Abstral: detailed information

Patient Information Leaflet

Abstral 100 microgram sublingual tablets, 200 microgram sublingual tablets, 300 microgram sublingual tablets, 400 microgram sublingual tablets, 600 microgram sublingual tablets, 800 microgram sublingual tablets

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

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people. Even if their symptoms are the same as yours, it could be harmful.
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Abstral is and what it is used for
What you need to know before taking Abstral
How to take Abstral
Possible side effects
How to store Abstral
Contents of the pack and other information

1. What Abstral is and what it is used for

Abstral is a treatment intended for adults who are already taking regularly strong
opioid painkillers for persistent cancer-related pain, but who require additional treatment for breakthrough pain.
If you have any doubts, consult your doctor.
Breakthrough pain is sudden, intense pain that occurs even though you have already taken your usual opioid painkiller.
The active substance in Abstral sublingual tablets is fentanyl. Fentanyl belongs to a group of potent painkillers known as opioids.

2. What you should know before taking Abstral

Do not take Abstral

if you are allergic to fentanyl or to any of the excipients of this medicine (listed in section 6)
if you have severe respiratory problems
if you are not regularly using an opioid medicine prescribed by your doctor (e.g. codeine, fentanyl, hydromorphone, morphine, oxycodone, meperidine), taken every day on a regular schedule, for at least one week to manage persistent pain. If you are not using these medicines, you must not use Abstral, as it may increase the risk of breathing becoming slow and/or difficult in a dangerous way, or even stopping
if you suffer from short-term pain other than breakthrough pain
if you are being treated with medicines containing sodium oxybate.

Warnings and precautions
Keep this medicine in a safe and secure place, out of reach of other people (see section 5 “How to store Abstral” for more information).
Talk to your doctor or pharmacist before taking Abstral if you have or have recently had any of the following conditions, as your doctor will need to consider these when prescribing the dose:

a head injury, as Abstral may mask the severity of the injury
respiratory problems or myasthenia gravis (a condition characterized by muscle weakness)
heart problems, particularly a slow heartbeat
low blood pressure
kidney or liver disease, as this may require your doctor to adjust the dose more carefully
brain tumor and/or increased intracranial pressure (increased pressure in the brain causing severe headache, nausea/vomiting, and blurred vision)
mouth sores or mucositis (swelling and redness inside the mouth)
if you are taking antidepressants or antipsychotics, refer to the section “Other medicines and Abstral”
if you have previously developed adrenal insufficiency or lack of sex hormones (androgen deficiency) while using opioids

During treatment with Abstral, inform your doctor or dentist that you are taking this medicine if:

you are about to undergo surgery
you experience pain or increased sensitivity to pain (hyperalgesia) that does not respond to an increase in the dose of your prescribed medicine
you experience a combination of the following symptoms: nausea, vomiting, loss of appetite, 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

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 during treatment with Abstral. This is known as hyperalgesia. Increasing the dose of Abstral may help reduce pain for a short time, but it may also be harmful. If you notice that the medicine becomes less effective, talk to your doctor. Your doctor will decide whether it is better to increase the dose or gradually reduce the use of Abstral.

Dependence and substance abuse
This medicine contains fentanyl, an opioid. It may cause dependence and/or substance abuse.
Repeated use of fentanyl may also lead to dependence, abuse, and substance abuse, 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 substance abuse 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 does not help relieve your pain.
The risk of developing dependence or substance abuse varies from person to person. You may have a higher risk of becoming dependent on or abusing Abstral if:

you or a family member has previously suffered from alcohol, prescription medicine, or illegal substance abuse or dependence (“substance abuse”)
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 Abstral may be a sign of dependence or substance abuse:

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 tried several times to stop or control the 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 symptoms”)

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

Sleep-related breathing disorders
Abstral 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 during sleep). Symptoms may include pauses in breathing during sleep, waking up at night due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else notices these symptoms, talk to your doctor. Your doctor may consider reducing the dose.

