Leaflet: information for the user

Avaric 67microgram sublingual tablets

Avaric 133microgram sublingual tablets

Avaric 267microgram sublingual tablets

Avaric 400microgram sublingual tablets

Avaric 533microgram sublingual tablets

Avaric 800microgram sublingual tablets

fentanyl

Read this leaflet carefully before you start taking this medicine,because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask yourdoctor or pharmacist.
• This medicine has been prescribedonlyfor you, and you should not give it to others even if they havethe same symptomsas you, as it may harm them.
• If you experience any side effects,consult your doctor or pharmacist,even if they are not listed in this leaflet. See section 4.

1. What Avaric is and what it is used for

2. What you need to know before you start taking Avaric

3. How to take Avaric

4. Possible side effects

5. Storage of Avaric

6. Contents of the pack and additional information

Avariccontains the active ingredient fentanilo, which belongs to a group of potent pain medications called opioids.

Avaricis used for the treatment of breakthrough pain in adult patients with cancer who are alreadytakingotheropioid pain medications for persistent pain (present all the time).

Breakthrough pain is a type of pain that occurs suddenly, even though you have taken or used your usual opioid pain medication.

Do not takeAvaric

• if you are allergic to fentanyl or any of the other ingredients of this medicine (listed in section 6).
• if you have severe respiratory problems or lung disorders;
• if you are currently taking monoamine oxidase inhibitors (MAO) for severe depression (or have taken them in the last 2 weeks).
• if you are not regularly taking a prescribed opioid medication (e.g., codeine, fentanyl, hydromorphone, morphine, oxycodone, meperidine), every day at the same time, for at least a week to control persistent pain. If you have not been taking those medications,do not takeAvaric as its use may increase the risk of your breathing becoming slower and/or shallower, and even stopping;

• if you have short-term pain other than breakthrough pain;

• if you are being treated with medications containing sodium oxibate.

Warnings and precautions

Avaric contains an active substance in such a quantity that it may be fatal to a child. Therefore, keep all tablets out of sight and reach of children and those who are not patients at all times.

Keep the tablets in a closed container with a lock and do not store the tablets once they have been removed from the blister pack.

Consult your doctor or pharmacist before starting to takeAvaric.

Store this medicine in a safe place where others cannot access it (see section 5. Storage of Avaric for more information).

Before starting treatment, inform your doctor if you have or have had any of the following symptoms, as you will need to take them into account when prescribing your dose:

• your other opioid analgesic medication for chronic cancer pain has not yet stabilized;
• you have any respiratory disorder (such as asthma, wheezing or shortness of breath);
• you have had a head injury;
• you have heart problems, especially slow heart rate, irregular heartbeat, low blood volume or low blood pressure;
• you have liver or kidney problems, as these organs affect the way your body eliminates the medicine.
• you are taking antidepressants or antipsychotics; see the section “Use of Avaric with other medicines”.

While taking Avaric, consult your doctor if:

• you feel pain or increased sensitivity to pain (hyperalgesia) that does not respond to a higher dose of the medicine as prescribed by your doctor.
• you experience a combination of the following symptoms: nausea, vomiting, loss of appetite, fatigue, weakness, dizziness and low blood pressure. Together, these symptoms may be an indication of a potentially life-threatening condition called adrenal insufficiency, in which the adrenal glands do not produce enough hormones.
• you have ever had adrenal insufficiency or hormone deficiency (androgen deficiency) with the use of opioids.
• Long-term use and tolerance
• This medicine contains fentanyl, an opioid. Repeated use of opioid analgesics may make the medicine less effective (your body becomes accustomed to it, known as pharmacological tolerance). You may also become more sensitive to pain when taking Avaric. This is known as hyperalgesia. Increasing the dose of Avaric may continue to reduce pain for a while, but it may also be harmful. If you notice that the medicine is losing its effectiveness, consult your doctor. Your doctor will decide whether it is better to increase the dose or to gradually reduce the use of Avaric.
• Dependence and addiction
• The repeated use of Avaric may 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 may cause you to feel a lack of control over the amount of medicine you should use or the frequency with which you should use it. You may feel the need to continue using the medicine even though it does not help to relieve pain.
• The risk of dependence or addiction varies from person to person. The risk of becoming dependent or addicted to Avaric may be higher if:
• -you or any member of your family have abused alcohol or experienced dependence on it, prescription medicines 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 illnesses.
• If you notice any of the following symptoms while using Avaric, it could be a sign of dependence or addiction:
• -you need to use the medicine for longer than indicated 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 and unsuccessful attempts to stop using the medicine or control its use.
• -you feel unwell when you stop using the medicine (e.g., nausea, vomiting, diarrhea, anxiety, chills, tremors and sweating), 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 taking the medicine and how to do it safely.

