EFFENTORA 400 micrograms BUCCAL TABLETS

Introduction

Package Leaflet: Information for the User

Effentora 100micrograms buccal tablets

Effentora 200micrograms buccal tablets

Effentora 400micrograms buccal tablets

Effentora 600micrograms buccal tablets

Effentora 800micrograms buccal tablets

Fentanyl

Read all of this leaflet carefully before you start using 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 signs of illness are the same as yours.
• If you get 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 and other information

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

1. What is Effentora and what is it used for

The active substance of Effentora is fentanyl citrate. Effentora is a medicine for the treatment of pain, this medicine is known as an opioid that is used to treat breakthrough pain in adult patients who are already receiving maintenance treatment with other opioids for their persistent (always present) cancer pain.

Breakthrough pain is additional, sudden pain that appears even though you are already receiving your regular opioid pain medicine.

2. What you need to know before you use Effentora

Do not use Effentora:

• if you are not already using a prescribed opioid medicine every day, at the same time, for at least one week, to control your persistent pain. If you have not been using these medicines, do not useEffentora as its use may increase the risk that your breathing becomes slower and/or shallower, and even stops.
• 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 obstructive lung disease.
• if you have short-term pain which is not breakthrough pain.
• if you are taking a medicine that contains sodium oxybate.

Warnings and precautions

During treatment with Effentora, keep using the opioid pain medicine you take for your persistent (always present) cancer pain.

While you are being treated with Effentora, do not use other fentanyl treatments that you have been prescribed previously for breakthrough pain. If you still have these fentanyl products at home, contact your pharmacist who will advise you how to dispose of them.

Keep this medicine out of the sight and reach of other people, in a safe and protected place (see section 5 Storage of Effentorafor more information).

Tell your doctor or pharmacist BEFOREyou start using Effentora:

• if the other opioid medicine you are taking for your persistent (always present) cancer pain has not yet been stabilised.
• if you have any breathing problems (such as asthma, wheezing, or breathing difficulties).
• if you have had a head injury.
• if you have an exceptionally low heart rate or other heart problems.
• if you have liver or kidney problems, as these organs affect how your body breaks down the medicine.
• if you have low blood volume or low blood pressure.
• if you are over 65 years old; you may need a lower dose and your doctor will review any dose increase carefully.
• if you have heart problems, especially a low heart rate.
• if you are using benzodiazepines (see section 2, in “Using Effentora with other medicines”). Using benzodiazepines can increase the likelihood of you experiencing serious side effects, including death.
• if you are using antidepressants or antipsychotics (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs)); see section 2, in “Do not use Effentora” and “Using Effentora with other medicines”). Using these medicines with Effentora can cause a serotonin syndrome, a potentially life-threatening condition(see section 2, in “Using Effentora with other medicines”).
• if you have ever had adrenal insufficiency, a condition where the adrenal glands do not produce enough hormones, or a lack of sex hormones (androgen deficiency) with the use of opioids (see section 4, in “Serious side effects”).
• if you have ever abused or been dependent on opioids or any other medicine, alcohol, or drugs.
• if you drink alcohol, see the section “Using Effentora with food, drinks, and alcohol”.

Tell your doctor DURINGtreatment with Effentora:

• 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.
• if 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 an indication of a potentially life-threatening condition called adrenal insufficiency, where the adrenal glands do not produce enough hormones.
• if you experience sleep-related breathing disorders: Effentora can cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include breathing pauses during sleep, waking up at night due to difficulty breathing, difficulty staying asleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.
• repeated use of Effentora can lead to dependence and abuse, which can cause a potentially life-threatening overdose. If you are concerned about becoming dependent on Effentora, it is important that you talk to your doctor.

Long-term use and tolerance

This medicine contains fentanyl, an opioid. Repeated use of opioid pain medicines 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 Effentora. This is known as hyperalgesia. Increasing the dose of Effentora may continue to reduce pain for a while, but it can also be harmful. If you notice that the medicine is becoming less effective, talk to your doctor. Your doctor will decide whether it is better for you to increase the dose or to gradually reduce your use of Effentora.

Dependence and addiction

Repeated use of Effentora can also lead to dependence, abuse, and addiction, which can cause a potentially life-threatening overdose. The risk of these side effects may be greater with higher doses and longer use. Dependence or addiction can cause a feeling of loss of control over the amount of medicine you need to use or how often you need to use it. You may feel the need to keep using the medicine even if it is no longer helping to relieve pain.

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

• you or a family member 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 personality disorder) or have been treated by a psychiatrist for other mental health diseases.

