Leaflet: information for the user

Effentora 100microgram buccal tablets

Effentora 200microgram buccal tablets

Effentora 400microgram buccal tablets

Effentora 600microgram buccal tablets

Effentora 800microgram buccal tablets

Fentanyl

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as 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 section4.

The active ingredient of Effentora is fentanyl citrate. Effentora is a medication for pain relief, this medication is known as an opioid used to treat breakthrough pain in adult patients who already receive maintenance treatment with other opioids for their persistent pain (present all the time) associated with cancer.

Breakthrough pain is additional and sudden pain that appears despite already receiving routine analgesic treatment with opioids.

Do not use Effentora:

• if you are not regularly using a prescribed opioid medication (e.g., codeine, fentanyl, hydromorphone, morphine, oxycodone, meperidine) every day at the same time for at least one week to control persistent pain. If you have not been using those medications,do not useEffentora as its use may increase the risk of your breathing becoming slower and/or shallower, and even stopping.
• if you are allergic to fentanyl or any of the other components of this medication (listed in section6).
• if you have severe respiratory problems or chronic obstructive pulmonary disease.
• if you have short-term pain other than breakthrough pain.
• if you are taking a medication that contains sodium oxibate.

Warnings and precautions

During treatment with Effentora, continue to use the opioid analgesic medication you take for your persistent pain (present all the time) associated with cancer.

While under treatment with Effentora, do not use other fentanyl-based treatments that you were previously prescribed for breakthrough pain. If you still have these fentanyl products at home, contact your pharmacist who will instruct you on how to dispose of them.

Keep this medication in a safe and protected place, where others cannot access it (see section5Effentora Storagefor more information).

Inform your doctor or pharmacistBEFOREstarting to use Effentora:

• if the other opioid medication you take for your persistent pain (present all the time) associated with cancer has not yet stabilized.
• if you have any respiratory disorder (such as asthma, wheezing, or difficulty breathing).
• if you have head injuries.
• if you have an abnormally low heart rate or other heart problems.
• if you have liver or kidney problems, as these organs affect how your body metabolizes the medication.
• if you have low blood volume or hypotension.
• if you are over 65years old; you may need a lower dose and your doctor will carefully review any dose increase.
• if you have heart problems, especially low heart rate.
• if you are taking benzodiazepines (see section2, in “Effentora Use with Other Medications”). The use of benzodiazepines may increase the likelihood of severe adverse effects, including death.
• if you are taking antidepressants or antipsychotics(selective serotonin reuptake inhibitors [SSRIs],serotonin and norepinephrine reuptake inhibitors (SNRIs),monoamine oxidase inhibitors [MAOIs]); see section2, in “Do not use Effentora” and “Effentora Use with Other Medications”). The use of these medications with Effentora may cause aserotonin syndrome, a potentially life-threatening situation(see section2, in “Effentora Use with Other Medications”).
• if you have ever had adrenal insufficiency, a disorder in which the adrenal glands do not produce enough hormones, or hormone deficiency (androgen deficiency)with opioid use (see section4, in “Severe Adverse Effects”).
• if you have ever abused or been dependent on opioids or any other medication, alcohol, or drugs.
• if you drink alcohol, see the section “Effentora Use with Food, Beverages, and Alcohol”.

Consult your doctorDURINGEffentora use:

• if you feel pain or increased pain sensitivity (hyperalgesia) that does not respond to a higher dose of the medication as prescribed by your doctor.
• if you present a combination of the following symptoms: nausea, vomiting, anorexia, 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.
• if you experience sleep-related respiratory problems: Effentora may cause sleep-related respiratory problems such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include pauses in breathing during sleep, nocturnal awakening due to difficulty breathing, difficulty maintaining sleep, or excessive daytime somnolence. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.
• the repeated use of Effentora may lead to dependence and abuse that can cause a potentially life-threatening overdose. If you are concerned about the possibility of becoming dependent on Effentora, it is essential to consult your doctor.

Long-term use and tolerance

This medication contains fentanyl, an opioid. The repeated use of opioid analgesics may make the medication less effective (your body becomes accustomed to it, known as pharmacological tolerance). You may also become more sensitive to pain when using Effentora. This is known as hyperalgesia. Increasing the dose of Effentora 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 Effentora.

Dependence and addiction

The repeated use of Effentora may also cause dependence, abuse, and addiction, which could lead to a potentially life-threatening 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 medication you should use or the frequency with which you should use it. You may feel the need to continue using the medication even if it does not help alleviate pain.

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

• you or any family member have abused alcohol or experienced dependence on it, prescription medications, or illicit drugs (“addiction”).
• you smoke.
• you have had any mental health problems (depression, anxiety, or personality disorder) orhave been treated by a psychiatrist for other mental health conditions.

