Effentora

Package leaflet: Information for the user

Effentora 100 micrograms orodispersible tablets, 200 micrograms orodispersible tablets, 400 micrograms orodispersible tablets, 600 micrograms orodispersible tablets, 800 micrograms orodispersible tablets

Fentanyl
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Effentora is and what it is used for

The active substance in Effentora is fentanyl citrate. Effentora is an analgesic known as an opioid,
used to treat breakthrough cancer pain in adult patients with cancer who are already receiving
treatment with another opioid for persistent, chronic pain (24 hours a day) due to cancer.
Breakthrough cancer pain is a sudden, additional pain that occurs even after you have taken your
regular opioid painkillers.

2. What you need to know before using Effentora

Do not use Effentora:

• If you are not already taking, on a daily and regular basis for at least one week, an opioid medicine prescribed for persistent pain (e.g. codeine, fentanyl, hydromorphone, morphine, oxycodone, meperidine). If you are not taking these medicines, you must not use Effentora, as this could increase the risk that your breathing becomes dangerously slow and/or shallow, or even stops.
• 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 severe obstructive bronchopulmonary disease.
• If you suffer from short-term pain other than breakthrough cancer pain.
• If you are taking a medicine containing sodium oxybate.

Warnings and precautions
While being treated with Effentora, continue taking the opioid painkiller you are using for your persistent (24-hour) cancer pain.
While taking Effentora, do not use any other fentanyl-containing treatments previously prescribed for your breakthrough pain. If you still have any of these treatments at home, contact your pharmacist for advice on how to dispose of them safely.
Keep this medicine in a secure and safe place, out of reach of other people (see section 5 How to store Effentora for more information).
Tell your doctor or pharmacist BEFORE using Effentora if:

• The correct dose has not yet been established for the other opioid you are taking for your persistent (all-day) cancer pain.
• You have any condition affecting your respiratory function (such as asthma, wheezing, shortness of breath).
• You have a head injury.
• You have an unusually slow heart rate or other heart problems.
• You have liver or kidney problems, as these organs affect how the medicine is metabolized.
• You have low blood fluid volume or low blood pressure.
• You are over 65 years of age – you may require a lower dose, and any dose increase will be carefully monitored by your doctor.
• You have heart problems, particularly a slow heartbeat.
• You are taking benzodiazepines (see section 2 under “Other medicines and Effentora”). The use of benzodiazepines may increase the likelihood of serious adverse effects, including death.
• You are taking antidepressants or antipsychotics (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], monoamine oxidase inhibitors [MAOIs]; see section 2 under “Do not use Effentora” and “Other medicines and Effentora”). Taking these medicines with Effentora may lead to serotonin syndrome, a potentially life-threatening condition (see section 2 under “Other medicines and Effentora”).
• You have previously developed adrenal insufficiency, a condition in which the adrenal glands do not produce enough hormones, or a lack of sex hormones (androgen deficiency) due to opioid use (see section 4 under “Serious side effects”).
• You have previously abused or been dependent on opioids or any other drugs, alcohol, or illegal drugs.
• You drink alcohol; refer to the section “Effentora with food, drink and alcohol”.

Consult your doctor WHILE using Effentora:

• If you experience pain or increased sensitivity to pain (hyperalgesia) that does not respond to an increase in the dose of medicine 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 may be a sign of a potentially life-threatening condition called adrenal insufficiency, in which the adrenal glands do not produce enough hormones.
• Sleep-related breathing disorders: Effentora may cause sleep-related breathing disorders, 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, nighttime awakenings due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else notices these symptoms, contact your doctor, who may consider reducing your dose.

