Package Insert: Information for the User

Durogesic Matrix 100 micrograms/hour Transdermal Patches

fentanyl

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you (or your child), and should not be given to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section4.

This medication is called Durogesic Matrix

The patches help to relieve very strong and persistent pain:

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

Durogesic Matrix contains a medication called fentanil. It belongs to a group of strong pain-relieving medications called opioids.

No use Durogesic Matrix

Do not use this medication if you or your child is in any of the above circumstances. If you are unsure, consult your doctor or pharmacist before using Durogesic Matrix.

Warnings and precautions

If the patch sticks to another person

The patch should only be used on the skin of the person for whom the doctor has prescribed it. There have been some cases where the patch has accidentally stuck to another family member by close physical contact or sharing the same bed with the person wearing the patch. If the patch accidentally sticks to another person (particularly a child), the medication from the patch may pass through the other person's skin and cause serious adverse effects, such as difficulty breathing, slow or weak breathing that can be fatal. In the event that the patch sticks to someone else's skin, it should be removed immediately and the person should see a doctor.

Be especially careful with Durogesic Matrix

Consult your doctor or pharmacist beforeusing this medication if you are in any of the following circumstances. Your doctor will have to monitor you more closely:

• If you have ever had respiratory 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 medication.
• If you have a condition called "myasthenia gravis," in which your muscles become weak and easily fatigued.

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

While using the patch, report to your doctor if you have breathing problems while sleeping.Opioids like Durogesic Matrix can cause sleep-related breathing disorders such as sleep apnea (pauses in breathing while sleeping) and sleep-related hypoxemia (low oxygen levels in the blood). Talk to your doctor if you, your partner, or caregiver observe any of the following symptoms:

• pauses in breathing while sleeping
• waking up at night due to lack of air
• difficulty staying asleep
• excessive daytime sleepiness.

Your doctor may decide to modify the dose.

While using the patch, report to your doctor if you notice a change in the pain you feel.If you feel:

• that the patch no longer relieves the pain
• an increase in pain
• a change in the way you feel the pain (for example, you feel pain in another part of your body)
• pain when you come into contact with your body that should not cause pain.

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

Adverse effects and Durogesic Matrix

• Durogesic Matrix may make you feel exceptionally sleepy and cause your breathing to be slower or weaker. In rare cases, these breathing problemscan be life-threatening or even fatal, especially in people who have not used strong prescribed opioids before. If you, or your partner or caregiver, observe that the person wearing the patch is unusually sleepy, with slow or weak breathing:

• Remove the patch;
• Call a doctor or go to the nearest hospital immediately;
• Make the person move and talk as much as possible.

• If you have a feverwhile using Durogesic Matrix, talk to your doctor. This can increase the amount of medication that passes through your skin.
• Durogesic Matrix may cause constipation; talk to your doctor or pharmacist for advice on how to prevent or relieve constipation.

See section 4 for the complete list of possible adverse effects.

Durogesic Matrix, like other opioids, can affect normal hormone production in the body, such as cortisol, prolactin, or sex hormones, especially if you have used Durogesic Matrix for a long time. The effects of these hormonal changes may include feeling unwell or discomfort (including vomiting), loss of appetite, fatigue, weakness, dizziness, low blood pressure, infertility, or decreased sex drive. Additionally, female patients may experience changes in menstrual cycles, while male patients may experience impotence or breast enlargement. If you notice any of these signs, consult your doctor.

When wearing the patch, do not expose it to direct heat, such as heating pads, electric blankets, hot water bottles, hot tubs, or heat lamps or tanning beds. Do not take the sun or long hot baths and do not use saunas or hot tubs. If you do, it may increase the amount of medication released from the patch.

Long-term use and tolerance

This medication contains fentanyl, an opioid. Repeated use of opioid analgesics can make the medication less effective (your body becomes accustomed to it, known as pharmacological tolerance). It is also possible that you may become more sensitive to pain when using Durogesic Matrix. This is known as hyperalgesia. Increasing the dose of the patches may continue to reduce pain for a while, but it may also be harmful. If you notice that the medication is losing its effectiveness, consult your doctor. Your doctor will decide whether it is better to increase the dose or gradually reduce the use of Durogesic Matrix.

