AVARIC 133 micrograms SUBLINGUAL TABLETS

Introduction

Package Leaflet: Information for the User

Avaric 67micrograms sublingual tablets

Avaric 133micrograms sublingual tablets

Avaric 267micrograms sublingual tablets

Avaric 400micrograms sublingual tablets

Avaric 533micrograms sublingual tablets

Avaric 800micrograms sublingual tablets

fentanyl

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Avaric and what is it used for
2. What you need to know before you take Avaric
3. How to take Avaric
4. Possible side effects
5. Storing Avaric
6. Contents of the pack and other information

1. What is Avaric and what is it used for

Avaric contains the active substance fentanyl, which belongs to a group of strong pain-relieving medicines called opioids.

Avaric is used to treat breakthrough pain in adult patients with cancer who are already taking other opioid pain medicines for their persistent (ongoing) pain.

Breakthrough pain is a type of pain that happens suddenly, even when you have taken your usual opioid pain medicine for your persistent pain.

2. What you need to know before you take Avaric

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 breathing problems or severe lung disease;
• if you are currently taking monoamine oxidase inhibitors (MAOIs) for severe depression (or have taken them in the last 2 weeks).
• if you are not already taking a prescribed opioid pain medicine every day for your persistent pain (e.g. codeine, fentanyl, hydromorphone, morphine, oxycodone, meperidine), all at the same time, for at least one week. If you have not been taking these medicines, 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 that is not breakthrough pain;

• if you are being treated with medicines that contain sodium oxybate.

Warnings and precautions

Avaric contains an active substance in such an amount that it can be fatal for a child. Therefore, always keep all tablets out of the sight and reach of children and those who are not patients.

Keep the tablets in a locked cupboard and do not store the tablets once they have been removed from the blister pack.

Talk to your doctor or pharmacist before you start taking Avaric.

Keep this medicine in a safe place where others cannot get to it (see section 5. Storing Avaric for more information).

Before starting treatment, tell your doctor if you have or have had any of the following symptoms, as they will need to be taken into account when prescribing your dose:

• your other prescribed opioid pain medicine for your chronic cancer pain has not yet been stabilized;
• you have any breathing problems (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 have effects on how your body gets rid of the medicine.
• you are taking antidepressants or antipsychotics; see the section “Using Avaric with other medicines”.

While taking Avaric, talk to 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 can be a sign of a potentially life-threatening condition called adrenal insufficiency, where the adrenal glands do not produce enough hormones.
• you have ever had adrenal insufficiency or a lack of sex hormones (androgen deficiency) with the use of opioids.
• Long-term use and tolerance
• This medicine contains fentanyl, an opioid. Repeated use of opioid pain relievers can make the medicine less effective (your body gets used to it, which is known as pharmacological tolerance). You may also become more sensitive to pain when using Avaric. This is known as hyperalgesia. Increasing the dose of Avaric may continue to reduce the pain for a while, but it can also be harmful. If you find that the medicine is becoming less effective, talk to your doctor. Your doctor will decide whether it is best for you to increase the dose or gradually reduce your use of Avaric.
• Dependence and addiction

• The repeated use of Avaric can also lead to dependence, abuse, and addiction, which could result in a potentially life-threatening overdose. The risk of these side effects may be greater with a higher dose and longer use. Dependence or addiction can cause a feeling of lack of control over the amount of medicine you use or how often you use it. You may feel the need to keep using the medicine even if it does not help relieve the pain.
• The risk of dependence or addiction varies from person to person. The risk of becoming dependent on or addicted to Avaric may be greater if:
• - you or a family member have abused alcohol or have been dependent on prescription medicines or illegal drugs (“addiction”).
• - you smoke.
• - you have ever had mood problems (depression, anxiety or personality disorder) or have been treated by a psychiatrist for other mental health problems.
• 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 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 feel calm” or “to help you sleep”.
• - you have made repeated unsuccessful attempts to stop using the medicine or control your 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, talk to your doctor to determine the best course of treatment for you, when it is appropriate to stop the medicine, and how to do so safely.