Respiratory sleep disorders

Avaric may cause respiratory sleep disorders, including sleep apnea (interrupted breathing during sleep) and sleep hypoxemia (low oxygen levels in the blood). Symptoms may include interrupted breathing during sleep, waking up at night due to lack of air, difficulty maintaining sleep or excessive daytime somnolence. If you or someone else observes these symptoms, contact your doctor to evaluate the possibility of reducing the dose.

Children and adolescents

Avaric should not be used in children and adolescents under 18 years old.

Use of Avaric with other medicines

Inform your doctor or pharmacist that you are taking, have taken recently or may need to take any other medicine. Specifically:

• Medicines called monoamine oxidase inhibitors (MAO) (used for the treatment of severe depression), see “Do not take Avaric”. Inform your doctor if you have taken this type of medicine in the last 2 weeks.
• Sleeping pills, anxiety medications, antihistamines, tranquilizers, some muscle relaxants or any medicine that can normally make you sleep (that have a sedative effect).
• Any medicine that can influence the effect of Avaric (affecting the way your body breaks down Avaric), such as:

• medicines for HIV infection control (such as ritonavir, indinavir, nelfinavir, saquinavir),
• medicines for fungal infections (such as ketoconazole, itraconazole, fluconazole),
• medicines for bacterial infections (such as clarithromycin, erythromycin, telithromycin), including tuberculosis (such as rifabutin, rifampicin),
• medicines for severe nausea (such as aprepitant, dronabinol)
• medicines for high blood pressure and cardiovascular diseases (such as diltiazem, verapamil),
• medicines for depression (such as fluoxetine or St. John's Wort),
• medicines for acid or indigestion (such as cimetidine),
• sleeping pills or sedatives (such as phenobarbital),
• medicines for controlling convulsions/epileptic seizures (such as carbamazepine, phenytoin, oxcarbazepine),
• antiviral medicines (such as efavirenz, nevirapine),
• anti-inflammatory or immunosuppressive medicines (such as glucocorticoids),
• medicines for diabetes (such as pioglitazone),
• psycho-stimulants (such as modafinil),

• Determined types of powerful analgesics, known as partial agonists/antagonists, such as buprenorphine, nalbuphine, pentazocine (medicines for pain) and some analgesics for neuropathic pain (gabapentin and pregabalin). You may experience withdrawal symptoms (nausea, vomiting, diarrhea, anxiety, chills, tremors and sweating) while using these medicines. These medicines may reduce or reverse the effect of Avaric.

• The risk of adverse effects increases if you are taking medicines such as certain antidepressants or antipsychotics. Avaric may interact with these medicines and you may experience changes in mental state (e.g., agitation, hallucinations, coma) and other effects such as high body temperature, increased heart rate, unstable blood pressure and exaggerated reflexes, muscle rigidity, lack of coordination and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Your doctor will tell you if Avaric is suitable for you.

• The concomitant use of Avaric and sedatives, such as benzodiazepines or related medicines, increases the risk of drowsiness, difficulty breathing (respiratory depression), coma and may be potentially fatal. Therefore, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes Avaric along with sedatives, your doctor must limit the dose and duration of concomitant treatment. Inform your doctor about all sedatives you are taking and follow your doctor's recommendations closely. It may be helpful to inform friends or family members who are aware of the signs and symptoms mentioned above. Contact your doctor when you experience such symptoms.

• The concomitant use of medicines containing sodium oxibate and fentanyl is contraindicated (see section “Do not take Avaric”). Treatment with sodium oxibate should be discontinued before starting treatment with Avaric.

Taking Avaric with food, drinks and alcohol

• Avariccan be taken before or after meals, but not during meals. You can drink a little water before takingAvaricto help moisten your mouth, but you should not drink or eat anything while taking this medicine.
• Do not drink grapefruit juice while takingAvaric, as it may affect the way your body breaks down Avaric.
• Do not drink alcohol while takingAvaric. It may increase the risk of experiencing dangerous side effects.

Pregnancy and breastfeeding

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

You should not useAvaricif you are pregnant, unless you have consulted your doctor. You should not useAvaricduring labor, as fentanyl may cause respiratory depression and withdrawal symptoms in the fetus or newborn.