Dependence and addiction

The repeated use of Durogesic Matrix can also cause dependence, abuse, and addiction, which could lead to a potentially fatal overdose. The risk of these adverse effects may be higher with a higher dose and longer use. Dependence or addiction can cause you to feel a lack of control over the amount of medication you should use or how often you should use it. You may feel the need to continue using the medication even if it no longer helps to relieve pain.

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

• You or any member of your family have abused alcohol or experienced dependence on it, prescription medications, or illegal drugs ("addiction").
• You smoke.
• You have ever had mood problems (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental health conditions.

If you notice any of the following symptoms while using Durogesic Matrix, it could be a sign of dependence or addiction.

• You need to use the medication for longer than indicated by your doctor.

• You need to use a higher dose than recommended.
• You are using the medication for reasons other than those prescribed, such as "to stay calm" or "to help you sleep".
• You have made repeated and unsuccessful attempts to stop using the medication or control its use.
• You feel unwell when you stop using the medication, and you feel better once you take it again ("withdrawal symptoms").

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

Withdrawal symptoms from stopping Durogesic Matrix

Do not stop using this medication abruptly. Withdrawal symptoms such as restlessness, difficulty sleeping, irritability, agitation, anxiety, feeling your heart rate (palpitations), increased blood pressure, feeling or being sick, diarrhea, loss of appetite, tremors, chills, or sweating may occur. If you want to stop using this medication, talk to your doctor first. Your doctor will advise you on how to do it, usually the dose will be gradually reduced to minimize unpleasant withdrawal symptoms.

Other medications and Durogesic Matrix

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. This includes over-the-counter medications and herbal remedies. You should also inform your pharmacist that you are using Durogesic Matrix if you buy any medication at the pharmacy.

Your doctor will know which medications can be taken safely with Durogesic Matrix. You may need to be closely monitored if you are taking any of the types of medications listed below or if you stop taking any of the types of medications listed, as this may affect the dose of Durogesic Matrix you need.

Especially, inform your doctor or pharmacist if you are taking:

• Other pain medications, such as other opioid analgesics (e.g., buprenorphine, nalbuphine, or pentazocine) and some analgesics for neuropathic pain (gabapentin and pregabalin).
• Medications to help you sleep (e.g., temazepam, zaleplon, or zolpidem).
• Medications to help you calm down (tranquilizers, e.g., alprazolam, clonazepam, diazepam, hydroxyzine, or lorazepam) and medications for mental health conditions (antipsychotics, e.g., aripiprazole, haloperidol, olanzapine, risperidone, or phenothiazines).
• Medications to relax muscles (e.g., cyclobenzaprine or diazepam).
• Some medications used to treat depression called SSRIs or SNRIs (e.g., citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or venlafaxine) – see below for more information.
• Some medications used to treat depression or Parkinson's disease called MAOIs (e.g., isocarboxazid, phenelzine, selegiline, or tranylcypromine). Do not use Durogesic Matrix in the 14days following discontinuation of these medications – see below for more information.
• Some antihistamines, especially those that cause drowsiness (e.g., chlorpheniramine, clemastine, ciproheptadine, diphenhydramine, or hydroxyzine).
• Some antibiotics used to treat infections (e.g., erythromycin or clarithromycin).
• Medications used to treat fungal infections (e.g., itraconazole, ketoconazole, fluconazole, or voriconazole).
• Medications used to treat HIV infection (e.g., ritonavir).
• Medications used to treat irregular heartbeats (e.g., amiodarone, diltiazem, or verapamil).
• Medications used to treat tuberculosis (e.g., rifampicin).
• Some medications used to treat epilepsy (e.g., carbamazepine, phenobarbital, or phenytoin).
• Some medications used to treat nausea or dizziness (e.g., phenothiazines).
• Some medications used to treat heartburn or ulcers (e.g., cimetidine).
• Some medications used to treat angina (chest pain) or high blood pressure (e.g., nicardipine).
• Some medications used to treat blood cancers (e.g., idelalisib).

Using Durogesic Matrix with antidepressants

The risk of adverse effects increases if you are taking certain antidepressants. Durogesic Matrix may interact with these medications 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 heart rate, high body temperature, hyperactive reflexes, lack of coordination, muscle stiffness, nausea, vomiting, and diarrhea (these may be signs of a serotonin syndrome). If used together, your doctor may want to closely monitor you to detect these adverse effects, especially when starting treatment or when changing the dose of the medication.