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

• you need to use the medication for a longer period 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 (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 discontinue the medication, and how to do it safely.

Seek medical attentionURGENTLY:

• if you noticesymptoms such as difficulty breathing or dizziness, swelling of the tongue, lips, or throat during Effentora use. These may be early signs of a severe allergic reaction (anaphylaxis, hypersensitivity; see section4, in “Severe Adverse Effects”).

What to do if someone accidentally takes Effentora

If you believe someone has accidentally taken Effentora, seek immediate medical attention. Try to keep the person awake until emergency services arrive.

If someone accidentally takes Effentora, they may experience the same side effects described in the section “If you take more Effentora than you should.”

Children and adolescents

Do not administer this medication to children and adolescents under 18years old.

Effentora use with other medications

Inform your doctor or pharmacist before starting treatment with Effentora if you aretaking, have taken recently, or may need to take any other medication, including the following:

• the concomitant use of Effentora and sedatives, such as benzodiazepines or related medications, increases the risk of drowsiness, difficulty breathing (respiratory depression), and 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 Effentora with sedatives, the dose and duration of concomitant treatment should be limited by your doctor.

Inform your doctor about all sedatives you are taking (such as sleep aids, anxiety medications, some allergy medications [antihistamines], or tranquilizers) and follow your doctor's recommended dose strictly. It may be helpful to inform friends or family members to alert them to the symptoms and signs described above. Contact your doctor if you experience these symptoms.

• some muscle relaxants, such as baclofen, diazepam (also see the section “Warnings and precautions”).
• any medication that may affect how your body metabolizes Effentora, such as ritonavir, nelfinavir, amprenavir, and fosamprenavir (medications that help control HIV infection) or other CYP3A4 inhibitors, such as ketoconazole, itraconazole, or fluconazole (used to treat fungal infections), troleandomycin, clarithromycin, or erythromycin (medications for bacterial infections), aprepitant (used for severe nausea), diltiazem, and verapamil (medications for hypertension or heart disease).
• medications called monoamine oxidase inhibitors (MAOIs) (used for severe depression), also if you have used them in the past two weeks.
• a certain type of potent pain relievers, called agonist/antagonist partials, such as buprenorphine, nalbuphine, and pentazocine (medications for pain). While using these medications, you may experience withdrawal symptoms (nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating).
• some pain relievers for neuropathic pain (gabapentin and pregabalin).
• The risk of adverse effects increases if you are taking medications such as certain antidepressants or antipsychotics. Effentora may interact with these medications, and you may experience changes in mental state (e.g., agitation, hallucinations, coma) and other effects such as high body temperature (over38°C), 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 Effentora is suitable for you.

Inform your doctor or pharmacist if you aretaking, have taken recently, or may need to take any other medication.

Effentora use with food, beverages, and alcohol

• Effentora can be taken before or after meals, but not during them. You can drink a little water before taking Effentora to help moisten your mouth, but do not eat or drink anything while taking the medication.
• Do not drink grapefruit juice while using Effentora, as it may affect how your body metabolizes this medication.
• Do not drink alcohol during Effentora treatment. It may increase the risk of severe adverse effects, including death.

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.

Pregnancy

Do not use Effentora during pregnancy, unless you have consulted your doctor.

If you use Effentora for an extended period during pregnancy, there is also a risk that the newborn may experience withdrawal symptoms that can be potentially life-threatening if not identified and treated by a doctor.

Do not use Effentora during labor, as fentanyl can cause respiratory depression in the newborn.

Breastfeeding

Fentanyl may pass into breast milk and cause adverse effects in the infant. Do not use Effentora if you are breastfeeding your child. Do not initiate breastfeeding until at least 5days have passed since the last dose of Effentora.

Driving and operating machinery

Ask your doctor if you can drive or operate machinery safely after taking Effentora. Do not drive or operate machinery if: you feel drowsy or dizzy, have blurred vision, see double, or have difficulty concentrating. It is essential to know how you react to Effentora before driving or operating machinery.

Effentora contains sodium

Effentora100micrograms

This medication contains 10mg of sodium (main component of table salt/for cooking) in each buccal tablet. This is equivalent to 0.5% of the recommended daily maximum sodium intake for an adult.

Effentora200micrograms, Effentora400micrograms, Effentora600micrograms, Effentora800micrograms

This medication contains 20mg of sodium (main component of table salt/for cooking) in each buccal tablet. This is equivalent to 1% of the recommended daily maximum sodium intake for an adult.

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

Your doctor will also explain to you what you can expect from the use of Effentora, 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).

Dosage and frequency

When you start using Effentora for the first time, your doctor will help you find the dose that will relieve your breakthrough pain. It is very important that you use Effentora exactly as your doctor tells you to. The initial dose is 100 micrograms.

