Sublifen

Patient Information Leaflet

Sublifen 100 micrograms sublingual tablets, 200 micrograms sublingual tablets, 300 micrograms sublingual tablets, 400 micrograms sublingual tablets

fentanyl
Generic medicine
Please read all of this leaflet carefully before you start taking this medicine, as 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 they have the same symptoms as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Sublifen is and what it is used for

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

2. What you need to know before taking Sublifen

Do not take Sublifen

• 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.
• if you are not regularly using an opioid painkiller prescribed by your doctor (e.g. codeine, fentanyl, hydromorphone, morphine, oxycodone, pethidine), taken daily on a regular schedule, for at least one week to manage persistent pain. If you are not taking these medicines, you must not use Sublifen, as it may increase the risk of dangerously slow and/or difficult breathing, or even respiratory arrest.
• if you have short-term pain other than breakthrough pain.
• if you are being treated with a medicine 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 Sublifen” for more information).
Talk to your doctor or pharmacist before taking Sublifen if you have or have recently had any of the following conditions, as your doctor will need to consider these when prescribing your dose:

• a head injury, as Sublifen may mask the severity of the injury.
• breathing problems or myasthenia gravis (a condition characterized by muscle weakness).
• heart problems, particularly slow heart rate.
• low blood pressure.
• kidney or liver disease, as this may require your doctor to adjust your dose more carefully.
• brain tumour 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 Sublifen”.
• if you have previously developed adrenal insufficiency or deficiency of sex hormones (androgen deficiency) while using opioids.

During treatment with Sublifen, 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 develop 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 Sublifen. This is known as hyperalgesia. Increasing the dose of Sublifen may help reduce pain for a while, 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 Sublifen.

Dependence and substance abuse
This medicine contains fentanyl, an opioid. It may cause dependence and/or substance abuse.
Repeated use of Sublifen may 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 that you no longer have control over the amount of 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 Sublifen 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 Sublifen may indicate dependence or substance abuse:

• you feel the need to use the medicine for longer 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, e.g. “to stay calm” or “to help sleep”
• you have made repeated unsuccessful attempts to stop or control use of this medicine
• when you stop taking the medicine, you feel unwell (e.g. nausea, vomiting, diarrhoea, anxiety, chills, tremors and sweating) and 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
Sublifen may cause sleep-related breathing disorders such as sleep apnoea (pauses in breathing during sleep) and sleep-related hypoxaemia (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 your dose.

For athletes:
Using this medicine without a therapeutic need constitutes doping and may lead to a positive anti-doping test.

Other medicines and Sublifen
Tell 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 decrease the effects of Sublifen. Therefore, if you start or stop taking any of the following medicines, or change their dose, inform your doctor, as your Sublifen dose may need to be adjusted:

• certain antifungal agents containing, for example, ketoconazole or itraconazole (used to treat fungal infections);
• certain types of antibiotics called macrolides, containing, for example, erythromycin (used to treat infections);
• 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 medicines 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 potent analgesics called partial agonist/antagonists, for example buprenorphine, nalbuphine and pentazocine (medicines used to treat pain). When used together with these medicines, withdrawal symptoms (nausea, vomiting, diarrhoea, anxiety, chills, tremors and sweating) may occur.

Sublifen may intensify the effects of medicines that cause drowsiness (sedatives), such as:

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

Concomitant use of Sublifen and medicines that may 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 Sublifen with sedative medicines should only be considered when no other treatment options are possible.
However, if your doctor prescribes Sublifen 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 your doctor’s dosage recommendations carefully. 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 adverse effects increases if you are taking certain antidepressants or antipsychotics. Sublifen 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, diarrhoea). Your doctor will advise you whether Sublifen is suitable for you.

Sublifen with food, drinks and alcohol
In some people, Sublifen 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 Sublifen, as it may increase the side effects of Sublifen.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding,
ask your doctor or pharmacist for advice before taking this medicine.
Do not use Sublifen during pregnancy unless specifically instructed by your doctor.
Fentanyl may pass into breast milk and cause adverse effects in the breastfed infant. Do not use Sublifen while breastfeeding. You may resume breastfeeding only at least 5 days after taking the last dose of Sublifen.