Using with central nervous system depressants, including alcohol and some narcotics

The use of Durogesic Matrix with sedatives such as benzodiazepines or related medications increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and can be life-threatening. For this reason, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes Durogesic Matrix along with sedatives, your doctor should limit the dose and duration of concomitant treatment.

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

Do not drink alcohol while using Durogesic Matrix, unless you have talked to your doctor first.

Use in athletes

It is reported to athletes that this medication contains a component that may result in a positive analytical result for doping control.

Surgeries

If you think you will receive anesthesia, inform your doctor or dentist that you are using Durogesic Matrix.

Pregnancy and breastfeeding

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

Durogesic Matrix should not be used during pregnancy, unless you have talked to your doctor.

Durogesic Matrix should not be used during childbirth, as the medication may affect the newborn's breathing.

Prolonged use of Durogesic Matrix during pregnancy may cause withdrawal symptoms (such as loud crying, feeling restless, convulsions, poor feeding, and diarrhea) in your newborn, which can be potentially fatal if not recognized and treated. Talk to your doctor immediately if you think your baby may be experiencing withdrawal symptoms.

Do not use Durogesic Matrix if you are breastfeeding. Do not breastfeed for 3days after removing the Durogesic Matrix patch. This is because the medication may pass into breast milk.

Driving and operating machinery

Durogesic Matrix may affect your ability to drive and operate machinery, as it may cause drowsiness or dizziness. If this is the case, do not drive or operate machinery. Do not drive while using this medication 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 medication.

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

Your doctor will decide on the most suitable concentration of Durogesic Matrix for you, taking into account the intensity of your pain, your general condition, and the type of pain treatment you have received so far.

Before starting treatment and regularly during it, your doctor will also explain what you can expect from the use of Durogesic Matrix, when and for how long you should use it, when you should contact your doctor, and when you should discontinue use (see also section 2, “Withdrawal syndrome when stopping treatment with Durogesic Matrix”).

How to apply and change the patches

• Each patch contains a sufficient amount of medication for3days (72hours).
• You should change the patch every three days, unless your doctor has told you otherwise.
• Always remove the used patchbeforeapplying a new one.
• Change the patch alwaysat the same timeof the day every3días (72horas).
• If you are using more than one patch, change them all at the same time.
• Make a note of the day of the week, date, and time each time you apply a patch to remember when to change it.
• The following table shows when to change the patch:

Where to apply the patch

Adults

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

Children

• Apply the patch always to the upper back so that your child has difficulty reaching or removing it.
• Check occasionally that the patch is still adhered to the skin.
• It is essential that the child does not remove the patch and put it in their mouth, as this could put their life in danger or be fatal.
• Keep your child under close observation for 48hours after:

• Applying the first patch
• Applying a patch with a higher dose

• The patch may take some time to reach its maximum effect. Therefore, your child may need other painkillers until the patch is 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), irritated skin, or wounds.
• Areas of skin with a lot of hair. If there is hair, do not shave it (the skin irritates with shaving). Instead, cut it as close to the skin as possible.

How to apply the patch

Step 1: Prepare the skin

• Before applying the patch, check that the skin is completely dry, clean, and fresh.
• If you need to wash the skin, use only cold water.
• Do not use soap or other cleaners, creams, moisturizers, oils, or talc before applying the patch.
• Do not apply the patch immediately after a bath or shower.

Step 2: Open the package

• Each patch is sealed in its own package.
• Open the package by tearing or cutting along the perforated line, indicated by an arrow.
• Tear the package edge gently or cut it completely along the sealed edge (if using scissors, make the cut next to the sealed edge to avoid damaging the patch).

• Hold the two package parts open and pull them apart.
• Remove the patch and use it immediately.
• Save the empty package to dispose of the used patch later.
• Use each patch only once.
• Do not remove the patch from its package until you are ready to use it.
• Check that the patch is not damaged.
• Do not use the patch if it is divided or cut or has any damage.
• Never divide or cut the patch.

Step 3: Peel and press

• Make sure the patch will be covered by a loose garment and do not adhere it under elastic or tight clothing.
• Peel off the shiny plastic protective layer from the center of the patch, taking care not to touch the adhesive part of the patch.
• Press the adhesive part of the patch onto the skin.
• Remove the other protective layer and press the entire patch onto the skin with the palm of your hand.
• Hold for at least 30seconds. Make sure the patch is well adhered, especially around the edges.