Sleep-related breathing disorders

Avaric may cause sleep-related breathing disorders, including sleep apnea (pauses in breathing while sleeping) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing while sleeping, waking up in the middle of the night due to lack of breath, difficulty staying asleep or excessive daytime sleepiness. If you or someone else notices these symptoms, contact your doctor to assess the possibility of reducing the dose.

Children and adolescents

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

Using Avaric with other medicines

Tell your doctor or pharmacist that you are taking, have recently taken or might take any other medicines. In particular:

• Medicines called monoamine oxidase inhibitors (MAOIs) (used to treat severe depression), see “Do not take Avaric”. Tell your doctor if you have taken this type of medicine in the last 2 weeks.
• Sleeping pills, medicines for anxiety, antihistamines, sedatives, some muscle relaxants or any medicine that can normally make you sleepy (has a sedative effect).
• Any medicine that may affect the effect of Avaric (affecting the way your body breaks down Avaric), such as:

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

• Certain types of strong pain relievers, called partial agonist/antagonists, such as buprenorphine, nalbuphine, pentazocine (medicines to treat pain) and some pain relievers 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 side 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 status (e.g. agitation, hallucinations, coma) and other effects such as body temperature above 38°C, increased heart rate, unstable blood pressure and exaggerated reflexes, muscle stiffness, 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 sedative medicines, such as benzodiazepines or related medicines, increases the risk of drowsiness, breathing difficulties (respiratory depression), coma and can be potentially life-threatening. Due to this, concomitant use should only be considered when other treatment options are not possible.

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

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

Taking Avaric with food, drinks and alcohol

• Avaric can be used before or after, but not during meals. You can drink a little water before taking Avaric to help moisten your mouth, but do not drink or eat anything while taking this medicine.
• Do not drink grapefruit juice while taking Avaric, as it can affect the way your body breaks down Avaric.
• Do not drink alcohol while taking Avaric. It can increase the risk of experiencing serious side effects.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should not use Avaric if you are pregnant, unless you have discussed it with your doctor. You should not use Avaric during labor, as fentanyl can cause respiratory depression and withdrawal symptoms in the fetus or newborn.

Fentanyl can pass into breast milk and cause side effects in the breastfed baby. Do not use Avaric if you are breastfeeding. You should not start breastfeeding until at least 5 days after the last dose of Avaric.

Driving and using machines

Ask your doctor if it is safe for you to drive or use machines after taking Avaric. You should not drive or use machines if you feel drowsy or dizzy, have blurred or double vision, or experience difficulty concentrating. It is important that you know how you react to Avaric before driving or using machinery.

Avaric contains sodium

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

3. How to Take Avaric

Before starting treatment and regularly during treatment, your doctor will also explain what you can expect from using Avaric, 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).

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

Follow your doctor's or pharmacist's instructions for administering this medication exactly. If in doubt, consult your doctor or pharmacist again.

If your doctor has switched you to Avaric, do not use the previous medication containing fentanyl for breakthrough pain treatment at the same time. Dispose of the previous medication. However, continue using the opioid medication you are using for persistent cancer pain during treatment with Avaric.

Initial Phase – Establishing the Most Suitable Dose

For treatment with Avaric to be successful, your doctor will need to identify the most suitable dose for treating breakthrough pain. Avaric is available in a wide range of doses. You may need to try different doses of Avaric during 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 obtain adequate pain relief with one tablet, your doctor may instruct you to take two tablets to treat a breakthrough pain episode. Do not take a second tablet unless your doctor instructs you to do so, as you could suffer an overdose. Your doctor will advise you on the tablet dose to use.

You should always use the Avaric dose prescribed by your doctor –this may be different from the dose you used with other medications to treat breakthrough pain.

Maintenance Phase – Once the Most Suitable Dose Has Been Established

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

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

Do not change your Avaric dose unless your doctor instructs you to do so.

Taking the Medication

Avaric should be used sublingually. This means that the tablet should be placed under the tongue, where it will dissolve quickly to allow fentanyl to be absorbed through the mouth lining.