During the determination of the correct dose for you, your doctor may have you take more than one tablet per episode. If your breakthrough pain is not relieved after 30 minutes, use only 1 more Effentora tablet during the dose adjustment period.

Once you have determined the correct dose with your doctor, use 1 tablet for a breakthrough pain episode as a general rule. The analgesic dose you need may vary throughout treatment. You may need higher doses. If your breakthrough pain is not relieved after 30 minutes, use only 1 more Effentora tablet during this dose adjustment period.

Consult your doctor if your correct dose of Effentora does not relieve your breakthrough pain. Your doctor will decide if it is necessary to modify your dose.

Wait at least 4 hours before treating another breakthrough pain episode with Effentora.

You must inform your doctor immediately if you need to take Effentora more than four times a day, as it may be necessary to change your treatment regimen.Your doctor may change the treatment you are receiving to control persistent pain;when persistent pain is controlled, your doctor may need to change your Effentora dose.If your doctor suspects a greater sensitivity to pain (hyperalgesia) related to Effentora, it may be necessary to reduce the Effentora dose (see section 2, in “Warnings and precautions”).To achieve more effective relief, inform your doctor of the pain you suffer and how Effentora is acting in your case, so that your doctor can modify the dose as needed.

Do not change the doses of Effentora or other analgesics on your own. Any change in dosing must be prescribed and monitored by your doctor.

If you are unsure of the correct dose, or if you wish to ask any questions about the use of this medication, contact your doctor.

Administration form

The administration form of Effentora oral tablets is by the oral route. By placing a tablet in the mouth, it dissolves and the medication is absorbed by the buccal mucosa and passes into the blood. This form of taking the medication allows it to be absorbed quickly to relieve your breakthrough pain.

How to use the medication

• Open the blister pack only when you are going to use the tablet. The tablet must be used immediately after it has been removed from the blister pack.
• Separate one of the units from the blister pack by tearing along the perforations.
• Double the blister unit along the indicated line.
• Peel the back of the blister pack to expose the tablet. DO NOT try to press the tablet to remove it from the blister pack, as this may damage it.

• Remove the tablet from the blister pack and place itimmediatelywithout breaking it near a molar, between the gum and the cheek (as indicated in the photograph). Your doctor may also instruct you to place the tablet under the tongue.
• Do not try to crush or split the tablet.

• Do not bite, suck, chew, or swallow the tablet, as this will make the analgesic effect less than if you follow these instructions.
• The tablet must remain between the cheek and the gum until it dissolves, which usually takes between 14and 25minutes.
• You may feel a slight effervescent sensation between the cheek and the gum as the tablet dissolves.
• If you experience irritation, you can change the placement of the tablet in the gum.
• After 30minutes, if there are still remnants of the Effentora tablet, you can swallow them with a glass of water.

If you use more Effentora than you should

• The most common adverse effects are drowsiness, dizziness, or discomfort. If you start to feel very dizzy or drowsy before the tablet has completely dissolved, rinse your mouth with water and spit out the remaining tablet immediately in the sink or toilet.
• A serious adverse effect of Effentora is slow and/or shallow breathing. This can occur if the dose of Effentora is too high or if you have taken too much Effentora.In severe cases, taking too much Effentora can lead to coma. If you feel very dizzy, very drowsy, or have slow and/or shallow breathing,seek medical attention immediately.
• A overdose can also cause a brain disorder known as toxic leukoencephalopathy.

If you forgot to use Effentora

If the breakthrough pain persists, you can take Effentora according to your doctor's instructions. If the breakthrough pain has disappeared, do not take Effentora until the next breakthrough pain episode.

If you interrupt the treatment with Effentora

You must discontinue Effentora when you no longer have any breakthrough pain. However, you must continue taking your usual opioid analgesic medication to treat persistent cancer pain, as instructed by your doctor. When you discontinue Effentora treatment, you may experience withdrawal symptoms similar to possible adverse effects of Effentora. If you experience withdrawal symptoms or if you are concerned about pain relief, consult your doctor. Your doctor will evaluate if you need medications to reduce or eliminate withdrawal symptoms.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them. If you notice any of them, inform your doctor.

Severe side effects

• The most severe side effects are shallow breathing, hypotension, and shock. Effentora, like other fentanyl-based products, can cause very serious respiratory problems that can lead to death. If you feel extremely drowsy or have slow and/or shallow breathing, you or your caregiver should contact your doctor immediately and request urgent help.

• Contact your doctor immediately if you experience a combination of the following symptoms

• Nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, and low blood pressure.

Combined, these symptoms may be a sign of a potentially fatal condition called adrenal insufficiency, in which the adrenal glands do not produce enough hormones.