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 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 of it.
• you feel unwell when you stop using the medicine (for example, nausea, vomiting, diarrhoea, anxiety, shivering, shaking, 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.

Seek IMMEDIATEmedical help:

• if you notice symptoms such as difficulty breathing or dizziness, swelling of the tongue, lips, or throat while using Effentora. These can be early symptoms of a severe allergic reaction (anaphylaxis, hypersensitivity; see section 4, in “Serious side effects”).

What to do if someone accidentally takes Effentora

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

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

Children and adolescents

Do not give this medicine to children and adolescents under 18 years of age.

Using Effentora with other medicines

Tell your doctor or pharmacist before you start treatment with Effentora if you are taking, have recently taken, or might take any other medicines, including:

• using Effentora with sedative medicines, such as benzodiazepines or related drugs, increases the risk of drowsiness, breathing difficulties (respiratory depression), and coma, and can be life-threatening. Therefore, using them together should only be considered when no other treatment options are possible.

However, if your doctor prescribes Effentora with sedative medicines, the dose and duration of concomitant treatment should be limited by your doctor.

Tell your doctor about all sedative medicines you are taking (such as sleeping pills, medicines to treat anxiety, some medicines to treat allergic reactions [antihistamines], or tranquillisers) and strictly follow the dose recommended by your doctor. It may be useful to inform friends or family to alert them to the signs and symptoms described above. Contact your doctor if you experience these symptoms.

• certain muscle relaxants, such as baclofen, diazepam (see also the section “Warnings and precautions”).
• any medicine that may affect how your body breaks down Effentora, such as ritonavir, nelfinavir, amprenavir, and fosamprenavir (medicines that help control HIV infection) or other CYP3A4 inhibitors, such as ketoconazole, itraconazole, or fluconazole (used to treat fungal infections), troleandomycin, clarithromycin, or erythromycin (medicines to treat bacterial infections), aprepitant (used for severe nausea), diltiazem, and verapamil (medicines to treat high blood pressure or heart disease).
• monoamine oxidase inhibitors (MAOIs) (used to treat severe depression), even if you have used them in the last two weeks.
• certain powerful painkillers, called partial agonist/antagonists, such as buprenorphine, nalbuphine, and pentazocine (medicines to treat pain). While using these medicines, you may experience symptoms of a withdrawal syndrome (nausea, vomiting, diarrhoea, anxiety, shivering, shaking, and sweating).
• certain painkillers for nerve pain (gabapentin and pregabalin).
• The risk of side effects increases if you are taking medicines such as certain antidepressants or antipsychotics. Effentora can 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, diarrhoea). Your doctor will tell you if Effentora is suitable for you.

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

Using Effentora with food, drinks, and alcohol

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

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 using this medicine.

Pregnancy

Effentora should not be used during pregnancy, unless you have discussed it with your doctor.

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

Do not use Effentora during labour, as fentanyl can cause breathing difficulties in the newborn baby.

Breastfeeding

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

Driving and using machines

Ask your doctor if you can drive or use machines safely after taking Effentora. Do not drive or use machines if: you feel drowsy or dizzy, you have blurred vision or double vision, or you have difficulty concentrating. It is important that you know how you react to Effentora before you drive or use machines.

Effentora contains sodium

Effentora100micrograms

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

Effentora200micrograms, Effentora400micrograms, Effentora600micrograms, Effentora800micrograms

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

3. How to Take Effentora

Follow your doctor's instructions for taking this medication exactly. If you are unsure, consult your doctor or pharmacist again.

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

Dosage and Frequency

When you first start using Effentora, 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 instructs. 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 dose of pain reliever you need may vary over time. 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 change your dose.

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

You should 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 the persistent pain is controlled, your doctor may need to change your dose of Effentora. If your doctor suspects increased sensitivity to pain (hyperalgesia) related to Effentora, a reduction in the dose of Effentora may be considered (see section 2, under "Warnings and Precautions"). For more effective relief, inform your doctor of the pain you are experiencing and how Effentora is working for you, so that your doctor can modify the dose as needed.

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

If you are unsure of the correct dose or want to ask a question about using this medication, contact your doctor.

Method of Administration

The method of administration of Effentora buccal tablets is by the oral route. When you place a tablet in your mouth, it dissolves and the medication is absorbed through the buccal mucosa and into the bloodstream. This way 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 ready to use the tablet. The tablet should be used immediately after removal from the blister pack.
• Separate one unit from the blister pack by tearing along the perforations.
• Fold the blister unit along the indicated line.
• Peel back the backing of the blister to expose the tablet. DO NOT attempt to push the tablet through the blister, as this may damage it.