For athletes: using the medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and Abstral
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine (other than your usual opioid painkiller).

Some medicines may increase or reduce the effects of Abstral. Therefore, if you start or stop taking any of the following medicines, or change their dose, inform your doctor, as they may need to adjust your Abstral dose:

certain types of antifungal agents containing, for example, ketoconazole or itraconazole (used to treat fungal infections)
certain types of antibiotics used to treat infections (called macrolides, containing, for example, erythromycin)
certain types of antiviral medicines called protease inhibitors, containing, for example, ritonavir (used to treat viral infections)
rifampicin or rifabutin (medicines used to treat bacterial infections)
carbamazepine, phenytoin, or phenobarbital (medicines used to treat seizures/epileptic fits)
herbal remedies containing St. John’s wort (Hypericum perforatum)
medicines containing alcohol
medicines called monoamine oxidase inhibitors (MAOIs), used for severe depression and Parkinson’s disease; inform your doctor if you have taken this type of medicine within the last two weeks
certain types of strong analgesics called partial agonist/antagonists, for example buprenorphine, nalbuphine, and pentazocine (medicines used to treat pain). When used in combination with these medicines, withdrawal symptoms (nausea, vomiting, diarrhea, anxiety, chills, tremors, and sweating) may occur.

Abstral may enhance the effect of medicines that cause drowsiness (sedatives), such as:

other strong painkillers (opioid-type medicines, e.g. for pain and cough)
certain nerve pain medicines (gabapentin and pregabalin)
general anesthetics (used to induce sleep during surgery)
muscle relaxants
sleeping pills
medicines used to treat depression, allergies, or anxiety (such as benzodiazepines, e.g. diazepam) and psychosis
medicines containing clonidine (used to treat high blood pressure)

Concomitant use of Abstral and medicines that cause drowsiness (sedatives), such as benzodiazepines, increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be life-threatening. For this reason, concomitant use of Abstral and sedative medicines should only be considered when no other treatment options are possible.
However, if your doctor prescribes Abstral together with sedative medicines, the dose and duration of concomitant treatment must be limited by your doctor.
Inform your doctor about all sedative medicines you are taking and follow carefully the dose recommendations provided by your doctor. It may be helpful to inform friends or family members about the signs and symptoms listed above. Contact your doctor if these symptoms occur.

The risk of certain other adverse effects increases if you are taking certain antidepressants or antipsychotics. Abstral 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 Abstral is suitable for you.

Abstral with food, drinks, and alcohol
In some people, Abstral may cause drowsiness. Do not drink alcohol without consulting your doctor, as it may cause increased drowsiness.
Do not drink grapefruit juice if you have been prescribed Abstral, as it may increase the side effects of Abstral.

Pregnancy and breastfeeding
Do not use Abstral during pregnancy unless explicitly instructed by your doctor.
Fentanyl can pass into breast milk and cause adverse effects in the breastfed infant. Do not take Abstral while breastfeeding. You may only resume breastfeeding your baby at least 5 days after taking the last dose of Abstral.
Ask your doctor or pharmacist for advice before taking any medicine during pregnancy or breastfeeding.

Driving and using machines
Abstral may affect your physical or mental ability to perform potentially dangerous activities, such as driving or operating machinery.
If you experience dizziness, drowsiness, or blurred vision when taking Abstral, do not drive or operate machinery.

Abstral contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take Abstral

Before taking Abstral for the first time, your doctor will explain how to take it effectively to treat breakthrough pain.
Before starting treatment and regularly during treatment, your doctor will also discuss with you what to expect from using Abstral, 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).
Take this medicine exactly as your doctor has instructed. If you have any doubts, consult your doctor or pharmacist.
This product must be used only by you, based on the instructions provided by your doctor. It must not be used by anyone else, as it may pose a SERIOUS risk to their health, especially in children.
Abstral is different from other medicines you may have used to treat breakthrough pain. You must always use the dose of Abstral prescribed by your doctor – this may be a different dose from what you have used with other medicines for breakthrough pain.