Long-term use and tolerance
This medicine contains fentanyl, an opioid medicine. Repeated use of opioid painkillers may make the medicine less effective (you become accustomed to it, a phenomenon known as drug tolerance). You may also become more sensitive to pain while taking Effentora. This is known as hyperalgesia. Increasing the dose of Effentora may help reduce pain for a while, but it may also be harmful. If you notice the medicine becoming less effective, speak to your doctor. Your doctor will decide whether it is better to increase the dose or gradually reduce your use of Effentora.
Dependence and substance abuse

Repeated use of Effentora may also lead to dependence, abuse, and drug addiction, which could result in a potentially fatal overdose. The risk of these adverse effects may increase with higher doses and prolonged duration of use. Dependence or drug addiction may make you feel as though you have lost control over how much medicine you need or how often you must take it. You may feel a need to continue using the medicine even if it no longer helps relieve your pain.

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

• you or a family member have previously suffered from alcohol abuse, prescription drug abuse, or illegal substance abuse ("drug addiction");
• you are a smoker;
• you have previously had mood disorders (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

The appearance of any of the following signs during use of Effentora may indicate dependence or drug addiction:

• You feel the need to use the medicine for a longer period than prescribed by your doctor.
• You feel the need to use a higher dose than recommended.
• You use the medicine for reasons other than those prescribed, for example, "to stay calm" or "to help sleep."
• You have repeatedly tried to stop or control your use of this medicine without success.
• When you stop taking the medicine, you feel unwell (e.g., nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating), and you feel better when you start taking it again ("withdrawal effects").

If you notice any of these signs, consult your doctor to discuss the best treatment approach for you, including whether it is appropriate to discontinue treatment and how to do so safely.

Seek medical attention IMMEDIATELY if:

• you experience symptoms such as difficulty breathing or dizziness, or swelling of the tongue, lips, or throat while using Effentora. These may be early signs of a serious allergic reaction (anaphylaxis, hypersensitivity; see section 4, "Serious adverse reactions").

What to do if someone accidentally takes Effentora
If you think someone has accidentally taken Effentora, call a doctor immediately. Try to keep the person awake until medical help arrives.
Accidental ingestion of Effentora may cause the same adverse effects described in section 3, "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.

Other medicines and Effentora
Before starting Effentora, inform your doctor or pharmacist if you are taking, have recently taken, or might take any of the following medicines:

• Concomitant use of Effentora with sedative medicines such as benzodiazepines or related drugs increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be potentially fatal. Therefore, concomitant use should only be considered when no other therapeutic options are available.

In any case, if your doctor prescribes Effentora together with sedative medicines, the dose and duration of concomitant treatment should be limited.
Inform your doctor about any sedative medicines you are taking (such as sleeping pills, anxiolytics, certain medicines used to treat allergic reactions (antihistamines), or tranquilizers), and strictly follow the dose recommended by your doctor. It may be helpful to ask friends or family members to watch for the signs and symptoms listed above. Contact your doctor if these symptoms occur.

• Certain muscle relaxants – such as baclofen, diazepam (see also section "Warnings and precautions").
• Any medicine that may affect how your body metabolizes Effentora, such as ritonavir, nelfinavir, amprenavir, and fosamprenavir (medicines used in the management of HIV infection), or other so-called CYP3A4 inhibitors such as ketoconazole, itraconazolo, or fluconazole (medicines used to treat fungal infections), troleandomycin, clarithromycin, or erythromycin (medicines used to treat bacterial infections), aprepitant (a medicine used for severe nausea), and diltiazem and verapamil (medicines used to treat hypertension or heart failure).
• Medicines called monoamine oxidase inhibitors (MAO inhibitors) (used in severe depression) taken within the last two weeks.
• Certain types of painkillers called partial agonist/antagonists, e.g., buprenorphine, nalbuphine, and pentazocine (medicines used to treat pain). You may experience withdrawal symptoms (nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating) while using these medicines.
• Certain nerve pain medicines (gabapentin and pregabalin).
• The risk of adverse effects increases if you are taking medicines such as certain antidepressants or antipsychotics. Effentora may interact with these medicines, leading to changes in mental status (e.g., agitation, hallucinations, coma) and other effects such as body temperature above 38°C, rapid heartbeat, 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 Effentora is suitable for you.