Driving and using machines
Sublifen 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 Sublifen, do not drive or operate machinery.

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

3. How to take Sublifen

Before taking Sublifen for the first time, your doctor will explain how to take it effectively to treat
episodic intense pain.
Before starting treatment and regularly during treatment, your doctor will also discuss with you what
you can expect from using Sublifen, 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).
Always take this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor or pharmacist.
This medicine 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 health, especially in children.
Sublifen is different from other medicines you may have used to treat episodic intense pain. You must
always use the dose of Sublifen prescribed by your doctor – this may be a different dose from what
you have used with other medicines for episodic intense pain.

Initial treatment – finding the most suitable dose
For Sublifen to work, your doctor must identify the most suitable dose for treating your episodic
intense pain. Sublifen is available in a range of dosage strengths. You may need to try different doses
of Sublifen during separate episodes of episodic intense pain to find the most suitable dose. Your
doctor will help you find the best dose to use.
If you do not achieve adequate pain relief from one dose, your doctor may ask you to take an extra
dose to treat an episode of episodic intense pain.
Do not take a second dose unless your doctor tells you that you may do so, as this could lead to
overdose.
Your doctor may advise you to take a dose consisting of more than one tablet at a time. Take this dose
only if prescribed by your doctor.
Wait at least 2 hours after taking the last dose before treating a new episode of episodic intense pain
with Sublifen.

Continuing treatment – once the most suitable dose has been found
Once you and your doctor have found a dose of Sublifen that controls your episodic intense pain, you
should take this dose no more than four times a day. A dose of Sublifen may consist of more than one
tablet.
Wait at least 2 hours after taking the last dose before treating a new episode of episodic intense pain
with Sublifen.
If you feel that the dose of Sublifen you are using does not satisfactorily control your episodic intense
pain, inform your doctor, as they may need to adjust your dose.
Do not change the dose of Sublifen unless your doctor has instructed you to do so.

How to take the medicine
Sublifen must be used sublingually, which means that the tablet must be placed under the tongue,
where it dissolves rapidly, allowing fentanyl to be absorbed through the inner lining of the mouth. Once
absorbed, fentanyl begins to exert its analgesic effect.
When you experience an episode of episodic intense pain, take the dose prescribed by your doctor in
the following way:

• If your mouth is dry, take a sip of water to moisten it. Spit out or swallow the water.
• Remove one or more tablets from the blister pack immediately before use, as follows:
  o Separate one blister square from the pack by cutting along the dotted lines/perforations (leave the remaining blister squares intact).
  o Peel back the edge of the aluminium layer where the arrow is indicated and gently remove the tablet. Do not try to push Sublifen sublingual tablets through the upper aluminium layer, as this may damage them.
• Place the tablet under the tongue as deeply as possible and allow it to dissolve completely.
• Sublifen will dissolve rapidly under the tongue and be absorbed to exert its analgesic effect. It is therefore important not to suck, chew, or swallow the tablet.
• Do not drink or eat anything until the tablet has completely dissolved under the tongue.

If you take more Sublifen 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 the doctor, the person should be kept awake by talking to them or continuously shaking them.

Symptoms of overdose include:

• extreme drowsiness
• slowed or difficult breathing
• coma

In such an event, seek immediate emergency medical treatment.
An overdose may also cause a brain disorder known as toxic leukoencephalopathy.
If you suspect that someone has accidentally taken Sublifen, seek immediate emergency medical
treatment.