Initial treatment – finding the most suitable dose
For Abstral to work effectively, your doctor must determine the most suitable dose to treat your breakthrough pain. Abstral is available in a range of strengths. You may need to try different strengths of Abstral during separate episodes of breakthrough pain to find the most suitable dose. Your doctor will help you identify the best dose to use.
If you do not get adequate pain relief from one dose, your doctor may instruct you to take an additional dose to treat an episode of breakthrough pain. Do not take a second tablet unless your doctor tells you it is safe to do so, as you could risk an overdose.
Your doctor may advise you to take a dose consisting of more than one tablet at a time. Take this dose only if specifically prescribed by your doctor.
Wait at least 2 hours after taking the last dose before treating a new episode of breakthrough pain with Abstral.

Ongoing treatment – once the most suitable dose has been found
Once you and your doctor have identified a dose of Abstral that controls your breakthrough pain effectively, you should take this dose no more than four times a day. One dose of Abstral may consist of more than one tablet.
Wait at least 2 hours after taking the last dose before treating a new episode of breakthrough pain with Abstral.
If you feel that the dose of Abstral you are using does not adequately control your breakthrough pain, inform your doctor, as your dose may need adjustment.
Do not change the dose of Abstral unless your doctor tells you to do so.

How to take the medicine
Abstral must be used sublingually. This means that the tablet must be placed under the tongue, where it dissolves rapidly, allowing fentanyl to be absorbed through the mucous membranes inside the mouth. Once absorbed, fentanyl begins to work to provide pain relief.
When you experience an episode of breakthrough pain, 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 one or more tablets from the blister pack immediately before taking them, as follows:
- separate one blister cell from the pack by cutting along the dotted lines (leave the remaining blister cells intact).
- peel back the edge of the aluminium layer at the point indicated by the arrow and gently remove the tablet. Do not try to push Abstral sublingual tablets through the top aluminium layer, as this may damage them;
place the tablet under the tongue as far back as possible and allow it to dissolve completely;
Abstral will dissolve rapidly under the tongue and be absorbed to exert its analgesic effect. Therefore, it is important not to suck, chew, or swallow the tablet;
do not eat or drink anything until the tablet has completely dissolved under the tongue.

If you take more Abstral than you should:

remove any tablets from the mouth;
inform the person assisting you or anyone else about what has happened;
you or the person assisting you must immediately contact your doctor, pharmacist, or local hospital and discuss what action to take;
while waiting for medical help, keep the person awake by talking to them or gently shaking them.

Symptoms of an overdose include:

extreme drowsiness
slowed or difficult breathing
coma

An overdose may also cause a brain disorder known as toxic leukoencephalopathy.
In such a case, seek immediate emergency medical treatment.
If you think someone has accidentally taken Abstral, seek immediate emergency medical treatment.

If you stop taking Abstral
If you no longer experience breakthrough pain, you should stop treatment with Abstral. However, you must continue taking your usual opioid-based pain medication for persistent cancer pain, as directed by your doctor. When stopping Abstral treatment, you may experience withdrawal symptoms similar to possible side effects of Abstral.
Contact your doctor if you develop withdrawal symptoms or have concerns about pain control. Your doctor will assess whether to prescribe a medicine to reduce or eliminate withdrawal symptoms.
If you have any doubts 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 gets them.
If you start feeling unusually or extremely drowsy, or if you experience slow or difficult breathing,
you or the person assisting you must immediately contact a doctor or your local hospital for emergency
medical treatment (see also section 3 “If you take more Abstral than you should”).