Fentanyl may pass into breast milk and cause adverse effects in the infant. Do not useAvaricif you are breastfeeding. Do not start breastfeeding until at least 5 days have passed since your last dose of Avaric.

Driving and operating machinery

Consult your doctor if it is safe for you to drive a vehicle or operate machinery after takingAvaric. You should not drive or operate machinery if you feel drowsy or dizzy, experience blurred vision or double vision, or have difficulty concentrating. It is essential to know how you react toAvaricbefore driving or operating machinery.

Avaric contains sodium

This medicine contains less than 1 mmol of sodium per tablet; that is, it is essentially “sodium-free”.

Before starting treatment and regularly during it, your doctor will also explain what you can expect from the use of Avaric, when and for how long you should use it, when you should contact your doctor and when you should suspend its use (see also section 2).

This medication should be taken by placing the tablet under the tongue (sublingual use).

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist.In case of doubt, consult your doctor or pharmacist again.

If your doctor has changed you to Avaric,do not useat the same time the previous medication containing fentanil for the treatment of breakthrough pain. Eliminate the previous medication. However, continue using the opioid medication for persistent cancer pain that you are using for persistent cancer pain during treatment with Avaric.

Initial phase – Establishing the most suitable dose

To ensure the success of treatment with Avaric, your doctor will need to identify the most suitable dose for the treatment of breakthrough pain. Avaric sublingual tabletsare available in a wide range of doses. You may need to try different doses ofAvaric sublingual tabletsduring different episodes of pain before finding the most suitable dose. Your doctor will help you with this task and find the most suitable tablet dose for you.

If you do not get adequate pain relief with a tablet, your doctor may instruct you to take two tablets to treat an episode of breakthrough pain. Do not take a second tablet unless your doctor instructs you to do so, as you may suffer an overdose. Your doctor will advise you on the tablet dose to use.

You must always use the dose of Avaric prescribed by your doctor –it may be different from the dose you have used with other medications for treating breakthrough pain.

Maintenance phase – Once the most suitable dose has been established

Once you and your doctor have established a dose ofAvaricthat controls your breakthrough pain, you should not take this dose more than four times a day.A dose ofAvaricmay consist of more than one tablet.

If you think the dose ofAvaricyou are using does not control your breakthrough pain satisfactorily, inform your doctor because you may need to adjust the dose.

You should not change your dose ofAvaricunless your doctor instructs you to do so.

Medication intake

Avaricmust be used sublingually. This means that you should place the tablet under your tongue, where it will dissolve quickly to allow fentanil to be absorbed through the mucous membrane of the mouth.

When you have a breakthrough pain, take the dose indicated by your doctor as follows:

If you take more Avaric than you should

• eliminate any remaining tablet from your mouth,
• tell your caregiver or another person at home what has happened,
• you or your caregiver should immediately contact your doctor, pharmacist, or local hospital and ask for instructions

The symptoms of an overdose include altered mental state, loss of consciousness, extreme drowsiness, slow and shallow breathing. If this occurs, seek immediate medical assistance.

An overdose can also cause a brain disorder known as toxic leukoencephalopathy.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

Note for caregivers

While waiting for the doctor:

• keep the person awake by talking to them or shaking them occasionally,
• ensure that the person's airways are open and that they are breathing.

If you think someone has accidentally taken Avaric, seek immediate emergency medical help.

If you forget to take Avaric

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Avaric

You should stop using Avaric when you no longer have breakthrough pain. However, you should continue taking your usual opioid medications for persistent cancer pain as recommended by your doctor. You may experience withdrawal symptoms similar to the possible side effects of Avaric when you interrupt treatment with Avaric. If you experience withdrawal symptoms or are concerned about pain relief, consult your doctor, who will evaluate whether you need any medication to reduce or suppress withdrawal symptoms.

If you have any other questions about the use of thismedication, ask your doctororpharmacist.

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

The most serious side effects are:

• shallow and slow breathing(rare, may affect up to 1 in 100 people)
• extremely low blood pressure and shock.

If you start to feel drowsy or experience any of the previously mentioned side effects, stop taking Avaric and contact your doctor immediately, or have your caregiver do so, and call emergency services.

Other side effects that may appear:

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

• nausea,
• constipation,
• drowsiness,
• sedation,
• dizziness.

