and encourage the person wearing the patch to move and speak as much as possible. In very rare cases, these breathing difficulties can be life-threatening or even fatal, especially in people who have not previously used strong opioid painkillers (such as Fentanilo Matrix Normon or morphine). (Uncommon, may affect up to 1 in 100 people).

Sudden swelling of the face or throat, severe irritation, redness, or blisters on the skin.

All of these may be signs of a severe allergic reaction. (Frequency cannot be estimated from available data).

Seizures (convulsions). (Uncommon, may affect up to 1 in 100 people).
Reduced level of consciousness or loss of consciousness. (Uncommon, may affect up to 1 in 100 people).

The following adverse effects have also been reported

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

Nausea, vomiting, constipation
Feeling sleepy (drowsiness)
Feeling dizzy
Headache

Common (may affect up to 1 in 10 people)

Allergic reaction
Loss of appetite
Difficulty sleeping
Depression
Feeling anxious or confused
Seeing, feeling, hearing, or smelling things that are not present (hallucinations)
Tremors or muscle spasms
Abnormal skin sensations such as tingling or prickling (paraesthesia)
Sensation that everything is spinning (vertigo)
Fast or irregular heartbeat (palpitations, tachycardia)
Increased blood pressure
Feeling short of breath (dyspnoea)
Diarrhoea
Dry mouth
Stomach pain or indigestion
Excessive sweating
Itching, rash, or redness of the skin
Inability to urinate or empty the bladder completely
Severe tiredness, weakness, or general malaise
Feeling cold
Swelling of the hands, ankles, or feet (peripheral oedema)

Uncommon (may affect up to 1 in 100 people)

Feeling restless or disoriented
Feeling extremely happy (euphoria)
Decreased sensation or sensitivity, especially in the skin (hypoesthesia)
Memory loss
Blurred vision
Slow heart rate (bradycardia) or low blood pressure
Bluish discoloration of the skin due to reduced oxygen in the blood (cyanosis)
Loss of intestinal contractions (ileus)
Itchy skin rash (eczema), allergic reaction, or other skin disorders at the site of patch application
Flu-like illness
Sensation of body temperature change
Fever
Muscle cramps
Difficulty achieving or maintaining an erection (impotence) or problems with sexual performance

Rare side effects (may affect up to 1 in 1,000 people)

Constriction of the pupils (miosis)
Occasional interruption of breathing (apnoea)

The following side effects have also been reported, but their exact frequency is unknown:

Lack of male sex hormones (androgen deficiency)
Delirium (symptoms may include a combination of restlessness, agitation, disorientation, confusion, fear, seeing or hearing things that are not real, sleep disturbances, nightmares)
You may become dependent on Fentanilo Matrix Normon (see section 2).

You may experience rashes, redness, or mild itching of the skin at the site where the patch is applied. This is usually mild and disappears after removing the patch. If this does not happen, or if the patch causes significant skin irritation, inform your doctor.

Repeated use of the patches may cause the medicine to lose effectiveness (you may become tolerant to it or may become more sensitive to pain), or may lead to dependence.

If you switch from another painkiller to Fentanilo Matrix Normon, or if you stop using Fentanilo Matrix Normon abruptly, you may experience withdrawal symptoms such as dizziness, feeling unwell, diarrhoea, anxiety, or tremors. Inform your doctor if you notice any of these effects.

Cases have also been reported of newborn infants experiencing withdrawal symptoms after their mothers used Fentanilo Matrix Normon for a prolonged period during pregnancy.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Fentanilo Matrix Normon

Where to store the patches

Keep all patches (used and unused) out of sight and reach of children.

Store this medicine in a protected and secure place, where others cannot access it. It may be very harmful and cause death in people who accidentally or intentionally use this medicine when it has not been prescribed for them.

How long can Fentanilo Matrix Normon be kept

Do not use this medicine after the expiry date stated on the carton and sachet. The expiry date refers to the last day of the month indicated. If the patches have expired, return them to the pharmacy.

Do not use this medicine if you notice that the patches are damaged.

Store in the original packaging to protect from moisture.

How to dispose of used patches or patches no longer in use

Accidental exposure of another person to used or unused patches, especially in children, may result in a fatal outcome.

Used patches should be folded firmly in half so that the adhesive side sticks to itself. They should then be safely discarded by placing them back into the original sachet and kept out of sight and reach of others, especially children, until they can be safely disposed of. Ask your pharmacist how to properly dispose of unused medicines and their packaging.

Medicines must not be disposed of via wastewater or household waste. Take any unused medicines and their packaging to the SIGRE point at your pharmacy. If in doubt, ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Fentanilo Matrix Normon

The active substance is fentanyl.

Each transdermal patch (15 cm² release surface area) contains 4.8 mg of fentanyl, which delivers a dose of 25 micrograms/hour.

The other components of the patch are:

Adhesive layer: Acrylic polymer, lauryl alcohol

Backing layer: Silicone-treated polyester film

Removable liner: Polyester / ethylene vinyl acetate film

Printing ink

Appearance of the product and contents of the pack

Fentanilo Matrix Normon 25 micrograms/h is a thin, transparent transdermal patch with rounded edges, printed with the following: "fentanyl 25 µg/h".

Fentanilo Matrix Normon is available in packs containing 5 transdermal patches.

Marketing Authorization Holder and Manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Fentanyl Matrix Normon 25 micrograms/h transdermal patches EFG