Avaric 267 micrograms sublingual tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Avaric 67 micrograms sublingual tablets

Avaric 133 micrograms sublingual tablets

Avaric 267 micrograms sublingual tablets

Avaric 400 micrograms sublingual tablets

Avaric 533 micrograms sublingual tablets

Avaric 800 micrograms sublingual tablets

fentanyl

Read the entire 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 your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if these effects are not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Avaric is and what it is 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 cancer pain in adult patients who are already taking other opioid pain medicines for persistent pain (pain present all the time).

Breakthrough pain is a type of pain that suddenly occurs, even though you have taken or used your regular opioid medicine for your ongoing pain.

2. What you need to know before starting to take Avaric

Do not take Avaric

• if you are allergic to fentanyl or to any of the other ingredients of this medicine (listed in section 6);
• if you have severe respiratory problems or serious lung disorders;
• if you are currently taking monoamine oxidase inhibitors (MAO inhibitors) for severe depression (or have taken them within the past 2 weeks);
• if you are not already taking an opioid medicine prescribed by your doctor (e.g., codeine, fentanyl, hydromorphone, morphine, oxycodone, meperidine) regularly every day at the same time, for at least one week, to manage persistent pain. If you have not been taking such medicines, do not take Avaric, as its use may increase the risk of your breathing becoming slower and/or shallower, or even stopping completely;
• if you have short-term pain other than breakthrough pain;
• if you are being treated with medicines containing sodium oxybate.

Warnings and precautions

Avaric contains an active substance in an amount that could be fatal to a child. Therefore, always keep all tablets out of sight and out of reach of children and individuals who are not patients.

Store the tablets in a locked, secure place, and do not store tablets once they have been removed from the blister pack.

Talk to your doctor or pharmacist before starting to take Avaric.

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

Before starting treatment, inform your doctor if you have or have had any of the following conditions, as these must be considered when determining your dose:

• your other prescribed opioid pain medication for chronic cancer pain has not yet been stabilized;
• you have any disorder affecting your breathing (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 how your body eliminates the medicine;
• you are taking antidepressants or antipsychotics; see section “Use of Avaric with other medicines”.

While taking Avaric, consult your doctor if:

• you experience pain or increased sensitivity to pain (hyperalgesia) that does not respond to a higher dose of the medicine as prescribed;
• you develop a combination of the following symptoms: nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Together, these symptoms may indicate a potentially life-threatening condition called adrenal insufficiency, in which the adrenal glands do not produce enough hormones;
• you have ever experienced adrenal insufficiency or sex hormone deficiency (androgen deficiency) while using opioids.

Long-term use and tolerance

This medicine contains fentanyl, an opioid. Repeated use of opioid painkillers may cause the drug to become less effective (the body becomes accustomed to it, 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 pain for a time, but it may also be harmful. If you notice the medicine is losing effectiveness, speak to your doctor. Your doctor will decide whether it is better to increase the dose or gradually reduce the use of Avaric.

Dependence and addiction

• Repeated use of Avaric 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 loss of control over the amount of medication you need to take or how often you need to take it. You may feel a need to continue using the medication even though it no longer helps 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 alcohol, prescription medications, 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 Avaric, it could be a sign of dependence or addiction:

• • you need to use the medication for longer than prescribed by your doctor.
• • you need to take a higher dose than recommended.
• • you are using the medication 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 medication or control its use.
• • you feel unwell when you stop taking the medication (e.g., nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating), and you 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 discontinue the medication, and how to do so safely.

Sleep-related respiratory disorders

Avaric may cause sleep-related respiratory disorders, including sleep apnea (interruptions in breathing during sleep) and sleep hypoxemia (low oxygen levels in the blood). Symptoms may include interruptions in breathing during sleep, waking up in the middle of the night due to shortness of breath, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else notices these symptoms, contact your doctor, who may consider reducing the dose.

Children and adolescents

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

Use of Avaric with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. Specifically:

• Medicines called monoamine oxidase inhibitors (MAOIs) (used to treat severe depression) – see “Do not take Avaric”. Inform your doctor if you have taken this type of medicine within the last two weeks.

• Sleeping pills, medicines for treating anxiety, antihistamines, tranquilizers, certain muscle relaxants, or any medicine that usually causes drowsiness (sedative effect).