Common(may affect up to 1 in 10 people):

• confusion, anxiety, seeing or hearing things that are not real (hallucinations), abnormal thoughts,
• asthenia (weakness),
• headache, muscle cramps, sensation of dizziness, loss of consciousness,
• dry mouth, alteration of taste,
• low blood pressure,
• vomiting, abdominal pain, indigestion,
• sweating, itching of the skin,
• falls

Rare(may affect up to 1 in 100 people):

• decreased appetite,belching, abdominal distension, tooth decay, intestinal obstruction (ileus),
• general feeling of illness,
• tingling or numbness, difficulty coordinating movements, convulsions (epileptic seizures), coma,
• surreal dreams, feeling of detachment, depression, mood changes, excessive feeling of well-being,
• serious breathing problems,
• blurred or double vision,
• skin rash, increased or altered sensitivity to touch,
• difficulty urinating.

Unknown frequency(cannot be estimated from available data):

• retraction of the gums, tooth loss.
• flushing,
• sensation of excessive heat,
• diarrhea,
• inflammation of arms or legs,
• fatigue,

• insomnia,
• fever,

• withdrawal syndrome (which may manifest as the following side effects: nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating),
• drug dependence (addiction) (see section 2),
• drug abuse (see section 2),
• delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that are not real, sleep disturbances, nightmares),
• tolerance to drugs(see section 2).

Prolonged treatment with fentanil during pregnancy may cause withdrawal symptoms in the newborn, which can be potentially fatal (see section 2).

Reporting of side effects:

If you experience any type of side effect, consult your doctor or pharmacist, 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 Pharmacovigilance 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.

The pain medication, Avaric, is very strong and can be fatal if a child takes it accidentally.

Keep this medication out of sight and reach of children.

Store this medication in a safe place where other people cannot access it. It can cause serious harm and be fatal to people who take this medication by accident or intentionally when it has not been prescribed to them.

Keep Avaric in a locked, closed place.

Do not usethis medicationafter the expiration date that appears onthe box ofthe packaging after CAD. The expiration date is the last day of the month indicated.

This medication does not require special temperature conditions for its conservation.

Store in the original blister pack, to protect it from light.

Do not store the tablet once it has been removed from the blister pack.

Medicines should not be thrown away through the drains or in the trash. Deposit the containers and medications that you no longer need at the SIGRE point of the pharmacy. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Avaric

• The active ingredient is fentanil

Each sublingual tablet contains 67, 133, 267, 400, 533 or 800 micrograms of fentanil (as citrate).

• The other components (excipients) arecalcium hydrogen phosphate anhydrous, microcrystalline cellulose, anhydrous sodium hydrogen phosphate, hypromellose, macrogol, magnesium stearate, maltodextrin, titanium dioxide (E171), triacetin, printing ink [shellac, iron oxide black (E172)].

Appearance of the product and contents of the package

Avaric 67 micrograms is a white, convex, triangular tablet. Its height is 5.6 mm and has a “0” printed in black ink on one face.

Avaric 133 micrograms is a white, convex, triangular tablet. Its height is 5.6 mm and has a “1” printed in black ink on one face.

Avaric 267 micrograms is a white, convex, triangular tablet. Its height is 5.6 mm and has a “2” printed in black ink on one face.

Avaric 400 micrograms is a white, convex, triangular tablet. Its height is 5.6 mm and has a “4” printed in black ink on one face.

Avaric 533 micrograms is a white, convex, triangular tablet. Its height is 5.6 mm and has a “5” printed in black ink on one face.

Avaric 800 micrograms is a white, convex, triangular tablet. Its height is 5.6 mm and has an “8” printed in black ink on one face.

Avaric sublingual tablets are available in blister packs that can be removed, child-resistant, in presentations of 3, 4, 15 or 30 tablets.

Not all package sizes may be marketed.

Marketing Authorization Holder and Responsible Manufacturer

Marketing Authorization Holder

ANGELINI PHARMA ESPAÑA, S.L.

c/ Antonio Machado, 78-80.

3rd floor, module A-Edificio Australia

08840 Viladecans, Barcelona (Spain)

Responsible Manufacturer

Ethypharm

Chemin de la Poudrière

76120 Grand Quevilly

FRANCE

Acraf, S.P.A. (ACR ANGELINI FRANCESCO)

Via Vecchia del Pinocchio, 22

ANCONA , I-60131 - Italy

This medicine is authorized in the member states of the European Economic Area with the following names:

Sweden: Vellofent

Bulgaria: Vellofent

Czech Republic: Vellofent

Spain: Avaric

Greece: Vellofent

Italy: Vellofent

Poland: Vellofent

Portugal: Vellofent

Last review date of thisleaflet:March 2025

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