Other side effects

Very common:may affect more than 1 in 10 patients

• Dizziness, headache
• Nausea, vomiting
• At the site of the tablet: pain, ulcer, irritation, bleeding, numbness, loss of sensation, redness, swelling, or patches

Common::may affect up to 1 in 10 patients

• Feeling anxious or confused, depression, insomnia
• Altered taste, weight loss
• Drowsiness, sedation, excessive fatigue, weakness, migraine, numbness, inflammation of arms or legs, withdrawal syndrome (which may manifest as the following side effects: nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating), tremors, falls, chills
• Constipation, inflammation of the mouth, dry mouth, diarrhea, heartburn, loss of appetite, stomach pain, stomach discomfort, indigestion, toothache, mouth ulcers
• Itching, excessive sweating, rash
• Shortness of breath, throat pain
• Decreased white blood cells, decreased red blood cells, decreased or increased blood pressure, high heart rate
• Muscle pain, back pain
• Fatigue

Uncommon:may affect up to 1 in 100 patients

• Throat pain;
• Decreased cells that help blood to clot;
• Euphoria, nervousness, strangeness, restlessness, or slowness; seeing or hearing things that are not real (hallucinations), altered state of consciousness, changes in mental state, disorientation, lack of concentration, loss of balance, dizziness, speech problems, ringing in the ears, ear discomfort;
• Altered or blurred vision, red eyes;
• Too high or too low heart rate, feeling too hot (heatstroke), high blood pressure;
• Severe respiratory problems, difficulty breathing during sleep;
• One or more of the following problems in the mouth: ulcer, loss of sensation, discomfort, abnormal color, alteration of soft tissues, alteration of the tongue, pain, blisters, or ulcers on the tongue, gum pain, cracked lips, dental problems;
• Inflammation of the esophagus, intestinal paralysis, bile duct disorder;
• Cold sweat, facial edema, generalized itching, hair loss, muscle cramps, muscle weakness, general discomfort, chest discomfort, thirst, feeling cold, feeling hot, difficulty urinating;
• General discomfort;
• Flush.

Rare:may affect up to 1 in 1,000 patients

• Mental disorders, movement disorder
• Mouth ulcers, dry lips, presence of pus under the skin in the mouth
• Lack of testosterone, strange sensation in the eye, observation of flashes of light, brittle nails
• Allergic reactions such as skin rash, redness, swelling of lips and face, urticaria

Unknown:the frequency cannot be estimated from available data

• Loss of consciousness, respiratory arrest, convulsion (epileptic crisis)
• Lack of sex hormones (androgen deficiency)
• Drug dependence (addiction) (see section 2)
• Drug abuse (see section 2)
• Pharmacological tolerance (see section2)
• Delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that are not real, altered sleep, and nightmares)
• Prolonged treatment with fentanyl during pregnancy may cause withdrawal symptoms in the newborn, which may be potentially fatal (see section2).

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 national notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Conserve this medication in a safe and protected place, to which other people cannot access. This medication can cause severe damage and even be fatal for people who use it accidentally, or intentionally when it has not been prescribed to them.

The analgesic Effentora is very strong and can be a life-threatening risk if taken accidentally by a child. This medication must be kept out of the sight and reach of children.

• Do not use this medication after the expiration date that appears on the blister packaging and on the box.The expiration date is the last day of the month indicated.
• Store in the original packaging to protect it from moisture.
• Medications should not be thrown down the drains or in the trash. 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 Effentora

The active ingredient is fentanil. Each tablet contains:

• 100micrograms of fentanil (as citrate)
• 200micrograms of fentanil (as citrate)
• 400micrograms of fentanil (as citrate)
• 600micrograms of fentanil (as citrate)
• 800micrograms of fentanil (as citrate)

The other components are mannitol, carboxymethylcellulose sodium type A, sodium hydrogen carbonate, sodium carbonate, citric acid, magnesium stearate.

Appearance of the product and contents of the package

The buccal tablets are flat-faced, round, beveled-edged, and engraved on one face with a “C” and on the other with “1”for Effentora 100micrograms, with “2”for Effentora 200micrograms, with “4”for Effentora 400micrograms, with “6”for Effentora 600micrograms, and with “8”for Effentora 800micrograms.

Each blister pack contains 4tablets, which are presented in boxes of 4or 28tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

TEVA B.V.

Swensweg 5

2031 GA Haarlem

Netherlands

Responsible for manufacturing

Teva Pharmaceuticals Europe B.V.

Swensweg 5

2031 GA HAARLEM

Netherlands

or

Merckle GmbH

Ludwig-Merckle-Straße 3

89143 Blaubeuren

Germany

For more information about this medicine, please contact the local representative of the marketing authorization holder or call the following number:

Last update of this leaflet:

The detailed information about this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/