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

Effentora with food, drinks, and alcohol

• Effentora may be taken before or after, but not during meals. Before using Effentora, you may drink water to moisten your mouth, but you must not eat or drink while taking the medicine.
• While using Effentora, do not drink grapefruit juice, as it may affect how your body metabolizes the medicine.
• Do not drink alcohol while using Effentora. This could increase the risk of serious adverse effects, including death.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
Effentora must not be used during pregnancy unless you have discussed this with your doctor.
If Effentora is used for a prolonged period during pregnancy, there is also a risk that the newborn may experience withdrawal symptoms, which could be potentially fatal if not diagnosed and treated by a doctor.
Effentora must not be used during childbirth, as fentanyl may cause respiratory depression in the newborn.

Breastfeeding
Fentanyl may pass into breast milk and may cause adverse effects in the breastfed newborn. Do not use Effentora if you are breastfeeding. You must not start breastfeeding until at least 5 days after your last dose of Effentora.

Driving and using machines
You should discuss with your doctor whether it is safe for you to drive or operate machinery after taking Effentora. Do not drive or operate machinery if: you feel drowsy or dizzy; you have blurred vision or double vision; or you have difficulty concentrating. It is important that you understand how you react to Effentora before driving or operating machinery.

Effentora contains sodium

Effentora 100 micrograms
This medicine contains 10 mg of sodium (a main component of table salt) per orosoluble tablet. This is equivalent to 0.5% of the maximum daily dietary intake recommended for an adult.

Effentora 200 micrograms, Effentora 400 micrograms, Effentora 600 micrograms, Effentora 800 micrograms
This medicine contains 20 mg of sodium (a main component of table salt) per orosoluble tablet. This is equivalent to 1% of the maximum daily dietary intake recommended for an adult.

3. How to use Effentora

Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Before starting treatment and regularly during treatment, your doctor will discuss with you what you can expect from using Effentora, when and for how long it is necessary to use it, when to contact your doctor, and when you should stop treatment (see also section 2).

Dosage and frequency of administration
When you first start using Effentora, your doctor will work with you to determine the optimal dose to relieve your episodes of intense breakthrough pain. It is very important that you use Effentora exactly as directed by your doctor. The initial dose is 100 micrograms. During the dose titration phase, your doctor may instruct you to take more than one tablet per episode. If your episode of intense pain is not relieved after 30 minutes, use only one additional Effentora tablet during the titration phase.

Once your doctor has established the correct dose for you, generally use 1 tablet per episode of intense breakthrough pain. In subsequent treatment cycles, your need for analgesic therapy may vary. Higher doses may be required. If your pain is not relieved after 30 minutes, take one additional Effentora tablet only during the dose re-adjustment phase.

Contact your doctor if your prescribed dose of Effentora does not relieve your breakthrough pain. Your doctor will decide whether your dose needs to be changed.

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

If you use Effentora more than four times a day, you must inform your doctor immediately, as your treatment regimen may need to be changed. Your doctor may adjust your treatment for persistent pain; once your persistent pain is under control, your doctor may need to modify your Effentora dosage. If your doctor suspects increased pain sensitivity (hyperalgesia) related to Effentora, a reduction in Effentora dose may be considered (see section 2, “Warnings and precautions”). For more effective pain relief, inform your doctor about your pain and how Effentora works for you, so that the dose can be adjusted if necessary.

Do not change the dose of Effentora or any other painkiller on your own initiative. Any dosage change must be prescribed and monitored by your doctor.

If you are unsure about the correct dose or have any other questions about how to take this medicine, contact your doctor.

Method of administration
Effentora orosoluble tablets are for oromucosal use (through the oral mucosa). When you place a tablet in your mouth, it dissolves and the medicine is absorbed into the bloodstream through the lining of your mouth. Taking the medicine this way allows for rapid absorption to relieve your episodes of intense breakthrough pain.