If you stop taking Sublifen
If you no longer experience episodic intense pain, you should stop treatment with Sublifen. However,
you must continue taking your usual opioid-based analgesic medicine for the treatment of persistent
tumour pain, as directed by your doctor. If you stop treatment with Sublifen, you may experience
withdrawal symptoms similar to possible side effects of Sublifen. Contact your doctor if you develop
withdrawal symptoms or have concerns regarding pain relief. Your doctor will assess whether to
prescribe a medicine 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 start feeling unusually or extremely sleepy, or if you experience slow or shallow breathing,
you or the person assisting you must immediately contact your doctor or the local hospital for emergency medical assistance (see also section 3 “If you take more Sublifen 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 drowsiness
• 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, blurred or disturbed vision, increased or decreased heart rate, low blood pressure, memory loss
• depression, paranoia / unexplained fear, confusion, disorientation, anxiety / unhappiness / restlessness, unusual sense of well-being / happiness, 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 alteration of taste/smell
• difficulty sleeping or disturbed sleep, attention disturbances / easy 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
• 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 determined from the available data)

• swelling of the tongue, severe breathing problems, falls, flushing, feeling very hot, diarrhoea, seizures (epileptic fits), swelling of arms or legs, seeing or hearing things that do not exist (hallucinations), fever
• drug tolerance, drug dependence (addiction)
• drug abuse (see section 2)
• reduced level or loss of consciousness
• itchy skin rash
• delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, visual or auditory hallucinations, sleep disturbances, nightmares)

Prolonged fentanyl treatment during pregnancy may cause withdrawal symptoms in the newborn, which may be fatal (see section 2).
Reporting of side effects
If you experience any side effect, 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 at https://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 Sublifen

The painkiller contained in Sublifen is very potent and could be life-threatening if accidentally taken by a child. Keep Sublifen out of sight and reach of children.
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.
Store in the original blister to protect the medicine from moisture.
This medicine does not require any special storage conditions.
Keep this medicine in a safe and secure place, inaccessible to other people. Accidental or intentional ingestion of this medicine by individuals for whom it has not been prescribed may cause serious harm or be fatal.
It is recommended to store Sublifen in a secure, locked storage location.
Any unused product should, if possible, be returned to the pharmacist for safe disposal. Do not dispose of medicines via wastewater or household waste. This will help protect the environment.

6. Package contents and other information

What Sublifen contains

• The active substance is fentanyl. One sublingual tablet contains:
  157 micrograms of fentanyl citrate equivalent to 100 micrograms of fentanyl
  314 micrograms of fentanyl citrate equivalent to 200 micrograms of fentanyl
  471 micrograms of fentanyl citrate equivalent to 300 micrograms of fentanyl
  628 micrograms of fentanyl citrate equivalent to 400 micrograms of fentanyl
• The other components are: mannitol (E421), silicified microcrystalline cellulose (E460/E551), sodium croscarmellose (E468), and magnesium stearate (E470b).

Description of the appearance of Sublifen and the contents of the pack
Sublifen is a small white sublingual tablet intended to be placed under the tongue. It is available in a range of different strengths and forms. Your doctor will prescribe the appropriate strength (form) and number of tablets for you.
The 100 microgram tablet is a round, white tablet, 6 mm in diameter.
The 200 microgram tablet is an oval-shaped, white tablet, 7x5 mm.
The 300 microgram tablet is a triangular-shaped, white tablet, 6x6 mm.
The 400 microgram tablet is a rhombus-shaped, white tablet, 9x7 mm.
Sublifen 100 micrograms is available in packs of 5 x 1, 10 x 1 and 30 x 1 tablets.
Sublifen 200 micrograms is available in packs of 5 x 1, 10 x 1 and 30 x 1 tablets.
Sublifen 300 micrograms is available in packs of 10 x 1 and 30 x 1 tablets.
Sublifen 400 micrograms is available in packs of 5 x 1, 10 x 1 and 30 x 1 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
G.L. Pharma GmbH,
Schlossplatz 1,
8502 Lannach,
Austria

Manufacturer
PRASFARMA S.L.,
C. Sant Joan, 11-15,
08560 Manlleu (Barcelona),
Spain
G.L. Pharma GmbH,
Schlossplatz 1,
8502 Lannach,
Austria
KERN PHARMA S.L.,
Polígono Ind. Colón II,
C/Venus 72,
08228 Terrassa (Barcelona),
Spain

Sales Concessionaire:
G.L. Pharma Italy S.r.l., [email protected]

This medicinal product is authorised in the European Economic Area Member States under the following names:
Netherlands, Slovakia, Poland, Sweden, Austria: Submena
Italy, Belgium, Denmark: Sublifen
Czech Republic: Menasu