• Any medicine that may influence the effect of Avaric (affecting how your body breaks down Avaric), such as:

• medicines for treating HIV infection (such as ritonavir, indinavir, nelfinavir, saquinavir),

• medicines for treating fungal infections (such as ketoconazole, itraconazol, fluconazole),

• medicines for treating bacterial infections (such as clarithromycin, erythromycin, telithromycin), including tuberculosis (such as rifabutin, rifampicin),

• medicines for severe nausea (such as aprepitant, dronabinol),

• medicines for treating high blood pressure and cardiovascular diseases (such as diltiazem, verapamil),

• medicines for treating 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 for controlling seizures/epileptic attacks (such as carbamazepine, phenytoin, oxcarbazepine),

• antiviral medicines (such as efavirenz, nevirapine),

• anti-inflammatory or immunosuppressive medicines (such as glucocorticoids),

• medicines for treating diabetes (such as pioglitazone),

• psycho-stimulant medicines (such as modafinil),

• Certain types of strong painkillers, known as partial agonists/antagonists, such as buprenorphine, nalbuphine, pentazocine (medicines for treating pain), and some painkillers 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 status (e.g., agitation, hallucinations, coma) and other effects such as body temperature above 38°C, increased heart rate, unstable blood pressure, exaggerated reflexes, muscle rigidity, lack of coordination, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Your doctor will advise you whether Avaric is suitable for you.

• Concomitant use of Avaric and sedative medicines, such as benzodiazepines or related medicines, increases the risk of drowsiness, difficulty breathing (respiratory depression), coma, and may be potentially fatal. Because of this, concomitant use should only be considered when no other treatment options are 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 helpful to inform friends or family members who are aware of the signs and symptoms mentioned above. Contact your doctor if you experience such symptoms.

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

Taking Avaric with food, drinks, and alcohol

• Avaric may be taken before or after, but not during meals. You may drink some water before taking Avaric to help moisten your mouth, but you must not drink or eat anything while taking this medicine.
• Do not drink grapefruit juice while taking Avaric, as it may affect how your body metabolizes Avaric.
• Do not drink alcohol while taking Avaric. It may increase the risk of experiencing dangerous adverse effects.

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.

You must not use Avaric if you are pregnant unless you have discussed it with your doctor. You must not use Avaric during childbirth, as fentanyl may cause respiratory depression and withdrawal syndrome in the fetus or newborn.

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

Driving and using machines

Consult your doctor whether it is safe for you to drive or operate machinery after taking Avaric. You must not drive or operate machinery 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 operating machinery.

Avaric contains sodium

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

3. How to take Avaric

Before starting treatment and regularly during treatment, your doctor will also explain to you what to 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 medicine must be taken by placing the tablet under the tongue (sublingual use).

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

If your doctor has switched you to Avaric, you must not continue using the previous fentanyl-containing medicine for breakthrough pain. Dispose of the previous medicine. However, continue taking the opioid medicine you are using for persistent cancer pain during treatment with Avaric.

Initial phase – Determining the most appropriate dose

For Avaric treatment to be successful, your doctor will need to identify the most appropriate dose for treating breakthrough pain episodes. Avaric is available in a wide range of doses. You may need to try different doses of Avaric during different pain episodes before finding the most appropriate dose. Your doctor will assist you with this and determine the most suitable tablet dose for you.

If you do not achieve 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 instructed by your doctor, as you could experience an overdose. Your doctor will advise you on the appropriate tablet dose to use.

You must always use the dose of Avaric prescribed by your doctor – this may differ from the dose you previously used with other medicines for breakthrough pain.

Maintenance phase – Once the most appropriate dose has been established

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

If you feel that the Avaric dose you are using does not satisfactorily control your breakthrough pain episodes, inform your doctor, as your dose may need adjustment.

Do not change your Avaric dose unless instructed by your doctor.

How to take the medicine

Avaric must be used sublingually. This means that the tablet must be placed under the tongue, where it will dissolve rapidly, allowing fentanyl to be absorbed through the lining of the mouth.

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

• If your mouth is dry, take a sip of water to moisten it. Spit or swallow the water.
• Remove the tablet(s) from the blister pack immediately before use.
• Carefully peel back the top layer of the blister pack, as indicated on the aluminum blister, and gently remove the tablet. Do not attempt to push the Avaric sublingual tablets through the top foil.
• Place the tablet under your tongue as far back as possible and allow it to dissolve completely.
• Avaric will dissolve rapidly 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 any residue of the tablet remains, it should be swallowed.
• Do not eat or drink anything until the tablet has completely dissolved under your tongue.