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

• If you have a dry mouth, take a sip of water to moisten it. Spit out or swallow the water.
• Remove the tablet(s) from the blister pack immediately before use.
• Peel back the top layer of the blister pack, as indicated on the aluminum blister, and carefully remove the tablet. Do not attempt to push the Avaric sublingual tablets through the top layer.
• Place the tablet under your tongue as far back as possible, and let it dissolve completely.
• Avaric will dissolve quickly under the tongue and be absorbed to provide pain relief. It is therefore important that you do not suck, chew, or swallow the tablet.
• After 30 minutes, if there are any remaining tablet fragments, swallow them.
• Do not drink or eat anything until the tablet has dissolved completely under your tongue.

If You Take More Avaric Than You Should

• remove any remaining tablet from your mouth,
• tell your caregiver or another person in your household what has happened,
• you or your caregiver should immediately contact your doctor, pharmacist, or local hospital and ask for advice on what to do.

The symptoms of an overdose include altered mental state, loss of consciousness, extreme drowsiness, slow, shallow breathing. If this happens, seek medical help immediately.

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

In the event of an overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, stating 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,
• make sure the person has open airways and is breathing.

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

If You Forget to Take Avaric

Do not take a double dose to make up for forgotten 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 to treat persistent cancer pain as recommended by your doctor. You may experience withdrawal symptoms similar to the possible side effects of Avaric when you stop treatment with Avaric. If you have withdrawal symptoms or are concerned about pain relief, consult your doctor, who will assess whether you need any medication to reduce or suppress withdrawal symptoms.

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

4. Possible Side Effects

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

The most serious side effects are:

• shallow and slow breathing (uncommon, 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 above side effects, stop taking Avaric and contact your doctor immediately, or have your caregiver contact your doctor and call for emergency services.

Other side effects that may occur:

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,
• weakness (asthenia),
• headache, muscle cramps, feeling of dizziness, loss of consciousness,
• dry mouth, altered taste,
• low blood pressure,
• vomiting, abdominal pain, indigestion,
• sweating, skin itching,
• falls.

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

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

Frequency Not Known(cannot be estimated from available data):

• gum recession, tooth loss.
• flushing,
• feeling of excessive heat,
• diarrhea,
• inflammation of arms or legs,
• fatigue,

• insomnia,
• pyrexia,

• withdrawal syndrome (which can manifest with 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 do not really exist, sleep disturbances, nightmares),
• drug tolerance (see section 2).

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

Reporting Side Effects:

If you experience any side effects, consult your doctor or pharmacist, even if they are possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency's online system: https://www.notificaram.es.

By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Avaric

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 others cannot access it. It can cause serious harm and be fatal for people who take this medication accidentally or intentionally when it has not been prescribed for them.

Keep Avaric in a locked cabinet.

Do not use this medication after the expiration date stated on the carton after EXP. The expiration date is the last day of the month indicated.

This medication does not require special temperature conditions for storage.

Store in the original blister pack to protect from light.

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

Medications should not be disposed of via wastewater or household waste. Return the packaging and any unused medication to the pharmacy's SIGRE collection point. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Avaric Composition

• The active ingredient is fentanyl.

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

• The other ingredients (excipients) are anhydrous calcium hydrogen phosphate, microcrystalline cellulose, anhydrous disodium hydrogen phosphate, hypromellose, macrogol, magnesium stearate, maltodextrin, titanium dioxide (E171), triacetin, and printing ink [shellac, black iron oxide (E172)].

Appearance of the Product and Package Contents

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

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

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

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

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

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

Avaric sublingual tablets are available in child-resistant blister packs in packs of 3, 4, 15, or 30 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

ANGELINI PHARMA ESPAÑA, S.L.

c/ Antonio Machado, 78-80.

3rd floor, module A-Australia Building

08840 Viladecans, Barcelona (Spain)

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 medication is authorized in the Member States of the European Economic Area under the following names:

Sweden: Vellofent

Bulgaria: Vellofent

Czech Republic: Vellofent

Spain: Avaric

Greece: Vellofent

Italy: Vellofent

Poland: Vellofent

Portugal: Vellofent

Date of Last Revision of this Leaflet:March 2025

Detailed and up-to-date information on this medication is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es/