Very common side effects (may affect more than 1 in 10 people) include:

nausea

Common side effects (may affect up to 1 in 10 people) include:

dizziness, headache, excessive sleepiness
dyspnea/shortness of breath
inflammation of the oral mucosa, vomiting, constipation, dry mouth
sweating, fatigue/tiredness/lack of energy

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

allergic reaction, tremor/shaking, blurred or disturbed vision, increased or slowed heart rate, low blood pressure, memory loss
depression, paranoia/unexplained fear, confusion, disorientation, anxiety/unhappiness/restlessness, unusual sense of well-being, mood swings
feeling of fullness in the stomach, stomach ache, indigestion
mouth ulcers, tongue disorders, mouth or throat pain, throat tightness, lip or gum ulcers
loss of appetite, loss or change in taste/smell
difficulty sleeping or disturbed sleep, attention disorders/distractibility, lack of energy/weakness/loss of strength
skin abnormalities, skin rashes, itching, night sweats, reduced sensitivity to touch, tendency to bruise easily
joint pain or stiffness, muscle stiffness
drug withdrawal symptoms (may occur if the following side effects appear: nausea, vomiting, diarrhoea, anxiety, chills, tremors and sweating), accidental overdose, in men inability to achieve and/or maintain an erection, general feeling of malaise

Side effects of unknown frequency: (frequency cannot be estimated from the available data)

swelling of the tongue, severe breathing problems, falls, flushing, feeling very hot, diarrhoea, seizures (epileptic fits), swelling of the arms or legs, seeing or hearing things that are not there (hallucinations), fever, decreased level or loss of consciousness, itching, and delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that are not there, sleep disturbances, nightmares).
drug tolerance, substance abuse dependence (addiction), drug abuse (see section 2).

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

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Abstral

The pain medicine contained in Abstral is very potent and could be life-threatening if accidentally
taken by a child. Keep Abstral out of sight and reach of children.
Store this medicine in a safe and secure place, inaccessible to other people. Accidental or intentional
use of this medicine by individuals for whom it has not been prescribed may cause serious harm or be fatal.
It is recommended to store Abstral in a secure, locked storage location.
Do not use this medicine after the expiry date stated on the blister after EXP. The expiry date refers to the last day of that month.
Do not store above 25°C.
Keep in the original blister to protect the medicine from moisture.
Any unused product should, if possible, be returned to the pharmacist for safe disposal. Do not dispose of any medicine via wastewater or household waste. This will help protect the environment.

6. Package contents and other information

What Abstral contains
The active substance is fentanyl. One sublingual tablet contains:
100 micrograms of fentanyl (citrate)
200 micrograms of fentanyl (citrate)
300 micrograms of fentanyl (citrate)
400 micrograms of fentanyl (citrate)
600 micrograms of fentanyl (citrate)
800 micrograms of fentanyl (citrate)
The excipients are mannitol (E421), silicified microcrystalline cellulose, sodium croscarmellose, and magnesium stearate.

Description of the appearance of Abstral and contents of the pack
Abstral is a small white sublingual tablet, designed to be placed under the tongue. It is available in a range of different strengths and shapes. Your doctor will prescribe the appropriate strength (form) and number of tablets for you.

The 100 microgram tablet is white and round
The 200 microgram tablet is white and oval
The 300 microgram tablet is white and triangular
The 400 microgram tablet is white and pentagonal
The 600 microgram tablet is white and D-shaped
The 800 microgram tablet is white and capsule-shaped

Abstral tablets are available in packs of 10 or 30 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder:
Grünenthal Italia S.r.l.
Via Vittor Pisani, 16
20124 Milan, Italy

Manufacturer:
RECIPHARM LEGANÉS S.L.U.
Calle Severo Ochoa 13
Leganés, 28914 (Madrid), Spain

This medicinal product is authorised in the European Economic Area (EEA) Member States and in the United Kingdom (Northern Ireland) under the following names:
Abstral:
Cyprus, Denmark, Finland, France, Germany, Greece, Ireland, Iceland, Italy, Norway, the Netherlands, Portugal, United Kingdom (Northern Ireland), Spain, Sweden.
Lunaldin:
Estonia, Latvia, Lithuania, Czech Republic, Romania, Slovakia.