Step 4: Dispose of the patch

• As soon as you remove the patch, fold it in half, with the adhesive side sticking to itself.
• Put it back in the original package and dispose of it according to your pharmacist's instructions.
• Keep used patches out of sight and reach of children; although used, the patches contain medication that can harm children and even be fatal.

Step 5: Wash your hands

• Wash your hands only with water after handling the patches.

More information about using Durogesic Matrix

Activities during patch use

• The patches are water-resistant.
• You can take a shower or bath with the patch on, but do not rub it.
• If your doctor agrees, you can exercise or engage in sports with the patch on.
• You can also swim with the patch on, but:

• Do not use hot tubs.
• Do not cover the patch with elastic or tight clothing.

• When wearing the patch, do not expose it to direct heat, such as heating pads, electric blankets, hot water bottles, hot water beds, or heat lamps or tanning beds.Do not take the sun or prolonged hot baths, and do not use saunas. If you do, you may increase the amount of medication released from the patch.

How long does it take for the patches to work?

• The first patch may take some time to reach its maximum effect.
• Your doctor may give you additional painkillers during the first few days.
• After that, the patch should help relieve pain continuously, allowing you to stop taking other painkillers. However, your doctor may prescribe occasional additional painkillers.

How long will you need to use the patches?

• The patches of Durogesic Matrix are indicated for prolonged pain. Your doctor will tell you how long you can expect to use the patches.

If the pain worsens

• If your pain worsens suddenly after applying the last patch, check the patch. If it no longer adheres well or has fallen off, replace it (see also the section If the patch falls 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 and contact your doctor immediately or call the Toxicology Information Service. Tel.: (91) 562 04 20, indicating the medication and the amount applied, or go to the hospital.

The signs of overdose include breathing problems or shallow breathing, fatigue, extreme drowsiness, inability to think clearly or walk or speak normally, and dizziness or confusion. An overdose can 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 day and time. Change the patch again after3days (72hours), as usual.
• If you are delayed, you should talk to your doctor, as you may need additional painkillers, butdo notapply additional patches.

If the patch falls off

• If the patch falls off before it should be changed, apply a new one immediately and note the day and time. Choose a new skin area:
• On the trunk or arm
• On the upper back of your child
• Inform your doctor about this and leave the patch on for another3days (72hours)or for the time your doctor tells you, before changing the patch in the usual way.
• If the patches tend to fall off, consult your doctor, pharmacist, or nurse.

If you want to stop using the patches

• Do not stop using this medication abruptly. If you want to stop using this medication, talk to your doctor first. Your doctor will tell you how to do it, usually by gradually reducing the dose to minimize withdrawal symptoms. See also section 2, “Withdrawal symptoms when stopping Durogesic Matrix use”.
• If you stop using the patches, do not use them again without consulting your doctor first. You may need a different dose when you resume treatment.

If you have any other questions about using this medication, ask your doctor or pharmacist.

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

If you, or your partner or caregiver, observe any of the following signs in the person wearing the patch, remove the patch and call a doctor or go immediately to the nearest hospital. You may need urgent medical treatment.

• Unusual drowsiness, slower or weaker breathing than expected.

Follow the previous recommendations and have the person wearing the patch move and talk as much as possible. In very rare cases, these breathing difficulties can compromise life or even be fatal, especially in people who have not used strong opioid analgesics (such as Durogesic Matrix or morphine) before. (Rare, may affect up to 1 in 100 people)

• Brusque swelling of the face or throat, severe irritation, redness, or blisters on the skin. All of them can be signs of a severe allergic reaction. (The frequency cannot be estimated from the available data)

• Seizures (convulsions). (Rare, may affect up to 1 in 100 people)

• Decreased level of consciousness or loss of consciousness. (Rare, may affect up to 1 in 100 people)