If you take more Avaric than you should

• remove any remaining tablet from your mouth,
• inform your caregiver or another person in your household about what has happened,
• you or your caregiver must contact your doctor, pharmacist, or local hospital immediately and ask what actions to take.

Symptoms of overdose include altered mental state, loss of consciousness, extreme drowsiness, slow or shallow breathing. If this occurs, seek immediate medical assistance.

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

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at 91 562 04 20, stating the medicine and the amount ingested.

Note for caregivers

While waiting for the doctor:

• keep the person awake by talking to them or gently shaking them from time to time,
• ensure the person has open airways and is breathing.

If you suspect someone has accidentally taken Avaric, seek emergency medical help immediately.

If you forget to take Avaric

Do not take a double dose to make up for a missed dose.

If you stop treatment with Avaric

Avaric should be discontinued when you no longer have breakthrough pain. However, you must continue taking your regular opioid medicines for persistent cancer pain as directed by your doctor. You may experience withdrawal symptoms similar to possible adverse effects of Avaric when stopping treatment with Avaric. If you experience 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 the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, Avaric may cause adverse effects, although not everyone experiences them.

The most serious adverse effects are:

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

If you begin to feel drowsy or experience any of the adverse effects listed above, stop taking Avaric and contact your doctor immediately, or have your caregiver call emergency services.

Other possible adverse effects:

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, altered taste,
• hypotension,
• vomiting, abdominal pain, indigestion,
• sweating, skin itching,
• falls.

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

• decreased appetite, heart murmurs, abdominal distension, dental caries, intestinal obstruction (ileus),
• general malaise,
• tingling or numbness, difficulty coordinating movements, seizures (epileptic fits), 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,
• sensation of intense heat,
• diarrhoea,
• swelling of arms or legs,
• fatigue,
• insomnia,
• pyrexia,
• withdrawal syndrome (which may present with the following adverse effects: nausea, vomiting, diarrhoea, 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),
• drug tolerance (see section 2).

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

Reporting of adverse effects:

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through 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 Avaric

Avaric, a pain medicine, is very strong and can be fatal if taken accidentally by a child.

Keep this medicine out of sight and reach of children.

Store this medicine in a safe place where others cannot access it. It may cause serious harm or be fatal to individuals who take this medicine accidentally or intentionally when it has not been prescribed for them.

Keep Avaric in a locked place.

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require special temperature conditions for storage.

Keep in the original blister pack to protect from light.

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

Medicines must not be disposed of via wastewater or household waste. Return unused packaging and medicines to your pharmacy’s SIGRE collection point. 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 Avaric

• The active substance is fentanyl.

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

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

Nature and contents of the pack

Avaric 67 micrograms is a white, convex, triangular tablet. It is 5.6 mm high and has a "0" printed in black ink on one side.

Avaric 133 micrograms is a white, convex, triangular tablet. It is 5.6 mm high and has a "1" printed in black ink on one side.

Avaric 267 micrograms is a white, convex, triangular tablet. It is 5.6 mm high and has a "2" printed in black ink on one side.

Avaric 400 micrograms is a white, convex, triangular tablet. It is 5.6 mm high and has a "4" printed in black ink on one side.

Avaric 533 micrograms is a white, convex, triangular tablet. It is 5.6 mm high and has a "5" printed in black ink on one side.

Avaric 800 micrograms is a white, convex, triangular tablet. It is 5.6 mm high and has a "8" printed in black ink on one side.

Avaric sublingual tablets are available in peelable, child-resistant blisters containing 3, 4, 15 or 30 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

ANGELINI PHARMA ESPAÑA, S.L.
C/ Antonio Machado, 78-80.
3rd floor, module A-Edificio Australia
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 medicinal product is authorised in the Member States of the European Economic Area (EEA) under the following names:

Sweden: Vellofent
Bulgaria: Vellofent
Czech Republic: Vellofent
Spain: Avaric
Greece: Vellofent
Italy: Vellofent
Poland: Vellofent
Portugal: Vellofent

Date of the most recent revision of the text: March 2025

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