Taking the medicine

• Open the blister pack only when you are ready to use the tablet. The tablet should be used immediately after removal from the blister.
• Separate one unit from the entire blister by tearing along the perforated line.
• Fold the unit along the indicated line.
• To remove the tablet, peel back the backing film on the back of the blister. DO NOT try to push the tablet through the film, as this may damage it.

• Remove the tablet from the unit and place immediately the entire tablet next to a molar tooth, between the gum and the cheek (as shown in the figure). Sometimes, your doctor may instruct you to place the tablet under the tongue instead.
• Do not crush or break the tablet.

• Do not bite, suck, chew, or swallow the tablet, as this will result in less effective pain relief than when the tablet is taken as directed.
• Keep the tablet between the cheek and gum until it has completely dissolved, which will take between 14 and 25 minutes.
• You may feel a slight tingling sensation between the cheek and gum as the tablet dissolves.
• If irritation occurs, you may move the tablet to another position on the gum.
• After 30 minutes, if any residue of the tablet remains in the mouth, it may be swallowed with a glass of water.

If you use more Effentora than you should

• The most common side effects are drowsiness, nausea, or dizziness. If, before the tablet has completely dissolved, you begin to feel pronounced dizziness or drowsiness, rinse your mouth with water and completely expel the remaining tablet residue into a sink or toilet.
• A serious side effect of Effentora is slow and/or shallow breathing. This may occur if the dose of Effentora taken is too high or if you take an excessive amount of the medicine. In severe cases, taking too high a dose of Effentora may lead to coma. If you experience dizziness, severe drowsiness, or slow or shallow breathing, seek immediate medical attention.
• Overdose may also cause a brain disorder known as toxic leukoencephalopathy.

If you forget to use Effentora
If the episode of breakthrough pain is still ongoing, you may take Effentora as prescribed by your doctor. If the pain has already subsided, do not take Effentora until the next painful episode occurs.

If you stop using Effentora
You should stop treatment with Effentora when you no longer experience episodes of intense breakthrough pain. You must continue taking your usual opioid analgesic for persistent cancer pain as directed by your doctor. When you stop taking Effentora, you may experience withdrawal symptoms similar to the possible side effects of Effentora. If you experience withdrawal symptoms or are concerned about pain relief, contact your doctor. Your doctor will assess whether medications are needed to reduce or eliminate withdrawal symptoms.

If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Serious side effects

• The most serious side effects include shallow breathing, low blood pressure and shock. As with other fentanyl-containing products, Effentora may cause very serious breathing problems that may lead to death. If you experience marked drowsiness or slow and/or shallow breathing, you or your caregiver must contact your doctor immediately and seek emergency medical 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. If these symptoms occur together, they may be signs of a potentially life-threatening condition called adrenal insufficiency, in which the adrenal glands do not produce sufficient amounts of hormones.

Other side effects
Very common: may affect more than 1 in 10 people

• dizziness, headache
• nausea, vomiting
• at the tablet application site: pain, ulcers, irritation, bleeding, numbness, loss of sensation, redness, swelling or blisters.

Common: may affect up to 1 in 10 people

• anxiety or confusion, depression, insomnia
• altered taste sensation, weight loss
• drowsiness, sedation, excessive tiredness, weakness, migraine, numbness, swelling of the arms or legs, drug withdrawal syndrome (which may present with the following side effects: nausea, vomiting, diarrhoea, anxiety, chills, tremor and sweating), falls, chills
• constipation, stomatitis, dry mouth, diarrhoea, stomach burning, loss of appetite, stomach pain, stomach discomfort, indigestion, toothache, oral candidiasis
• itching, excessive sweating, rash
• shortness of breath, sore throat
• reduced white and red blood cells, increased or decreased blood pressure, rarely increased heart rate
• muscle pain, back pain
• fatigue