• Remove the tablet from the blister pack and place it immediatelywithout 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 your tongue.
• Do not attempt to crush or break the tablet.

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

If You Take More Effentora Than You Should

• The most common adverse effects are drowsiness, dizziness, or nausea. If you start to feel very dizzy or drowsy before the tablet has dissolved completely, rinse your mouth with water and spit out the remaining tablet immediately into 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 or shallow breathing, seek immediate medical attention.
• An overdose can also cause a brain disorder known as toxic leukoencephalopathy.

If You Miss a Dose of Effentora

If your breakthrough pain persists, you can take Effentora as directed by your doctor. If your breakthrough pain has disappeared, do not take Effentora until the next episode of breakthrough pain.

If You Stop Treatment with Effentora

You should stop Effentora when you no longer have any breakthrough pain. However, you should continue taking your usual opioid pain medication to treat persistent cancer pain, as directed by your doctor. When you stop treatment with Effentora, you may experience withdrawal symptoms similar to the possible adverse effects of Effentora. If you experience withdrawal symptoms or are concerned about pain relief, you should consult your doctor. Your doctor will assess whether you need medication to reduce or eliminate withdrawal symptoms.

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

4. Possible Side Effects

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

Serious Side Effects

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

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

• Nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.

Together, these symptoms can be a sign of a potentially life-threatening disorder 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 application of the tablet: pain, ulcer, irritation, bleeding, numbness, loss of sensation, redness, swelling, or spots

Common:may affect up to 1 in 10 patients

• feeling of anxiety or confusion, depression, insomnia
• altered taste, weight loss
• drowsiness, sedation, excessive fatigue, weakness, migraine, numbness, inflammation of arms or legs, withdrawal syndrome (which can manifest with the following adverse 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 upset, indigestion, toothache, mouth ulcers
• itching, excessive sweating, rash
• shortness of breath, sore throat
• decrease in white blood cells, decrease in red blood cells, decrease or increase in blood pressure, high heart rate
• muscle pain, back pain
• fatigue

Uncommon:may affect up to 1 in 100 patients

• throat problems;
• decrease in 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, vertigo, speech problems, ringing in the ears, ear problems;
• altered or blurred vision, red eyes;
• very slow heart rate, feeling of excessive heat (hot flashes), high blood pressure;
• serious breathing 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 disorders;
• inflammation of the esophagus, intestinal paralysis, gallbladder disorder;
• cold sweat, facial swelling, generalized itching, hair loss, muscle cramps, muscle weakness, general malaise, chest discomfort, thirst, feeling of cold, feeling of heat, difficulty urinating;
• general malaise;
• flushing.

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

• thought disorders, movement disorders
• blisters in the mouth, dry lips, presence of pus under the skin in the mouth
• testosterone deficiency, strange feeling in the eye, observation of flashes of light, fragile nails
• allergic reactions such as skin rash, redness, swelling of lips and face, hives

Unknown:frequency cannot be estimated from available data

• loss of consciousness, respiratory arrest, convulsion (seizure)
• sex hormone deficiency (androgen deficiency)
• drug dependence (addiction) (see section 2)
• drug abuse (see section 2)
• pharmacological tolerance (see section 2)
• 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 can cause withdrawal symptoms in the newborn, which can be potentially life-threatening (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 national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Effentora

Keep this medication in a safe and protected place, out of reach of others. This medication can cause serious harm and even be life-threatening if taken accidentally or intentionally by someone who has not been prescribed it.

The pain reliever Effentora is very strong and can be life-threatening if taken accidentally by a child. This medication should be kept out of sight and reach of children.

• Do not use this medication after the expiration date shown on the label of the blister packs and carton. 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 disposed of through wastewater or household waste. 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

Composition of Effentora

The active ingredient is fentanyl. Each tablet contains:

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

The other ingredients are mannitol, sodium carboxymethyl starch type A, sodium hydrogen carbonate, sodium carbonate, citric acid, magnesium stearate.

Appearance of the Product and Package Contents

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

Each blister pack contains 4 buccal tablets, which are available in cartons of 4 or 28 buccal tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder

TEVA B.V.

Swensweg 5

2031 GA Haarlem

Netherlands

Manufacturer

Teva Pharmaceuticals Europe B.V.

Swensweg 5

2031 GA Haarlem

Netherlands

or

Merckle GmbH

Ludwig-Merckle-Straße 3

89143 Blaubeuren

Germany

You can obtain further information on this medication by contacting the local representative of the marketing authorization holder or by calling the following number:

Date of Last Revision of this Leaflet:

Detailed information on this medication is available on the European Medicines Agency website: http://www.ema.europa.eu/