The following side 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, or hearing things that are not present (hallucinations)
• Trembling or muscle spasms
• Strange sensation in the skin, such as tingling or prickling (paresthesia)
• Sensation of spinning (vertigo)
• Fast or irregular heartbeats (palpitations, tachycardia)
• Increased blood pressure
• Sensation of lack of air (dyspnea)
• Diarrhea
• Dry mouth
• Stomach pain or indigestion
• Excessive sweating
• Itching, rash, or redness of the skin
• Difficulty urinating or emptying the bladder completely
• Intense fatigue, weakness, or general discomfort
• Sensation of cold
• Swelling of the hands, ankles, or feet (peripheral edema)

Rare (may affect up to 1 in 100 people)

• Feeling agitated or disoriented
• Sensation of being extremely happy (euphoria)
• Decreased sensation or sensitivity, especially in the skin (hypoesthesia)
• Memory loss
• Blurred vision
• Slow heart rate (bradycardia) or low blood pressure
• Blue skin color caused by a decrease in oxygen in the blood (cyanosis)
• Loss of intestinal contractions (ileus)
• Skin rash with itching (eczema), allergic reaction, or other skin disorders where the patch is applied
• Flu-like illness
• Sensation of change in body temperature
• Fever
• Muscle contraction
• Difficulty obtaining or maintaining an erection (impotence) or problems with sexual relations
• Difficulty swallowing

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

• Pupil constriction (miosis)
• Occasional interruption of breathing (apnea)

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 agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that are not present, sleep disturbances, nightmares)
• You may become dependent on Durogesic Matrix (see section 2).

You may notice rashes, redness, or a mild itching sensation on the skin where the patch is applied. It is usually mild and disappears after removing the patch. If not, or if the patch irritates your skin a lot, inform your doctor.

Repeated use of the patches may make the medication less effective (you become accustomed to it or become more sensitive to pain) or may cause dependence.

If you change from another analgesic to Durogesic Matrix or if you stop using Durogesic Matrix abruptly, you may experience withdrawal symptoms, such as dizziness, feeling sick, diarrhea, anxiety, or tremors. Inform your doctor if you notice any of these effects.

There have also been reported cases of newborn babies experiencing withdrawal symptoms after their mothers used Durogesic Matrix for an extended period during pregnancy.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Vigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Where to Store the Patches

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

Store in the original packaging to protect it from light. This medication does not require any special storage temperature.

Store this medication in a protected and secure location where other people cannot access it. It can be very harmful and cause death to people who may accidentally or intentionally use this medication when it has not been prescribed.

How Long Can You Store Durogesic Matrix

Do not use this medication after the expiration date, which appears on the box and packaging. The expiration date is the last day of the month indicated. If the patches are expired, take them to the pharmacy.

Do not use this medication if you observe that the patches are damaged.

How to Dispose of Used or Unused Patches

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

Used patches should be folded firmly in half, so that the adhesive side of the patch adheres to itself. Then, they should be safely disposed of by placing them in the original packaging and storing them out of sight and reach of other people, especially children, until they are safely disposed of. Ask your pharmacist how to dispose of the packaging and medications that you no longer need.

Medications should not be thrown away through the drains or in the trash. Deposit the packaging and medications that you no longer need in the SIGRE point at the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications that you no longer need. This way, you will help protect the environment.

Composition ofDurogesic Matrix

The active ingredient of Durogesic Matrix is fentanil. Each transdermal patch contains 16.8mg of fentanil, which releases a dose of 100micrograms/hour.

The other components of the patch are:

Backing layer:Polyester/copolymer of ethylene-acetate vinyl film,

Protective layer:Silicone-coated polyester film,

Medication layer:Acrylic adhesive.

Printing inks (on the back):

The Durogesic Matrix 100 micrograms/hour patch also contains grey printing ink.

Appearance of the product and contents of the package

Durogesic is a translucent, rectangular patch with rounded edges. Each patch measures 42.0cm2, and is marked with a border and with “Durogesic Matrix 100 µg fentanil/h” in grey printing ink.

The patches come in individually sealed heat-sealed (acrylonitrile or cyclic olefin copolymer) pouches, and are supplied in carton containers containing 3, 4, 5, 8, 10, 16, 20 or 30pouches.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Janssen-Cilag, S.A.

Pº de Las Doce Estrellas, 5-7

28042 Madrid

Spain

Manufacturer

Janssen Pharmaceutica N.V.

Turnhoutseweg 30

2340 Beerse

Belgium

This medicine is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Last review date of this leaflet:October 2024.

Other sources of information

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.