Uncommon: may affect up to 1 in 100 people

• irritation or sore throat
• decreased platelets
• feeling of euphoria, nervousness, general malaise, agitation or slowing down; visual or auditory hallucinations, reduced level of consciousness, mental status changes, disorientation, difficulty concentrating, loss of balance, dizziness, difficulty speaking, tinnitus, ear discomfort
• visual disturbances or blurred vision, eye redness
• unusually slow heart rate, sensation of intense heat (hot flushes)
• severe breathlessness, breathing problems during sleep
• one or more of the following mouth disorders: ulcers, loss of sensation, discomfort, discoloration, soft tissue disorders, tongue disorders, tongue pain, blisters or ulcers on the tongue, gum pain, dry or cracked lips, dental disorders
• inflammation of the oesophagus, intestinal paralysis, gallbladder disorders
• cold sweating, facial swelling, generalized itching, hair loss, muscle contractions, muscle weakness, feeling unwell, chest discomfort, thirst, feeling hot or cold, difficulty urinating
• feeling unwell
• redness

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

• disturbances in thinking, movement disorders
• blisters in the mouth, dry lips, collection of pus under the oral mucosa
• lack of testosterone, abnormal sensation in the eye, seeing flashes of light, brittle nails
• allergic reactions such as rash, redness, swelling of the lips and face, hives

Not known: frequency cannot be estimated from the available data

• loss of consciousness, breathing stoppage, seizures (convulsive seizures)
• lack of sex hormones (androgen deficiency)
• drug dependence (addiction) (see section 2)
• drug abuse (see section 2)
• drug tolerance (see section 2)
• delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, visual or auditory hallucinations, sleep disturbances, nightmares)
• prolonged use of fentanyl during pregnancy may cause withdrawal symptoms in the newborn baby, which may be fatal (see section 2)
• difficulty swallowing

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Effentora

Keep this medicine in a safe and secure place, out of reach of other people. Accidental or intentional use of this medicine by individuals for whom it has not been prescribed may cause serious harm and can be fatal.
The pain-relieving ingredient contained in Effentora is very potent and could be life-threatening if accidentally taken by a child. This medicine must be kept out of the sight and reach of children.

• Do not use this medicine after the expiry date stated on the blister pack label and on the outer packaging. The expiry date refers to the last day of that month.
• Store in the original packaging to protect the medicine from moisture.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to properly dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Effentora contains
The active substance 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 components are mannitol, sodium starch glycolate type A, sodium bicarbonate, sodium carbonate, citric acid, magnesium stearate.

Description of the appearance of Effentora and package contents
The orodispersible tablets are round, with flat surfaces and bevelled edges, marked on one side with the letter "C" and on the other side with the number "1" for Effentora 100 micrograms, "2" for Effentora 200 micrograms, "4" for Effentora 400 micrograms, "6" for Effentora 600 micrograms and "8" for Effentora 800 micrograms.
Each blister contains 4 orodispersible tablets. Packs contain either 4 or 28 orodispersible tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Phoenix Labs Unlimited Company
Suite 12, Bunkilla Plaza
Bracetown Business Park
Clonee, County Meath
Ireland

Manufacturer
Merckle GmbH
Ludwig-Merckle-Straße 3
89143 Blaubeuren
Germany

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder or call the following telephone number:

BE, BG, CZ, DK, DE, EE, EL, IE,
HR, IT, CY, LV, LT, LU, HU,
MT, NL, AT, PL, PT, RO, SI,
SK, FI, SE and XI
Phoenix Labs Unlimited Company
Suite 12, Bunkilla Plaza
Bracetown Business Park
Clonee, County Meath
Ireland
Email: [email protected]
Tel: +353 1 5742410

España
Euromed Pharma Spain S.L
Tel: +34 932 684 208

France
Centre Spécialités Pharmaceutiques (CSP)
Tél: +33 147048046

More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu